Effect of Pediatric Behavioral Health Screening and Colocated Services on Ambulatory and Inpatient Utilization.

Science.gov (United States)

Hacker, Karen A; Penfold, Robert B; Arsenault, Lisa N; Zhang, Fang; Soumerai, Stephen B; Wissow, Lawrence S

2015-11-01

The study sought to determine the impact of a pediatric behavioral health screening and colocation model on utilization of behavioral health care. In 2003, Cambridge Health Alliance, a Massachusetts public health system, introduced behavioral health screening and colocation of social workers sequentially within its pediatric practices. An interrupted time-series study was conducted to determine the impact on behavioral health care utilization in the 30 months after model implementation compared with the 18 months prior. Specifically, the change in trends of ambulatory, emergency, and inpatient behavioral health utilization was examined. Utilization data for 11,223 children ages ≥4 years 9 months to <18 years 3 months seen from 2003 to 2008 contributed to the study. In the 30 months after implementation of pediatric behavioral health screening and colocation, there was a 20.4% cumulative increase in specialty behavioral health visit rates (trend of .013% per month, p=.049) and a 67.7% cumulative increase in behavioral health primary care visit rates (trend of .019% per month, p<.001) compared with the expected rates predicted by the 18-month preintervention trend. In addition, behavioral health emergency department visit rates increased 245% compared with the expected rate (trend .01% per month, p=.002). After the implementation of a behavioral health screening and colocation model, more children received behavioral health treatment. Contrary to expectations, behavioral health emergency department visits also increased. Further study is needed to determine whether this is an effect of how care was organized for children newly engaged in behavioral health care or a reflection of secular trends in behavioral health utilization or both.

Design of novel nano-carriers for multi-enzyme co-localization

Energy Technology Data Exchange (ETDEWEB)

Jia, Feng [Iowa State Univ., Ames, IA (United States)

2013-01-01

The main objective of this project is to design novel nano-structured carriers and strategies to co-localize multiple enzymes to mimic the functionalities of MECs. In order to achieve this goal, distinct approaches for enzyme co-localization were developed and evaluated. Specifically, we investigated different polymeric nano-carriers, both flexible and rigid, as platforms for co-localization, as well as distinct enzyme attachment techniques using model enzyme systems using glucose oxidase and horseradish peroxidase to control the spatial arrangement of the multiple enzymes on the nanocarriers. This platform technology can be potentially used to co-localize various enzyme systems and its broad applicability will be tested using the sclareol biosynthesis process to control the formation of products through the formation of MECs with multiple enzymes NgCPS and sSsSS to regulate the pathway of reactive intermediate to enhance the final product conversion rate.

The colocalization transition of homologous chromosomes at meiosis

Science.gov (United States)

Nicodemi, Mario; Panning, Barbara; Prisco, Antonella

2008-06-01

Meiosis is the specialized cell division required in sexual reproduction. During its early stages, in the mother cell nucleus, homologous chromosomes recognize each other and colocalize in a crucial step that remains one of the most mysterious of meiosis. Starting from recent discoveries on the system molecular components and interactions, we discuss a statistical mechanics model of chromosome early pairing. Binding molecules mediate long-distance interaction of special DNA recognition sequences and, if their concentration exceeds a critical threshold, they induce a spontaneous colocalization transition of chromosomes, otherwise independently diffusing.

Dual channel rank-based intensity weighting for quantitative co-localization of microscopy images

LENUS (Irish Health Repository)

Singan, Vasanth R

2011-10-21

Abstract Background Accurate quantitative co-localization is a key parameter in the context of understanding the spatial co-ordination of molecules and therefore their function in cells. Existing co-localization algorithms consider either the presence of co-occurring pixels or correlations of intensity in regions of interest. Depending on the image source, and the algorithm selected, the co-localization coefficients determined can be highly variable, and often inaccurate. Furthermore, this choice of whether co-occurrence or correlation is the best approach for quantifying co-localization remains controversial. Results We have developed a novel algorithm to quantify co-localization that improves on and addresses the major shortcomings of existing co-localization measures. This algorithm uses a non-parametric ranking of pixel intensities in each channel, and the difference in ranks of co-localizing pixel positions in the two channels is used to weight the coefficient. This weighting is applied to co-occurring pixels thereby efficiently combining both co-occurrence and correlation. Tests with synthetic data sets show that the algorithm is sensitive to both co-occurrence and correlation at varying levels of intensity. Analysis of biological data sets demonstrate that this new algorithm offers high sensitivity, and that it is capable of detecting subtle changes in co-localization, exemplified by studies on a well characterized cargo protein that moves through the secretory pathway of cells. Conclusions This algorithm provides a novel way to efficiently combine co-occurrence and correlation components in biological images, thereby generating an accurate measure of co-localization. This approach of rank weighting of intensities also eliminates the need for manual thresholding of the image, which is often a cause of error in co-localization quantification. We envisage that this tool will facilitate the quantitative analysis of a wide range of biological data sets

Selecting optimum locations for co-located wave and wind energy farms. Part I: The Co-Location Feasibility index

International Nuclear Information System (INIS)

Astariz, S.; Iglesias, G.

2016-01-01

Highlights: • New approach to identifying suitable sites for co-located wave and wind farms. • A new tool, the Co-Location Feasibility (CLF) index, is defined. • Its application is analysed by means of a case study off the Danish coast. • Hindcast and measured wave and wind data from 2005 to 2015 are used. • Third-generation models of winds and waves (WAsP and SWAN) are used. - Abstract: Marine energy is poised to play a fundamental role in meeting renewable energy and carbon emission targets thanks to the abundant, and still largely untapped, wave and tidal resources. However, it is often considered difficult and uneconomical – as is usually the case of nascent technologies. Combining various renewables, such as wave and offshore wind energy, has emerged as a solution to improve their competitiveness and in the process overcome other challenges that hinder their development. The objective of this paper is to develop a new approach to identifying suitable sites for co-located wave and wind farms based on the assessment of the available resources and technical constraints, and to illustrate its application by means of a case study off the Danish coast – an area of interest for combining wave and wind energy. The method is based on an ad hoc tool, the Co-Location Feasibility (CLF) index, and is based on a joint characterisation of the wave and wind resources, which takes into account not only the available power but also the correlation between both resources and the power variability. The analysis is carried out based on hindcast data and observations from 2005 to 2015, and using third-generation models of winds and waves – WAsP and SWAN, respectively. Upon selection and ranking, it is found that a number of sites in the study region are indeed suited to realising the synergies between wave and offshore wind energy. The approach developed in this work can be applied elsewhere.

The benefits of co-location in primary care practices: the perspectives of general practitioners and patients in 34 countries.

Science.gov (United States)

Bonciani, M; Schäfer, W; Barsanti, S; Heinemann, S; Groenewegen, P P

2018-02-21

There is no clear evidence as to whether the co-location of primary care professionals in the same facility positively influences their way of working and the quality of healthcare as perceived by patients. The aim of this study was to identify the relationships between general practitioner (GP) co-location with other GPs and/or other professionals and the GP outcomes and patients' experiences. We wanted to test whether GP co-location is related to a broader range of services provided, the use of clinical governance tools and inter-professional collaboration, and whether the patients of co-located GPs perceive a better quality of care in terms of accessibility, comprehensiveness and continuity of care with their GPs. The source of data was the QUALICOPC study (Quality and Costs of Primary Care in Europe), which involved surveys of GPs and their patients in 34 countries, mostly in Europe. In order to study the relationships between GP co-location and both GPs' outcomes and patients' experience, multilevel linear regression analysis was carried out. The GP questionnaire was filled in by 7183 GPs and the patient experience questionnaire by 61,931 patients. Being co-located with at least one other professional is the most common situation of the GPs involved in the study. Compared with single-handed GP practices, GP co-location are positively associated with the GP outcomes. Considering the patients' perspective, comprehensiveness of care has the strongest negative relationship of GP co-location of all the dimensions of patient experiences analysed. The paper highlights that GP mono- and multi-disciplinary co-location is related to positive outcomes at a GP level, such as a broader provision of technical procedures, increased collaboration among different providers and wider coordination with secondary care. However, GP co-location, particularly in a multidisciplinary setting, is related to less positive patient experiences, especially in countries with health systems

Photosynthetic and Heterotrophic Ferredoxin Isoproteins Are Colocalized in Fruit Plastids of Tomato1

Science.gov (United States)

Aoki, Koh; Yamamoto, Miyuki; Wada, Keishiro

1998-01-01

Fruit tissues of tomato (Lycopersicon esculentum Mill.) contain both photosynthetic and heterotrophic ferredoxin (FdA and FdE, respectively) isoproteins, irrespective of their photosynthetic competence, but we did not previously determine whether these proteins were colocalized in the same plastids. In isolated fruit chloroplasts and chromoplasts, both FdA and FdE were detected by immunoblotting. Colocalization of FdA and FdE in the same plastids was demonstrated using double-staining immunofluorescence microscopy. We also found that FdA and FdE were colocalized in fruit chloroplasts and chloroamyloplasts irrespective of sink status of the plastid. Immunoelectron microscopy demonstrated that FdA and FdE were randomly distributed within the plastid stroma. To investigate the significance of the heterotrophic Fd in fruit plastids, Glucose 6-phosphate dehydrogenase (G6PDH) activity was measured in isolated fruit and leaf plastids. Fruit chloroplasts and chromoplasts showed much higher G6PDH activity than did leaf chloroplasts, suggesting that high G6PDH activity is linked with FdE to maintain nonphotosynthetic production of reducing power. This result suggested that, despite their morphological resemblance, fruit chloroplasts are functionally different from their leaf counterparts. PMID:9765529

The polyomavirus BK agnoprotein co-localizes with lipid droplets

International Nuclear Information System (INIS)

Unterstab, Gunhild; Gosert, Rainer; Leuenberger, David; Lorentz, Pascal; Rinaldo, Christine H.; Hirsch, Hans H.

2010-01-01

Agnoprotein encoded by human polyomavirus BK (BKV) is a late cytoplasmic protein of 66 amino acids (aa) of unknown function. Immunofluorescence microscopy revealed a fine granular and a vesicular distribution in donut-like structures. Using BKV(Dunlop)-infected or agnoprotein-transfected cells, we investigated agnoprotein co-localization with subcellular structures. We found that agnoprotein co-localizes with lipid droplets (LD) in primary human renal tubular epithelial cells as well as in other cells supporting BKV replication in vitro (UTA, Vero cells). Using agnoprotein-enhanced green fluorescent protein (EGFP) fusion constructs, we demonstrate that agnoprotein aa 20-42 are required for targeting LD, whereas aa 1-20 or aa 42-66 were not. Agnoprotein aa 22-40 are predicted to form an amphipathic helix, and mutations A25D and F39E, disrupting its hydrophobic domain, prevented LD targeting. However, changing the phosphorylation site serine-11 to alanine or aspartic acid did not alter LD co-localization. Our findings provide new clues to unravel agnoprotein function.

Solid-phase single molecule biosensing using dual-color colocalization of fluorescent quantum dot nanoprobes

Science.gov (United States)

Liu, Jianbo; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Liu, Wei; Wang, Dong

2013-10-01

The development of solid-phase surface-based single molecule imaging technology has attracted significant interest during the past decades. Here we demonstrate a sandwich hybridization method for highly sensitive detection of a single thrombin protein at a solid-phase surface based on the use of dual-color colocalization of fluorescent quantum dot (QD) nanoprobes. Green QD560-modified thrombin binding aptamer I (QD560-TBA I) were deposited on a positive poly(l-lysine) assembled layer, followed by bovine serum albumin blocking. It allowed the thrombin protein to mediate the binding of the easily detectable red QD650-modified thrombin binding aptamer II (QD650-TBA II) to the QD560-TBA I substrate. Thus, the presence of the target thrombin can be determined based on fluorescent colocalization measurements of the nanoassemblies, without target amplification or probe separation. The detection limit of this assay reached 0.8 pM. This fluorescent colocalization assay has enabled single molecule recognition in a separation-free detection format, and can serve as a sensitive biosensing platform that greatly suppresses the nonspecific adsorption false-positive signal. This method can be extended to other areas such as multiplexed immunoassay, single cell analysis, and real time biomolecule interaction studies.The development of solid-phase surface-based single molecule imaging technology has attracted significant interest during the past decades. Here we demonstrate a sandwich hybridization method for highly sensitive detection of a single thrombin protein at a solid-phase surface based on the use of dual-color colocalization of fluorescent quantum dot (QD) nanoprobes. Green QD560-modified thrombin binding aptamer I (QD560-TBA I) were deposited on a positive poly(l-lysine) assembled layer, followed by bovine serum albumin blocking. It allowed the thrombin protein to mediate the binding of the easily detectable red QD650-modified thrombin binding aptamer II (QD650-TBA II) to

Designing for social play in co-located mobile games

DEFF Research Database (Denmark)

Goddard, William; Garner, Jayden; Jensen, Mads Møller

2016-01-01

In this paper we explore how mobile devices and co-location in mobile contexts contribute social play in game design, addressing the limited understanding of social interactivity in mobile games. Using the Mechanics-Dynamics-Aesthetics (MDA) framework, we code four games illustrating effective use...... of mobile, social, and colocated elements. Subsequently, we analyse and discuss this data to identify generalisability in these games. In our discussion we identify how these findings address game design problems of designing collaborative games. Furthermore, we contribute to theory of designing for social...

Colocation as a hybrid ICT sourcing strategy to improve operational agility

DEFF Research Database (Denmark)

Beck, Roman; Pahlke, Immanuel; Vykoukal, Jens

2016-01-01

a hybrid ICT sourcing strategy called colocation that allows firms to operate their own ICT resources in facilities of special-ized data center providers. Grounded in the theory of dynamic capabilities, we theorize and empirically ex-amine how colocation and top management support enable firms to improve...... their operational agility in the presence of environmental turbulence....

Non-Colocated Kinesthetic Display Limits Compliance Discrimination in the Absence of Terminal Force Cues.

Science.gov (United States)

Brown, Jeremy D; Shelley, Mackenzie K; Gardner, Duane; Gansallo, Emmanuel A; Gillespie, R Brent

2016-01-01

An important goal of haptic display is to make available the action/reaction relationships that define interactions between the body and the physical world. While in physical world interactions reaction cues invariably impinge on the same part of the body involved in action (reaction and action are colocated), a haptic interface is quite capable of rendering feedback to a separate body part than that used for producing exploratory actions (non-colocated action and reaction). This most commonly occurs with the use of vibrotactile display, in which a cutaneous cue has been substituted for a kinesthetic cue (a kind of sensory substitution). In this paper, we investigate whether non-colocated force and displacement cues degrade the perception of compliance. Using a custom non-colocated kinesthetic display in which one hand controls displacement and the other senses force, we ask participants to discriminate between two virtual springs with matched terminal force and adjustable non-linearity. An additional condition includes one hand controlling displacement while the other senses force encoded in a vibrotactile cue. Results show that when the terminal force cue is unavailable, and even when sensory substitution is not involved, non-colocated kinesthetic displays degrade compliance discrimination relative to colocated kinesthetic displays. Compliance discrimination is also degraded with vibrotactile display of force. These findings suggest that non-colocated kinesthetic displays and, likewise, cutaneous sensory substitution displays should be avoided when discrimination of compliance is necessary for task success.

Intrasite motions and monument instabilities at Medicina ITRF co-location site

Science.gov (United States)

Sarti, Pierguido; Abbondanza, Claudio; Legrand, Juliette; Bruyninx, Carine; Vittuari, Luca; Ray, Jim

2013-03-01

We process the total-station surveys performed at the ITRF co-location site Medicina (Northern Italy) over the decade (2001-2010) with the purpose of determining the extent of local intrasite motions and relating them to local geophysical processes, the geological setting and the design of the ground pillars. In addition, continuous observations acquired by two co-located GPS stations (MEDI and MSEL separated by ≈27 m) are analysed and their relative motion is cross-checked with the total-station results. The local ground control network extends over a small area (<100 × 100 m) but the results demonstrate significant anisotropic deformations with rates up to 1.6 mm a-1, primarily horizontal, a value comparable to intraplate tectonic deformations. The results derived from GPS and total-station observations are consistent and point to the presence of horizontal intrasite motions over very short distances possibly associated with varying environmental conditions in a very unfavourable local geological setting and unsuitable monument design, these latter being crucial aspects of the realization and maintenance of global permanent geodetic networks and the global terrestrial reference frame.

DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers

International Nuclear Information System (INIS)

Kim, Ki Hyung; Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Moon, Soo Hyun; Suh, Dong Soo; Yoon, Man Soo; Park, Eun-Sil; Jeong, Namkung; Eo, Wan-Kyu; Kim, Heung Yeol; Cha, Hee-Jae

2014-01-01

Highlights: • Germ cell marker DDX4 was significantly increased in ovarian cancer. • Ovarian cancer stem cell marker CD133 was significantly increased in ovarian cancer. • DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. • CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4. • Germ cell marker DDX4 has the potential of ovarian cancer stem cell marker. - Abstract: DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker

Feasibility and Acceptability of a Colocated Homeless-Tailored Primary Care Clinic and Emergency Department.

Science.gov (United States)

Gabrielian, Sonya; Chen, Jennifer C; Minhaj, Beena P; Manchanda, Rishi; Altman, Lisa; Koosis, Ella; Gelberg, Lillian

2017-10-01

Homeless adults have low primary care engagement and high emergency department (ED) utilization. Homeless-tailored, patient-centered medical homes (PCMH) decrease this population's acute care use. We studied the feasibility (focused on patient recruitment) and acceptability (conceptualized as clinicians' attitudes/beliefs) of a pilot initiative to colocate a homeless-tailored PCMH with an ED. After ED triage, low-acuity patients appropriate for outpatient care were screened for homelessness; homeless patients chose between a colocated PCMH or ED visit. To study feasibility, we captured (from May to September 2012) the number of patients screened for homelessness, positive screens, unique patients seen, and primary care visits. We focused on acceptability to ED clinicians (physicians, nurses, social workers); we sent a 32-item survey to ED clinicians (n = 57) who worked during clinic hours. Questions derived from an instrument measuring clinician attitudes toward homeless persons; acceptability of homelessness screening and the clinic itself were also explored. Over the 5 months of interest, 281 patients were screened; 172 (61.2%) screened positive for homelessness; 112 (65.1%) of these positive screens were seen over 215 visits. Acceptability data were obtained from 56% (n = 32) of surveyed clinicians. Attitudes toward homeless patients were similar to prior studies of primary care physicians. Most (54.6%) clinicians agreed with the homelessness screening procedures. Nearly all (90.3%) clinicians supported expansion of the homeless-tailored clinic; a minority (42.0%) agreed that ED colocation worked well. Our data suggest the feasibility of recruiting patients to a homeless-tailored primary care clinic colocated with the ED; however, the clinic's acceptability was mixed. Future quality improvement work should focus on tailoring the clinic to increase its acceptability among ED clinicians, while assessing its impact on health, housing, and costs.

Selecting optimum locations for co-located wave and wind energy farms. Part II: A case study

International Nuclear Information System (INIS)

Astariz, S.; Iglesias, G.

2016-01-01

Highlights: • The benefits of wave and wind combined systems relative to independent farms are analysed. • This purpose is carried out through a case study off the Danish coast. • The power production, power smoothing and shadow effect are analysed. • Hindcast and measured wave and wind data from 2005 to 2015 are used. • Third-generation models of winds and waves (WAsP and SWAN) are used. - Abstract: Combined energy systems present an opportunity to enhance the competitiveness of renewables and overcome other challenges of these novel renewables by realising the synergies between them. Among the different possibilities for combined systems, this work focuses on wave and wind co-located farms with the aim of assessing their benefits relative to standalone wind farms. To this end we estimate the energy production, investigate the power smoothing and shadow effect, and quantify the reduction in downtime achieved by the co-located farm through a case study off the Danish coast – a promising area for co-located farms based on the available resource and other considerations including technical constraints. The analysis is carried out based on hindcast data and observations extending from 2005 to 2015, and by means of state-of-the-art numerical models of the wind and wave fields – WAsP and SWAN, respectively. It is found that the energy yield per unit area with the combined wave-wind farm increases by 3.4% relative to a standalone wind farm, the downtime periods decrease by 58% and the power output variability reduces by 12.5%. Moreover, the capital and operational expenditures (CAPEX and OPEX, respectively) would also be significantly reduced thanks to the synergies realised through the combination of wind and wave power.

Colocalization analysis in fluorescence micrographs: verification of a more accurate calculation of pearson's correlation coefficient.

Science.gov (United States)

Barlow, Andrew L; Macleod, Alasdair; Noppen, Samuel; Sanderson, Jeremy; Guérin, Christopher J

2010-12-01

One of the most routine uses of fluorescence microscopy is colocalization, i.e., the demonstration of a relationship between pairs of biological molecules. Frequently this is presented simplistically by the use of overlays of red and green images, with areas of yellow indicating colocalization of the molecules. Colocalization data are rarely quantified and can be misleading. Our results from both synthetic and biological datasets demonstrate that the generation of Pearson's correlation coefficient between pairs of images can overestimate positive correlation and fail to demonstrate negative correlation. We have demonstrated that the calculation of a thresholded Pearson's correlation coefficient using only intensity values over a determined threshold in both channels produces numerical values that more accurately describe both synthetic datasets and biological examples. Its use will bring clarity and accuracy to colocalization studies using fluorescent microscopy.

General practitioners: Between integration and co-location. The case of primary care centers in Tuscany, Italy.

Science.gov (United States)

Barsanti, Sara; Bonciani, Manila

2018-01-01

Healthcare systems have followed several strategies aimed at integrating primary care services and professionals. Medical homes in the USA and Canada, and primary care centres across Europe have collocated general practitioners and other health and social professionals in the same building in order to boost coordination among services and the continuity of care for patients. However, in the literature, the impact of co-location on primary care has led to controversial results. This article analyses the possible benefits of the co-location of services in primary care focusing on the Italian model of primary care centres (Case della Salute) in terms of general practitioners' perception. We used the results of a web survey of general practitioners in Tuscany to compare the experiences and satisfaction of those general practitioners involved and not involved in a primary care centre, performed a MONAVA and ANOVA analysis. Our case study highlights the positive impact of co-location on the integration of professionals, especially with nurses and social workers, and on organizational integration, in terms of frequency of meeting to discuss about quality of care. Conversely, no significant differences were found in terms of either clinical or system integration. Furthermore, the collaboration with specialists is still weak. Considering the general practitioners' perspective in terms of experience and satisfaction towards primary care, co-location strategies is a necessary step in order to facilitate the collaboration among professionals and to prevent unintended consequences in terms of an even possible isolation of primary care as an involuntary 'disintegration of the integration'.

A Qualitative Exploration of Co-location as an Intervention to Strengthen Home Visiting Implementation in Addressing Maternal Child Health.

Science.gov (United States)

Kellom, Katherine S; Matone, Meredith; Adejare, Aderinola; Barg, Frances K; Rubin, David M; Cronholm, Peter F

2018-06-01

Objectives The aim of this paper is to explore the process and impact of co-locating evidence-based maternal and child service models to inform future implementation efforts. Methods As part of a state-wide evaluation of maternal and child home visiting programs, we conducted semi-structured interviews with administrators and home visitors from home visiting agencies across Pennsylvania. We collected 33 interviews from 4 co-located agencies. We used the Consolidated Framework for Implementation Research (CFIR) to describe the key elements mitigating implementation of multiple home visiting models. Results A primary advantage of co-location described by participants was the ability to increase the agency's base of eligible clients through the implementation of a model with different program eligibility (e.g. income, child age) than the existing agency offering. Model differences related to curriculum (e.g. content or intensity/meeting frequency) enabled programs to more selectively match clients to models. To recruit eligible clients, new models were able to build upon the existing service networks of the initial program. Co-location provided organizational opportunities for shared trainings, enabling administrative efficiencies and collaborative staff learning. Programs implemented strategies to build synergies with complementary model features, for instance using the additional program option to serve waitlisted clients and to transition services after one model is completed. Conclusions for Practice Considerable benefits are experienced when home visiting models co-locate. This research builds on literature encouraging collaboration among community agencies and provides insight on a specific facilitative approach. This implementation strategy informs policy across the social services spectrum and competitive funding contexts.

Reducing severity of comorbid psychiatric symptoms in an epilepsy clinic using a colocation model: results of a pilot intervention.

Science.gov (United States)

Chen, Jasper J; Caller, Tracie A; Mecchella, John N; Thakur, Devendra S; Homa, Karen; Finn, Christine T; Kobylarz, Erik J; Bujarski, Krzysztof A; Thadani, Vijay M; Jobst, Barbara C

2014-10-01

Patients with epilepsy (PWEs) and patients with nonepileptic seizures (PWNESs) constitute particularly vulnerable patient populations and have high rates of psychiatric comorbidities. This potentially decreases quality of life and increases health-care utilization and expenditures. However, lack of access to care or concern of stigma may preclude referral to outpatient psychiatric clinics. Furthermore, the optimal treatment for NESs includes longitudinal psychiatric management. No published literature has assessed the impact of colocated psychiatric services within outpatient epilepsy clinics. We, therefore, evaluated the colocation of psychiatric services within a level 4 epilepsy center. From July 2013 to June 2014, we piloted an intervention to colocate a psychiatrist in the Dartmouth-Hitchcock Epilepsy Center outpatient clinic one afternoon a week (0.1 FTE) to provide medication management and time-limited structural psychotherapeutic interventions to all patients who scored greater than 15 on the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and who agreed to referral. Psychiatric symptom severity was assessed at baseline and follow-up visits using validated scales including NDDI-E, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and cognitive subscale items from Quality of Life in Epilepsy-31 (QOLIE-31) scores. Forty-three patients (18 males; 25 females) were referred to the clinic over a one-year interval; 27 (64.3%) were seen in follow-up with a median of 3 follow-up visits (range: 1 to 7). Thirty-seven percent of the patients had NESs exclusive of epilepsy, and 11% of the patients had dual diagnosis of epilepsy and NESs. Psychiatric symptom severity decreased in 84% of the patients, with PHQ-9 and GAD-7 scores improving significantly from baseline (4.6±0.4 SD improvement in PHQ-9 and 4.0±0.4 SD improvement in GAD-7, p-valuesintegrated models of collaborative and colocated care are becoming more

Strict Anatomical Colocalization of Vitiligo and Elastolytic Granulomas

Directory of Open Access Journals (Sweden)

N. Merino de Paz

2010-02-01

Full Text Available Vitiligo is the most common depigmenting disorder, with a worldwide occurrence of 0.1–2% in the general population. Multiple conditions have been described colocalized in vitiligo patches, like psoriasis or lichen planus. However, actinic granuloma has not been described in association with vitiligo lesions so far.

Proximity matters : synergies through co-location of logistics establishments

NARCIS (Netherlands)

Heuvel, van den F.P.; Langen, de P.W.; Donselaar, van K.H.; Fransoo, J.C.

2012-01-01

Purpose: The purpose of this paper is to contribute to the understanding of spatial concentration of logistics firms by empirically analyzing synergies through co-location and investigating whether spatial concentration of logistics activities indeed results in classical agglomeration economies as

Mental health measurement among women veterans receiving co-located, collaborative care services.

Science.gov (United States)

Lilienthal, Kaitlin R; Buchholz, Laura J; King, Paul R; Vair, Christina L; Funderburk, Jennifer S; Beehler, Gregory P

2017-12-01

Routine use of measurement to identify patient concerns and track treatment progress is critical to high quality patient care. This is particularly relevant to the Primary Care Behavioral Health model, where rapid symptom assessment and effective referral management are critical to sustaining population-based care. However, research suggests that women who receive treatment in co-located collaborative care settings utilizing the PCBH model are less likely to be assessed with standard measures than men in these settings. The current study utilized regional retrospective data obtained from the Veterans Health Administration's electronic medical record system to: (1) explore rates of mental health measurement for women receiving co-located collaborative care services (N = 1008); and (2) to identify predictors of mental health measurement in women veterans in these settings. Overall, only 8% of women had documentation of standard mental health measures. Measurement was predicted by diagnosis, facility size, length of care episode and care setting. Specifically, women diagnosed with depression were less likely than those with anxiety disorders to have standard mental health measurement documented. Several suggestions are offered to increase the quality of mental health care for women through regular use of measurement in integrated care settings.

GNSS-SLR satellite co-location for the estimate of local ties

Science.gov (United States)

Bruni, Sara; Zerbini, Susanna; Errico, Maddalena; Santi, Efisio

2013-04-01

The current realization of the International Terrestrial Reference Frame (ITRF) is based on four different space-geodetic techniques, so that the benefits brought by each observing system to the definition of the frame can compensate for the drawbacks of the others and technique-specific systematic errors might be identified. The strategy used to combine the observations from the different techniques is then of prominent importance for the realization of a precise and stable reference frame. This study concentrates, in particular, on the combination of Satellite Laser Ranging (SLR) and Global Navigation Satellite System (GNSS) observations by exploiting satellite co-locations. This innovative approach is based on the fact that laser tracking of GNSS satellites, carrying on board laser reflector arrays, allows for the combination of optical and microwave signals in the determination of the spacecraft orbit. Besides, the use of satellite co-locations differs quite significantly from the traditional combination method in which each single technique solution is carried out autonomously and is interrelated in a second step. One of the benefits of the approach adopted in this study is that it allows for an independent validation of the local tie, i.e. of the vector connecting the SLR and GNSS reference points in a multi-techniques station. Typically, local ties are expressed by a single value, measured with ground-based geodetic techniques and taken as constant. In principle, however, local ties might show time variations likely caused by the different monumentation characteristics of the GNSS antennas with respect to those of a SLR system. This study evaluates the possibility of using the satellite co-location approach to generate local-ties time series by means of observations available for a selected network of ILRS stations. The data analyzed in this study were acquired as part of the NASA's Earth Science Data Systems and are archived and distributed by the Crustal

Clus-DoC: a combined cluster detection and colocalization analysis for single-molecule localization microscopy data

Science.gov (United States)

Pageon, Sophie V.; Nicovich, Philip R.; Mollazade, Mahdie; Tabarin, Thibault; Gaus, Katharina

2016-01-01

Advances in fluorescence microscopy are providing increasing evidence that the spatial organization of proteins in cell membranes may facilitate signal initiation and integration for appropriate cellular responses. Our understanding of how changes in spatial organization are linked to function has been hampered by the inability to directly measure signaling activity or protein association at the level of individual proteins in intact cells. Here we solve this measurement challenge by developing Clus-DoC, an analysis strategy that quantifies both the spatial distribution of a protein and its colocalization status. We apply this approach to the triggering of the T-cell receptor during T-cell activation, as well as to the functionality of focal adhesions in fibroblasts, thereby demonstrating an experimental and analytical workflow that can be used to quantify signaling activity and protein colocalization at the level of individual proteins. PMID:27582387

Opportunities for co-location of solar PV with agriculture for cost reductions and carbon, water, and energy footprint mitigation in the tropics

Science.gov (United States)

Choi, C. S.; Macknick, J.; Ravi, S.

2017-12-01

Recently, co-locating the production of agricultural crops or biofuels with solar photovoltaics (PV) installations has been studied as a possible strategy to mitigate the environmental impacts and the high cost of solar PV in arid and semi-arid regions. Co-located PV and agricultural systems can provide multiple benefits in these areas related to water savings, erosion control, energy access, and rural economic development. However, such studies have been rare for water-rich, land-limited tropical countries, where ideal agricultural growing conditions can be substantially different from those in arid regions. We consider a case study in Indonesia to address this research gap. As the fourth most populous nation with an ever-growing energy demand and high vulnerability to the effects of climate change, Indonesia is being prompted to develop means to electrify approximately one-fifth of its population that still lacks access to the grid without incurring increases in its carbon footprint. We address the following questions to explore the feasibility and the benefits of co-location of solar PV with patchouli cultivation and essential oil production: i) How do the lifetime carbon, water, and energy footprints per unit land area of co-located solar PV/patchouli compare to those of standalone diesel microgrid, solar PV or patchouli cultivation? ii) Does energy production from standalone solar PV, diesel/solar PV microgrid, or co-located solar PV/patchouli systems satisfy energy demands of a typical rural Indonesian village? iii) How does the net economic return of the co-located system compare to each standalone land use? iv) How can surplus energy from the co-located system benefit rural socioeconomics? To answer these questions, life cycle assessment and economic analysis are performed for each of the standalone and the co-located land uses utilizing known values and data collected from a field visit to the island of Java in Indonesia. Then, sensitivity analyses and

Towards a robust algorithm to determine topological domains from colocalization data

Directory of Open Access Journals (Sweden)

Alexander P. Moscalets

2015-09-01

Full Text Available One of the most important tasks in understanding the complex spatial organization of the genome consists in extracting information about this spatial organization, the function and structure of chromatin topological domains from existing experimental data, in particular, from genome colocalization (Hi-C matrices. Here we present an algorithm allowing to reveal the underlying hierarchical domain structure of a polymer conformation from analyzing the modularity of colocalization matrices. We also test this algorithm on several model polymer structures: equilibrium globules, random fractal globules and regular fractal (Peano conformations. We define what we call a spectrum of cluster borders, and show that these spectra behave strikingly di erently for equilibrium and fractal conformations, allowing us to suggest an additional criterion to identify fractal polymer conformations.

NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program

DEFF Research Database (Denmark)

Hiraike, Yuta; Waki, Hironori; Yu, Jing

2017-01-01

. NFIA and the master transcriptional regulator of adipogenesis, PPARγ, co-localize at the brown-fat-specific enhancers. Moreover, the binding of NFIA precedes and facilitates the binding of PPARγ, leading to increased chromatin accessibility and active transcription. Introduction of NFIA into myoblasts...... results in brown adipocyte differentiation. Conversely, the brown fat of NFIA-knockout mice displays impaired expression of the brown-fat-specific genes and reciprocal elevation of muscle genes. Finally, expression of NFIA and the brown-fat-specific genes is positively correlated in human brown fat...

Integrating molecular QTL data into genome-wide genetic association analysis: Probabilistic assessment of enrichment and colocalization.

Directory of Open Access Journals (Sweden)

Xiaoquan Wen

2017-03-01

Full Text Available We propose a novel statistical framework for integrating the result from molecular quantitative trait loci (QTL mapping into genome-wide genetic association analysis of complex traits, with the primary objectives of quantitatively assessing the enrichment of the molecular QTLs in complex trait-associated genetic variants and the colocalizations of the two types of association signals. We introduce a natural Bayesian hierarchical model that treats the latent association status of molecular QTLs as SNP-level annotations for candidate SNPs of complex traits. We detail a computational procedure to seamlessly perform enrichment, fine-mapping and colocalization analyses, which is a distinct feature compared to the existing colocalization analysis procedures in the literature. The proposed approach is computationally efficient and requires only summary-level statistics. We evaluate and demonstrate the proposed computational approach through extensive simulation studies and analyses of blood lipid data and the whole blood eQTL data from the GTEx project. In addition, a useful utility from our proposed method enables the computation of expected colocalization signals using simple characteristics of the association data. Using this utility, we further illustrate the importance of enrichment analysis on the ability to discover colocalized signals and the potential limitations of currently available molecular QTL data. The software pipeline that implements the proposed computation procedures, enloc, is freely available at https://github.com/xqwen/integrative.

Whither voluntary communities of co-located patients in Vietnam? Empirical evidence from a 2016 medical survey dataset

Directory of Open Access Journals (Sweden)

Quan-Hoang Vuong

2016-12-01

Full Text Available Background: Empirical evidence on quality of life of poor patients falls short for policy-making in Vietnam. Financial burdens and isolation give rise to Vietnamese voluntary co-location clusters where patients seek to rely on each other. These communities, although important, have been under-researched. Increasingly, there are questions about their sustainability. Aim & Objectives: This study aims to identify factors that affect sustainability of such co-location clusters, seeking to measure the community prospect through critical determinants as seen by member patients. An in-depth analysis is expected to yield insights that help shape future policies contributing to improvement of healthcare systems.  Material & Method: A dataset containing responses from 336 patients living in four clusters in Hanoi was obtained from a survey during 2015Q4-2016Q1. The processing of data is performed using R 3.2.3, employing baseline category logit models (BCL. Coefficients are estimated to compute empirical probabilities. Results: 1 There is a 50% probability that a patient seeing his/her benefits as unsatisfactory views the community prospect as dim; 2 The more a patient contributes time/effort, the less he/she believes in future growth; 3 There is a 80.8% probability that a patient who makes a significant financial contribution and receives back in-kind benefits predicts no growth. Conclusion: Patients predict community growth when receiving what they need/expect. There exists a kind of “liquidity preference”. Only 14% and 32% make significant financial and labor contributions, respectively. There exists a “risk aversion” attitude, viewing contribution as certain while future benefits to be uncertain.

Better Together: Co-Location of Dental and Primary Care Provides Opportunities to Improve Oral Health.

Science.gov (United States)

Pourat, Nadereh; Martinez, Ana E; Crall, James J

2015-09-01

Community Health Centers (CHCs) are one of the principal safety-net providers of health care for low-income and uninsured populations. Co-locating dental services in primary care settings provides an opportunity to improve access to dental care. Yet this study of California CHCs that provide primary care services shows that only about one-third of them co-located primary and dental care services on-site. An additional one-third were members of multisite organizations in which at least one other site provided dental care. The remaining one-third of CHC sites had no dental care capacity. Policy options to promote co-location include requiring on-site availability of dental services, providing infrastructure funding to build and equip dental facilities, and offering financial incentives to provide dental care and recruit dental providers.

Analisis Perbandingan Antara Colocation Server Dengan Amazon Web Services (Cloud Untuk Usabilitas Portal Swa.co.id Di PT. Swa Media Bisnis

Directory of Open Access Journals (Sweden)

Lipur Sugiyanta

2017-06-01

Full Text Available Untuk mendukung usabilitas web portal nya, SWA Media Online menggunakan layanan web hosting Colocation Server dari Wowrack. Layanan Colocation Server dari Wowrack ini memiliki lokasi server fisik atau pusat data di Surabaya, Indonesia. Seiring berjalannya waktu, penggunaan Colocation Server dirasa semakin menghambat perkembangan perusahaan, terbukti dengan melambatnya akses ke web portal swa.co.id. Untuk itu, pada bulan Mei - Juni 2015 SWA Media Online memutuskan berpaling dari Colocation Server ke teknologi cloud terbaru. Pada akhir bulan Juni 2015, SWA Media Online resmi bermigrasi dari colocation ke Amazon Web Services. Dimana server fisik nya berada di Singapura (untuk pelanggan ASEAN. Untuk fitur yang digunakan, hampir sama seperti saat menggunakan colocation yaitu yang sesuai dengan kebutuhan perusahaan. Namun, pada Amazon Web Services memberikan service atau fitur tambahan berupa adanya load balancer, auto scaling, dan bucket atau media penyimpanan. Metodologi yang peneliti terapkan dalam penelitian ini adalah metodologi analisis secara kualitatif. Berdasarkan hasil penelitian, didapatkan hasil bahwa fitur tambahan yang diberikan Amazon Web Services mampu meningkatkan usabilitas portal dalam segi kemudahan dalam kecepatan akses portal. Kecepatan akses web portal meningkat lebih baik dibandingkan saat menggunakan Colocation Server.

Squeeze: designing for playful experiences among co-located people in homes. (received first prize people's choice award)

DEFF Research Database (Denmark)

Petersen, Marianne Graves

2007-01-01

Squeeze is a multi-person, flexible and interactive furniture that allows for collective and playful exploration of the family history among co-located people in homes. It is designed to explore how we can use digital technology to create settings where co-located family members can collectively ...

Look together : Using gaze for assisting co-located collaborative search

NARCIS (Netherlands)

Zhang, Y.; Pfeuffer, Ken; Chong, Ming Ki; Alexander, Jason; Bulling, Andreas; Gellersen, Hans

2017-01-01

Gaze information provides indication of users focus which complements remote collaboration tasks, as distant users can see their partner’s focus. In this paper, we apply gaze for co-located collaboration, where users’ gaze locations are presented on the same display, to help collaboration between

Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis.

Science.gov (United States)

Alshikho, Mohamad J; Zürcher, Nicole R; Loggia, Marco L; Cernasov, Paul; Chonde, Daniel B; Izquierdo Garcia, David; Yasek, Julia E; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R; Cudkowicz, Merit E; Hooker, Jacob M; Atassi, Nazem

2016-12-13

In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [ 11 C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [ 11 C]-PBR28 uptake. In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [ 11 C]-PBR28 binding in the left motor cortex was correlated with FA (r = -0.68, p < 0.05) and cortical thickness (r = -0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = -0.77, p < 0.05), and cortical thickness (r = -0.75, p < 0.05) in the motor cortex. Increased uptake of the glial marker [ 11 C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. © 2016 American Academy of Neurology.

A method for improved clustering and classification of microscopy images using quantitative co-localization coefficients

LENUS (Irish Health Repository)

Singan, Vasanth R

2012-06-08

AbstractBackgroundThe localization of proteins to specific subcellular structures in eukaryotic cells provides important information with respect to their function. Fluorescence microscopy approaches to determine localization distribution have proved to be an essential tool in the characterization of unknown proteins, and are now particularly pertinent as a result of the wide availability of fluorescently-tagged constructs and antibodies. However, there are currently very few image analysis options able to effectively discriminate proteins with apparently similar distributions in cells, despite this information being important for protein characterization.FindingsWe have developed a novel method for combining two existing image analysis approaches, which results in highly efficient and accurate discrimination of proteins with seemingly similar distributions. We have combined image texture-based analysis with quantitative co-localization coefficients, a method that has traditionally only been used to study the spatial overlap between two populations of molecules. Here we describe and present a novel application for quantitative co-localization, as applied to the study of Rab family small GTP binding proteins localizing to the endomembrane system of cultured cells.ConclusionsWe show how quantitative co-localization can be used alongside texture feature analysis, resulting in improved clustering of microscopy images. The use of co-localization as an additional clustering parameter is non-biased and highly applicable to high-throughput image data sets.

Construction of EMSC-islet co-localizing composites for xenogeneic porcine islet transplantation.

Science.gov (United States)

Kim, Jung-Sik; Chung, Hyunwoo; Byun, Nari; Kang, Seong-Jun; Lee, Sunho; Shin, Jun-Seop; Park, Chung-Gyu

2018-03-04

Pancreatic islet transplantation is an ultimate solution for treating patients with type 1 diabetes (T1D). The pig is an ideal donor of islets for replacing scarce human islets. Besides immunological hurdles, non-immunological hurdles including fragmentation and delayed engraftment of porcine islets need solutions to succeed in porcine islet xenotransplantation. In this study, we suggest a simple but effective modality, a cell/islet co-localizing composite, to overcome these challenges. Endothelial-like mesenchymal stem cells (EMSCs), differentiated from bone-marrow derived mouse mesenchymal stem cells (MSCs), and MSCs evenly coated the surface of porcine islets (>85%) through optimized culture conditions. Both MSCs and EMSCs significantly reduced the fragmentation of porcine islets and increased the islet masses, designated as islet equivalents (IEQs). In fibrin in vitro and in vivo angiogenesis analysis, constructed EMSC-islet composites showed higher angiogenic potentials than naked islets, MSC-islet composites, or human endothelial cell-islet composites. This novel delivery method of porcine islets may have beneficial effects on the engraftment of transplanted islets by prevention of fragmentation and enhancement of revascularization. Copyright © 2018 Elsevier Inc. All rights reserved.

Co-location satellite GPS and SLR geodetic techniques at the Felix Aguilar Astronomical Observatory of San Juan, Argentina

Science.gov (United States)

Podestá, R.; Pacheco, A. M.; Alvis Rojas, H.; Quinteros, J.; Podestá, F.; Albornoz, E.; Navarro, A.; Luna, M.

2018-01-01

This work shows the strategy followed for the co-location of the Satellite Laser Ranging (SLR) ILRS 7406 telescope and the antenna of the permanent Global Positioning System (GPS) station, located at the Félix Aguilar Astronomical Observatory (OAFA) in San Juan, Argentina. The accomplishment of the co-location consisted in the design, construction, measurement, adjustment and compensation of a geodesic net between the stations SLR and GPS, securing support points solidly built in the soil. The co-location allows the coordinates of the station to be obtained by combining the data of both SLR and GPS techniques, achieving a greater degree of accuracy than individually. The International Earth Rotation and Reference Systems Service (IERS) considers the co-located stations as the most valuable and important points for the maintenance of terrestrial reference systems and their connection with the celestial ones. The 3 mm precision required by the IERS has been successfully achieved.

Registration of whole immunohistochemical slide images: an efficient way to characterize biomarker colocalization.

Science.gov (United States)

Moles Lopez, Xavier; Barbot, Paul; Van Eycke, Yves-Rémi; Verset, Laurine; Trépant, Anne-Laure; Larbanoix, Lionel; Salmon, Isabelle; Decaestecker, Christine

2015-01-01

Extracting accurate information from complex biological processes involved in diseases, such as cancers, requires the simultaneous targeting of multiple proteins and locating their respective expression in tissue samples. This information can be collected by imaging and registering adjacent sections from the same tissue sample and stained by immunohistochemistry (IHC). Registration accuracy should be on the scale of a few cells to enable protein colocalization to be assessed. We propose a simple and efficient method based on the open-source elastix framework to register virtual slides of adjacent sections from the same tissue sample. We characterize registration accuracies for different types of tissue and IHC staining. Our results indicate that this technique is suitable for the evaluation of the colocalization of biomarkers on the scale of a few cells. We also show that using this technique in conjunction with a sequential IHC labeling and erasing technique offers improved registration accuracies. Brightfield IHC enables to address the problem of large series of tissue samples, which are usually required in clinical research. However, this approach, which is simple at the tissue processing level, requires challenging image analysis processes, such as accurate registration, to view and extract the protein colocalization information. The method proposed in this work enables accurate registration (on the scale of a few cells) of virtual slides of adjacent tissue sections on which the expression of different proteins is evidenced by standard IHC. Furthermore, combining our method with a sequential labeling and erasing technique enables cell-scale colocalization. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.comFor numbered affiliations see end of article.

Searching for Stochastic Gravitational Waves Using Data from the Two Co-Located LIGO Hanford Detectors

Science.gov (United States)

Aasi, J.; Abadie, J.; Abbott, B. P.; Abbott, R.; Abbott, T.; Abernathy, M. R.; Accadia, T.; Acernese, F.; Adams, C.; Adams, T.;

Clinician's perspectives of the relocation of a regional child and adolescent mental health service from co-located to stand alone premises.

Science.gov (United States)

Francis, K J; Boyd, C P; Sewell, J; Nurse, S

2008-01-01

Australia's National Mental Health Strategy's statement of rights and responsibilities states that children and adolescents admitted to a mental health facility or community program have the right to be separated from adult patients and provided with programs suited to their developmental needs. However, in rural Australia, where a lack of healthcare services, financial constraints, greater service delivery areas and fewer mental healthcare specialists represent the norm, Child and Adolescent Mental Health Services (CAMHS) are sometimes co-located with adult mental health services. The aim of the present study was to evaluate the impact of a recent relocation of a regional CAMHS in Victoria from co-located to stand alone premises. Six CAMHS clinicians who had experienced service delivery at a co-located setting and the current stand-alone CAMHS setting were interviewed about their perceptions of the impact of the relocation on service delivery. An exploratory interviewing methodology was utilized due to the lack of previous research in this area. Interview data were transcribed and analysed according to interpretative phenomenological analysis techniques. Findings indicated a perception that the relocation was positive for clients due to the family-friendly environment at the new setting and separation of CAMHS from adult psychiatric services. However, the impact of the relocation on clinicians was marked by a perceived loss of social capital from adult psychiatric service clinicians. These results provide increased understanding of the effects of service relocation and the influence of co-located versus stand-alone settings on mental health service delivery - an area where little prior research exists.

A Partial Join Approach for Mining Co-Location Patterns: A Summary of Results

National Research Council Canada - National Science Library

Yoo, Jin S; Shekhar, Shashi

2005-01-01

.... They propose a novel partial-join approach for mining co-location patterns efficiently. It transactionizes continuous spatial data while keeping track of the spatial information not modeled by transactions...

Co-localization patterns of neurotensin receptor 1 and tyrosine hydroxylase in brain regions involved in motivation and social behavior in male European starlings.

Science.gov (United States)

Merullo, Devin P; Spool, Jeremy A; Zhao, Changjiu; Riters, Lauren V

2018-04-01

Animals communicate in distinct social contexts to convey information specific to those contexts, such as sexual or agonistic motivation. In seasonally-breeding male songbirds, seasonal changes in day length and increases in testosterone stimulate sexually-motivated song directed at females for courtship and reproduction. Dopamine and testosterone may act in the same brain regions to stimulate sexually-motivated singing. The neuropeptide neurotensin, acting at the neurotensin receptor 1 (NTR1), can strongly influence dopamine transmission. The goal of this study was to gain insight into the degree to which seasonal changes in physiology modify interactions between neurotensin and dopamine to adjust context-appropriate communication. Male European starlings were examined in physiological conditions that stimulate season-typical forms of communication: late summer/early fall non-breeding condition (low testosterone; birds sing infrequently), late fall non-breeding condition (low testosterone; birds produce non-sexually motivated song), and spring breeding condition (high testosterone; males produce sexually-motivated song). Double fluorescent immunolabeling was performed to detect co-localization patterns between tyrosine hydroxylase (TH; the rate-limiting enzyme in dopamine synthesis) and NTR1 in brain regions implicated in motivation and song production (the ventral tegmental area, medial preoptic nucleus, periaqueductal gray, and lateral septum). Co-localization between TH and NTR1 was present in the ventral tegmental area for all physiological conditions, and the number of co-localized cells did not differ across conditions. Immunolabeling for TH and NTR1 was also present in the other examined regions, although no co-localization was seen. These results support the hypothesis that interactions between NTR1 and dopamine in the ventral tegmental area may modulate vocalizations, but suggest that testosterone- or photoperiod-induced changes in NTR1/TH co-localization

Adipophilin distribution and colocalization with lipid droplets in skeletal muscle.

LENUS (Irish Health Repository)

Shaw, Christopher S

2009-05-01

Intramyocellular lipids (IMCL) are stored as discrete lipid droplets which are associated with a number of proteins. The lipid droplet-associated protein adipophilin (the human orthologue of adipose differentiation-related protein) is ubiquitously expressed and is one of the predominant lipid droplet-proteins in skeletal muscle. The aim of this study was to investigate the subcellular distribution of adipophilin in human muscle fibres and to measure the colocalization of adipophilin with IMCL. Muscle biopsies from six lean male cyclists (BMI 23.4 +\\/- 0.4, aged 31 +\\/- 2 years, W (max) 346 +\\/- 8) were stained for myosin heavy chain type 1, IMCL, adipophilin and mitochondria using immunofluorescence and viewed with widefield and confocal fluorescence microscopy. The present study shows that like IMCL, the adipophilin content is ~twofold greater in type I skeletal muscle fibres and is situated in the areas between the mitochondrial network. Colocalization analysis demonstrated that 61 +\\/- 2% of IMCL contain adipophilin. Although the majority of adipophilin is contained within IMCL, 36 +\\/- 4% of adipophilin is not associated with IMCL. In conclusion, this study indicates that the IMCL pool is heterogeneous, as the majority but not all IMCL contain adipophilin.

An Intercomparison of GPS RO Retrievals with Colocated Analysis and In Situ Observations within Tropical Cyclones

Directory of Open Access Journals (Sweden)

Henry R. Winterbottom

2010-01-01

Full Text Available Observations from four Global Position System (GPS Radio Occultation (RO missions: Global Positioning System/Meteorology, CHAallenging Minisatellite Payload, Satellite de Aplicaciones Cientificas-C, and Constellation Observing System for Meteorology, Ionosphere and Climate and Taiwan's FORMOsa SATellite Mission #3 (COSMIC/FORMOSAT-3 are collected within a 600 km radius and ±180 minute temporal window of all observed tropical cyclones (TCs from 1995 to 2006 that were recorded in the global hurricane best-track reanalysis data set (Jarvinen et al. (1984; Davis et al. (1984. A composite analysis of tropical cyclone radial mean temperature and water vapor profiles is carried out using the GPS RO retrievals which are colocated with global analysis profiles and available in situ radiosonde observations. The differences between the respective observations and analysis profiles are quantified and the preliminary results show that the observations collected within TCs correspond favorably with both the analysis and radiosonde profiles which are colocated. It is concluded that GPS RO observations will contribute significantly to the understanding and modeling of TC structures, especially those related to vertical variability of the atmospheric state within TCs.

The role of co-located storage for wind power producers in conventional electricity markets

KAUST Repository

Bitar, E.

2011-06-01

In this paper we study the problem of optimizing contract offerings for an independent wind power producer (WPP) participating in conventional day-ahead forward electricity markets for energy. As wind power is an inherently variable source of energy and is difficult to predict, we explore the extent to which co-located energy storage can be used to improve expected profit and mitigate the the financial risk associated with shorting on the offered contracts. Using a simple stochastic model for wind power production and a model for the electricity market, we show that the problem of determining optimal contract offerings for a WPP with co-located energy storage can be solved using convex programming.

Co-Location versus Disintegration of Manufacturing and R&D in Emerging Markets

DEFF Research Database (Denmark)

Søberg, Peder Veng; Wæhrens, Brian Vejrum

2012-01-01

The paper investigates what makes it more or less relevant to co-locate manufacturing activities and R&D activities in emerging markets within multinational companies. A framework to this end is developed and illustrated in relation to four cases from multinational companies, which have established...

Gas revenue increasingly significant

International Nuclear Information System (INIS)

Megill, R.E.

1991-01-01

This paper briefly describes the wellhead prices of natural gas compared to crude oil over the past 70 years. Although natural gas prices have never reached price parity with crude oil, the relative value of a gas BTU has been increasing. It is one of the reasons that the total amount of money coming from natural gas wells is becoming more significant. From 1920 to 1955 the revenue at the wellhead for natural gas was only about 10% of the money received by producers. Most of the money needed for exploration, development, and production came from crude oil. At present, however, over 40% of the money from the upstream portion of the petroleum industry is from natural gas. As a result, in a few short years natural gas may become 50% of the money revenues generated from wellhead production facilities

Head-camera video recordings of trauma core competency procedures can evaluate surgical resident's technical performance as well as colocated evaluators.

Science.gov (United States)

Mackenzie, Colin F; Pasley, Jason; Garofalo, Evan; Shackelford, Stacy; Chen, Hegang; Longinaker, Nyaradzo; Granite, Guinevere; Pugh, Kristy; Hagegeorge, George; Tisherman, Samuel A

2017-07-01

Unbiased evaluation of trauma core competency procedures is necessary to determine if residency and predeployment training courses are useful. We tested whether a previously validated individual procedure score (IPS) for individual procedure vascular exposure and fasciotomy (FAS) performance skills could discriminate training status by comparing IPS of evaluators colocated with surgeons to blind video evaluations. Performance of axillary artery (AA), brachial artery (BA), and femoral artery (FA) vascular exposures and lower extremity FAS on fresh cadavers by 40 PGY-2 to PGY-6 residents was video-recorded from head-mounted cameras. Two colocated trained evaluators assessed IPS before and after training. One surgeon in each pretraining tertile of IPS for each procedure was randomly identified for blind video review. The same 12 surgeons were video-recorded repeating the procedures less than 4 weeks after training. Five evaluators independently reviewed all 96 randomly arranged deidentified videos. Inter-rater reliability/consistency, intraclass correlation coefficients were compared by colocated versus video review of IPS, and errors. Study methodology and bias were judged by Medical Education Research Study Quality Instrument and the Quality Assessment of Diagnostic Accuracy Studies criteria. There were no differences (p ≥ 0.5) in IPS for AA, FA, FAS, whether evaluators were colocated or reviewed video recordings. Evaluator consistency was 0.29 (BA) - 0.77 (FA). Video and colocated evaluators were in total agreement (p = 1.0) for error recognition. Intraclass correlation coefficient was 0.73 to 0.92, dependent on procedure. Correlations video versus colocated evaluations were 0.5 to 0.9. Except for BA, blinded video evaluators discriminated (p competency. Prognostic study, level II.

[Tripartite motif-containing protein 34 (TRIM34) colocalized with micronuclei chromosome and hampers its movement to equatorial plate during the metaphase stage of mitosis].

Science.gov (United States)

Sun, Dakang; An, Xinye; Ji, Bing; Cheng, Yanli; Gao, Honglian; Tian, Mingming

2016-06-01

Objective To examine whether tripartite motif-containing protein 34 (TRIM34) is colocalized with micronuclei and investigate the influence on the movement of micronuclei chromosome in mitosis. Methods The eukaryotic expression vector TRIM34-pEGFP-N3 was constructed, identified and then transfected into HEK293T cells. With 4', 6-diamidino-2-phenylindole 2HCI (DAPI) staining, the colocalization between TRIM34 and micronuclei was observed under a fluorescence microscope. Moreover, MitoTracker(R)Deep Red was used to identify the colocalization between the complex of TRIM34-micronulei and mitochondria under a confocal microscope. Finally, the effect of TRIM34 on the movement of micronuclei chromosome in mitosis was examined. Results DNA sequencing confirmed that the vector TRIM34-pEGFP-N3 was constructed successfully. A fluorescence microscope revealed that TRIM34 could be colocalized with micronuclei in HEK293T cells transfected with TRIM34-pEGFP-N3. In the same manner, a confocal microscope distinctly showed that TRIM34 was colocalized with micronuclei similarly in appearance. However, there was no distinguished colocalization relationship between the complex of TRIM34-micronulei and mitochondria. Interestingly, the micronuclei chromosome conjugated with TRIM34 was hardly transferred to equatorial plate during the metaphase stage of mitosis. Conclusion TRIM34 is colocalized with micronuclei chromosome and hampers its movement to equatorial plate in mitosis.

Assessment of local GNSS baselines at co-location sites

Science.gov (United States)

Herrera Pinzón, Iván; Rothacher, Markus

2018-01-01

As one of the major contributors to the realisation of the International Terrestrial Reference System (ITRS), the Global Navigation Satellite Systems (GNSS) are prone to suffer from irregularities and discontinuities in time series. While often associated with hardware/software changes and the influence of the local environment, these discrepancies constitute a major threat for ITRS realisations. Co-located GNSS at fundamental sites, with two or more available instruments, provide the opportunity to mitigate their influence while improving the accuracy of estimated positions by examining data breaks, local biases, deformations, time-dependent variations and the comparison of GNSS baselines with existing local tie measurements. With the use of co-located GNSS data from a subset sites of the International GNSS Service network, this paper discusses a global multi-year analysis with the aim of delivering homogeneous time series of coordinates to analyse system-specific error sources in the local baselines. Results based on the comparison of different GNSS-based solutions with the local survey ties show discrepancies of up to 10 mm despite GNSS coordinate repeatabilities at the sub-mm level. The discrepancies are especially large for the solutions using the ionosphere-free linear combination and estimating tropospheric zenith delays, thus corresponding to the processing strategy used for global solutions. Snow on the antennas causes further problems and seasonal variations of the station coordinates. These demonstrate the need for a permanent high-quality monitoring of the effects present in the short GNSS baselines at fundamental sites.

Co-location as a Driver for Cross-Sectoral Collaboration with General Practitioners as Coordinators

DEFF Research Database (Denmark)

Scheele, Christian Elling; Vrangbæk, Karsten

2016-01-01

The issue of integrated care and inter-sectoral collaboration is on the health policy agenda in many countries. Yet, there is limited knowledge about the effects of the different policy instruments used to achieve this. This paper studies co-location as a driver for cross-sectoral collaboration...... with general practitioners (GPs) acting as coordinators in a municipal health centre. The purpose of the health centre, which is staffed by health professionals from municipal, regional and private sectors, is to provide primary health services to the citizens of the municipality. Co......-locating these professionals is supposed to benefit e.g., elder citizens and patients with chronic diseases who frequently require services from health professionals across administrative sectors. Methodologically, the analysis is based on qualitative data in the form of semi-structured interviews with the health...

Ground Motion Analysis of Co-Located DAS and Seismometer Sensors

Science.gov (United States)

Wang, H. F.; Fratta, D.; Lord, N. E.; Lancelle, C.; Thurber, C. H.; Zeng, X.; Parker, L.; Chalari, A.; Miller, D.; Feigl, K. L.; Team, P.

2016-12-01

The PoroTomo research team deployed 8700-meters of Distributed Acoustic Sensing (DAS) cable in a shallow trench and 400-meters in a borehole at Brady Hot Springs, Nevada in March 2016 together with an array of 246, three-component geophones. The seismic sensors occupied a natural laboratory 1500 x 500 x 400 meters overlying the Brady geothermal field. The DAS cable was laid out in three parallel zig-zag lines with line segments approximately 100-meters in length and geophones were spaced at approximately 50-m intervals. In several line segments, geophones were co-located within one meter of the DAS cable. Both DAS and the conventional geophones recorded continuously over 15 days. A large Vibroseis truck (T-Rex) provided the seismic source at approximately 250 locations outside and within the array. The Vibroseis protocol called for excitation in one vertical and two orthogonal horizontal directions at each location. For each mode, three, 5-to-80-Hz upsweeps were made over 20 seconds. In addition, a moderate-sized earthquake with a local magnitude of 4.3 was recorded on March 21, 2016. Its epicenter was approximately 150-km away. Several DAS line segments with co-located geophone stations were used to test relationships between the strain rate recorded by DAS and ground velocity recorded by the geophones.

An Isometric Mapping Based Co-Location Decision Tree Algorithm

Science.gov (United States)

Zhou, G.; Wei, J.; Zhou, X.; Zhang, R.; Huang, W.; Sha, H.; Chen, J.

2018-05-01

Decision tree (DT) induction has been widely used in different pattern classification. However, most traditional DTs have the disadvantage that they consider only non-spatial attributes (ie, spectral information) as a result of classifying pixels, which can result in objects being misclassified. Therefore, some researchers have proposed a co-location decision tree (Cl-DT) method, which combines co-location and decision tree to solve the above the above-mentioned traditional decision tree problems. Cl-DT overcomes the shortcomings of the existing DT algorithms, which create a node for each value of a given attribute, which has a higher accuracy than the existing decision tree approach. However, for non-linearly distributed data instances, the euclidean distance between instances does not reflect the true positional relationship between them. In order to overcome these shortcomings, this paper proposes an isometric mapping method based on Cl-DT (called, (Isomap-based Cl-DT), which is a method that combines heterogeneous and Cl-DT together. Because isometric mapping methods use geodetic distances instead of Euclidean distances between non-linearly distributed instances, the true distance between instances can be reflected. The experimental results and several comparative analyzes show that: (1) The extraction method of exposed carbonate rocks is of high accuracy. (2) The proposed method has many advantages, because the total number of nodes, the number of leaf nodes and the number of nodes are greatly reduced compared to Cl-DT. Therefore, the Isomap -based Cl-DT algorithm can construct a more accurate and faster decision tree.

AN ISOMETRIC MAPPING BASED CO-LOCATION DECISION TREE ALGORITHM

Directory of Open Access Journals (Sweden)

G. Zhou

2018-05-01

Full Text Available Decision tree (DT induction has been widely used in different pattern classification. However, most traditional DTs have the disadvantage that they consider only non-spatial attributes (ie, spectral information as a result of classifying pixels, which can result in objects being misclassified. Therefore, some researchers have proposed a co-location decision tree (Cl-DT method, which combines co-location and decision tree to solve the above the above-mentioned traditional decision tree problems. Cl-DT overcomes the shortcomings of the existing DT algorithms, which create a node for each value of a given attribute, which has a higher accuracy than the existing decision tree approach. However, for non-linearly distributed data instances, the euclidean distance between instances does not reflect the true positional relationship between them. In order to overcome these shortcomings, this paper proposes an isometric mapping method based on Cl-DT (called, (Isomap-based Cl-DT, which is a method that combines heterogeneous and Cl-DT together. Because isometric mapping methods use geodetic distances instead of Euclidean distances between non-linearly distributed instances, the true distance between instances can be reflected. The experimental results and several comparative analyzes show that: (1 The extraction method of exposed carbonate rocks is of high accuracy. (2 The proposed method has many advantages, because the total number of nodes, the number of leaf nodes and the number of nodes are greatly reduced compared to Cl-DT. Therefore, the Isomap -based Cl-DT algorithm can construct a more accurate and faster decision tree.

[Colocalization of nucleoli in cell nuclei of HeLa line].

Science.gov (United States)

Petrov, Iu P; Neguliaev, Iu A; Tsupkina, N V

2014-01-01

The pattern of localization of nucleoli relative to each other and to cell nucleus was studied in M-HeLa cell line. For this puspose, the following morphometric parameters were introduced. For the two-nucleolar cells: 1) the ratio of the nucleus long axis to the length of a segment between the centers of the nucleoli, and 2) the angle between the segment connecting the centers of the nucleoli and a longitudinal axis of cell nucleus. For the three-nucleolar cells: the ratio perimeter of the nucleus to perimeter of a triangle with vertexes in the centre of nucleoli. We have shown that the values of these parameters are individual for each cell but their values remain constant for the cell in spite of the changes in cell shape. These results allow us to conclude that, on the one hand, the nucleoli colocalization is individual for each cell, and, on the other hand, location of nucleoli in relation to nucleus is not changed during interphase. Thereby, the distance between nucleoli increases proportionally with nucleus growth.

Plasma membrane cholesterol level and agonist-induced internalization of δ-opioid receptors; colocalization study with intracellular membrane markers of Rab family.

Science.gov (United States)

Brejchova, Jana; Vosahlikova, Miroslava; Roubalova, Lenka; Parenti, Marco; Mauri, Mario; Chernyavskiy, Oleksandr; Svoboda, Petr

2016-08-01

Decrease of cholesterol level in plasma membrane of living HEK293 cells transiently expressing FLAG-δ-OR by β-cyclodextrin (β-CDX) resulted in a slight internalization of δ-OR. Massive internalization of δ-OR induced by specific agonist DADLE was diminished in cholesterol-depleted cells. These results suggest that agonist-induced internalization of δ-OR, which has been traditionally attributed exclusively to clathrin-mediated pathway, proceeds at least partially via membrane domains. Identification of internalized pools of FLAG-δ-OR by colocalization studies with proteins of Rab family indicated the decreased presence of receptors in early endosomes (Rab5), late endosomes and lysosomes (Rab7) and fast recycling vesicles (Rab4). Slow type of recycling (Rab11) was unchanged by cholesterol depletion. As expected, agonist-induced internalization of oxytocin receptors was totally suppressed in β-CDX-treated cells. Determination of average fluorescence lifetime of TMA-DPH, the polar derivative of hydrophobic membrane probe diphenylhexatriene, in live cells by FLIM indicated a significant alteration of the overall PM structure which may be interpreted as an increased "water-accessible space" within PM area. Data obtained by studies of HEK293 cells transiently expressing FLAG-δ-OR by "antibody feeding" method were extended by analysis of the effect of cholesterol depletion on distribution of FLAG-δ-OR in sucrose density gradients prepared from HEK293 cells stably expressing FLAG-δ-OR. Major part of FLAG-δ-OR was co-localized with plasma membrane marker Na,K-ATPase and β-CDX treatment resulted in shift of PM fragments containing both FLAG-δ-OR and Na,K-ATPase to higher density. Thus, the decrease in content of the major lipid constituent of PM resulted in increased density of resulting PM fragments.

Precise colocalization of interacting structural and pigmentary elements generates extensive color pattern variation in Phelsuma lizards

Science.gov (United States)

2013-01-01

Background Color traits in animals play crucial roles in thermoregulation, photoprotection, camouflage, and visual communication, and are amenable to objective quantification and modeling. However, the extensive variation in non-melanic pigments and structural colors in squamate reptiles has been largely disregarded. Here, we used an integrated approach to investigate the morphological basis and physical mechanisms generating variation in color traits in tropical day geckos of the genus Phelsuma. Results Combining histology, optics, mass spectrometry, and UV and Raman spectroscopy, we found that the extensive variation in color patterns within and among Phelsuma species is generated by complex interactions between, on the one hand, chromatophores containing yellow/red pteridine pigments and, on the other hand, iridophores producing structural color by constructive interference of light with guanine nanocrystals. More specifically, we show that 1) the hue of the vivid dorsolateral skin is modulated both by variation in geometry of structural, highly ordered narrowband reflectors, and by the presence of yellow pigments, and 2) that the reflectivity of the white belly and of dorsolateral pigmentary red marks, is increased by underlying structural disorganized broadband reflectors. Most importantly, these interactions require precise colocalization of yellow and red chromatophores with different types of iridophores, characterized by ordered and disordered nanocrystals, respectively. We validated these results through numerical simulations combining pigmentary components with a multilayer interferential optical model. Finally, we show that melanophores form dark lateral patterns but do not significantly contribute to variation in blue/green or red coloration, and that changes in the pH or redox state of pigments provide yet another source of color variation in squamates. Conclusions Precisely colocalized interacting pigmentary and structural elements generate extensive

Dopamine in the Auditory Brainstem and Midbrain: Co-localization with Amino Acid Neurotransmitters and Gene Expression following Cochlear Trauma

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Avril Genene eHolt

2015-07-01

Full Text Available Dopamine (DA modulates the effects of amino acid neurotransmitters, including GABA and glutamate, in motor, visual, olfactory and reward systems (Hnasko et al., 2010; Stuber et al., 2010; Hnasko and Edwards, 2012. The results suggest that DA may play a similar modulatory role in the auditory pathways. Previous studies have shown that deafness results in decreased GABA release, changes in excitatory neurotransmitter levels, and increased spontaneous neuronal activity within brainstem regions related to auditory function. Modulation of the expression and localization of tyrosine hydroxylase (TH; the rate limiting enzyme in the production of DA in the IC following cochlear trauma has been previously reported (Tong et al., 2005. In the current study the possibility of co-localization of TH with amino acid neurotransmitters (AANs was examined. Changes in the gene expression of TH were compared with changes in the gene expression of markers for AANs in the cochlear nucleus (CN and IC to determine whether those deafness related changes occur concurrently. The results indicate that bilateral cochlear ablation significantly reduced TH gene expression in the CN after two months while in the IC the reduction in TH was observed at both three days and two months following ablation. Furthermore, in the CN, glycine transporter 2 (GlyT2 and the GABA transporter (GABAtp were also significantly reduced only after two months. However, in the IC, DA receptor 1 (DRDA1, vesicular glutamate transporters 2 and 3 (vGluT2, vGluT3, GABAtp and GAD67 were reduced in expression both at the three day and two month time points. A close relationship between the distribution of TH and several of the AANs was determined in both the CN and the IC. In addition, GlyT2 and vGluT3 each co-localized with TH within IC somata and dendrites. Therefore, the results of the current study suggest that DA is spatially well positioned to influence the effects of AANs on auditory neurons.

Feasibility study for co-locating and integrating ethanol production plants from corn starch and lignocellulosic feedstocks

Energy Technology Data Exchange (ETDEWEB)

Wallace, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States); Ibsen, Kelly [National Renewable Energy Lab. (NREL), Golden, CO (United States); McAloon, Andrew [U.S. Department of Agriculture, Washington, D.C. (United States); Yee, Winnie [U.S. Department of Agriculture, Washington, D.C. (United States)

2005-01-01

Analysis of the feasibility of co-locating corn-grain-to-ethanol and lignocellulosic ethanol plants and potential savings from combining utilities, ethanol purification, product processing, and fermentation.

Sensitive detection of nucleic acids by PNA hybridization directed co-localization of fluorescent beads

DEFF Research Database (Denmark)

Shiraishi, Takehiko; Deborggraeve, Stijn; Büscher, Philippe

2011-01-01

)avidin-coated fluorescent beads, differing in size and color [green beads (1 µm) and red beads (5.9 µm)], thereby allowing distinct detection of each PNA probe by conventional fluorescence microscopy. These two PNA beads showed easily detectable co-localization when simultaneously hybridizing to a target nucleic acid...

Visualization of cholinoceptive neurons in the rat neocortex : colocalization of muscarinic and nicotinic acetylcholine receptors

NARCIS (Netherlands)

Zee, E.A. van der; Streefland, C.; Strosberg, A.D.; Schröder, H.; Luiten, P.G.M.

The present investigation analyzes the cellular distribution of muscarinic and nicotinic acetylcholine receptors in rat neocortex, by use of monoclonal antibodies raised against purified receptor proteins. The degree of colocalization of both types of receptors was determined by way of

Enhancing Wave Energy Competitiveness through Co-Located Wind and Wave Energy Farms. A Review on the Shadow Effect

Directory of Open Access Journals (Sweden)

Sharay Astariz

2015-07-01

Full Text Available Wave energy is one of the most promising alternatives to fossil fuels due to the enormous available resource; however, its development may be slowed as it is often regarded as uneconomical. The largest cost reductions are expected to be obtained through economies of scale and technological progress. In this sense, the incorporation of wave energy systems into offshore wind energy farms is an opportunity to foster the development of wave energy. The synergies between both renewables can be realised through these co-located energy farms and, thus, some challenges of offshore wind energy can be met. Among them, this paper focuses on the longer non-operational periods of offshore wind turbines—relative to their onshore counterparts—typically caused by delays in maintenance due to the harsh marine conditions. Co-located wave energy converters would act as a barrier extracting energy from the waves and resulting in a shielding effect over the wind farm. On this basis, the aim of this paper is to analyse wave energy economics in a holistic way, as well as the synergies between wave and offshore wind energy, focusing on the shadow effect and the associated increase in the accessibility to the wind turbines.

An Active-Radio-Frequency-Identification system capable of identifying co-locations and social-structure: validation with a wild free-ranging animal

OpenAIRE

Ellwood, SA; Newman, C; Montgomery, RA; Nicosia, V; Buesching, CD; Markham, A; Mascolo, C; Trigoni, N; Pasztor, B; Dyo, V; Latora, V; Baker, SE; Macdonald, DW

2017-01-01

Behavioural events that are important for understanding sociobiology and movement ecology are often rare, transient and localised, but can occur at spatially distant sites e.g. territorial incursions and co-locating individuals. Existing animal tracking technologies, capable of detecting such events, are limited by one or more of: battery life; data resolution; location accuracy; data security; ability to co-locate individuals both spatially and temporally. Technology that at least partly res...

IGFBP3 colocalizes with and regulates hypocretin (orexin.

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Makoto Honda

Full Text Available The sleep disorder narcolepsy is caused by a vast reduction in neurons producing the hypocretin (orexin neuropeptides. Based on the tight association with HLA, narcolepsy is believed to result from an autoimmune attack, but the cause of hypocretin cell loss is still unknown. We performed gene expression profiling in the hypothalamus to identify novel genes dysregulated in narcolepsy, as these may be the target of autoimmune attack or modulate hypocretin gene expression.We used microarrays to compare the transcriptome in the posterior hypothalamus of (1 narcoleptic versus control postmortem human brains and (2 transgenic mice lacking hypocretin neurons versus wild type mice. Hypocretin was the most downregulated gene in human narcolepsy brains. Among many additional candidates, only one, insulin-like growth factor binding protein 3 (IGFBP3, was downregulated in both human and mouse models and co-expressed in hypocretin neurons. Functional analysis indicated decreased hypocretin messenger RNA and peptide content, and increased sleep in transgenic mice overexpressing human IGFBP3, an effect possibly mediated through decreased hypocretin promotor activity in the presence of excessive IGFBP3. Although we found no IGFBP3 autoantibodies nor a genetic association with IGFBP3 polymorphisms in human narcolepsy, we found that an IGFBP3 polymorphism known to increase serum IGFBP3 levels was associated with lower CSF hypocretin-1 in normal individuals.Comparison of the transcriptome in narcolepsy and narcolepsy model mouse brains revealed a novel dysregulated gene which colocalized in hypocretin cells. Functional analysis indicated that the identified IGFBP3 is a new regulator of hypocretin cell physiology that may be involved not only in the pathophysiology of narcolepsy, but also in the regulation of sleep in normal individuals, most notably during adolescence. Further studies are required to address the hypothesis that excessive IGFBP3 expression may

Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models

Science.gov (United States)

Shin, Jin Young; Park, Hyun Jung; Kim, Ha Na; Oh, Se Hee; Bae, Jae-Sung; Ha, Hee-Jin; Lee, Phil Hyu

2014-01-01

Current evidence suggests a central role for autophagy in Alzheimer disease (AD), and dysfunction in the autophagic system may lead to amyloid-β (Aβ) accumulation. Using in vitro and in vivo AD models, the present study investigated whether mesenchymal stem cells (MSCs) could enhance autophagy and thus exert a neuroprotective effect through modulation of Aβ clearance In Aβ-treated neuronal cells, MSCs increased cellular viability and enhanced LC3-II expression compared with cells treated with Aβ only. Immunofluorescence revealed that MSC coculture in Aβ-treated neuronal cells increased the number of LC3-II-positive autophagosomes that were colocalized with a lysosomal marker. Ultrastructural analysis revealed that most autophagic vacuoles (AVs) in Aβ-treated cells were not fused with lysosomes, whereas a large portion of autophagosomes were conjoined with lysosomes in MSCs cocultured with Aβ-treated neuronal cells. Furthermore, MSC coculture markedly increased Aβ immunoreactivity colocalized within lysosomes and decreased intracellular Aβ levels compared with Aβ-treated cells. In Aβ-treated animals, MSC administration significantly increased autophagosome induction, final maturation of late AVs, and fusion with lysosomes. Moreover, MSC administration significantly reduced the level of Aβ in the hippocampus, which was elevated in Aβ-treated mice, concomitant with increased survival of hippocampal neurons. Finally, MSC coculture upregulated BECN1/Beclin 1 expression in AD models. These results suggest that MSCs significantly enhance autolysosome formation and clearance of Aβ in AD models, which may lead to increased neuronal survival against Aβ toxicity. Modulation of the autophagy pathway to repair the damaged AD brain using MSCs would have a significant impact on future strategies for AD treatment. PMID:24149893

Ubiquitous computing to support co-located clinical teams: using the semiotics of physical objects in system design.

Science.gov (United States)

Bang, Magnus; Timpka, Toomas

2007-06-01

Co-located teams often use material objects to communicate messages in collaboration. Modern desktop computing systems with abstract graphical user interface (GUIs) fail to support this material dimension of inter-personal communication. The aim of this study is to investigate how tangible user interfaces can be used in computer systems to better support collaborative routines among co-located clinical teams. The semiotics of physical objects used in team collaboration was analyzed from data collected during 1 month of observations at an emergency room. The resulting set of communication patterns was used as a framework when designing an experimental system. Following the principles of augmented reality, physical objects were mapped into a physical user interface with the goal of maintaining the symbolic value of those objects. NOSTOS is an experimental ubiquitous computing environment that takes advantage of interaction devices integrated into the traditional clinical environment, including digital pens, walk-up displays, and a digital desk. The design uses familiar workplace tools to function as user interfaces to the computer in order to exploit established cognitive and collaborative routines. Paper-based tangible user interfaces and digital desks are promising technologies for co-located clinical teams. A key issue that needs to be solved before employing such solutions in practice is associated with limited feedback from the passive paper interfaces.

Synchronous gesture manipulation for collaboration and coordination of co-located Business Process Modelling

Directory of Open Access Journals (Sweden)

Brenda Scholtz

2015-12-01

Full Text Available The purpose of this study was to investigate approaches (techniques and technologies for the coordination of collaborative tasks using synchronous gesture manipulation. Business Process Modelling (BPM tasks are often performed in teams of modellers who need to collaborate with each other in order to coordinate and integrate their individual contributions into the various process models in a co-located environment. These collaborative BPM tasks were used as a case study in order to develop the artifact (the BPM-Touch approach as a proof of concept. The BPM-Touch approach allows for the coordination and collaboration of BPM tasks in co-located modelling teams using synchronous gesture manipulation approaches. The Design Science Research (DSR methodology was used and several cycles of developing and evaluating the artifact took place. This paper reports on the last cycle and set of evaluations. The proposed approach was implemented in a BPM software package in order to provide empirical validation. Usability evaluations of the software were undertaken with both students and BPM professionals as participants. The empirical results of the evaluations revealed that the participants found the approach to be effective and rated the usability and satisfaction of the collaboration and gesture manipulation aspects of the software positively.

Metabolic markers in relation to hypoxia; staining patterns and colocalization of pimonidazole, HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4

International Nuclear Information System (INIS)

Rademakers, Saskia E; Lok, Jasper; Kogel, Albert J van der; Bussink, Johan; Kaanders, Johannes HAM

2011-01-01

The cellular response of malignant tumors to hypoxia is diverse. Several important endogenous metabolic markers are upregulated under hypoxic conditions. We examined the staining patterns and co-expression of HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4 with the exogenous hypoxic cell marker pimonidazole and the association of marker expression with clinicopathological characteristics. 20 biopsies of advanced head and neck carcinomas were immunohistochemically stained and analyzed. All patients were given the hypoxia marker pimonidazole intravenously 2 h prior to biopsy taking. The tumor area positive for each marker, the colocalization of the different markers and the distribution of the markers in relation to the blood vessels were assessed by semiautomatic quantitative analysis. MCT1 staining was present in hypoxic (pimonidazole stained) as well as non-hypoxic areas in almost equal amounts. MCT1 expression showed a significant overall correlation (r = 0.75, p < 0.001) and strong spatial relationship with CAIX. LDH-5 showed the strongest correlation with pimonidazole (r = 0.66, p = 0.002). MCT4 and GLUT-1 demonstrated a typical diffusion-limited hypoxic pattern and showed a high degree of colocalization. Both MCT4 and CAIX showed a higher expression in the primary tumor in node positive patients (p = 0.09 both). Colocalization and staining patterns of metabolic and hypoxia-related proteins provides valuable additional information over single protein analyses and can improve the understanding of their functions and environmental influences

New algorithm to determine true colocalization in combination with image restoration and time-lapse confocal microscopy to MAP kinases in mitochondria.

Directory of Open Access Journals (Sweden)

Jorge Ignacio Villalta

Full Text Available The subcellular localization and physiological functions of biomolecules are closely related and thus it is crucial to precisely determine the distribution of different molecules inside the intracellular structures. This is frequently accomplished by fluorescence microscopy with well-characterized markers and posterior evaluation of the signal colocalization. Rigorous study of colocalization requires statistical analysis of the data, albeit yet no single technique has been established as a standard method. Indeed, the few methods currently available are only accurate in images with particular characteristics. Here, we introduce a new algorithm to automatically obtain the true colocalization between images that is suitable for a wide variety of biological situations. To proceed, the algorithm contemplates the individual contribution of each pixel's fluorescence intensity in a pair of images to the overall Pearsońs correlation and Manders' overlap coefficients. The accuracy and reliability of the algorithm was validated on both simulated and real images that reflected the characteristics of a range of biological samples. We used this algorithm in combination with image restoration by deconvolution and time-lapse confocal microscopy to address the localization of MEK1 in the mitochondria of different cell lines. Appraising the previously described behavior of Akt1 corroborated the reliability of the combined use of these techniques. Together, the present work provides a novel statistical approach to accurately and reliably determine the colocalization in a variety of biological images.

Colocalization of low-methylesterified pectins and Pb deposits in the apoplast of aspen roots exposed to lead

International Nuclear Information System (INIS)

Rabęda, Irena; Bilski, Henryk; Mellerowicz, Ewa J.; Napieralska, Anna; Suski, Szymon; Woźny, Adam; Krzesłowska, Magdalena

2015-01-01

Low-methylesterified homogalacturonans have been suggested to play a role in the binding and immobilization of Pb in CW. Using root apices of hybrid aspen, a plant with a high phytoremediation potential, as a model, we demonstrated that the in situ distribution pattern of low-methylesterified homogalacturonan, pectin epitope (JIM5-P), reflects the pattern of Pb occurrence. The region which indicated high JIM5-P level corresponded with “Pb accumulation zone”. Moreover, JIM5-P was especially abundant in cell junctions, CWs lining the intercellular spaces and the corners of intercellular spaces indicating the highest accumulation of Pb. Furthermore, JIM5-P and Pb commonly co-localized. The observations indicate that low-methylesterified homogalacturonan is the CW polymer that determines the capacity of CW for Pb sequestration. Our results suggest a promising directions for CW modification for enhancing the efficiency of plant roots in Pb accumulation, an important aspect in the phytoremediation of soils contaminated with trace metals. - Highlights: • Co-localization of low-methylesterified pectins and Pb was analysed in situ. • The pattern of Pb accumulation matched low-methylesterified pectins distribution. • Low-methylesterified pectins and Pb commonly co-localized in cell walls. • Low-methylesterified pectins revealed an important compound in Pb sequestration. • We suggest a new direction in enhancing plant efficiency for phytoremediation. - The distribution of lead in developing tissues of aspen root tips exposed to short-term lead treatment mimics the distribution of low-methylesterified pectin epitope

Impact of co-located general practitioner (GP) clinics and patient choice on duration of wait in the emergency department.

Science.gov (United States)

Sharma, Anurag; Inder, Brett

2011-08-01

To empirically model the determinants of duration of wait of emergency (triage category 2) patients in an emergency department (ED) focusing on two questions: (i) What is the effect of enhancing the degree of choice for non-urgent (triage category 5) patients on duration of wait for emergency (category 2) patients in EDs; and (ii) What is the effect of co-located GP clinics on duration of wait for emergency patients in EDs? The answers to these questions will help in understanding the effectiveness of demand management strategies, which are identified as one of the solutions to ED crowding. The duration of wait for each patient (difference between arrival time and time first seen by treating doctor) was modelled as a function of input factors (degree of choice, patient characteristics, weekend admission, metro/regional hospital, concentration of emergency (category 2) patients in hospital service area), throughput factors (availability of doctors and nurses) and output factor (hospital bed capacity). The unit of analysis was a patient episode and the model was estimated using a survival regression technique. The degree of choice for non-urgent (category 5) patients has a non-linear effect: more choice for non-urgent patients is associated with longer waits for emergency patients at lower values and shorter waits at higher values of degree of choice. Thus more choice of EDs for non-urgent patients is related to a longer wait for emergency (category 2) patients in EDs. The waiting time for emergency patients in hospital campuses with co-located GP clinics was 19% lower (1.5 min less) on average than for those waiting in campuses without co-located GP clinics. These findings suggest that diverting non-urgent (category 5) patients to an alternative model of care (co-located GP clinics) is a more effective demand management strategy and will reduce ED crowding.

The tumor suppressor SHIP1 colocalizes in nucleolar cavities with p53 and components of PML nuclear bodies.

Science.gov (United States)

Ehm, Patrick; Nalaskowski, Marcus M; Wundenberg, Torsten; Jücker, Manfred

2015-01-01

The inositol 5-phosphatase SHIP1 is a negative regulator of signaling processes in haematopoietic cells. By converting PI(3,4,5)P3 to PtdIns(3,4)P2 at the plasma membrane, SHIP1 modifies PI3-kinase mediated signaling. We have recently demonstrated that SHIP1 is a nucleo-cytoplasmic shuttling protein and SHIP1 nuclear puncta partially colocalize with FLASH, a component of nuclear bodies. In this study, we demonstrate that endogenous SHIP1 localizes to intranucleolar regions of both normal and leukemic haematopoietic cells. In addition, we report that ectopically expressed SHIP1 accumulates in nucleolar cavities and colocalizes with the tumor suppressor protein p53 and components of PML nuclear bodies (e.g. SP100, SUMO-1 and CK2). Moreover, SHIP1 also colocalizes in nucleolar cavities with components of the ubiquitin-proteasome pathway. By using confocal microscopy data, we generated 3D-models revealing the enormous extent of the SHIP1 aggresomes in the nucleolus. Furthermore, treatment of cells with the proteasome inhibitor MG132 causes an enlargement of nucleolar SHIP1 containing structures. Unexpectedly, this accumulation can be partially prevented by treatment with the inhibitor of nuclear protein export Leptomycin B. In recent years, several proteins aggregating in nucleolar cavities were shown to be key factors of neurodegenerative diseases and cancerogenesis. Our findings support current relevance of nuclear localized SHIP1.

Observations on Stratospheric-Mesospheric-Thermospheric temperatures using Indian MST radar and co-located LIDAR during Leonid Meteor Shower (LMS

Directory of Open Access Journals (Sweden)

R. Selvamurugan

2002-11-01

Full Text Available The temporal and height statistics of the occurrence of meteor trails during the Leonid meteor shower revealed the capability of the Indian MST radar to record large numbers of meteor trails. The distribution of radio meteor trails due to a Leonid meteor shower in space and time provided a unique opportunity to construct the height profiles of lower thermospheric temperatures and winds, with good time and height resolution. There was a four-fold increase in the meteor trails observed during the LMS compared to a typical non-shower day. The temperatures were found to be in excellent continuity with the temperature profiles below the radio meteor region derived from the co-located Nd-Yag LIDAR and the maximum height of the temperature profile was extended from the LIDAR to ~110 km. There are, how-ever, some significant differences between the observed profiles and the CIRA-86 model profiles. The first results on the meteor statistics and neutral temperature are presented and discussed below.  Key words. Atmospheric composition and structure (pres-sure, density, and temperature History of geophysics (at-mospheric sciences Meteorology and atmospheric dynamics (middle atmosphere dynamics

Feasibility Study for Bioethanol Co-Location with a Coal Fired Power Plant: 29 November 2001--28 July 2002

Energy Technology Data Exchange (ETDEWEB)

2002-12-01

This study looks at the feasibility of co-locating 30, 50, and 70 million gallon per year bioethanol facilities with coal fired power plants in Indiana and Nebraska. Corn stover is the feedstock for ethanol production in both cases.

COLOCALIZATION OF MUSCARINIC AND NICOTINIC RECEPTORS IN CHOLINOCEPTIVE NEURONS OF THE SUPRACHIASMATIC REGION IN YOUNG AND AGED RATS

NARCIS (Netherlands)

VANDERZEE, EA; STREEFLAND, C; STROSBERG, AD; SCHRODER, H; LUITEN, PGM; Schröder, H.

1991-01-01

In the present study muscarinic and nicotinic cholinergic receptors in the SCN region were demonstrated and analyzed, employing monoclonal antibodies to purified muscarinic and nicotinic cholinergic receptor proteins. A near-total colocalization of the two acetylcholine receptor subclasses in

Identification and characterization of pleiotropic and co-located resistance loci to leaf rust and stripe rust in bread wheat cultivar Sujata.

Science.gov (United States)

Lan, Caixia; Zhang, Yelun; Herrera-Foessel, Sybil A; Basnet, Bhoja R; Huerta-Espino, Julio; Lagudah, Evans S; Singh, Ravi P

2015-03-01

Two new co-located resistance loci, QLr.cim - 1AS/QYr.cim - 1AS and QLr.cim - 7BL/YrSuj , in combination with Lr46 / Yr29 and Lr67/Yr46 , and a new leaf rust resistance quantitative trait loci, conferred high resistance to rusts in adult plant stage. The tall Indian bread wheat cultivar Sujata displays high and low infection types to leaf rust and stripe rust, respectively, at the seedling stage in greenhouse tests. It was also highly resistant to both rusts at adult plant stage in field trials in Mexico. The genetic basis of this resistance was investigated in a population of 148 F5 recombinant inbred lines (RILs) derived from the cross Avocet × Sujata. The parents and RIL population were characterized in field trials for resistance to leaf rust during 2011 at El Batán, and 2012 and 2013 at Ciudad Obregón, Mexico, and for stripe rust during 2011 and 2012 at Toluca, Mexico; they were also characterized three times for stripe rust at seedling stage in the greenhouse. The RILs were genotyped with diversity arrays technology and simple sequence repeat markers. The final genetic map was constructed with 673 polymorphic markers. Inclusive composite interval mapping analysis detected two new significant co-located resistance loci, QLr.cim-1AS/QYr.cim-1AS and QLr.cim-7BL/YrSuj, on chromosomes 1AS and 7BL, respectively. The chromosomal position of QLr.cim-7BL overlapped with the seedling stripe rust resistance gene, temporarily designated as YrSuj. Two previously reported pleiotropic adult plant resistance genes, Lr46/Yr29 and Lr67/Yr46, and a new leaf rust resistance quantitative trait loci derived from Avocet were also mapped in the population. The two new co-located resistance loci are expected to contribute to breeding durable rust resistance in wheat. Closely linked molecular markers can be used to transfer all four resistance loci simultaneously to modern wheat varieties.

Colocalization of coregulated genes: a steered molecular dynamics study of human chromosome 19.

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Marco Di Stefano

Full Text Available The connection between chromatin nuclear organization and gene activity is vividly illustrated by the observation that transcriptional coregulation of certain genes appears to be directly influenced by their spatial proximity. This fact poses the more general question of whether it is at all feasible that the numerous genes that are coregulated on a given chromosome, especially those at large genomic distances, might become proximate inside the nucleus. This problem is studied here using steered molecular dynamics simulations in order to enforce the colocalization of thousands of knowledge-based gene sequences on a model for the gene-rich human chromosome 19. Remarkably, it is found that most (≈ 88% gene pairs can be brought simultaneously into contact. This is made possible by the low degree of intra-chromosome entanglement and the large number of cliques in the gene coregulatory network. A clique is a set of genes coregulated all together as a group. The constrained conformations for the model chromosome 19 are further shown to be organized in spatial macrodomains that are similar to those inferred from recent HiC measurements. The findings indicate that gene coregulation and colocalization are largely compatible and that this relationship can be exploited to draft the overall spatial organization of the chromosome in vivo. The more general validity and implications of these findings could be investigated by applying to other eukaryotic chromosomes the general and transferable computational strategy introduced here.

Sustainable use of marine resources through offshore wind and mussel farm co-location

DEFF Research Database (Denmark)

Di Tullio, Giacomo R.; Mariani, Patrizio; Benassai, Guido

2018-01-01

wind farms and open-water mussel cultivation. An index of co-location sustainability (SI) was developed based on the application of MCE technique constructed with physical and biological parameters on the basis of remote-sensing data. The relevant physical factors considered were wind velocity, depth...... range, concerning the site location for energy production, and sea surface temperature anomaly. The biological variables used were Chlorofill-a (as a measurement of the productivity) and Particle Organic Carbon(POC) concentration, in order to assess their influence on the probable benefits and complete...

The impact of HIV status and antiretroviral treatment on TB treatment outcomes of new tuberculosis patients attending co-located TB and ART services in South Africa: a retrospective cohort study.

Science.gov (United States)

Nglazi, Mweete D; Bekker, Linda-Gail; Wood, Robin; Kaplan, Richard

2015-11-19

The implementation of collaborative TB-HIV services is challenging. We, therefore, assessed TB treatment outcomes in relation to HIV infection and antiretroviral therapy (ART) among TB patients attending a primary care service with co-located ART and TB clinics in Cape Town, South Africa. In this retrospective cohort study, all new TB patients aged ≥ 15 years who registered and initiated TB treatment between 1 October 2009 and 30 June 2011 were identified from an electronic database. The effects of HIV-infection and ART on TB treatment outcomes were analysed using a multinomial logistic regression model, in which treatment success was the reference outcome. The 797 new TB patients included in the analysis were categorized as follows: HIV- negative, in 325 patients (40.8 %); HIV-positive on ART, in 339 patients (42.5 %) and HIV-positive not on ART, in 133 patients (16.7 %). Overall, bivariate analyses showed no significant difference in death and default rates between HIV-positive TB patients on ART and HIV-negative patients. Statistically significant higher mortality rates were found among HIV-positive patients not on ART compared to HIV-negative patients (unadjusted odds ratio (OR) 3.25; 95 % confidence interval (CI) 1.53-6.91). When multivariate analyses were conducted, the only significant difference between the patient categories on TB treatment outcomes was that HIV-positive TB patients not on ART had significantly higher mortality rates than HIV-negative patients (adjusted OR 4.12; 95 % CI 1.76-9.66). Among HIV-positive TB patients (n = 472), 28.2 % deemed eligible did not initiate ART in spite of the co-location of TB and ART services. When multivariate analyses were restricted to HIV-positive patients in the cohort, we found that being HIV-positive not on ART was associated with higher mortality (adjusted OR 7.12; 95 % CI 2.95-18.47) and higher default rates (adjusted OR 2.27; 95 % CI 1.15-4.47). There was no significant difference in death and

Altered TGF-β endocytic trafficking contributes to the increased signaling in Marfan syndrome.

Science.gov (United States)

Siegert, Anna-Maria; Serra-Peinado, Carla; Gutiérrez-Martínez, Enric; Rodríguez-Pascual, Fernando; Fabregat, Isabel; Egea, Gustavo

2018-02-01

The main cardiovascular alteration in Marfan syndrome (MFS) is the formation of aortic aneurysms in which augmented TGF-β signaling is reported. However, the primary role of TGF-β signaling as a molecular link between the genetic mutation of fibrillin-1 and disease onset is controversial. The compartmentalization of TGF-β endocytic trafficking has been shown to determine a signaling response in which clathrin-dependent internalization leads to TGF-β signal propagation, and caveolin-1 (CAV-1) associated internalization leads to signal abrogation. We here studied the contribution of endocytic trafficking compartmentalization to increased TGF-β signaling in vascular smooth muscle cells (VSMC) from MFS patients. We examined molecular components involved in clathrin- (SARA, SMAD2) and caveolin-1- (SMAD7, SMURF2) dependent endocytosis. Marfan VSMC showed higher recruitment of SARA and SMAD2 to membranes and their increased interaction with TGF-β receptor II, as well as higher colocalization of SARA with the early endosome marker EEA1. We assessed TGF-β internalization using a biotinylated ligand (b-TGF-β), which colocalized equally with either EEA1 or CAV-1 in VSMC from Marfan patients and controls. However, in Marfan cells, colocalization of b-TGF-β with SARA and EEA1 was increased and accompanied by decreased colocalization with CAV-1 at EEA1-positive endosomes. Moreover, Marfan VSMC showed higher transcriptional levels and membrane enrichment of RAB5. Our results indicate that increased RAB5-associated SARA localization to early endosomes facilitates its TGF-β receptor binding and phosphorylation of signaling mediator SMAD2 in Marfan VSMC. This is accompanied by a reduction of TGF-β sorting into multifunctional vesicles containing cargo from both internalization pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

Feasibility Study for Co-Locating and Integrating Ethanol Production Plants from Corn Starch and Lignocellulosic Feedstocks (Revised)

Energy Technology Data Exchange (ETDEWEB)

Wallace, R.; Ibsen, K.; McAloon, A.; Yee, W.

2005-01-01

Analysis of the feasibility of co-locating corn-grain-to-ethanol and lignocellulosic ethanol plants and potential savings from combining utilities, ethanol purification, product processing, and fermentation. Although none of the scenarios identified could produce ethanol at lower cost than a straight grain ethanol plant, several were lower cost than a straight cellulosic ethanol plant.

Organizational correlates of implementation of colocation of mental health and primary care in the Veterans Health Administration.

Science.gov (United States)

Guerrero, Erick G; Heslin, Kevin C; Chang, Evelyn; Fenwick, Karissa; Yano, Elizabeth

2015-07-01

This study explored the role of organizational factors in the ability of Veterans Health Administration (VHA) clinics to implement colocated mental health care in primary care settings (PC-MH). The study used data from the VHA Clinical Practice Organizational Survey collected in 2007 from 225 clinic administrators across the United States. Clinic degree of implementation of PC-MH was the dependent variable, whereas independent variables included policies and procedures, organizational context, and leaders' perceptions of barriers to change. Pearson bivariate correlations and multivariable linear regression were used to test hypotheses. Results show that depression care training for primary care providers and clinics' flexibility and participation were both positively correlated with implementation of PC-MH. However, after accounting for other factors, regressions show that only training primary care providers in depression care was marginally associated with degree of implementation of PC-MH (p = 0.051). Given the importance of this topic for implementing integrated care as part of health care reform, these null findings underscore the need to improve theory and testing of more proximal measures of colocation in future work.

LONG-TERM STABILITY OF THE LOCAL GROUND CONTROL NETWORK AT THE CO-LOCATION SITE OF MEDICINA

Science.gov (United States)

Abbondanza, C.; Sarti, P.; Legrand, J.

2009-12-01

ITRF combinations rely on the availability of accurate tie vectors linking reference points of space geodetic techniques. Co-located instruments are assumed to move consistently and no local relative motion is taken into account. Instabilities may degrade the quality of the co-location itself and perturb the result of ITRF combinations. This work aims to determine the stability of the local ground control network at Medicina (Italy) with independent surveying methods. The observatory hosts a co-location between a VLBI telescope and two GPS antennas, MEDI and MSEL. It is located in the Po Plain where thick layers of clays are the prevalent soil characteristics. Hence, provision of long term stability of geodetic monuments is a challenge and monitoring their stability is an issue. MEDI and the VLBI station regularly contribute to the determination of ITRF, while MSEL is part of the EUREF network. A set of five tie vectors observations linking the VLBI and MEDI reference points was acquired between 2001 and 2007. It is our main tool for performing local deformation analysis. Additionally, the GPS time series of MEDI and MSEL were used to cross check and confirm the local instability detected by terrestrial methods. To achieve a rigorous and reliable investigation of the local stability, multi-epoch terrestrial observations were homogeneously processed according to common parameterizations in a consistent reference frame. Similarly, continuous GPS observations from MEDI and MSEL were analysed according to the new EPN reprocessing strategy in order to monitor the short baseline between MEDI and MSEL; to spotlight any change in its length. Both approaches confirm differential motions at the site which can be related to monument instabilities originated by the particularly unfavourable local geological setting and the inapt design of the monuments foundation. The monuments move non homogeneously at rates reaching up to 1.6 mm/year, this value being comparable to intra

Detecting Kerogen as a Biosignature Using Colocated UV Time-Gated Raman and Fluorescence Spectroscopy.

Science.gov (United States)

Shkolyar, Svetlana; Eshelman, Evan J; Farmer, Jack D; Hamilton, David; Daly, Michael G; Youngbull, Cody

2018-04-01

The Mars 2020 mission will analyze samples in situ and identify any that could have preserved biosignatures in ancient habitable environments for later return to Earth. Highest priority targeted samples include aqueously formed sedimentary lithologies. On Earth, such lithologies can contain fossil biosignatures as aromatic carbon (kerogen). In this study, we analyzed nonextracted kerogen in a diverse suite of natural, complex samples using colocated UV excitation (266 nm) time-gated (UV-TG) Raman and laser-induced fluorescence spectroscopies. We interrogated kerogen and its host matrix in samples to (1) explore the capabilities of UV-TG Raman and fluorescence spectroscopies for detecting kerogen in high-priority targets in the search for possible biosignatures on Mars; (2) assess the effectiveness of time gating and UV laser wavelength in reducing fluorescence in Raman spectra; and (3) identify sample-specific issues that could challenge rover-based identifications of kerogen using UV-TG Raman spectroscopy. We found that ungated UV Raman spectroscopy is suited to identify diagnostic kerogen Raman bands without interfering fluorescence and that UV fluorescence spectroscopy is suited to identify kerogen. These results highlight the value of combining colocated Raman and fluorescence spectroscopies, similar to those obtainable by SHERLOC on Mars 2020, to strengthen the confidence of kerogen detection as a potential biosignature in complex natural samples. Key Words: Raman spectroscopy-Laser-induced fluorescence spectroscopy-Mars Sample Return-Mars 2020 mission-Kerogen-Biosignatures. Astrobiology 18, 431-453.

Resolving colocalization of bacteria and metal(loid)s on plant root surfaces by combining fluorescence in situ hybridization (FISH) with multiple-energy micro-focused X-ray fluorescence (ME μXRF).

Science.gov (United States)

Honeker, Linnea K; Root, Robert A; Chorover, Jon; Maier, Raina M

2016-12-01

Metal(loid)-contamination of the environment due to anthropogenic activities is a global problem. Understanding the fate of contaminants requires elucidation of biotic and abiotic factors that influence metal(loid) speciation from molecular to field scales. Improved methods are needed to assess micro-scale processes, such as those occurring at biogeochemical interfaces between plant tissues, microbial cells, and metal(loid)s. Here we present an advanced method that combines fluorescence in situ hybridization (FISH) with synchrotron-based multiple-energy micro-focused X-ray fluorescence microprobe imaging (ME μXRF) to examine colocalization of bacteria and metal(loid)s on root surfaces of plants used to phytostabilize metalliferous mine tailings. Bacteria were visualized on a small root section using SytoBC nucleic acid stain and FISH probes targeting the domain Bacteria and a specific group (Alphaproteobacteria, Gammaproteobacteria, or Actinobacteria). The same root region was then analyzed for elemental distribution and metal(loid) speciation of As and Fe using ME μXRF. The FISH and ME μXRF images were aligned using ImageJ software to correlate microbiological and geochemical results. Results from quantitative analysis of colocalization show a significantly higher fraction of As colocalized with Fe-oxide plaques on the root surfaces (fraction of overlap 0.49±0.19) than to bacteria (0.072±0.052) (proots, metal(loid)s and microbes, information that should lead to improved mechanistic models of metal(loid) speciation and fate. Copyright © 2016 Elsevier B.V. All rights reserved.

Half a Year of Co-located Gaseous Elemental Mercury Measurements: Investigation of Temporal Changes in Measurement Differences

Czech Academy of Sciences Publication Activity Database

Veselík, P.; Dvorská, Alice; Michálek, J.

2017-01-01

Roč. 26, č. 5 (2017), s. 3128-3137 ISSN 1018-4619 R&D Projects: GA MŠk(CZ) LO1415 Institutional support: RVO:67179843 Keywords : gaseous elemental mercury * Tekran 2537B * co-located measurement * capability indices * regression * cluster analysis Subject RIV: EH - Ecology, Behaviour OBOR OECD: Environmental sciences (social aspects to be 5.7) Impact factor: 0.425, year: 2016

Localization of Nitric Oxide Synthase-containing Neurons in the Bat Visual Cortex and Co-localization with Calcium-binding Proteins

International Nuclear Information System (INIS)

Gu, Ya-Nan; Kim, Hang-Gu; Jeon, Chang-Jin

2015-01-01

Microchiroptera (microbats) is a suborder of bats thought to have degenerated vision. However, many recent studies have shown that they have visual ability. In this study, we labeled neuronal nitric oxide synthase (nNOS)—the synthesizing enzyme of the gaseous non-synaptic neurotransmitter nitric oxide—and co-localized it with calbindin D28K (CB), calretinin (CR), and parvalbumin (PV) in the visual cortex of the greater horseshoe bat (Rhinolophus ferrumequinum, a species of microbats). nNOS-immunoreactive (IR) neurons were found in all layers of the visual cortex. Intensely labeled neurons were most common in layer IV, and weakly labeled neurons were most common in layer VI. Majority of the nNOS-IR neurons were round- or oval-type neurons; no pyramidal-type neurons were found. None of these neurons co-localized with CB, CR, or PV. However, the synthesis of nitric oxide in the bat visual cortex by nNOS does not depend on CB, CR, or PV

Colocalization coefficients evaluating the distribution of molecular targets in microscopy methods based on pointed patterns

Czech Academy of Sciences Publication Activity Database

Pastorek, Lukáš; Sobol, Margaryta; Hozák, Pavel

2016-01-01

Roč. 146, č. 4 (2016), s. 391-406 ISSN 0948-6143 R&D Projects: GA TA ČR(CZ) TE01020118; GA ČR GA15-08738S; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) LM2015062 Grant - others:Human Frontier Science Program(FR) RGP0017/2013 Institutional support: RVO:68378050 Keywords : Colocalization * Quantitative analysis * Pointed patterns * Transmission electron microscopy * Manders' coefficients * Immunohistochemistry Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.553, year: 2016

Avaliação do efeito da colostomia proximal na cicatrização de anastomoses colocólicas em ratos com obstrução intestinal

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Marcelo Betim Paes Leme

Full Text Available OBJETIVO: Avaliar o efeito da colostomia proximal na cicatrização de anastomoses colocólicas em ratos com obstrução intestinal. MÉTODO: 72 ratos foram divididos em três grupos: grupo controle (C, submetido à anastomose colocólica e à colostomia proximal na ausência de oclusão intestinal; grupo sem colostomia (SC, submetido à oclusão intestinal de 72 horas e à anastomose colocólica primária; grupo com colostomia (CC submetido à oclusão intestinal de 72 horas, à anastomose colocólica primária e à colostomia proximal. A cicatrização anastomótica foi avaliada em dois períodos, nos 2º e 7º dias de pós-operatório, em relação à deiscência anastomótica, aderências, epitelização mucosa, pressão de ruptura e a variáveis histológicas por estudo convencional e informatizado. RESULTADOS: verificou-se maior tendência a deiscência anastomótica no grupo SC (12,5%, e elevada incidência de complicações da colostomia no grupo CC (13%, entretanto tais resultados não apresentaram diferença estatística significante. No que se refere às demais variáveis analisadas para verificação da cicatrização anastomótica deve-se considerar que houve equivalência entre os três grupos nos dois períodos analisados. CONCLUSÃO: Não há diferença entre a cicatrização de anastomoses colocólicas associadas ou não à colostomia proximal, em ratos com obstrução intestinal.

Analysis of co-located MODIS and CALIPSO observations near clouds

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T. Várnai

2012-02-01

Full Text Available This paper aims at helping synergistic studies in combining data from different satellites for gaining new insights into two critical yet poorly understood aspects of anthropogenic climate change, aerosol-cloud interactions and aerosol radiative effects. In particular, the paper examines the way cloud information from the MODIS (MODerate resolution Imaging Spectroradiometer imager can refine our perceptions based on CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization lidar measurements about the systematic aerosol changes that occur near clouds.

The statistical analysis of a yearlong dataset of co-located global maritime observations from the Aqua and CALIPSO (Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation satellites reveals that MODIS's multispectral imaging ability can greatly help the interpretation of CALIOP observations. The results show that imagers on Aqua and CALIPSO yield very similar pictures, and that the discrepancies – due mainly to wind drift and differences in view angle – do not significantly hinder aerosol measurements near clouds. By detecting clouds outside the CALIOP track, MODIS reveals that clouds are usually closer to clear areas than CALIOP data alone would suggest. The paper finds statistical relationships between the distances to clouds in MODIS and CALIOP data, and proposes a rescaling approach to statistically account for the impact of clouds outside the CALIOP track even when MODIS cannot reliably detect low clouds, for example at night or over sea ice. Finally, the results show that the typical distance to clouds depends on both cloud coverage and cloud type, and accordingly varies with location and season. In maritime areas perceived cloud free, the global median distance to clouds below 3 km altitude is in the 4–5 km range.

Strategic Co-Location in a Hybrid Process Involving Desalination and Pressure Retarded Osmosis (PRO

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William B. Krantz

2013-07-01

Full Text Available This paper focuses on a Hybrid Process that uses feed salinity dilution and osmotic power recovery from Pressure Retarded Osmosis (PRO to achieve higher overall water recovery. This reduces the energy consumption and capital costs of conventional seawater desalination and water reuse processes. The Hybrid Process increases the amount of water recovered from the current 66.7% for conventional seawater desalination and water reuse processes to a potential 80% through the use of reclaimed water brine as an impaired water source. A reduction of up to 23% in energy consumption is projected via the Hybrid Process. The attractiveness is amplified by potential capital cost savings ranging from 8.7%–20% compared to conventional designs of seawater desalination plants. A decision matrix in the form of a customizable scorecard is introduced for evaluating a Hybrid Process based on the importance of land space, capital costs, energy consumption and membrane fouling. This study provides a new perspective, looking at processes not as individual systems but as a whole utilizing strategic co-location to unlock the synergies available in the water-energy nexus for more sustainable desalination.

Strategic Co-Location in a Hybrid Process Involving Desalination and Pressure Retarded Osmosis (PRO)

Science.gov (United States)

Sim, Victor S.T.; She, Qianhong; Chong, Tzyy Haur; Tang, Chuyang Y.; Fane, Anthony G.; Krantz, William B.

2013-01-01

This paper focuses on a Hybrid Process that uses feed salinity dilution and osmotic power recovery from Pressure Retarded Osmosis (PRO) to achieve higher overall water recovery. This reduces the energy consumption and capital costs of conventional seawater desalination and water reuse processes. The Hybrid Process increases the amount of water recovered from the current 66.7% for conventional seawater desalination and water reuse processes to a potential 80% through the use of reclaimed water brine as an impaired water source. A reduction of up to 23% in energy consumption is projected via the Hybrid Process. The attractiveness is amplified by potential capital cost savings ranging from 8.7%–20% compared to conventional designs of seawater desalination plants. A decision matrix in the form of a customizable scorecard is introduced for evaluating a Hybrid Process based on the importance of land space, capital costs, energy consumption and membrane fouling. This study provides a new perspective, looking at processes not as individual systems but as a whole utilizing strategic co-location to unlock the synergies available in the water-energy nexus for more sustainable desalination. PMID:24956940

The Impact of Co-Locating American Job Centers on Community College Campuses in North Carolina. A CAPSEE Working Paper

Science.gov (United States)

Van Noy, Michelle

2015-01-01

Relationships between community colleges and the public workforce system might have an important role in promoting students' success in the labor market and in college. In particular, the co-location of American Job Centers (AJC) on community college campuses is a particularly strong form of relationship that might benefit students. Yet little is…

Ankyrin repeat and SOCS box containing protein 4 (Asb-4 colocalizes with insulin receptor substrate 4 (IRS4 in the hypothalamic neurons and mediates IRS4 degradation

Directory of Open Access Journals (Sweden)

Xia Zefeng

2011-09-01

Full Text Available Abstract Background The arcuate nucleus of the hypothalamus regulates food intake. Ankyrin repeat and SOCS box containing protein 4 (Asb-4 is expressed in neuropeptide Y and proopiomelanocortin (POMC neurons in the arcuate nucleus, target neurons in the regulation of food intake and metabolism by insulin and leptin. However, the target protein(s of Asb-4 in these neurons remains unknown. Insulin receptor substrate 4 (IRS4 is an adaptor molecule involved in the signal transduction by both insulin and leptin. In the present study we examined the colocalization and interaction of Asb-4 with IRS4 and the involvement of Asb-4 in insulin signaling. Results In situ hybridization showed that the expression pattern of Asb-4 was consistent with that of IRS4 in the rat brain. Double in situ hybridization showed that IRS4 colocalized with Asb-4, and both Asb-4 and IRS4 mRNA were expressed in proopiomelanocortin (POMC and neuropeptide Y (NPY neurons within the arcuate nucleus of the hypothalamus. In HEK293 cells co-transfected with Myc-tagged Asb-4 and Flag-tagged IRS4, Asb-4 co-immunoprecipitated with IRS4; In these cells endogenous IRS4 also co-immunoprecipitated with transfected Myc-Asb-4; Furthermore, Asb-4 co-immunoprecipitated with IRS4 in rat hypothalamic extracts. In HEK293 cells over expression of Asb-4 decreased IRS4 protein levels and deletion of the SOCS box abolished this effect. Asb-4 increased the ubiquitination of IRS4; Deletion of SOCS box abolished this effect. Expression of Asb-4 decreased both basal and insulin-stimulated phosphorylation of AKT at Thr308. Conclusions These data demonstrated that Asb-4 co-localizes and interacts with IRS4 in hypothalamic neurons. The interaction of Asb-4 with IRS4 in cell lines mediates the degradation of IRS4 and decreases insulin signaling.

The Epstein-Barr virus nuclear antigen-6 protein co-localizes with EBNA-3 and survival of motor neurons protein

International Nuclear Information System (INIS)

Krauer, Kenia G.; Buck, Marion; Belzer, Deanna K.; Flanagan, James; Chojnowski, Grace M.; Sculley, Tom B.

2004-01-01

The Epstein-Barr virus nuclear antigen (EBNA)-6 protein is essential for Epstein-Barr virus (EBV)-induced immortalization of primary human B-lymphocytes in vitro. In this study, fusion proteins of EBNA-6 with green fluorescent protein (GFP) have been used to characterize its nuclear localization and organization within the nucleus. EBNA-6 associates with nuclear structures and in immunofluorescence demonstrate a punctate staining pattern. Herein, we show that the association of EBNA-6 with these nuclear structures was maintained throughout the cell cycle and with the use of GFP-E6 deletion mutants, that the region amino acids 733-808 of EBNA-6 contains a domain that can influence the association of EBNA-6 with these nuclear structures. Co-immunofluorescence and confocal analyses demonstrated that EBNA-6 and EBNA-3 co-localize in the nucleus of cells. Expression of EBNA-6, but not EBNA-3, caused a redistribution of nuclear survival of motor neurons protein (SMN) to the EBNA-6 containing nuclear structures resulting in co-localization of SMN with EBNA-6

Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

Energy Technology Data Exchange (ETDEWEB)

Olszewski, Pawel K., E-mail: olsze005@umn.edu [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Fredriksson, Robert; Eriksson, Jenny D. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Mitra, Anaya [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Radomska, Katarzyna J. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Gosnell, Blake A. [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Solvang, Maria N. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Levine, Allen S. [Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Schioeth, Helgi B. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden)

2011-05-13

Highlights: {yields} The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. {yields} The level of colocalization is similar in the male and female brain. {yields} Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. {yields} Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

International Nuclear Information System (INIS)

Olszewski, Pawel K.; Fredriksson, Robert; Eriksson, Jenny D.; Mitra, Anaya; Radomska, Katarzyna J.; Gosnell, Blake A.; Solvang, Maria N.; Levine, Allen S.; Schioeth, Helgi B.

2011-01-01

Highlights: → The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. → The level of colocalization is similar in the male and female brain. → Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. → Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

Sixteen-Day Bedrest Significantly Increases Plasma Colloid Osmotic Pressure

Science.gov (United States)

Hargens, Alan R.; Hsieh, S. T.; Murthy, G.; Ballard, R. E.; Convertino, V. A.; Wade, Charles E. (Technical Monitor)

1994-01-01

Upon exposure to microgravity, astronauts lose up to 10% of their total plasma volume, which may contribute to orthostatic intolerance after space flight. Because plasma colloid osmotic pressure (COP) is a primary factor maintaining plasma volume, our objective was to measure time course changes in COP during microgravity simulated by 6 deg. head-down tilt (HDT). Seven healthy male subjects (30-55 years of age) were placed in HDT for 16 days. For the purpose of another study, three of the seven subjects were chosen to exercise on a cycle ergometer on day 16. Blood samples were drawn immediately before bedrest on day 14 of bedrest, 18-24 hours following exercise while all subjects were still in HDT and 1 hour following bedrest termination. Plasma COP was measured in all 20 microliter EDTA-treated samples using an osmometer fitted with a PM 30 membrane. Data were analyzed with paired and unpaired t-tests. Plasma COP on day 14 of bedrest (29.9 +/- 0.69 mmHg) was significantly higher (p less than 0.005) than the control, pre-bedrest value (23.1 +/- 0.76 mmHg). At one hour of upright recovery after HDT, plasma COP remained significantly elevated (exercise: 26.9 +/- 0.87 mmHg; no exercise: 26.3 +/- 0.85 mmHg). Additionally, exercise had no significant effect on plasma COP 18-24 hours following exercise (exercise: 27.8 +/- 1.09 mmHg; no exercise: 27.1 +/- 0.78 mmHg). Our results demonstrate that plasma COP increases significantly with microgravity simulated by HDT. However, preliminary results indicate exercise during HDT does not significantly affect plasma COP.

Tissue- and Cell-Specific Co-localization of Intracellular Gelatinolytic Activity and Matrix Metalloproteinase 2

Science.gov (United States)

Solli, Ann Iren; Fadnes, Bodil; Winberg, Jan-Olof; Uhlin-Hansen, Lars

2013-01-01

Matrix metalloproteinase 2 (MMP-2) is a proteolytic enzyme that degrades extracellular matrix proteins. Recent studies indicate that MMP-2 also has a role in intracellular proteolysis during various pathological conditions, such as ischemic injuries in heart and brain and in tumor growth. The present study was performed to map the distribution of intracellular MMP-2 activity in various mouse tissues and cells under physiological conditions. Samples from normal brain, heart, lung, liver, spleen, pancreas, kidney, adrenal gland, thyroid gland, gonads, oral mucosa, salivary glands, esophagus, intestines, and skin were subjected to high-resolution in situ gelatin zymography and immunohistochemical staining. In hepatocytes, cardiac myocytes, kidney tubuli cells, epithelial cells in the oral mucosa as well as in excretory ducts of salivary glands, and adrenal cortical cells, we found strong intracellular gelatinolytic activity that was significantly reduced by the metalloprotease inhibitor EDTA but not by the cysteine protease inhibitor E-64. Furthermore, the gelatinolytic activity was co-localized with MMP-2. Western blotting and electron microscopy combined with immunogold labeling revealed the presence of MMP-2 in different intracellular compartments of isolated hepatocytes. Our results indicate that MMP-2 takes part in intracellular proteolysis in specific tissues and cells during physiological conditions. PMID:23482328

Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin.

Science.gov (United States)

Dursun, Erdinç; Gezen-Ak, Duygu

2017-01-01

Our recent study indicated that vitamin D and its receptors are important parts of the amyloid processing pathway in neurons. Yet the role of vitamin D receptor (VDR) in amyloid pathogenesis is complex and all regulations over the production of amyloid beta cannot be explained solely with the transcriptional regulatory properties of VDR. Given that we hypothesized that VDR might exist on the neuronal plasma membrane in close proximity with amyloid precursor protein (APP) and secretase complexes. The present study primarily focused on the localization of VDR in neurons and its interaction with amyloid pathology-related proteins. The localization of VDR on neuronal membranes and its co-localization with target proteins were investigated with cell surface staining followed by immunofluorescence labelling. The FpClass was used for protein-protein interaction prediction. Our results demonstrated the localization of VDR on the neuronal plasma membrane and the co-localization of VDR and APP or ADAM10 or Nicastrin and limited co-localization of VDR and PS1. E-cadherin interaction with APP or the γ-secretase complex may involve NOTCH1, NUMB, or FHL2, according to FpClass. This suggested complex might also include VDR, which greatly contributes to Ca+2 hemostasis with its ligand vitamin D. Consequently, we suggested that VDR might be a member of this complex also with its own non-genomic action and that it can regulate the APP processing pathway in this way in neurons.

Advantages of co-located spent fuel reprocessing, repository and underground reactor facilities

International Nuclear Information System (INIS)

Mahar, James M.; Kunze, Jay F.; Wes Myers, Carl; Loveland, Ryan

2007-01-01

The purpose of this work is to extend the discussion of potential advantages of the underground nuclear park (UNP) concept by making specific concept design and cost estimate comparisons for both present Generation III types of reactors and for some of the modular Gen IV or the GNEP modular concept. For the present Gen III types, we propose co-locating reprocessing and (re)fabrication facilities along with disposal facilities in the underground park. The goal is to determine the site costs and facility construction costs of such a complex which incorporates the advantages of a closed fuel cycle, nuclear waste repository, and ultimate decommissioning activities all within the UNP. Modular power generation units are also well-suited for placement underground and have the added advantage of construction using current and future tunnel boring machine technology. (authors)

GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell

Energy Technology Data Exchange (ETDEWEB)

Park, Jiyoung; Kim, Ki-Suk; Kim, Kang-Hoon; Lee, In-Seung; Jeong, Hyeon-soo; Kim, Yumi; Jang, Hyeung-Jin, E-mail: hjjang@khu.ac.kr

2015-12-04

Glucagon-like peptide-1 (GLP-1) hormone is known to regulate blood glucose by an insulinotropic effect and increases proliferation as and also prevents apoptosis of pancreatic β cells. We know that GLP-1 is secreted by nutrients such as fatty acids and sweet compounds but also bitter compounds via stimulation of G-protein coupled receptors (GPCRs) in the gut. Among these, bitter compounds are multiply-contained in phytochemicals or artificial materials and perceived as ligands of various bitter taste receptors. We hypothesized that GLP-1 hormone is secreted through stimulation of a single bitter taste receptor by 1,10-phenanthroline which is known agonist of taste receptor type 2 member 5 (T2R5). To prove this hypothesis, we used the representatively well-known 1,10-phenanthroline as ligand of single receptor and evaluated the existence of T2R5 by double-labeling immunofluorescence and then 1,10-phenanthroline is able to secrete GLP-1 hormone through stimulation of T2R5 in human enteroendocrine cells. Consequently, we verify that GLP-1 hormone is colocalized with T2R5 in the human duodenum and ileum tissue and is secreted by 1,10-phenanthroline via T2R5 signal transduction in differentiated human enteroendocrine L cells. - Highlights: • Taste receptor type 2 member 5 (T2R5) is colocalized with GLP-1 hormone in human enteroendocrine cells. • GLP-1 secretion is stimulated by 1,10-phenanthroline via stimulation of T2R5. • Inhibition of the bitter taste pathway reduce GLP-1 secretion.

GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell

International Nuclear Information System (INIS)

Park, Jiyoung; Kim, Ki-Suk; Kim, Kang-Hoon; Lee, In-Seung; Jeong, Hyeon-soo; Kim, Yumi; Jang, Hyeung-Jin

2015-01-01

Glucagon-like peptide-1 (GLP-1) hormone is known to regulate blood glucose by an insulinotropic effect and increases proliferation as and also prevents apoptosis of pancreatic β cells. We know that GLP-1 is secreted by nutrients such as fatty acids and sweet compounds but also bitter compounds via stimulation of G-protein coupled receptors (GPCRs) in the gut. Among these, bitter compounds are multiply-contained in phytochemicals or artificial materials and perceived as ligands of various bitter taste receptors. We hypothesized that GLP-1 hormone is secreted through stimulation of a single bitter taste receptor by 1,10-phenanthroline which is known agonist of taste receptor type 2 member 5 (T2R5). To prove this hypothesis, we used the representatively well-known 1,10-phenanthroline as ligand of single receptor and evaluated the existence of T2R5 by double-labeling immunofluorescence and then 1,10-phenanthroline is able to secrete GLP-1 hormone through stimulation of T2R5 in human enteroendocrine cells. Consequently, we verify that GLP-1 hormone is colocalized with T2R5 in the human duodenum and ileum tissue and is secreted by 1,10-phenanthroline via T2R5 signal transduction in differentiated human enteroendocrine L cells. - Highlights: • Taste receptor type 2 member 5 (T2R5) is colocalized with GLP-1 hormone in human enteroendocrine cells. • GLP-1 secretion is stimulated by 1,10-phenanthroline via stimulation of T2R5. • Inhibition of the bitter taste pathway reduce GLP-1 secretion.

Significance in the increase of women psychiatrists in Korea.

Science.gov (United States)

Kim, Ha Kyoung; Kim, Soo In

2008-01-01

The number of female doctors has increased in Korea; 18.9% (13,083) of the total medical doctors registered (69,097) were women in 2006, compared to 13.6% (2,216) in 1975. The proportion of female doctors will jump up by 2010 considering that nearly 40% of the medical students are women as of today. This trend has had strong influence on the field of psychiatry; the percentage of women psychiatrists rose from 1.6 (6)% to 18% (453), from 1975 to 2006 and now women residents comprise 39% (206) of all. This is not only a reflection of a social phenomenon of the increase in professional women but also attributed to some specific characteristics of the psychiatry. Psychiatric practice may come more natural to women. While clinical activities of women psychiatrists are expanding, there are few women leaders and much less women are involving in academic activities in this field as yet. Though there is less sexual discrimination in the field of psychiatry, women psychiatrists are still having a lot of difficulties in balancing work and family matters. Many women psychiatrists also report they've ever felt an implied discrimination in their careers. In this study, we are to identify the characteristics of women psychiatrists and to explore the significance of the increase in women psychiatrists in Korea and the situation in which they are.

Gibberellins Promote Brassinosteroids Action and Both Increase Heterosis for Plant Height in Maize (Zea mays L.

Directory of Open Access Journals (Sweden)

Songlin Hu

2017-06-01

Full Text Available Brassinosteroids (BRs and Gibberellins (GAs are two classes of plant hormones affecting plant height (PHT. Thus, manipulation of BR and GA levels or signaling enables optimization of crop grain and biomass yields. We established backcross (BC families, selected for increased PHT, in two elite maize inbred backgrounds. Various exotic accessions used in the germplasm enhancement in maize project served as donors. BC1-derived doubled haploid lines in the same two elite maize inbred backgrounds established without selection for plant height were included for comparison. We conducted genome-wide association studies to explore the genetic control of PHT by BR and GA. In addition, we used BR and GA inhibitors to compare the relationship between PHT, BR, and GA in inbred lines and heterozygotes from a physiological and biological perspective. A total of 73 genomic loci were discovered to be associated with PHT, with seven co-localized with GA, and two co-localized with BR candidate genes. PHT determined in field trials was significantly correlated with seedling stage BR and GA inhibitor responses. However, this observation was only true for maize heterozygotes, not for inbred lines. Path analysis results suggest that heterozygosity increases GA levels, which in turn promote BR levels. Thus, at least part of heterosis for PHT in maize can be explained by increased GA and BR levels, and seedling stage hormone inhibitor response is promising to predict heterosis for PHT.

Concept for a small, colocated fuel cycle facility for oxide breeder fuels

International Nuclear Information System (INIS)

Burch, W.D.; Stradley, J.G.; Lerch, R.E.

1987-01-01

As part of a United States Department of Energy (USDOE) program to examine innovative liquid-metal reactor (LMR) system designs over the past three years, the Oak Ridge National Laboratory (ORNL) and the Westinghouse Hanford Company (WHC) collaborated on studies of mixed oxide fuel cycle options. A principal effort was an advanced concept for a small integrated fuel cycle colocated with a 1300-MW(e) reactor station. The study provided a scoping design and a basis on which to proceed with implementation of such a facility if future plans so dictate. The facility integrated reprocessing, waste management, and refabrication functions in a single facility of nominal 35-t/year capacity utilizing the latest technology developed in fabrication programs at WHC and in reprocessing at ORNL. The concept was based on many years of work at both sites and extensive design studies of prior years

Concept for a small, colocated fuel cycle facility for oxide breeder fuels

International Nuclear Information System (INIS)

Burch, W.D.; Lerch, R.E.; Stradley, J.G.

1987-01-01

As part of a United States Department of Energy (USDOE) program to examine innovative liquid-metal reactor (LMR) system designs over the past three years, the Oak Ridge National Laboratory (ORNL) and the Westinghouse Hanford Company (WHC) collaborated on studies of mixed oxide fuel cycle options. A principal effort was an advanced concept for a small integrated fuel cycle colocated with a 1300-MW(e) reactor station. The study provided a scoping design, capital and operating cost estimates, and a basis on which to proceed with implementation of such a facility if future plans so dictate. The facility integrated reprocessing, waste management, and refabrication functions in a single facility of nominal 35-t/year capacity utilizing the latest technology developed in fabrication programs at WHC and in reprocessing at ORNL. The concept was based on many years of work at both sites and extensive design studies of prior years

Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM(197) conjugate vaccine co-localizes with MHC II on the antigen processing cell surface.

Science.gov (United States)

Lai, Zengzu; Schreiber, John R

2009-05-21

Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM(197) induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but the fate of the PS attached to the carrier is unknown. To determine the location of the PS component of PnPS-CRM(197) in the APC, we separately labeled PS and protein and tracked their location. The PS of types 14-CRM(197) and 19F-CRM(197) was specifically labeled by Alexa Fluor 594 hydrazide (red). The CRM(197) was separately labeled red in a reaction that did not label PS. Labeled antigens were incubated with APC which were fixed, permeabilized and incubated with anti-MHC II antibody labeled green by Alexa Fluor 488, followed by confocal microscopy. Labeled CRM(197) was presented on APC surface and co-localized with MHC II (yellow). Labeled unconjugated 14 or 19F PS did not go to the APC surface, but PS labeled 14-CRM(197) and 19F-CRM(197) was internalized and co-localized with MHC II. Monoclonal antibody to type 14 PS bound to intracellular type 14 PS and PS-CRM(197). Brefeldin A and chloroquine blocked both CRM(197) and PS labeled 14-CRM(197) and 19F-CRM(197) from co-localizing with MHC II. These data suggest that the PS component of the CRM(197) glycoconjugate enters the endosome, travels with CRM(197) peptides to the APC surface and co-localizes with MHC II.

Simulations of VLBI observations of a geodetic satellite providing co-location in space

Science.gov (United States)

Anderson, James M.; Beyerle, Georg; Glaser, Susanne; Liu, Li; Männel, Benjamin; Nilsson, Tobias; Heinkelmann, Robert; Schuh, Harald

2018-02-01

We performed Monte Carlo simulations of very-long-baseline interferometry (VLBI) observations of Earth-orbiting satellites incorporating co-located space-geodetic instruments in order to study how well the VLBI frame and the spacecraft frame can be tied using such measurements. We simulated observations of spacecraft by VLBI observations, time-of-flight (TOF) measurements using a time-encoded signal in the spacecraft transmission, similar in concept to precise point positioning, and differential VLBI (D-VLBI) observations using angularly nearby quasar calibrators to compare their relative performance. We used the proposed European Geodetic Reference Antenna in Space (E-GRASP) mission as an initial test case for our software. We found that the standard VLBI technique is limited, in part, by the present lack of knowledge of the absolute offset of VLBI time to Coordinated Universal Time at the level of microseconds. TOF measurements are better able to overcome this problem and provide frame ties with uncertainties in translation and scale nearly a factor of three smaller than those yielded from VLBI measurements. If the absolute time offset issue can be resolved by external means, the VLBI results can be significantly improved and can come close to providing 1 mm accuracy in the frame tie parameters. D-VLBI observations with optimum performance assumptions provide roughly a factor of two higher uncertainties for the E-GRASP orbit. We additionally simulated how station and spacecraft position offsets affect the frame tie performance.

Co-located monogenetic eruptions similar to 200 kyr apart driven by tapping vertically separated mantle source regions, Chagwido, Jeju Island, Republic of Korea

NARCIS (Netherlands)

Brenna, M.; Nemeth, K.; Cronin, S.J.; Sohn, Y.K.; Smith, I.E.M.; Wijbrans, J.R.

2015-01-01

New eruptions in monogenetic volcanic fields conceptually occur independently of previous ones. In some instances, however, younger volcanic structures and vents may overlap with older edifices. The genetic links between such co-located eruptions remain unclear. We mapped and analysed the

Microfibril-associated Protein 4 Binds to Surfactant Protein A (SP-A) and Colocalizes with SP-A in the Extracellular Matrix of the Lung

DEFF Research Database (Denmark)

Schlosser, Anders; Thomsen, Theresa H.; Shipley, J. Michael

2006-01-01

for phagocytes. Here we describe the molecular interaction between the extracellular matrix protein microfibril-associated protein 4 (MFAP4) and SP-A. MFAP4 is a collagen-binding molecule containing a C-terminal fibrinogen-like domain and a N-terminal located integrin-binding motif. We produced recombinant MFAP4......-A composed of the neck region and carbohydrate recognition domain of SP-A indicating that the interaction between MFAP4 and SP-A is mediated via the collagen domain of SP-A. Monoclonal antibodies directed against MFAP4 and SP-A were used for immunohistochemical analysis, which demonstrates that the two...... molecules colocalize both on the elastic fibres in the interalveolar septum and in elastic lamina of pulmonary arteries of chronically inflamed lung tissue. We conclude, that MFAP4 interacts with SP-A via the collagen region in vitro, and that MFAP4 and SP-A colocates in different lung compartments...

Cell junction protein armadillo repeat gene deleted in velo-cardio-facial syndrome is expressed in the skin and colocalizes with autoantibodies of patients affected by a new variant of endemic pemphigus foliaceus in Colombia.

Science.gov (United States)

Abreu-Velez, Ana Maria; Yi, Hong; Howard, Michael S

2017-10-01

We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America (El Bagre-EPF, or pemphigus Abreu-Manu). El Bagre-EPF differs from other types of EPF clinically, epidemiologically, immunologically and in its target antigens. We reported the presence of patient autoantibodies colocalizing with armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), a catenin cell junction protein colocalizing with El Bagre-EPF autoantibodies in the heart and within pilosebaceous units along their neurovascular supply routes. Here we investigate the presence of ARVCF in skin and its possibility as a cutaneous El Bagre-EPF antigen. We used a case-control study, testing sera of 45 patients and 45 controls via direct and indirect immunofluorescence (DIF/IIF), confocal microscopy, immunoelectron microscopy and immunoblotting for the presence of ARVCF and its relationship with El Bagre-EPF autoantibodies in the skin. We also immunoadsorbed samples with desmoglein 1 (Dsg1) ectodomain (El Bagre-EPF antigen) by incubating with the positive ARVCF samples from DIF and IIF. ARVCF was expressed in all the samples from the cases and controls. Immunoadsorption with Dsg1 on positive ARVCF immunofluorescence DIF/IIF cases showed that the immune response was present against non-desmoglein 1 antigen(s). Overall, 40/45 patients showed colocalization of their autoantibodies with ARVCF in the epidermis; no controls from the endemic area displayed colocalization. We demonstrate that ARVCF is expressed in many areas of human skin, and colocalizes with the majority of El Bagre-EPF autoantibodies as a putative antigen.

THE SMALL BUT SIGNIFICANT AND NONTRANSITORY INCREASE IN PRICES (SSNIP TEST

Directory of Open Access Journals (Sweden)

Liviana Niminet

2008-12-01

Full Text Available The Small but Significant Nontransitory Increase in Price Test was designed to define the relevant market by concepts of product, geographical area and time. This test, also called the ,,hypothetical monopolistic test” is the subject of many researches both economical and legal as it deals with economic concepts as well as with legally aspects.

Increased frequency of retinopathy of prematurity over the last decade and significant regional differences.

Science.gov (United States)

Holmström, Gerd; Tornqvist, Kristina; Al-Hawasi, Abbas; Nilsson, Åsa; Wallin, Agneta; Hellström, Ann

2018-03-01

Retinopathy of prematurity (ROP) causes childhood blindness globally in prematurely born infants. Although increased levels of oxygen supply lead to increased survival and reduced frequency of cerebral palsy, increased incidence of ROP is reported. With the help of a Swedish register for ROP, SWEDROP, national and regional incidences of ROP and frequencies of treatment were evaluated from 2008 to 2015 (n = 5734), as well as before and after targets of provided oxygen changed from 85-89% to 91-95% in 2014. Retinopathy of prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a gestational age (GA) of <31 weeks at birth and 5.7% of the infants (329/5734) had been treated for ROP. Analyses of the national data revealed an increased incidence of ROP during the 8-year study period (p = 0.003), but there was no significant increase in the frequency of treatment. There were significant differences between the seven health regions of Sweden, regarding both incidence of ROP and frequency of treatment (p < 0.001). Comparison of regional data before and after the new oxygen targets revealed a significant increase in treated ROP in one region [OR: 2.24 (CI: 1.11-4.49), p = 0.024] and a borderline increase in one other [OR: 3.08 (CI: 0.99-9.60), p = 0.052]. The Swedish national ROP register revealed an increased incidence of ROP during an 8-year period and significant regional differences regarding the incidence of ROP and frequency of treatment. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Evaluation of Significance of Diffusely Increased Bilateral Renal Uptake on Bone Scan

International Nuclear Information System (INIS)

Sung, Mi Sook; Yang, Woo Jin; Byun, Jae Young; Park, Jung Mi; Shinn, Kyung Sub; Bahk, Yong Whee

1990-01-01

Unexpected renal abnormality can be detected on bone scan using 99m Tc-MDP. The purpose of the study is to evaluate the diagnostic significance of diffusely increased bilateral renal uptake on bone scan. 1,500 bone scan were reviewed and 43 scans which showed diffusely increased bilateral renal uptake were selected for analysis. Laboratory findings for renal and liver function tests including routine urinalysis were reviewed in 43 patients. 26 of 43 case showed abnormality in urinalysis and renal function study. 20 of 43 cases showed abnormal liver function study and 3 of these cases were diagnosed as hepatorenal syndrome later. 13 of those 20 cases had liver cirrhosis with or without hepatoma. 12 of 43 cases showed abnormality both in renal and liver function studies. 2 of 43 cases showed diffusely increased bilateral renal uptake after chemotherapy for cancer but not on previous scans before chemotherapy. 2 of 43 cases showed hypercalcaemia and 8 of 43 cases had multifocal bone uptake due to metastasis or benign bone lesion. But the latter showed no hypercalcaemia at all. There was no significant correlation between increased renal uptake and MDP uptake in soft tissue other than kidneys. This study raised the possibility that the impaired liver and/or renal function may result in diffuse increase of bilateral renal uptake of MDP of unknown mechanism. It seems to need further study on this correlation.

Evaluation of Significance of Diffusely Increased Bilateral Renal Uptake on Bone Scan

Energy Technology Data Exchange (ETDEWEB)

Sung, Mi Sook; Yang, Woo Jin; Byun, Jae Young; Park, Jung Mi; Shinn, Kyung Sub; Bahk, Yong Whee [Catholic University College of Medicine, Seoul (Korea, Republic of)

1990-03-15

Unexpected renal abnormality can be detected on bone scan using {sup 99m}Tc-MDP. The purpose of the study is to evaluate the diagnostic significance of diffusely increased bilateral renal uptake on bone scan. 1,500 bone scan were reviewed and 43 scans which showed diffusely increased bilateral renal uptake were selected for analysis. Laboratory findings for renal and liver function tests including routine urinalysis were reviewed in 43 patients. 26 of 43 case showed abnormality in urinalysis and renal function study. 20 of 43 cases showed abnormal liver function study and 3 of these cases were diagnosed as hepatorenal syndrome later. 13 of those 20 cases had liver cirrhosis with or without hepatoma. 12 of 43 cases showed abnormality both in renal and liver function studies. 2 of 43 cases showed diffusely increased bilateral renal uptake after chemotherapy for cancer but not on previous scans before chemotherapy. 2 of 43 cases showed hypercalcaemia and 8 of 43 cases had multifocal bone uptake due to metastasis or benign bone lesion. But the latter showed no hypercalcaemia at all. There was no significant correlation between increased renal uptake and MDP uptake in soft tissue other than kidneys. This study raised the possibility that the impaired liver and/or renal function may result in diffuse increase of bilateral renal uptake of MDP of unknown mechanism. It seems to need further study on this correlation.

St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

International Nuclear Information System (INIS)

Yang, Shih-Ying; Juang, Shin-Hun; Tsai, Shang-Yuan; Chao, Pei-Dawn Lee; Hou, Yu-Chi

2012-01-01

St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC 0−t and C max of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC 0−t of MTX by 55%. In addition, diclofenac enhanced the C max of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC 0−t and C max of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.

The tumor suppressor SHIP1 colocalizes in nucleolar cavities with p53 and components of PML nuclear bodies

OpenAIRE

Ehm, Patrick; Nalaskowski, Marcus M; Wundenberg, Torsten; Jücker, Manfred

2015-01-01

The inositol 5-phosphatase SHIP1 is a negative regulator of signaling processes in haematopoietic cells. By converting PI(3,4,5)P3 to PtdIns(3,4)P2 at the plasma membrane, SHIP1 modifies PI3-kinase mediated signaling. We have recently demonstrated that SHIP1 is a nucleo-cytoplasmic shuttling protein and SHIP1 nuclear puncta partially colocalize with FLASH, a component of nuclear bodies. In this study, we demonstrate that endogenous SHIP1 localizes to intranucleolar regions of both normal and ...

Single-Molecule Analysis of Pre-mRNA Splicing with Colocalization Single-Molecule Spectroscopy (CoSMoS).

Science.gov (United States)

Braun, Joerg E; Serebrov, Victor

2017-01-01

Recent development of single-molecule techniques to study pre-mRNA splicing has provided insights into the dynamic nature of the spliceosome. Colocalization single-molecule spectroscopy (CoSMoS) allows following spliceosome assembly in real time at single-molecule resolution in the full complexity of cellular extracts. A detailed protocol of CoSMoS has been published previously (Anderson and Hoskins, Methods Mol Biol 1126:217-241, 2014). Here, we provide an update on the technical advances since the first CoSMoS studies including slide surface treatment, data processing, and representation. We describe various labeling strategies to generate RNA reporters with multiple dyes (or other moieties) at specific locations.

Enhancing Macrophage Drug Delivery Efficiency via Co-Localization of Cells and Drug-Loaded Microcarriers in 3D Resonant Ultrasound Field.

Science.gov (United States)

Lee, Yu-Hsiang; Wu, Zhen-Yu

2015-01-01

In this study, a novel synthetic 3D molecular transfer system which involved the use of model drug calcein-AM-encapsulated poly(lactic-co-glycolic acid) microspheres (CAPMs) and resonant ultrasound field (RUF) with frequency of 1 MHz and output intensity of 0.5 W/cm2 for macrophage drug delivery was explored. We hypothesized that the efficiency of CAPMs-mediated drug delivery aided by RUF can be promoted by increasing the contact opportunities between cells and the micrometer-sized drug carriers due to effects of acoustic radiation forces generated by RUF. Through the fluoromicroscopic and flow cytometric analyses, our results showed that both DH82 macrophages and CAPMs can be quickly brought to acoustic pressure nodes within 20 sec under RUF exposure, and were consequently aggregated throughout the time course. The efficacy of cellular uptake of CAPMs was enhanced with increased RUF exposure time where a 3-fold augmentation (P CAPM delivery efficiency was mainly contributed by the co-localization of cells and CAPMs resulting from the application of the RUF, rather than from sonoporation. In summary, the developed molecular delivery approach provides a feasible means for macrophage drug delivery.

Continuous background light significantly increases flashing-light enhancement of photosynthesis and growth of microalgae.

Science.gov (United States)

Abu-Ghosh, Said; Fixler, Dror; Dubinsky, Zvy; Iluz, David

2015-01-01

Under specific conditions, flashing light enhances the photosynthesis rate in comparison to continuous illumination. Here we show that a combination of flashing light and continuous background light with the same integrated photon dose as continuous or flashing light alone can be used to significantly enhance photosynthesis and increase microalgae growth. To test this hypothesis, the green microalga Dunaliella salina was exposed to three different light regimes: continuous light, flashing light, and concomitant application of both. Algal growth was compared under three different integrated light quantities; low, intermediate, and moderately high. Under the combined light regime, there was a substantial increase in all algal growth parameters, with an enhanced photosynthesis rate, within 3days. Our strategy demonstrates a hitherto undescribed significant increase in photosynthesis and algal growth rates, which is beyond the increase by flashing light alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis.

Science.gov (United States)

Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

2009-01-01

Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute

Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

Science.gov (United States)

Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

2009-01-01

Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

Heterochromatin diversity and its co-localization with 5S and 45S rDNA sites in chromosomes of four Maxillaria species (Orchidaceae

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Juliano S. Cabral

2006-01-01

Full Text Available We investigated four orchids of the genus Maxillaria (M. discolor, M. acicularis, M. notylioglossa and M. desvauxiana in regard to the position of heterochromatin blocks as revealed using chromomycin A3 (CMA and 4'-6-diamidino-2-phenylindole (DAPI fluorochrome staining and 5S and 45S rDNA sites using fluorescence in situ hybridization (FISH. The species showed differences in chromosome number and a diversified pattern of CMA+ and DAPI+ bands, including heteromorphism for CMA+ bands. The 5S and 45S rDNA sites also varied in number and most of them were co-localized with CMA+ bands. The relationship between 5S rDNA sites and CMA+ bands was more evident in M. notylioglossa, in which the brighter CMA+ bands were associated with large 5S rDNA sites. However, not all 5S and 45S rDNA sites were co-localized with CMA+ bands, probably due to technical constraints. We compare these results to banding data from other species and suggest that not all blocks of tandemly repetitive sequences, such as 5S rDNA sites, can be observed as heterochromatin blocks.

Estimation of 557.7 nm Emission Altitude using Co-located Lidars and Photometers over Arecibo

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Franco, E.; Raizada, S.; Lautenbach, J.; Brum, C. G. M.

2017-12-01

Airglow at 557.7 nm (green line emission) is generated through the Barth mechanism in the E-region altitude and is sometimes associated with red line (630.0 nm) originating at F-region altitudes. Photons at 557.7 nm are produced through the quenching of excited atomic oxygen atoms, O(1S), while 630.0 nm results through the de-excitation of O(1D) atoms. Even though, the contribution of the green line from F-region is negligible and the significant component comes from the mesosphere, this uncertainty gives rise to a question related to its precise altitude. Previous studies have shown that perturbations generated by atmospheric gravity Waves (GWs) alter the airglow intensity and can be used for studying dynamics of the region where it originates. The uncertainty in the emission altitude of green line can be resolved by using co-located lidars, which provide altitude resolved metal densities. At Arecibo, the resonance lidars tuned to Na and K resonance wavelengths at 589 nm and 770 nm can be used in conjunction with simultaneous measurements from green line photometer to resolve this issue. Both photometer and lidars have narrow field of view as compared to airglow imagers, and hence provide an added advantage that these instruments sample same GW spectrum. Hence, correlation between density perturbations inferred from lidars and airglow intensity perturbations can shed light on the exact altitude of green line emission.

Determinants of Virulence and In Vitro Development Colocalize on a Genetic Map of Setosphaeria turcica.

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Mideros, Santiago X; Chung, Chia-Lin; Wiesner-Hanks, Tyr; Poland, Jesse A; Wu, Dongliang; Fialko, Ariel A; Turgeon, B Gillian; Nelson, Rebecca J

2018-02-01

Generating effective and stable strategies for resistance breeding requires an understanding of the genetics of host-pathogen interactions and the implications for pathogen dynamics and evolution. Setosphaeria turcica causes northern leaf blight (NLB), an important disease of maize for which major resistance genes have been deployed. Little is known about the evolutionary dynamics of avirulence (AVR) genes in S. turcica. To test the hypothesis that there is a genetic association between avirulence and in vitro development traits, we (i) created a genetic map of S. turcica, (ii) located candidate AVRHt1 and AVRHt2 regions, and (iii) identified genetic regions associated with several in vitro development traits. A cross was generated between a race 1 and a race 23N strain, and 221 progeny were isolated. Genotyping by sequencing was used to score 2,078 single-nucleotide polymorphism markers. A genetic map spanning 1,981 centimorgans was constructed, consisting of 21 linkage groups. Genetic mapping extended prior evidence for the location and identity of the AVRHt1 gene and identified a region of interest for AVRHt2. The genetic location of AVRHt2 colocalized with loci influencing radial growth and mycelial abundance. Our data suggest a trade-off between virulence on Ht1 and Ht2 and the pathogen's vegetative growth rate. In addition, in-depth analysis of the genotypic data suggests the presence of significant duplication in the genome of S. turcica.

Persistent Social Networks: Civil War Veterans Who Fought Together Co-Locate in Later Life.

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Costa, Dora L; Kahn, Matthew E; Roudiez, Christopher; Wilson, Sven

2018-05-01

We demonstrate the long reach of early social ties in the location decision of individuals and in their older age mortality risk using data on Union Army veterans of the US Civil War (1861-5). We estimate discrete choice migration models to quantify the trade-offs across locations faced by veterans. Veterans were more likely to move to a neighborhood or county where men from their same war company lived and were more likely to move to such areas than to areas where other veterans were located. Veterans also were less likely to move far from their origin and avoided urban immigrant areas and high mortality risk areas. They also avoided areas that opposed the Civil War. This co-location evidence highlights the existence of persistent social networks. Such social networks had long-term consequences: veterans living close to war-time comrades had a 6% lower probability of dying.

Early evolutionary colocalization of the nuclear ribosomal 5S and 45S gene families in seed plants: evidence from the living fossil gymnosperm Ginkgo biloba.

Science.gov (United States)

Galián, J A; Rosato, M; Rosselló, J A

2012-06-01

In seed plants, the colocalization of the 5S loci within the intergenic spacer (IGS) of the nuclear 45S tandem units is restricted to the phylogenetically derived Asteraceae family. However, fluorescent in situ hybridization (FISH) colocalization of both multigene families has also been observed in other unrelated seed plant lineages. Previous work has identified colocalization of 45S and 5S loci in Ginkgo biloba using FISH, but these observations have not been confirmed recently by sequencing a 1.8 kb IGS. In this work, we report the presence of the 45S-5S linkage in G. biloba, suggesting that in seed plants the molecular events leading to the restructuring of the ribosomal loci are much older than estimated previously. We obtained a 6.0 kb IGS fragment showing structural features of functional sequences, and a single copy of the 5S gene was inserted in the same direction of transcription as the ribosomal RNA genes. We also obtained a 1.8 kb IGS that was a truncate variant of the 6.0 kb IGS lacking the 5S gene. Several lines of evidence strongly suggest that the 1.8 kb variants are pseudogenes that are present exclusively on the satellite chromosomes bearing the 45S-5S genes. The presence of ribosomal IGS pseudogenes best reconciles contradictory results concerning the presence or absence of the 45S-5S linkage in Ginkgo. Our finding that both ribosomal gene families have been unified to a single 45S-5S unit in Ginkgo indicates that an accurate reassessment of the organization of rDNA genes in basal seed plants is necessary.

Tracking mobile users in wireless networks via semi-supervised colocalization.

Science.gov (United States)

Pan, Jeffrey Junfeng; Pan, Sinno Jialin; Yin, Jie; Ni, Lionel M; Yang, Qiang

2012-03-01

Recent years have witnessed the growing popularity of sensor and sensor-network technologies, supporting important practical applications. One of the fundamental issues is how to accurately locate a user with few labeled data in a wireless sensor network, where a major difficulty arises from the need to label large quantities of user location data, which in turn requires knowledge about the locations of signal transmitters or access points. To solve this problem, we have developed a novel machine learning-based approach that combines collaborative filtering with graph-based semi-supervised learning to learn both mobile users' locations and the locations of access points. Our framework exploits both labeled and unlabeled data from mobile devices and access points. In our two-phase solution, we first build a manifold-based model from a batch of labeled and unlabeled data in an offline training phase and then use a weighted k-nearest-neighbor method to localize a mobile client in an online localization phase. We extend the two-phase colocalization to an online and incremental model that can deal with labeled and unlabeled data that come sequentially and adapt to environmental changes. Finally, we embed an action model to the framework such that additional kinds of sensor signals can be utilized to further boost the performance of mobile tracking. Compared to other state-of-the-art systems, our framework has been shown to be more accurate while requiring less calibration effort in our experiments performed on three different testbeds.

VISTILES: Coordinating and Combining Co-located Mobile Devices for Visual Data Exploration.

Science.gov (United States)

Langner, Ricardo; Horak, Tom; Dachselt, Raimund

2017-08-29

We present VISTILES, a conceptual framework that uses a set of mobile devices to distribute and coordinate visualization views for the exploration of multivariate data. In contrast to desktop-based interfaces for information visualization, mobile devices offer the potential to provide a dynamic and user-defined interface supporting co-located collaborative data exploration with different individual workflows. As part of our framework, we contribute concepts that enable users to interact with coordinated & multiple views (CMV) that are distributed across several mobile devices. The major components of the framework are: (i) dynamic and flexible layouts for CMV focusing on the distribution of views and (ii) an interaction concept for smart adaptations and combinations of visualizations utilizing explicit side-by-side arrangements of devices. As a result, users can benefit from the possibility to combine devices and organize them in meaningful spatial layouts. Furthermore, we present a web-based prototype implementation as a specific instance of our concepts. This implementation provides a practical application case enabling users to explore a multivariate data collection. We also illustrate the design process including feedback from a preliminary user study, which informed the design of both the concepts and the final prototype.

Exploring the significance of human mobility patterns in social link prediction

KAUST Repository

Alharbi, Basma Mohammed; Zhang, Xiangliang

2014-01-01

Link prediction is a fundamental task in social networks. Recently, emphasis has been placed on forecasting new social ties using user mobility patterns, e.g., investigating physical and semantic co-locations for new proximity measure. This paper

A Sustainability Index of potential co-location of offshore wind farms and open water aquaculture

DEFF Research Database (Denmark)

Bennassai, G.; Mariani, Patrizio; Stenberg, Claus

2014-01-01

This paper presents the definition of a Sustainability Index for the co-location in marine areas of offshore wind farms and aquaculture plans. The development of the index is focused on the application of MCE technique based on physical constraints and biological parameters that are directly linked...... to the primary production. The relevant physical factors considered are wind velocity and depth range (which directly governs the choice of the site for energy production and for offshore technology), the relevant biological parameters are SST, SST anomaly and CHL-a concentration (as a measurement...... the computation of the Sustainability Index (SI) was identified in the Danish portion of the Baltic Sea and in the western part of the Danish North Sea. Results on the spatial distribution of the SI underline different responses as a function of the physical and biological main influencing parameters...

Market floors strategy and fixed pricing model for co-location under the traditional leaseback framework

DEFF Research Database (Denmark)

Osei-Owusu, Alexander

2016-01-01

Towers make up a substantial proportion of capital investments for telecoms operators and, in emerging markets, most of their operating costs. Mobile operators are opting to share towers, renting them from other tower companies instead of making ongoing and a single financial investments...... on the same towers. The higher the co-location ratio the better for the towers companies (and their financiers), as this drives up revenues from the same base costs. Traditional towers are often designed for a specific number of spaces or tenants’ and finding ways to get these “perishable” spaces filled up...... by infrastructure operators may help drive the needed revenues and investments. The research will also investigate whether the adoption of the fixed pricing strategy is primed on a business sense rather than institutional arrangement or influences. The implication of the pricing regime on expansion of telecom...

Significant increase of surface ozone at a rural site, north of eastern China

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Z. Ma

2016-03-01

Full Text Available Ozone pollution in eastern China has become one of the top environmental issues. Quantifying the temporal trend of surface ozone helps to assess the impacts of the anthropogenic precursor reductions and the likely effects of emission control strategies implemented. In this paper, ozone data collected at the Shangdianzi (SDZ regional atmospheric background station from 2003 to 2015 are presented and analyzed to obtain the variation in the trend of surface ozone in the most polluted region of China, north of eastern China or the North China Plain. A modified Kolmogorov–Zurbenko (KZ filter method was performed on the maximum daily average 8 h (MDA8 concentrations of ozone to separate the contributions of different factors from the variation of surface ozone and remove the influence of meteorological fluctuations on surface ozone. Results reveal that the short-term, seasonal and long-term components of ozone account for 36.4, 57.6 and 2.2 % of the total variance, respectively. The long-term trend indicates that the MDA8 has undergone a significant increase in the period of 2003–2015, with an average rate of 1.13 ± 0.01 ppb year−1 (R2 = 0.92. It is found that meteorological factors did not significantly influence the long-term variation of ozone and the increase may be completely attributed to changes in emissions. Furthermore, there is no significant correlation between the long-term O3 and NO2 trends. This study suggests that emission changes in VOCs might have played a more important role in the observed increase of surface ozone at SDZ.

Poliovirus infection induces the co-localization of cellular protein SRp20 with TIA-1, a cytoplasmic stress granule protein.

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Fitzgerald, Kerry D; Semler, Bert L

2013-09-01

Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Poliovirus infection induces the co-localization of cellular protein SRp20 with TIA-1, a cytoplasmic stress granule protein

Science.gov (United States)

Fitzgerald, Kerry D.; Semler, Bert L.

2013-01-01

Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection. PMID:23830997

Enhancement in statistical and image analysis for in situ µSXRF studies of elemental distribution and co-localization, using Dioscorea balcanica

International Nuclear Information System (INIS)

Dučić, Tanja; Borchert, Manuela; Savić, Aleksandar; Kalauzi, Aleksandar; Mitrović, Aleksandra; Radotić, Ksenija

2013-01-01

Synchrotron-radiation-based X-ray microfluorescence has been used for in situ investigation of the distribution of micronutrient and macronutrient elements in an unstained cross section of a stem of monocotyledonous liana plant Dioscorea balcanica Košanin. The elemental allocation has been quantified and the grouping/co-localization in straight and twisted stem internodes has been analysed. Synchrotron-based X-ray microfluorescence (µSXRF) is an analytical method suitable for in situ investigation of the distribution of micronutrient and macronutrient elements in several-micrometres-thick unstained biological samples, e.g. single cells and tissues. Elements are mapped and quantified at sub-p.p.m. concentrations. In this study the quantity, distribution and grouping/co-localization of various elements have been identified in straight and twisted internodes of the stems of the monocotyledonous climber D. balcanica Košanin. Three different statistical methods were employed to analyse the macro-nutrient and micronutrient distributions and co-localization. Macronutrient elements (K, P, Ca, Cl) are distributed homogeneously in both straight and twisted internodes. Micronutrient elements are mostly grouped in the vasculature and in the sclerenchyma cell layer. In addition, co-localization of micronutrient elements is much more prominent in twisted than in straight internodes. These image analyses and statistical methods provided very similar outcomes and could be applied to various types of biological samples imaged by µSXRF

Co-located hAT transposable element and 5S rDNA in an interstitial telomeric sequence suggest the formation of Robertsonian fusion in armored catfish.

Science.gov (United States)

Glugoski, Larissa; Giuliano-Caetano, Lucia; Moreira-Filho, Orlando; Vicari, Marcelo R; Nogaroto, Viviane

2018-04-15

Co-located 5S rDNA genes and interstitial telomeric sites (ITS) revealed the involvement of multiple 5S rDNA clusters in chromosome rearrangements of Loricariidae. Interstitial (TTAGGG)n vestiges, in addition to telomeric sites, can coincide with locations of chromosomal rearrangements, and they are considered to be hotspots for chromosome breaks. This study aimed the molecular characterization of 5S rDNA in two Rineloricaria latirostris populations and examination of roles of 5S rDNA in breakpoint sites and its in situ localization. Rineloricaria latirostris from Brazil's Das Pedras river (2n = 46 chromosomes) presented five pairs identified using a 5S rDNA probe, in addition to a pair bearing a co-located ITS/5S rDNA. Rineloricaria latirostris from the Piumhi river (2n = 48 chromosomes) revealed two pairs containing 5S rDNA, without ITS. A 702-bp amplified sequence, using 5S rDNA primers, revealed an insertion of the hAT transposable element (TE), referred to as a degenerate 5S rDNA. Double-FISH (fluorescence in situ hybridization) demonstrated co-localization of 5S rDNA/degenerate 5S rDNA, 5S rDNA/hAT and ITS/5S rDNA from the Das Pedras river population. Piumhi river isolates possessed only 5S rDNA sites. We suggest that the degenerate 5S rDNA was generated by unequal crossing over, which was driven by invasion of hAT, establishing a breakpoint region susceptible to chromosome breakage, non-homologous recombination and Robertsonian (Rb) fusion. Furthermore, the presence of clusters of 5S rDNA at fusion points in other armored catfish species suggests its re-use and that these regions represent hotspots for evolutionary rearrangements within Loricariidae genomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Fuel from Wastewater - Harnessing a Potential Energy Source in Canada through the Co-location of Algae Biofuel Production to Sources of Effluent, Heat and CO2

Science.gov (United States)

Klise, G. T.; Roach, J. D.; Passell, H. D.; Moreland, B. D.; O'Leary, S. J.; Pienkos, P. T.; Whalen, J.

2010-12-01

Sandia National Laboratories is collaborating with the National Research Council (NRC) Canada and the National Renewable Energy Laboratory (NREL) to develop a decision-support model that will evaluate the tradeoffs associated with high-latitude algae biofuel production co-located with wastewater, CO2, and waste heat. This project helps Canada meet its goal of diversifying fuel sources with algae-based biofuels. The biofuel production will provide a wide range of benefits including wastewater treatment, CO2 reuse and reduction of demand for fossil-based fuels. The higher energy density in algae-based fuels gives them an advantage over crop-based biofuels as the “production” footprint required is much less, resulting in less water consumed and little, if any conversion of agricultural land from food to fuel production. Besides being a potential source for liquid fuel, algae have the potential to be used to generate electricity through the burning of dried biomass, or anaerobically digested to generate methane for electricity production. Co-locating algae production with waste streams may be crucial for making algae an economically valuable fuel source, and will certainly improve its overall ecological sustainability. The modeling process will address these questions, and others that are important to the use of water for energy production: What are the locations where all resources are co-located, and what volumes of algal biomass and oil can be produced there? In locations where co-location does not occur, what resources should be transported, and how far, while maintaining economic viability? This work is being funded through the U.S. Department of Energy (DOE) Biomass Program Office of Energy Efficiency and Renewable Energy, and is part of a larger collaborative effort that includes sampling, strain isolation, strain characterization and cultivation being performed by the NREL and Canada’s NRC. Results from the NREL / NRC collaboration including specific

Beta 2-adrenergic receptors are colocalized and coregulated with whisker barrels in rat somatosensory cortex

International Nuclear Information System (INIS)

Vos, P.; Kaufmann, D.; Hand, P.J.; Wolfe, B.B.

1990-01-01

Autoradiography has been used to visualize independently the subtypes of beta-adrenergic receptors in rat somatosensory cortex. Beta 2-adrenergic receptors, but not beta 1-adrenergic receptors colocalize with whisker barrels in this tissue. Thus, each whisker sends a specific multisynaptic pathway to the somatosensory cortex that can be histochemically visualized and only one subtype of beta-adrenergic receptor is specifically associated with this cortical representation. Additionally, neonatal lesion of any or all of the whisker follicles results in loss of the corresponding barrel(s) as shown by histochemical markers. This loss is paralleled by a similar loss in the organization of beta 2-adrenergic receptors in the somatosensory cortex. Other results indicate that these beta 2-adrenergic receptors are not involved in moment-to-moment signal transmission in this pathway and, additionally, are not involved in a gross way in the development of whisker-barrel array

St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

Energy Technology Data Exchange (ETDEWEB)

Yang, Shih-Ying [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China); Juang, Shin-Hun [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Tsai, Shang-Yuan; Chao, Pei-Dawn Lee [School of Pharmacy, China Medical University, Taichung, Taiwan (China); Hou, Yu-Chi, E-mail: hou5133@gmail.com [School of Pharmacy, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China)

2012-08-15

St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC{sub 0−t} and C{sub max} of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC{sub 0−t} of MTX by 55%. In addition, diclofenac enhanced the C{sub max} of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC{sub 0−t} and C{sub max} of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.

Bacterial translation elongation factor EF-Tu interacts and colocalizes with actin-like MreB protein.

Science.gov (United States)

Defeu Soufo, Hervé Joël; Reimold, Christian; Linne, Uwe; Knust, Tobias; Gescher, Johannes; Graumann, Peter L

2010-02-16

We show that translation initiation factor EF-Tu plays a second important role in cell shape maintenance in the bacterium Bacillus subtilis. EF-Tu localizes in a helical pattern underneath the cell membrane and colocalizes with MreB, an actin-like cytoskeletal element setting up rod cell shape. The localization of MreB and of EF-Tu is interdependent, but in contrast to the dynamic MreB filaments, EF-Tu structures are more static and may serve as tracks for MreB filaments. In agreement with this idea, EF-Tu and MreB interact in vivo and in vitro. Lowering of the EF-Tu levels had a minor effect on translation but a strong effect on cell shape and on the localization of MreB, and blocking of the function of EF-Tu in translation did not interfere with the localization of MreB, showing that, directly or indirectly, EF-Tu affects the cytoskeletal MreB structure and thus serves two important functions in a bacterium.

Calibration and assessment of electrochemical air quality sensors by co-location with regulatory-grade instruments

Science.gov (United States)

Hagan, David H.; Isaacman-VanWertz, Gabriel; Franklin, Jonathan P.; Wallace, Lisa M. M.; Kocar, Benjamin D.; Heald, Colette L.; Kroll, Jesse H.

2018-01-01

The use of low-cost air quality sensors for air pollution research has outpaced our understanding of their capabilities and limitations under real-world conditions, and there is thus a critical need for understanding and optimizing the performance of such sensors in the field. Here we describe the deployment, calibration, and evaluation of electrochemical sensors on the island of Hawai`i, which is an ideal test bed for characterizing such sensors due to its large and variable sulfur dioxide (SO2) levels and lack of other co-pollutants. Nine custom-built SO2 sensors were co-located with two Hawaii Department of Health Air Quality stations over the course of 5 months, enabling comparison of sensor output with regulatory-grade instruments under a range of realistic environmental conditions. Calibration using a nonparametric algorithm (k nearest neighbors) was found to have excellent performance (RMSE 0.997) across a wide dynamic range in SO2 ( 2 ppm). However, since nonparametric algorithms generally cannot extrapolate to conditions beyond those outside the training set, we introduce a new hybrid linear-nonparametric algorithm, enabling accurate measurements even when pollutant levels are higher than encountered during calibration. We find no significant change in instrument sensitivity toward SO2 after 18 weeks and demonstrate that calibration accuracy remains high when a sensor is calibrated at one location and then moved to another. The performance of electrochemical SO2 sensors is also strong at lower SO2 mixing ratios (pollutant species in other areas (e.g., polluted urban regions), the calibration and validation approaches described here should be widely applicable to a range of pollutants, sensors, and environments.

Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs

Directory of Open Access Journals (Sweden)

David Juan

2016-02-01

Full Text Available Summary: Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity. Here, we propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in ESCs. The epigenetic communication network was inferred from genome-wide location data plus extensive manual annotation. Notably, we found that 5-hydroxymethylcytosine (5hmC is the most-influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency. Moreover, an evolutionary analysis revealed a central role of 5hmC in the co-evolution of chromatin-related proteins. Further analysis of regions where 5hmC co-localizes with specific interactors shows that each interaction points to chromatin remodeling, stemness, differentiation, or metabolism. Our results highlight the importance of cytosine modifications in the epigenetic communication of ESCs. : 5-hydroxymethylcytosine (5hmC plays a key role in the epigenomic communication network of embryonic stem cells. Juan et al. build a communication network based in co-localization of epigenomic data and literature. The analysis of the network and its components reveals that proteins reading and editing 5hmC co-evolve and serve as links between diverse molecular processes.

Stripe rust and leaf rust resistance QTL mapping, epistatic interactions, and co-localization with stem rust resistance loci in spring wheat evaluated over three continents.

Science.gov (United States)

Singh, A; Knox, R E; DePauw, R M; Singh, A K; Cuthbert, R D; Campbell, H L; Shorter, S; Bhavani, S

2014-11-01

In wheat, advantageous gene-rich or pleiotropic regions for stripe, leaf, and stem rust and epistatic interactions between rust resistance loci should be accounted for in plant breeding strategies. Leaf rust (Puccinia triticina Eriks.) and stripe rust (Puccinia striiformis f. tritici Eriks) contribute to major production losses in many regions worldwide. The objectives of this research were to identify and study epistatic interactions of quantitative trait loci (QTL) for stripe and leaf rust resistance in a doubled haploid (DH) population derived from the cross of Canadian wheat cultivars, AC Cadillac and Carberry. The relationship of leaf and stripe rust resistance QTL that co-located with stem rust resistance QTL previously mapped in this population was also investigated. The Carberry/AC Cadillac population was genotyped with DArT(®) and simple sequence repeat markers. The parents and population were phenotyped for stripe rust severity and infection response in field rust nurseries in Kenya (Njoro), Canada (Swift Current), and New Zealand (Lincoln); and for leaf rust severity and infection response in field nurseries in Canada (Swift Current) and New Zealand (Lincoln). AC Cadillac was a source of stripe rust resistance QTL on chromosomes 2A, 2B, 3A, 3B, 5B, and 7B; and Carberry was a source of resistance on chromosomes 2B, 4B, and 7A. AC Cadillac contributed QTL for resistance to leaf rust on chromosome 2A and Carberry contributed QTL on chromosomes 2B and 4B. Stripe rust resistance QTL co-localized with previously reported stem rust resistance QTL on 2B, 3B, and 7B, while leaf rust resistance QTL co-localized with 4B stem rust resistance QTL. Several epistatic interactions were identified both for stripe and leaf rust resistance QTL. We have identified useful combinations of genetic loci with main and epistatic effects. Multiple disease resistance regions identified on chromosomes 2A, 2B, 3B, 4B, 5B, and 7B are prime candidates for further investigation and

A Bayesian Framework for Multiple Trait Colo-calization from Summary Association Statistics.

Science.gov (United States)

Giambartolomei, Claudia; Zhenli Liu, Jimmy; Zhang, Wen; Hauberg, Mads; Shi, Huwenbo; Boocock, James; Pickrell, Joe; Jaffe, Andrew E; Pasaniuc, Bogdan; Roussos, Panos

2018-03-19

Most genetic variants implicated in complex diseases by genome-wide association studies (GWAS) are non-coding, making it challenging to understand the causative genes involved in disease. Integrating external information such as quantitative trait locus (QTL) mapping of molecular traits (e.g., expression, methylation) is a powerful approach to identify the subset of GWAS signals explained by regulatory effects. In particular, expression QTLs (eQTLs) help pinpoint the responsible gene among the GWAS regions that harbor many genes, while methylation QTLs (mQTLs) help identify the epigenetic mechanisms that impact gene expression which in turn affect disease risk. In this work we propose multiple-trait-coloc (moloc), a Bayesian statistical framework that integrates GWAS summary data with multiple molecular QTL data to identify regulatory effects at GWAS risk loci. We applied moloc to schizophrenia (SCZ) and eQTL/mQTL data derived from human brain tissue and identified 52 candidate genes that influence SCZ through methylation. Our method can be applied to any GWAS and relevant functional data to help prioritize disease associated genes. moloc is available for download as an R package (https://github.com/clagiamba/moloc). We also developed a web site to visualize the biological findings (icahn.mssm.edu/moloc). The browser allows searches by gene, methylation probe, and scenario of interest. claudia.giambartolomei@gmail.com. Supplementary data are available at Bioinformatics online.

Experience with procuring, deploying and maintaining hardware at remote co-location centre

International Nuclear Information System (INIS)

Bärring, O; Bonfillou, E; Clement, B; Santos, M Coelho Dos; Dore, V; Gentit, A; Grossir, A; Salter, W; Valsan, L; Xafi, A

2014-01-01

In May 2012 CERN signed a contract with the Wigner Data Centre in Budapest for an extension to CERN's central computing facility beyond its current boundaries set by electrical power and cooling available for computing. The centre is operated as a remote co-location site providing rack-space, electrical power and cooling for server, storage and networking equipment acquired by CERN. The contract includes a 'remote-hands' services for physical handling of hardware (rack mounting, cabling, pushing power buttons, ...) and maintenance repairs (swapping disks, memory modules, ...). However, only CERN personnel have network and console access to the equipment for system administration. This report gives an insight to adaptations of hardware architecture, procurement and delivery procedures undertaken enabling remote physical handling of the hardware. We will also describe tools and procedures developed for automating the registration, burn-in testing, acceptance and maintenance of the equipment as well as an independent but important change to the IT assets management (ITAM) developed in parallel as part of the CERN IT Agile Infrastructure project. Finally, we will report on experience from the first large delivery of 400 servers and 80 SAS JBOD expansion units (24 drive bays) to Wigner in March 2013. Changes were made to the abstract file on 13/06/2014 to correct errors, the pdf file was unchanged.

When students from different professions are co-located: the importance of interprofessional rapport for learning to work together.

Science.gov (United States)

Croker, Anne; Fisher, Karin; Smith, Tony

2015-01-01

With increasing interest and research into interprofessional learning, there is scope to more deeply understand what happens when students from different professions live and study in the same location. This study aimed to explore the issue of co-location and its effects on how students learn to work with other professions. The setting for this study was a rural health education facility in Australia with close links to local health care and community services. Philosophical hermeneutics informed the research method. Interviews were undertaken with 29 participants, including students, academic educators and clinical supervisors in diagnostic radiography, medicine, nursing, nutrition and dietetics, pharmacy, physiotherapy, occupational therapy, and speech pathology. Photo-elicitation was used to facilitate participant engagement with the topic. The findings foreground the value of interprofessional rapport building opportunities for students learning to work together. Enabled by the proximity of different professions in shared educational, clinical and social spaces, interprofessional rapport building was contingent on contextual conditions (balance of professions, shared spaces and adequate time) and individual's interpersonal capabilities (being interested, being inclusive, developing interpersonal bonds, giving and receiving respect, bringing a sense of own profession and being patient-centred). In the absence of these conditions and capabilities, negative professional stereotypes may be inadvertently re-enforced. From these findings suggestions are made for nurturing interprofessional rapport building opportunities to enable students of different professions to learn to work together.

Analysis of hepatitis C virus core/NS5A protein co-localization using novel cell culture systems expressing core-NS2 and NS5A of genotypes 1-7

DEFF Research Database (Denmark)

Galli, Andrea; Scheel, Troels K H; Prentoe, Jannick C

2013-01-01

Hepatitis C virus (HCV) is an important human pathogen infecting hepatocytes. With the advent of infectious cell culture systems, the HCV particle assembly and release processes are finally being uncovered. The HCV core and NS5A proteins co-localize on cytoplasmic lipid droplets (c......LDs) or on the endoplasmic reticulum (ER) at different stages of particle assembly. Current knowledge on assembly and release is primarily based on studies in genotype 2a cell culture systems; however, given the high genetic heterogeneity of HCV, variations might exist among genotypes. Here, we developed novel HCV strain...... JFH1-based recombinants expressing core-NS2 and NS5A from genotypes 1-7, and analysed core and NS5A co-localization in infected cells. Huh7.5 cells were transfected with RNA of core-NS2/NS5A recombinants and putative adaptive mutations were analysed by reverse genetics. Adapted core-NS2/NS5A...

Prominin-2 expression increases protrusions, decreases caveolae and inhibits Cdc42 dependent fluid phase endocytosis

Energy Technology Data Exchange (ETDEWEB)

Singh, Raman Deep, E-mail: Takhter.Ramandeep@mayo.edu; Schroeder, Andreas S.; Scheffer, Luana; Holicky, Eileen L.; Wheatley, Christine L.; Marks, David L., E-mail: Marks.david@mayo.edu; Pagano, Richard E.

2013-05-10

Highlights: •Prominin-2 expression induced protrusions that co-localized with lipid raft markers. •Prominin-2 expression decreased caveolae, caveolar endocytosis and increased pCav1. •Prominin-2 expression inhibited fluid phase endocytosis by inactivation of Cdc42. •These endocytic effects can be reversed by adding exogenous cholesterol. •Caveolin1 knockdown restored fluid phase endocytosis in Prominin2 expressing cells. -- Abstract: Background: Membrane protrusions play important roles in biological processes such as cell adhesion, wound healing, migration, and sensing of the external environment. Cell protrusions are a subtype of membrane microdomains composed of cholesterol and sphingolipids, and can be disrupted by cholesterol depletion. Prominins are pentaspan membrane proteins that bind cholesterol and localize to plasma membrane (PM) protrusions. Prominin-1 is of great interest as a marker for stem and cancer cells, while Prominin-2 (Prom2) is reportedly restricted to epithelial cells. Aim: To characterize the effects of Prom-2 expression on PM microdomain organization. Methods: Prom2-fluorescent protein was transfected in human skin fibroblasts (HSF) and Chinese hamster ovary (CHO) cells for PM raft and endocytic studies. Caveolae at PM were visualized using transmission electron microscopy. Cdc42 activation was measured and caveolin-1 knockdown was performed using siRNAs. Results: Prom2 expression in HSF and CHO cells caused extensive Prom2-positive protrusions that co-localized with lipid raft markers. Prom2 expression significantly decreased caveolae at the PM, reduced caveolar endocytosis and increased caveolin-1 phosphorylation. Prom2 expression also inhibited Cdc42-dependent fluid phase endocytosis via decreased Cdc42 activation. Effects on endocytosis were reversed by addition of cholesterol. Knockdown of caveolin-1 by siRNA restored Cdc42 dependent fluid phase endocytosis in Prom2-expressing cells. Conclusions: Prom2 protrusions primarily

Exploring the significance of human mobility patterns in social link prediction

KAUST Repository

Alharbi, Basma Mohammed

2014-01-01

Link prediction is a fundamental task in social networks. Recently, emphasis has been placed on forecasting new social ties using user mobility patterns, e.g., investigating physical and semantic co-locations for new proximity measure. This paper explores the effect of in-depth mobility patterns. Specifically, we study individuals\\' movement behavior, and quantify mobility on the basis of trip frequency, travel purpose and transportation mode. Our hybrid link prediction model is composed of two modules. The first module extracts mobility patterns, including travel purpose and mode, from raw trajectory data. The second module employs the extracted patterns for link prediction. We evaluate our method on two real data sets, GeoLife [15] and Reality Mining [5]. Experimental results show that our hybrid model significantly improves the accuracy of social link prediction, when comparing to primary topology-based solutions. Copyright 2014 ACM.

Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation

International Nuclear Information System (INIS)

Hazawa, Masaharu; Tomiyama, Kenichi; Saotome-Nakamura, Ai; Obara, Chizuka; Yasuda, Takeshi; Gotoh, Takaya; Tanaka, Izumi; Yakumaru, Haruko; Ishihara, Hiroshi; Tajima, Katsushi

2014-01-01

Highlights: • Radiation increases cellular uptake of exosomes. • Radiation induces colocalization of CD29 and CD81. • Exosomes selectively bind the CD29/CD81 complex. • Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation. - Abstract: Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome–cell interactions are crucial, but they are not well understood. Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC. Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced the initial cellular attachment to exosomes and induced the colocalization of integrin CD29 and tetraspanin CD81 on the cell surface without affecting their expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown of CD29 completely inhibited the radiation-induced uptake, and additional or single knockdown of CD81 inhibited basal uptake as well as the increase in radiation-induced uptake. We also examined possible exosome uptake processes affected by radiation. Radiation-induced changes did not involve dynamin2, reactive oxygen species, or their evoked p38 mitogen-activated protein kinase-dependent endocytic or pinocytic pathways. Radiation increased the cellular uptake of exosomes through CD29/CD81 complex formation. These findings provide essential basic insights for potential therapeutic applications of exosomes or MSC in combination with radiation

Increasing proportions of tyrosine hydroxylase-immunoreactive interneurons colocalize with choline acetyltransferase or vasoactive intestinal peptide in the developing rat cerebral cortex

Science.gov (United States)

Asmus, Stephen E.; Cocanougher, Benjamin T.; Allen, Donald L.; Boone, John B.; Brooks, Elizabeth A.; Hawkins, Sarah M.; Hench, Laura A.; Ijaz, Talha; Mayfield, Meredith N.

2011-01-01

Cortical interneurons are critical for information processing, and their dysfunction has been implicated in neurological disorders. One subset of this diverse cell population expresses tyrosine hydroxylase (TH) during postnatal rat development. Cortical TH-immunoreactive neurons appear at postnatal day (P) 16. The number of TH cells sharply increases between P16 and P20 and subsequently decreases to adult values. The absence of apoptotic markers in these cells suggests that the reduction in cell number is not due to cell death but is due to a decline in TH production. Cortical TH cells lack all additional catecholaminergic enzymes, and many coexpress GABA and calretinin, but little else is known about their phenotype or function. Because interneurons containing choline acetyltransferase (ChAT) or vasoactive intestinal peptide (VIP) share characteristics with cortical TH neurons, the coexpression of TH with ChAT or VIP was examined throughout the neocortex at P16, P20, and P30. The proportions of TH cell profiles double-labeled for ChAT or VIP significantly increased between P16 and P30. Based on their proximity to blood vessels, intrinsic cholinergic and VIPergic cells have been hypothesized to regulate cortical microcirculation. Labeling with the gliovascular marker aquaporin-4 revealed that at least half of the TH cells were apposed to microvessels at these ages, and many of these cells contained ChAT or VIP. Cortical TH neurons did not coproduce nitric oxide synthase. These results suggest that increasing proportions of cortical TH neurons express ChAT or VIP developmentally and that a subset of these TH neurons may regulate local blood flow. PMID:21295554

Introducing extra NADPH consumption ability significantly increases the photosynthetic efficiency and biomass production of cyanobacteria.

Science.gov (United States)

Zhou, Jie; Zhang, Fuliang; Meng, Hengkai; Zhang, Yanping; Li, Yin

2016-11-01

Increasing photosynthetic efficiency is crucial to increasing biomass production to meet the growing demands for food and energy. Previous theoretical arithmetic analysis suggests that the light reactions and dark reactions are imperfectly coupled due to shortage of ATP supply, or accumulation of NADPH. Here we hypothesized that solely increasing NADPH consumption might improve the coupling of light reactions and dark reactions, thereby increasing the photosynthetic efficiency and biomass production. To test this hypothesis, an NADPH consumption pathway was constructed in cyanobacterium Synechocystis sp. PCC 6803. The resulting extra NADPH-consuming mutant grew much faster and achieved a higher biomass concentration. Analyses of photosynthesis characteristics showed the activities of photosystem II and photosystem I and the light saturation point of the NADPH-consuming mutant all significantly increased. Thus, we demonstrated that introducing extra NADPH consumption ability is a promising strategy to increase photosynthetic efficiency and to enable utilization of high-intensity lights. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Genetic control of soybean seed oil: II. QTL and genes that increase oil concentration without decreasing protein or with increased seed yield.

Science.gov (United States)

Eskandari, Mehrzad; Cober, Elroy R; Rajcan, Istvan

2013-06-01

Soybean [Glycine max (L.) Merrill] seed oil is the primary global source of edible oil and a major renewable and sustainable feedstock for biodiesel production. Therefore, increasing the relative oil concentration in soybean is desirable; however, that goal is complex due to the quantitative nature of the oil concentration trait and possible effects on major agronomic traits such as seed yield or protein concentration. The objectives of the present study were to study the relationship between seed oil concentration and important agronomic and seed quality traits, including seed yield, 100-seed weight, protein concentration, plant height, and days to maturity, and to identify oil quantitative trait loci (QTL) that are co-localized with the traits evaluated. A population of 203 F4:6 recombinant inbred lines, derived from a cross between moderately high oil soybean genotypes OAC Wallace and OAC Glencoe, was developed and grown across multiple environments in Ontario, Canada, in 2009 and 2010. Among the 11 QTL associated with seed oil concentration in the population, which were detected using either single-factor ANOVA or multiple QTL mapping methods, the number of QTL that were co-localized with other important traits QTL were six for protein concentration, four for seed yield, two for 100-seed weight, one for days to maturity, and one for plant height. The oil-beneficial allele of the QTL tagged by marker Sat_020 was positively associated with seed protein concentration. The oil favorable alleles of markers Satt001 and GmDGAT2B were positively correlated with seed yield. In addition, significant two-way epistatic interactions, where one of the interacting markers was solely associated with seed oil concentration, were identified for the selected traits in this study. The number of significant epistatic interactions was seven for yield, four for days to maturity, two for 100-seed weight, one for protein concentration, and one for plant height. The identified molecular

Hydrologic effects of large southwestern USA wildfires significantly increase regional water supply: fact or fiction?

Science.gov (United States)

Wine, M. L.; Cadol, D.

2016-08-01

In recent years climate change and historic fire suppression have increased the frequency of large wildfires in the southwestern USA, motivating study of the hydrological consequences of these wildfires at point and watershed scales, typically over short periods of time. These studies have revealed that reduced soil infiltration capacity and reduced transpiration due to tree canopy combustion increase streamflow at the watershed scale. However, the degree to which these local increases in runoff propagate to larger scales—relevant to urban and agricultural water supply—remains largely unknown, particularly in semi-arid mountainous watersheds co-dominated by winter snowmelt and the North American monsoon. To address this question, we selected three New Mexico watersheds—the Jemez (1223 km2), Mogollon (191 km2), and Gila (4807 km2)—that together have been affected by over 100 wildfires since 1982. We then applied climate-driven linear models to test for effects of fire on streamflow metrics after controlling for climatic variability. Here we show that, after controlling for climatic and snowpack variability, significantly more streamflow discharged from the Gila watershed for three to five years following wildfires, consistent with increased regional water yield due to enhanced infiltration-excess overland flow and groundwater recharge at the large watershed scale. In contrast, we observed no such increase in discharge from the Jemez watershed following wildfires. Fire regimes represent a key difference between the contrasting responses of the Jemez and Gila watersheds with the latter experiencing more frequent wildfires, many caused by lightning strikes. While hydrologic dynamics at the scale of large watersheds were previously thought to be climatically dominated, these results suggest that if one fifth or more of a large watershed has been burned in the previous three to five years, significant increases in water yield can be expected.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH interaction with 3' ends of Japanese encephalitis virus RNA and colocalization with the viral NS5 protein

Directory of Open Access Journals (Sweden)

Chou Shih-Jie

2009-04-01

Full Text Available Abstract Replication of the Japanese encephalitis virus (JEV genome depends on host factors for successfully completing their life cycles; to do this, host factors have been recruited and/or relocated to the site of viral replication. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a cellular metabolic protein, was found to colocalize with viral RNA-dependent RNA polymerase (NS5 in JEV-infected cells. Subcellular fractionation further indicated that GAPDH remained relatively constant in the cytosol, while increasing at 12 to 24 hours postinfection (hpi and decreasing at 36 hpi in the nuclear fraction of infected cells. In contrast, the redistribution patterns of GAPDH were not observed in the uninfected cells. Co-immunoprecipitation of GAPDH and JEV NS5 protein revealed no direct protein-protein interaction; instead, GAPDH binds to the 3' termini of plus- and minus-strand RNAs of JEV by electrophoretic mobility shift assays. Accordingly, GAPDH binds to the minus strand more efficiently than to the plus strand of JEV RNAs. This study highlights the findings that infection of JEV changes subcellular localization of GAPDH suggesting that this metabolic enzyme may play a role in JEV replication.

Increasing the statistical significance of entanglement detection in experiments.

Science.gov (United States)

Jungnitsch, Bastian; Niekamp, Sönke; Kleinmann, Matthias; Gühne, Otfried; Lu, He; Gao, Wei-Bo; Chen, Yu-Ao; Chen, Zeng-Bing; Pan, Jian-Wei

2010-05-28

Entanglement is often verified by a violation of an inequality like a Bell inequality or an entanglement witness. Considerable effort has been devoted to the optimization of such inequalities in order to obtain a high violation. We demonstrate theoretically and experimentally that such an optimization does not necessarily lead to a better entanglement test, if the statistical error is taken into account. Theoretically, we show for different error models that reducing the violation of an inequality can improve the significance. Experimentally, we observe this phenomenon in a four-photon experiment, testing the Mermin and Ardehali inequality for different levels of noise. Furthermore, we provide a way to develop entanglement tests with high statistical significance.

Optimal combination of signals from colocated gravitational wave interferometers for use in searches for a stochastic background

International Nuclear Information System (INIS)

Lazzarini, Albert; Reilly, Kaice; Whitcomb, Stan; Bose, Sukanta; Fritschel, Peter; McHugh, Martin; Whelan, John T.; Regimbau, Tania; Romano, Joseph D.; Whiting, Bernard F.

2004-01-01

This article derives an optimal (i.e., unbiased, minimum variance) estimator for the pseudodetector strain for a pair of colocated gravitational wave interferometers (such as the pair of LIGO interferometers at its Hanford Observatory), allowing for possible instrumental correlations between the two detectors. The technique is robust and does not involve any assumptions or approximations regarding the relative strength of gravitational wave signals in the Hanford pair with respect to other sources of correlated instrumental or environmental noise. An expression is given for the effective power spectral density of the combined noise in the pseudodetector. This can then be introduced into the standard optimal Wiener filter used to cross-correlate detector data streams in order to obtain an optimal estimate of the stochastic gravitational wave background. In addition, a dual to the optimal estimate of strain is derived. This dual is constructed to contain no gravitational wave signature and can thus be used as an 'off-source' measurement to test algorithms used in the 'on-source' observation

Direction-of-arrival estimation for co-located multiple-input multiple-output radar using structural sparsity Bayesian learning

International Nuclear Information System (INIS)

Wen Fang-Qing; Zhang Gong; Ben De

2015-01-01

This paper addresses the direction of arrival (DOA) estimation problem for the co-located multiple-input multiple-output (MIMO) radar with random arrays. The spatially distributed sparsity of the targets in the background makes compressive sensing (CS) desirable for DOA estimation. A spatial CS framework is presented, which links the DOA estimation problem to support recovery from a known over-complete dictionary. A modified statistical model is developed to accurately represent the intra-block correlation of the received signal. A structural sparsity Bayesian learning algorithm is proposed for the sparse recovery problem. The proposed algorithm, which exploits intra-signal correlation, is capable being applied to limited data support and low signal-to-noise ratio (SNR) scene. Furthermore, the proposed algorithm has less computation load compared to the classical Bayesian algorithm. Simulation results show that the proposed algorithm has a more accurate DOA estimation than the traditional multiple signal classification (MUSIC) algorithm and other CS recovery algorithms. (paper)

The Focinator v2-0 - Graphical Interface, Four Channels, Colocalization Analysis and Cell Phase Identification.

Science.gov (United States)

Oeck, Sebastian; Malewicz, Nathalie M; Hurst, Sebastian; Al-Refae, Klaudia; Krysztofiak, Adam; Jendrossek, Verena

2017-07-01

The quantitative analysis of foci plays an important role in various cell biological methods. In the fields of radiation biology and experimental oncology, the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on DNA damage induction and repair is frequently performed by the analysis of protein clusters or phosphorylated proteins recruited to so called repair foci at DNA damage sites, involving for example γ-H2A.X, 53BP1 or RAD51. We recently developed "The Focinator" as a reliable and fast tool for automated quantitative and qualitative analysis of nuclei and DNA damage foci. The refined software is now even more user-friendly due to a graphical interface and further features. Thus, we included an R-script-based mode for automated image opening, file naming, progress monitoring and an error report. Consequently, the evaluation no longer required the attendance of the operator after initial parameter definition. Moreover, the Focinator v2-0 is now able to perform multi-channel analysis of four channels and evaluation of protein-protein colocalization by comparison of up to three foci channels. This enables for example the quantification of foci in cells of a specific cell cycle phase.

Phytohormone supplementation significantly increases growth of Chlamydomonas reinhardtii cultivated for biodiesel production.

Science.gov (United States)

Park, Won-Kun; Yoo, Gursong; Moon, Myounghoon; Kim, Chul Woong; Choi, Yoon-E; Yang, Ji-Won

2013-11-01

Cultivation is the most expensive step in the production of biodiesel from microalgae, and substantial research has been devoted to developing more cost-effective cultivation methods. Plant hormones (phytohormones) are chemical messengers that regulate various aspects of growth and development and are typically active at very low concentrations. In this study, we investigated the effect of different phytohormones on microalgal growth and biodiesel production in Chlamydomonas reinhardtii and their potential to lower the overall cost of commercial biofuel production. The results indicated that all five of the tested phytohormones (indole-3-acetic acid, gibberellic acid, kinetin, 1-triacontanol, and abscisic acid) promoted microalgal growth. In particular, hormone treatment increased biomass production by 54 to 69 % relative to the control growth medium (Tris-acetate-phosphate, TAP). Phytohormone treatments also affected microalgal cell morphology but had no effect on the yields of fatty acid methyl esters (FAMEs) as a percent of biomass. We also tested the effect of these phytohormones on microalgal growth in nitrogen-limited media by supplementation in the early stationary phase. Maximum cell densities after addition of phytohormones were higher than in TAP medium, even when the nitrogen source was reduced to 40 % of that in TAP medium. Taken together, our results indicate that phytohormones significantly increased microalgal growth, particularly in nitrogen-limited media, and have potential for use in the development of efficient microalgal cultivation for biofuel production.

Nine co-localized cytochrome P450 genes of the CYP2N, CYP2AD, and CYP2P gene families in the mangrove killifish Kryptolebias marmoratus genome: Identification and expression in response to B[α]P, BPA, OP, and NP.

Science.gov (United States)

Puthumana, Jayesh; Kim, Bo-Mi; Jeong, Chang-Bum; Kim, Duck-Hyun; Kang, Hye-Min; Jung, Jee-Hyun; Kim, Il-Chan; Hwang, Un-Ki; Lee, Jae-Seong

2017-06-01

The CYP2 genes are the largest and most diverse cytochrome P450 (CYP) subfamily in vertebrates. We have identified nine co-localized CYP2 genes (∼55kb) in a new cluster in the genome of the highly resilient ecotoxicological fish model Kryptolebias marmoratus. Molecular characterization, temporal and tissue-specific expression pattern, and response to xenobiotics of these genes were examined. The CYP2 gene clusters were characterized and designated CYP2N22-23, CYP2AD12, and CYP2P16-20. Gene synteny analysis confirmed that the cluster in K. marmoratus is similar to that found in other teleost fishes, including zebrafish. A gene duplication event with diverged catalytic function was observed in CYP2AD12. Moreover, a high level of divergence in expression was observed among the co-localized genes. Phylogeny of the cluster suggested an orthologous relationship with similar genes in zebrafish and Japanese medaka. Gene expression analysis showed that CYP2P19 and CYP2N20 were consecutively expressed throughout embryonic development, whereas CYP2P18 was expressed in all adult tissues, suggesting that members of each CYP2 gene family have different physiological roles even though they are located in the same cluster. Among endocrine-disrupting chemicals (EDCs), benzo[α]pyrene (B[α]P) induced expression of CYP2N23, bisphenol A (BPA) induced CYP2P18 and CYP2P19, and 4-octylphenol (OP) induced CYP2AD12, but there was no significant response to 4-nonylphenol (NP), implying differential catalytic roles of the enzyme. In this paper, we identify and characterize a CYP2 gene cluster in the mangrove killifish K. marmoratus with differing catalytic roles toward EDCs. Our findings provide insights on the roles of nine co-localized CYP2 genes and their catalytic functions for better understanding of chemical-biological interactions in fish. Copyright © 2017 Elsevier B.V. All rights reserved.

Increasing the statistical significance of entanglement detection in experiments

Energy Technology Data Exchange (ETDEWEB)

Jungnitsch, Bastian; Niekamp, Soenke; Kleinmann, Matthias; Guehne, Otfried [Institut fuer Quantenoptik und Quanteninformation, Innsbruck (Austria); Lu, He; Gao, Wei-Bo; Chen, Zeng-Bing [Hefei National Laboratory for Physical Sciences at Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei (China); Chen, Yu-Ao; Pan, Jian-Wei [Hefei National Laboratory for Physical Sciences at Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei (China); Physikalisches Institut, Universitaet Heidelberg (Germany)

2010-07-01

Entanglement is often verified by a violation of an inequality like a Bell inequality or an entanglement witness. Considerable effort has been devoted to the optimization of such inequalities in order to obtain a high violation. We demonstrate theoretically and experimentally that such an optimization does not necessarily lead to a better entanglement test, if the statistical error is taken into account. Theoretically, we show for different error models that reducing the violation of an inequality can improve the significance. We show this to be the case for an error model in which the variance of an observable is interpreted as its error and for the standard error model in photonic experiments. Specifically, we demonstrate that the Mermin inequality yields a Bell test which is statistically more significant than the Ardehali inequality in the case of a photonic four-qubit state that is close to a GHZ state. Experimentally, we observe this phenomenon in a four-photon experiment, testing the above inequalities for different levels of noise.

The Biological and Clinical Significance of Androgen Receptor Variants

Science.gov (United States)

2014-04-01

of AR-V7 in low- grade PCa might be associated with development of high-grade Pea . Aim 3 was to evaluate the role of AR-V7 in mediating primary... protein expression of AR-V7 in CRPC vs. hormone nai’ve prostate cancer (PCa).2 In addition, AR-V7 mRNA expression in bone metastases of men with CRPC...ISH method is compatible with IHC to enable the detection of RNA and protein markers in the same tissue section for colocalization and functional

Calibration and assessment of electrochemical air quality sensors by co-location with regulatory-grade instruments

Directory of Open Access Journals (Sweden)

D. H. Hagan

2018-01-01

Full Text Available The use of low-cost air quality sensors for air pollution research has outpaced our understanding of their capabilities and limitations under real-world conditions, and there is thus a critical need for understanding and optimizing the performance of such sensors in the field. Here we describe the deployment, calibration, and evaluation of electrochemical sensors on the island of Hawai`i, which is an ideal test bed for characterizing such sensors due to its large and variable sulfur dioxide (SO2 levels and lack of other co-pollutants. Nine custom-built SO2 sensors were co-located with two Hawaii Department of Health Air Quality stations over the course of 5 months, enabling comparison of sensor output with regulatory-grade instruments under a range of realistic environmental conditions. Calibration using a nonparametric algorithm (k nearest neighbors was found to have excellent performance (RMSE < 7 ppb, MAE < 4 ppb, r2 > 0.997 across a wide dynamic range in SO2 (< 1 ppb, > 2 ppm. However, since nonparametric algorithms generally cannot extrapolate to conditions beyond those outside the training set, we introduce a new hybrid linear–nonparametric algorithm, enabling accurate measurements even when pollutant levels are higher than encountered during calibration. We find no significant change in instrument sensitivity toward SO2 after 18 weeks and demonstrate that calibration accuracy remains high when a sensor is calibrated at one location and then moved to another. The performance of electrochemical SO2 sensors is also strong at lower SO2 mixing ratios (< 25 ppb, for which they exhibit an error of less than 2.5 ppb. While some specific results of this study (calibration accuracy, performance of the various algorithms, etc. may differ for measurements of other pollutant species in other areas (e.g., polluted urban regions, the calibration and validation approaches described here should be widely applicable

Patients with a new variant of endemic pemphigus foliaceus have autoantibodies against arrector pili muscle, colocalizing with MYZAP, p0071, desmoplakins 1 and 2 and ARVCF.

Science.gov (United States)

Abreu-Velez, A M; Valencia-Yepes, C A; Upegui-Zapata, Y A; Upegui-Quiceno, E; Mesa-Herrera, N R; Velazquez-Velez, J E; Howard, M S

2017-12-01

We identified a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America, which we term El Bagre-EPF, and observed reactivity to arrector pili muscle (APM), thus we tested for autoimmunity to APM. We took skin biopsies from 30 patients with El Bagre-EPF and 30 healthy controls (HCs) matched by age, sex and occupation, who were all from the endemic area, and tested these using direct immunofluorescence (DIF), confocal microscopy, immunohistochemistry and immunoblotting (IB). Of the 30 patients with El Bagre-EPF, 27 had autoantibodies to APM that colocalized with commercial antibodies to myocardium-enriched zonula occludens-1-associated protein (MYZAP), desmoplakin (DP)1 and DP2, plakophilin 4, and Armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) (P EPF have autoantibodies to APM, colocalizing with the antibodies MYZAP, ARVCF, p0071, DP1 and DP2, suggesting that these molecules are El Bagre-EPF antigens. Further, all of these antigens represent components of cell junctions, indicating that the immune response is directed, at least partially, against cell junctions. The immune response in patients affected by El Bagre-EPF is polyclonal, and it includes B and T lymphocytes, mast cells, IgG, IgA, IgM, IgD, IgE, fibrinogen, albumin, complement/C1q, C3c and C4. © 2017 British Association of Dermatologists.

Tat proteins as novel thylakoid membrane anchors organize a biosynthetic pathway in chloroplasts and increase product yield 5-fold

DEFF Research Database (Denmark)

Henriques de Jesus, Maria Perestrello Ramos; Nielsen, Agnieszka Janina Zygadlo; Mellor, Silas Busck

2017-01-01

to their complex structures. Some of the crucial enzymes catalyzing their biosynthesis are the cytochromes P450 (P450s) situated in the endoplasmic reticulum (ER), powered by electron transfers from NADPH. Dhurrin is a cyanogenic glucoside and its biosynthesis involves a dynamic metabolon formed by two P450s....... Nevertheless, translocation of the pathway from the ER to the chloroplast creates other difficulties, such as the loss of metabolon formation and intermediate diversion into other metabolic pathways. We show here that co-localization of these enzymes in the thylakoid membrane leads to a significant increase...... in product formation, with a concomitant decrease in off-pathway intermediates. This was achieved by exchanging the membrane anchors of the dhurrin pathway enzymes to components of the Twin-arginine translocation pathway, TatB and TatC, which have self-assembly properties. Consequently, we show 5-fold...

Significant increase of Echinococcus multilocularis prevalencein foxes, but no increased predicted risk for humans

NARCIS (Netherlands)

Maas, M.; Dam-Deisz, W.D.C.; Roon, van A.M.; Takumi, K.; Giessen, van der J.W.B.

2014-01-01

The emergence of the zoonotic tapeworm Echinococcus multilocularis, causative agent ofalveolar echinococcosis (AE), poses a public health risk. A previously designed risk mapmodel predicted a spread of E. multilocularis and increasing numbers of alveolar echinococ-cosis patients in the province of

Colocalization and Disposition of Cellulosomes in Clostridium clariflavum as Revealed by Correlative Superresolution Imaging

Directory of Open Access Journals (Sweden)

Lior Artzi

2018-02-01

Full Text Available Cellulosomes are multienzyme complexes produced by anaerobic, cellulolytic bacteria for highly efficient breakdown of plant cell wall polysaccharides. Clostridium clariflavum is an anaerobic, thermophilic bacterium that produces the largest assembled cellulosome complex in nature to date, comprising three types of scaffoldins: a primary scaffoldin, ScaA; an adaptor scaffoldin, ScaB; and a cell surface anchoring scaffoldin, ScaC. This complex can contain 160 polysaccharide-degrading enzymes. In previous studies, we proposed potential types of cellulosome assemblies in C. clariflavum and demonstrated that these complexes are released into the extracellular medium. In the present study, we explored the disposition of the highly structured, four-tiered cell-anchored cellulosome complex of this bacterium. Four separate, integral cellulosome components were subjected to immunolabeling: ScaA, ScaB, ScaC, and the cellulosome’s most prominent enzyme, GH48. Imaging of the cells by correlating scanning electron microscopy and three-dimensional (3D superresolution fluorescence microscopy revealed that some of the protuberance-like structures on the cell surface represent cellulosomes and that the components are highly colocalized and organized by a defined hierarchy on the cell surface. The display of the cellulosome on the cell surface was found to differ between cells grown on soluble or insoluble substrates. Cell growth on microcrystalline cellulose and wheat straw exhibited dramatic enhancement in the amount of cellulosomes displayed on the bacterial cell surface.

Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological, Immunohistochemical and Gene Expression Profiles

Directory of Open Access Journals (Sweden)

Marta Anna Szychlinska

2016-03-01

Full Text Available Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1 are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA, whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01. By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01. Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease.

Nanoparticle uptake and their co-localization with cell compartments - a confocal Raman microscopy study at single cell level

International Nuclear Information System (INIS)

Estrela-Lopis, I; Donath, E; Romero, G; Rojas, E; Moya, S E

2011-01-01

Confocal Raman Microscopy, a non-invasive, non-destructive and label-free technique, was employed to study the uptake and localization of nanoparticles (NPs) in the Hepatocarcinoma human cell line HepG2 at the level of single cells. Cells were exposed to carbon nanotubes (CNTs) the surface of which was engineered with polyelectrolytes and lipid layers, aluminium oxide and cerium dioxide nanoparticles. Raman spectra deconvolution was applied to obtain the spatial distributions of NPs together with lipids/proteins in cells. The colocalization of the NPs with different intracellular environments, lipid bodies, protein and DNA, was inferred. Lipid coated CNTs associated preferentially with lipid rich regions, whereas polyelectrolyte coated CNTs were excluded from lipid rich regions. Al 2 O 3 NPs were found in the cytoplasm. CeO 2 NPs were readily taken up and have been observed all over the cell. Raman z-scans proved the intracellular distribution of the respective NPs.

Nanoparticle uptake and their co-localization with cell compartments - a confocal Raman microscopy study at single cell level

Science.gov (United States)

Estrela-Lopis, I.; Romero, G.; Rojas, E.; Moya, S. E.; Donath, E.

2011-07-01

Confocal Raman Microscopy, a non-invasive, non-destructive and label-free technique, was employed to study the uptake and localization of nanoparticles (NPs) in the Hepatocarcinoma human cell line HepG2 at the level of single cells. Cells were exposed to carbon nanotubes (CNTs) the surface of which was engineered with polyelectrolytes and lipid layers, aluminium oxide and cerium dioxide nanoparticles. Raman spectra deconvolution was applied to obtain the spatial distributions of NPs together with lipids/proteins in cells. The colocalization of the NPs with different intracellular environments, lipid bodies, protein and DNA, was inferred. Lipid coated CNTs associated preferentially with lipid rich regions, whereas polyelectrolyte coated CNTs were excluded from lipid rich regions. Al2O3 NPs were found in the cytoplasm. CeO2 NPs were readily taken up and have been observed all over the cell. Raman z-scans proved the intracellular distribution of the respective NPs.

Coal-fired Power Plants with Flexible Amine-based CCS and Co-located Wind Power: Environmental, Economic and Reliability Outcomes

Science.gov (United States)

Bandyopadhyay, Rubenka

Carbon Capture and Storage (CCS) technologies provide a means to significantly reduce carbon emissions from the existing fleet of fossil-fired plants, and hence can facilitate a gradual transition from conventional to more sustainable sources of electric power. This is especially relevant for coal plants that have a CO2 emission rate that is roughly two times higher than that of natural gas plants. Of the different kinds of CCS technology available, post-combustion amine based CCS is the best developed and hence more suitable for retrofitting an existing coal plant. The high costs from operating CCS could be reduced by enabling flexible operation through amine storage or allowing partial capture of CO2 during high electricity prices. This flexibility is also found to improve the power plant's ramp capability, enabling it to offset the intermittency of renewable power sources. This thesis proposes a solution to problems associated with two promising technologies for decarbonizing the electric power system: the high costs of the energy penalty of CCS, and the intermittency and non-dispatchability of wind power. It explores the economic and technical feasibility of a hybrid system consisting of a coal plant retrofitted with a post-combustion-amine based CCS system equipped with the option to perform partial capture or amine storage, and a co-located wind farm. A techno-economic assessment of the performance of the hybrid system is carried out both from the perspective of the stakeholders (utility owners, investors, etc.) as well as that of the power system operator. (Abstract shortened by ProQuest.).

Changes in rocket salad phytochemicals within the commercial supply chain: Glucosinolates, isothiocyanates, amino acids and bacterial load increase significantly after processing.

Science.gov (United States)

Bell, Luke; Yahya, Hanis Nadia; Oloyede, Omobolanle Oluwadamilola; Methven, Lisa; Wagstaff, Carol

2017-04-15

Five cultivars of Eruca sativa and a commercial variety of Diplotaxis tenuifolia were grown in the UK (summer) and subjected to commercial growth, harvesting and processing, with subsequent shelf life storage. Glucosinolates (GSL), isothiocyanates (ITC), amino acids (AA), free sugars, and bacterial loads were analysed throughout the supply chain to determine the effects on phytochemical compositions. Bacterial load of leaves increased significantly over time and peaked during shelf life storage. Significant correlations were observed with GSL and AA concentrations, suggesting a previously unknown relationship between plants and endemic leaf bacteria. GSLs, ITCs and AAs increased significantly after processing and during shelf life. The supply chain did not significantly affect glucoraphanin concentrations, and its ITC sulforaphane significantly increased during shelf life in E. sativa cultivars. We hypothesise that commercial processing may increase the nutritional value of the crop, and have added health benefits for the consumer. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Triglyceride content in remnant lipoproteins is significantly increased after food intake and is associated with plasma lipoprotein lipase.

Science.gov (United States)

Nakajima, Katsuyuki; Tokita, Yoshiharu; Sakamaki, Koji; Shimomura, Younosuke; Kobayashi, Junji; Kamachi, Keiko; Tanaka, Akira; Stanhope, Kimber L; Havel, Peter J; Wang, Tao; Machida, Tetsuo; Murakami, Masami

2017-02-01

Previous large population studies reported that non-fasting plasma triglyceride (TG) reflect a higher risk for cardiovascular disease than TG in the fasting plasma. This is suggestive of the presence of higher concentration of remnant lipoproteins (RLP) in postprandial plasma. TG and RLP-TG together with other lipids, lipoproteins and lipoprotein lipase (LPL) in both fasting and postprandial plasma were determined in generally healthy volunteers and in patients with coronary artery disease (CAD) after consuming a fat load or a more typical moderate meal. RLP-TG/TG ratio (concentration) and RLP-TG/RLP-C ratio (particle size) were significantly increased in the postprandial plasma of both healthy controls and CAD patients compared with those in fasting plasma. LPL/RLP-TG ratio demonstrated the interaction correlation between RLP concentration and LPL activity The increased RLP-TG after fat consumption contributed to approximately 90% of the increased plasma TG, while approximately 60% after a typical meal. Plasma LPL in postprandial plasma was not significantly altered after either type of meal. Concentrations of RLP-TG found in the TG along with its particle size are significantly increased in postprandial plasma compared with fasting plasma. Therefore, non-fasting TG determination better reflects the presence of higher RLP concentrations in plasma. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Social marketing campaign significantly associated with increases in syphilis testing among gay and bisexual men in San Francisco.

Science.gov (United States)

Montoya, Jorge A; Kent, Charlotte K; Rotblatt, Harlan; McCright, Jacque; Kerndt, Peter R; Klausner, Jeffrey D

2005-07-01

Between 1999 and 2002, San Francisco experienced a sharp increase in early syphilis among gay and bisexual men. In response, the San Francisco Department of Public Health launched a social marketing campaign to increase testing for syphilis, and awareness and knowledge about syphilis among gay and bisexual men. A convenience sample of 244 gay and bisexual men (18-60 years of age) were surveyed to evaluate the effectiveness of the campaign. Respondents were interviewed to elicit unaided and aided awareness about the campaign, knowledge about syphilis, recent sexual behaviors, and syphilis testing behavior. After controlling for other potential confounders, unaided campaign awareness was a significant correlate of having a syphilis test in the last 6 months (odds ratio, 3.21; 95% confidence interval, 1.30-7.97) compared with no awareness of the campaign. A comparison of respondents aware of the campaign with those not aware also revealed significant increases in awareness and knowledge about syphilis. The Healthy Penis 2002 campaign achieved its primary objective of increasing syphilis testing, and awareness and knowledge about syphilis among gay and bisexual men in San Francisco.

Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma.

Science.gov (United States)

Yoo, Byoung Kwon; Santhekadur, Prasanna K; Gredler, Rachel; Chen, Dong; Emdad, Luni; Bhutia, Sujit; Pannell, Lewis; Fisher, Paul B; Sarkar, Devanand

2011-05-01

There is virtually no effective treatment for advanced hepatocellular carcinoma (HCC) and novel targets need to be identified to develop effective treatment. We recently documented that the oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis. Employing yeast two-hybrid assay and coimmunoprecipitation followed by mass spectrometry, we identified staphylococcal nuclease domain containing 1 (SND1), a nuclease in the RNA-induced silencing complex (RISC) facilitating RNAi-mediated gene silencing, as an AEG-1 interacting protein. Coimmunoprecipitation and colocalization studies confirmed that AEG-1 is also a component of RISC and both AEG-1 and SND1 are required for optimum RISC activity facilitating small interfering RNA (siRNA) and micro RNA (miRNA)-mediated silencing of luciferase reporter gene. In 109 human HCC samples SND1 was overexpressed in ≈74% cases compared to normal liver. Correspondingly, significantly higher RISC activity was observed in human HCC cells compared to immortal normal hepatocytes. Increased RISC activity, conferred by AEG-1 or SND1, resulted in increased degradation of tumor suppressor messenger RNAs (mRNAs) that are target of oncomiRs. Inhibition of enzymatic activity of SND1 significantly inhibited proliferation of human HCC cells. As a corollary, stable overexpression of SND1 augmented and siRNA-mediated inhibition of SND1 abrogated growth of human HCC cells in vitro and in vivo, thus revealing a potential role of SND1 in hepatocarcinogenesis. We unravel a novel mechanism that overexpression of AEG-1 and SND1 leading to increased RISC activity might contribute to hepatocarcinogenesis. Targeted inhibition of SND1 enzymatic activity might be developed as an effective therapy for HCC. Copyright © 2011 American Association for the Study of Liver Diseases.

Free ammonia pre-treatment of secondary sludge significantly increases anaerobic methane production.

Science.gov (United States)

Wei, Wei; Zhou, Xu; Wang, Dongbo; Sun, Jing; Wang, Qilin

2017-07-01

Energy recovery in the form of methane from sludge/wastewater is restricted by the poor and slow biodegradability of secondary sludge. An innovative pre-treatment technology using free ammonia (FA, i.e. NH 3 ) was proposed in this study to increase anaerobic methane production. The solubilisation of secondary sludge was significantly increased after FA pre-treatment at up to 680 mg NH 3 -N/L for 1 day, under which the solubilisation (i.e. 0.4 mg SCOD/mg VS; SCOD: soluble chemical oxygen demand; VS: volatile solids) was >10 times higher than that without FA pre-treatment (i.e. 0.03 mg SCOD/mg VS). Biochemical methane potential assays showed that FA pre-treatment at above 250 mg NH 3 -N/L is effective in improving anaerobic methane production. The highest improvement in biochemical methane potential (B 0 ) and hydrolysis rate (k) was achieved at FA concentrations of 420-680 mg NH 3 -N/L, and was determined as approximately 22% (from 160 to 195 L CH 4 /kg VS added) and 140% (from 0.22 to 0.53 d -1 ) compared to the secondary sludge without pre-treatment. More analysis revealed that the FA induced improvement in B 0 and k could be attributed to the rapidly biodegradable substances rather than the slowly biodegradable substances. Economic and environmental analyses showed that the FA-based technology is economically favourable and environmentally friendly. Since this FA technology aims to use the wastewater treatment plants (WWTPs) waste (i.e. anaerobic digestion liquor) to enhance methane production from the WWTPs, it will set an example for the paradigm shift of the WWTPs from 'linear economy' to 'circular economy'. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activation of human naïve Th cells increases surface expression of GD3 and induces neoexpression of GD2 that colocalize with TCR clusters.

Science.gov (United States)

Villanueva-Cabello, Tania M; Mollicone, Rosella; Cruz-Muñoz, Mario E; López-Guerrero, Delia V; Martínez-Duncker, Iván

2015-12-01

CD4+ T helper lymphocytes (Th) orchestrate the immune response after their activation by antigen-presenting cells. Activation of naïve Th cells is reported to generate the reduction in surface epitopes of sialic acid (Sia) in α2,3 and α2,6 linkages. In this work, we report that in spite of this glycophenotype, anti-CD3/anti-CD28-activated purified human naïve Th cells show a significant increase in surface Sia, as assessed by metabolic labeling, compared with resting naïve Th cells, suggesting an increased flux of Sia toward Siaα2,8 glycoconjugates. To understand this increase as a result of ganglioside up-regulation, we observed that very early after activation, human naïve Th cells show an increased expression in surface GD3 and neoexpression of surface GD2 gangliosides, the latter clustering with the T cell receptor (TCR). Also, we report that in contrast to GM2/GD2 synthase null mice, lentiviral vector-mediated silencing of the GM2/GD2 synthase in activated human naïve Th cells reduced efficient TCR clustering and downstream signaling, as assessed by proliferation assays and IL-2 and IL-2R expression, pointing to an important role of this enzyme in activation of human naive Th cells. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Action of multiple intra-QTL genes concerted around a co-localized transcription factor underpins a large effect QTL

Science.gov (United States)

Dixit, Shalabh; Kumar Biswal, Akshaya; Min, Aye; Henry, Amelia; Oane, Rowena H.; Raorane, Manish L.; Longkumer, Toshisangba; Pabuayon, Isaiah M.; Mutte, Sumanth K.; Vardarajan, Adithi R.; Miro, Berta; Govindan, Ganesan; Albano-Enriquez, Blesilda; Pueffeld, Mandy; Sreenivasulu, Nese; Slamet-Loedin, Inez; Sundarvelpandian, Kalaipandian; Tsai, Yuan-Ching; Raghuvanshi, Saurabh; Hsing, Yue-Ie C.; Kumar, Arvind; Kohli, Ajay

2015-01-01

Sub-QTLs and multiple intra-QTL genes are hypothesized to underpin large-effect QTLs. Known QTLs over gene families, biosynthetic pathways or certain traits represent functional gene-clusters of genes of the same gene ontology (GO). Gene-clusters containing genes of different GO have not been elaborated, except in silico as coexpressed genes within QTLs. Here we demonstrate the requirement of multiple intra-QTL genes for the full impact of QTL qDTY12.1 on rice yield under drought. Multiple evidences are presented for the need of the transcription factor ‘no apical meristem’ (OsNAM12.1) and its co-localized target genes of separate GO categories for qDTY12.1 function, raising a regulon-like model of genetic architecture. The molecular underpinnings of qDTY12.1 support its effectiveness in further improving a drought tolerant genotype and for its validity in multiple genotypes/ecosystems/environments. Resolving the combinatorial value of OsNAM12.1 with individual intra-QTL genes notwithstanding, identification and analyses of qDTY12.1has fast-tracked rice improvement towards food security. PMID:26507552

CLC-Nt1, a putative chloride channel protein of tobacco, co-localizes with mitochondrial membrane markers.

Science.gov (United States)

Lurin, C; Güclü, J; Cheniclet, C; Carde, J P; Barbier-Brygoo, H; Maurel, C

2000-06-01

The voltage-dependent chloride channel (CLC) family of membrane proteins has cognates in animals, yeast, bacteria and plants, and chloride-channel activity has been assigned to most of the animal homologues. Lack of evidence of CLC functions in plants prompted us to characterize the cellular localization of the tobacco CLC-Nt1 protein. Specific polyclonal antibodies were raised against an N-terminal polypeptide of CLC-Nt1. These antibodies were used to probe membrane proteins prepared by various cell-fractionation methods. These included aqueous two-phase partitioning (for plasma membranes), free-flow electrophoresis (for vacuolar and plasma membranes), intact vacuole isolation, Percoll-gradient centrifugation (for plastids and mitochondria) and stepped, linear, sucrose-density-gradient centrifugation (for mitochondria). Each purified membrane fraction was characterized with specific marker enzyme activities or antibodies. Our studies ruled out the possibility that the major cell localization of CLC-Nt1 was the vacuolar or plasma membranes, the endoplasmic reticulum, the Golgi apparatus or the plastids. In contrast, we showed that the tobacco CLC-Nt1 specifically co-localized with the markers of the mitochondrial inner membrane, cytochrome c oxidase and NAD9 protein. CLC-Nt1 may correspond to the inner membrane anion channel ('IMAC') described previously in animal and plant mitochondria.

Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism.

Science.gov (United States)

Backlund, Michael; Paukku, Kirsi; Kontula, Kimmo K; Lehtonen, Jukka Y A

2016-04-20

As the formation of ribonucleoprotein complexes is a major mechanism of angiotensin II type 1 receptor (AT1R) regulation, we sought to identify novel AT1R mRNA binding proteins. By affinity purification and mass spectroscopy, we identified TIA-1. This interaction was confirmed by colocalization of AT1R mRNA and TIA-1 by FISH and immunofluorescence microscopy. In immunoprecipitates of endogenous TIA- 1, reverse transcription-PCR amplified AT1R mRNA. TIA-1 has two binding sites within AT1R 3'-UTR. The binding site proximal to the coding region is glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-dependent whereas the distal binding site is not. TIA-1 functions as a part of endoplasmic reticulum (ER) stress response leading to stress granule (SG) formation and translational silencing. We and others have shown that AT1R expression is increased by ER stress-inducing factors. In unstressed cells, TIA-1 binds to AT1R mRNA and decreases AT1R protein expression. Fluorescence microscopy shows that ER stress induced by thapsigargin leads to the transfer of TIA-1 to SGs. In FISH analysis AT1R mRNA remains in the cytoplasm and no longer colocalizes with TIA-1. Thus, release of TIA-1-mediated suppression by ER stress increases AT1R protein expression. In conclusion, AT1R mRNA is regulated by TIA-1 in a ER stress-dependent manner. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Increased Mortality in Diabetic Foot Ulcer Patients: The Significance of Ulcer Type

Science.gov (United States)

Chammas, N. K.; Hill, R. L. R.; Edmonds, M. E.

2016-01-01

Diabetic foot ulcer (DFU) patients have a greater than twofold increase in mortality compared with nonulcerated diabetic patients. We investigated (a) cause of death in DFU patients, (b) age at death, and (c) relationship between cause of death and ulcer type. This was an eleven-year retrospective study on DFU patients who attended King's College Hospital Foot Clinic and subsequently died. A control group of nonulcerated diabetic patients was matched for age and type of diabetes mellitus. The cause of death was identified from death certificates (DC) and postmortem (PM) examinations. There were 243 DFU patient deaths during this period. Ischaemic heart disease (IHD) was the major cause of death in 62.5% on PM compared to 45.7% on DC. Mean age at death from IHD on PM was 5 years lower in DFU patients compared to controls (68.2 ± 8.7 years versus 73.1 ± 8.0 years, P = 0.015). IHD as a cause of death at PM was significantly linked to neuropathic foot ulcers (OR 3.064, 95% CI 1.003–9.366, and P = 0.049). Conclusions. IHD is the major cause of premature mortality in DFU patients with the neuropathic foot ulcer patients being at a greater risk. PMID:27213157

Increase of surface solar irradiance across East China related to changes in aerosol properties during the past decade

Science.gov (United States)

Li, Jing; Jiang, Yiwei; Xia, Xiangao; Hu, Yongyun

2018-03-01

Previously, it was widely documented that an overall decrease in surface solar radiation occurred in China at least until 2005, in contrast to the general background of ‘global brightening’. Increased anthropogenic aerosol emissions were speculated to be the source of the reduction. In this study, we extend the trend analysis to the most recent decade from 2005-2015 and find that surface solar radiation has shifted from ‘dimming’ to ‘brightening’ over East China, with the largest increase over the northeast and southeast parts. Meanwhile, satellite and ground observation both indicate a reduction in aerosol optical depth (AOD) during the same period, whereas no significant trends in cloud amount show up. Detailed analysis using co-located radiation and aerosol observation at the XiangHe station in North China suggests that both AOD and single scattering albedo (SSA) changes contribute to the radiation trends. AOD reduction contributes to the increase of direct solar radiation, also decreasing the diffuse radiation, while the increase of SSA serves to increase the diffuse fraction. Simple calculations using a radiative transfer model confirm that the two effects combined explain changes in the global solar radiation and its components effectively. Our results have implications for potential climate effects with the reduction of China’s aerosol emissions, and the necessity to monitor aerosol composition in addition to its loading.

DISCOVERY OF PULSED γ-RAYS FROM PSR J0034-0534 WITH THE FERMI LARGE AREA TELESCOPE: A CASE FOR CO-LOCATED RADIO AND γ-RAY EMISSION REGIONS

International Nuclear Information System (INIS)

Abdo, A. A.; Ackermann, M.; Ajello, M.; Allafort, A.; Bechtol, K.; Berenji, B.; Blandford, R. D.; Bloom, E. D.; Borgland, A. W.; Bouvier, A.; Baldini, L.; Bellazzini, R.; Bregeon, J.; Brez, A.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bonamente, E.; Brigida, M.; Bruel, P.

2010-01-01

Millisecond pulsars (MSPs) have been firmly established as a class of γ-ray emitters via the detection of pulsations above 0.1 GeV from eight MSPs by the Fermi Large Area Telescope (LAT). Using 13 months of LAT data, significant γ-ray pulsations at the radio period have been detected from the MSP PSR J0034-0534, making it the ninth clear MSP detection by the LAT. The γ-ray light curve shows two peaks separated by 0.274 ± 0.015 in phase which are very nearly aligned with the radio peaks, a phenomenon seen only in the Crab pulsar until now. The ≥0.1 GeV spectrum of this pulsar is well fit by an exponentially cutoff power law with a cutoff energy of 1.8 ± 0.6 ± 0.1 GeV and a photon index of 1.5 ± 0.2 ± 0.1, first errors are statistical and second are systematic. The near-alignment of the radio and γ-ray peaks strongly suggests that the radio and γ-ray emission regions are co-located and both are the result of caustic formation.

Space Geodetic Technique Co-location in Space: Simulation Results for the GRASP Mission

Science.gov (United States)

Kuzmicz-Cieslak, M.; Pavlis, E. C.

2011-12-01

The Global Geodetic Observing System-GGOS, places very stringent requirements in the accuracy and stability of future realizations of the International Terrestrial Reference Frame (ITRF): an origin definition at 1 mm or better at epoch and a temporal stability on the order of 0.1 mm/y, with similar numbers for the scale (0.1 ppb) and orientation components. These goals were derived from the requirements of Earth science problems that are currently the international community's highest priority. None of the geodetic positioning techniques can achieve this goal alone. This is due in part to the non-observability of certain attributes from a single technique. Another limitation is imposed from the extent and uniformity of the tracking network and the schedule of observational availability and number of suitable targets. The final limitation derives from the difficulty to "tie" the reference points of each technique at the same site, to an accuracy that will support the GGOS goals. The future GGOS network will address decisively the ground segment and to certain extent the space segment requirements. The JPL-proposed multi-technique mission GRASP (Geodetic Reference Antenna in Space) attempts to resolve the accurate tie between techniques, using their co-location in space, onboard a well-designed spacecraft equipped with GNSS receivers, a SLR retroreflector array, a VLBI beacon and a DORIS system. Using the anticipated system performance for all four techniques at the time the GGOS network is completed (ca 2020), we generated a number of simulated data sets for the development of a TRF. Our simulation studies examine the degree to which GRASP can improve the inter-technique "tie" issue compared to the classical approach, and the likely modus operandi for such a mission. The success of the examined scenarios is judged by the quality of the origin and scale definition of the resulting TRF.

The kunitz protease inhibitor form of the amyloid precursor protein (KPI/APP) inhibits the proneuropeptide processing enzyme prohormone thiol protease (PTP). Colocalization of KPI/APP and PTP in secretory vesicles.

Science.gov (United States)

Hook, V Y; Sei, C; Yasothornsrikul, S; Toneff, T; Kang, Y H; Efthimiopoulos, S; Robakis, N K; Van Nostrand, W

1999-01-29

Proteolytic processing of proenkephalin and proneuropeptides is required for the production of active neurotransmitters and peptide hormones. Variations in the extent of proenkephalin processing in vivo suggest involvement of endogenous protease inhibitors. This study demonstrates that "protease nexin 2 (PN2)," the secreted form of the kunitz protease inhibitor (KPI) of the amyloid precursor protein (APP), potently inhibited the proenkephalin processing enzyme known as prohormone thiol protease (PTP), with a Ki,app of 400 nM. Moreover, PTP and PN2 formed SDS-stable complexes that are typical of kunitz protease inhibitor interactions with target proteases. In vivo, KPI/APP (120 kDa), as well as a truncated form of KPI/APP that resembles PN2 in apparent molecular mass (110 kDa), were colocalized with PTP and (Met)enkephalin in secretory vesicles of adrenal medulla (chromaffin granules). KPI/APP (110-120 kDa) was also detected in pituitary secretory vesicles that contain PTP. In chromaffin cells, calcium-dependent secretion of KPI/APP with PTP and (Met)enkephalin demonstrated the colocalization of these components in functional secretory vesicles. These results suggest a role for KPI/APP inhibition of PTP in regulated secretory vesicles. In addition, these results are the first to identify an endogenous protease target of KPI/APP, which is developmentally regulated in aging and Alzheimer's disease.

Implementation of a geological disposal facility (GDF) in the UK by the NDA Radioactive Waste Management Directorate (RWMD): the potential for interaction between the co-located ILW/LLW and HLW/SF components of a GDF - 16306

International Nuclear Information System (INIS)

Towler, George; Hicks, Tim; Watson, Sarah; Norris, Simon

2009-01-01

In June 2008 the UK government published a 'White Paper' as part of the 'Managing Radioactive Waste Safety' (MRWS) programme to provide a framework for managing higher activity radioactive wastes in the long-term through geological disposal. The White Paper identifies that there are benefits to disposing all of the UK's higher activity wastes (Low and Intermediate Level Waste (LLW and ILW), High Level Waste (HLW), Spent Fuel (SF), Uranium (U) and Plutonium (Pu)) at the same site, and this is currently the preferred option. It also notes that research will be required to support the detailed design and safety assessment in relation to any potentially detrimental interactions between the different modules. Different disposal system designs and associated Engineered Barrier Systems (EBS) will be required for these different waste types, i.e. ILW/LLW and HLW/SF. If declared as waste U would be disposed as ILW and Pu as HLW/SF. The Geological Disposal Facility (GDF) would therefore comprise two co-located modules (respectively for ILW/LLW and HLW/SF). This paper presents an overview of a study undertaken to assess the implications of co-location by identifying the key Thermo-Hydro-Mechanical-Chemical (THMC) interactions that might occur during both the operational and post-closure phases, and their consequences for GDF design, performance and safety. The MRWS programme is currently seeking expressions of interest from communities to host a GDF. Therefore, the study was required to consider a wide range of potential GDF host rocks and consistent, conceptual disposal system designs. Two example disposal concepts (i.e. combinations of host rock, GDF design including wasteform and layout, etc.) were carried forward for detailed assessment and a third for qualitative analysis. Dimensional and 1D analyses were used to identify the key interactions, and 3D models were used to investigate selected interactions in more detail. The results of this study show that it is possible

Significant social events and increasing use of life-sustaining treatment: trend analysis using extracorporeal membrane oxygenation as an example.

Science.gov (United States)

Chen, Yen-Yuan; Chen, Likwang; Huang, Tien-Shang; Ko, Wen-Je; Chu, Tzong-Shinn; Ni, Yen-Hsuan; Chang, Shan-Chwen

2014-03-04

Most studies have examined the outcomes of patients supported by extracorporeal membrane oxygenation as a life-sustaining treatment. It is unclear whether significant social events are associated with the use of life-sustaining treatment. This study aimed to compare the trend of extracorporeal membrane oxygenation use in Taiwan with that in the world, and to examine the influence of significant social events on the trend of extracorporeal membrane oxygenation use in Taiwan. Taiwan's extracorporeal membrane oxygenation uses from 2000 to 2009 were collected from National Health Insurance Research Dataset. The number of the worldwide extracorporeal membrane oxygenation cases was mainly estimated using Extracorporeal Life Support Registry Report International Summary July 2012. The trend of Taiwan's crude annual incidence rate of extracorporeal membrane oxygenation use was compared with that of the rest of the world. Each trend of extracorporeal membrane oxygenation use was examined using joinpoint regression. The measurement was the crude annual incidence rate of extracorporeal membrane oxygenation use. Each of the Taiwan's crude annual incidence rates was much higher than the worldwide one in the same year. Both the trends of Taiwan's and worldwide crude annual incidence rates have significantly increased since 2000. Joinpoint regression selected the model of the Taiwan's trend with one joinpoint in 2006 as the best-fitted model, implying that the significant social events in 2006 were significantly associated with the trend change of extracorporeal membrane oxygenation use following 2006. In addition, significantly social events highlighted by the media are more likely to be associated with the increase of extracorporeal membrane oxygenation use than being fully covered by National Health Insurance. Significant social events, such as a well-known person's successful extracorporeal membrane oxygenation use highlighted by the mass media, are associated with the use of

Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels.

Science.gov (United States)

Kucharski, Timothy J; Ferralis, Nicola; Kolpak, Alexie M; Zheng, Jennie O; Nocera, Daniel G; Grossman, Jeffrey C

2014-05-01

Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol(-1), and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain.

Co-localization of a CD1d-binding glycolipid with an adenovirus-based malaria vaccine for a potent adjuvant effect.

Science.gov (United States)

Li, Xiangming; Huang, Jing; Kawamura, Akira; Funakoshi, Ryota; Porcelli, Steven A; Tsuji, Moriya

2017-05-31

A CD1d-binding, invariant (i) natural killer T (NKT)-cell stimulatory glycolipid, α-Galactosylceramide (αGalCer), has been shown to act as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying a higher binding affinity for CD1d molecule and more potent adjuvant activity than αGalCer. In the present study, 7DW8-5 co-administered intramuscularly (i.m.) with a recombinant adenovirus expressing a Plasmodium yoelii circumsporozoite protein (PyCSP), AdPyCS, has led to a co-localization of 7DW8-5 and a PyCSP in draining lymph nodes (dLNs), particularly in dendritic cells (DCs). This occurrence initiates a cascade of events, such as the recruitment of DCs to dLNs and their activation and maturation, and the enhancement of the ability of DCs to prime CD8+ T cells induced by AdPyCS and ultimately leading to a potent adjuvant effect and protection against malaria. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preliminary safety analysis of a PBMR supplying process heat to a co-located ethylene production plant

International Nuclear Information System (INIS)

Scarlat, Raluca O.; Cisneros, Anselmo T.; Koutchesfahani, Tawni; Hong, Rada; Peterson, Per F.

2012-01-01

This paper considers the safety analysis and licensing approach for co-locating a pebble bed modular reactor (PBMR) to provide process heat to an ethylene production unit. The PBMR is an advanced nuclear reactor design that provides 400 MW of thermal energy. Ethylene production is an energy intensive process that utilizes large gas furnaces to provide the heat for the process. Coupling a PBMR with an ethylene production plant would open a new market for nuclear power, and would provide the chemical industry with a cleaner power source, helping to achieve the Clean Air Act standards, and eliminating the 0.5 ton of CO 2 emissions per ton of produced ethylene. Our analysis uses the Chevron Phillips chemical plant in Sweeney, TX as a prototypical site. The plant has four ethylene production trains, with a total power consumption of 2.4 GW, for an ethylene output of 3.7 million tons per year, 4% of the global ethylene production capacity. This paper proposes replacement of the gas furnaces by low-emission PBMR modules, and presents the safety concerns and risk mitigation and management options for this coupled system. Two coupling design options are proposed, and the necessary changes to the design basis events and severe accidents for the PBMR licensing application are discussed. A joint effort between the chemical and the nuclear entities to optimize the coupling design, establish preventive maintenance procedures, and develop emergency response plans for both of the units is recommended.

Preliminary safety analysis of a PBMR supplying process heat to a co-located ethylene production plant

Energy Technology Data Exchange (ETDEWEB)

Scarlat, Raluca O., E-mail: rscarlat@nuc.berkeley.edu [University of California Berkeley, Nuclear Engineering, 4118 Etcheverry Hall, Berkeley, CA 94720 (United States); Cisneros, Anselmo T. [University of California Berkeley, Nuclear Engineering, 4118 Etcheverry Hall, Berkeley, CA 94720 (United States); Koutchesfahani, Tawni [University of California, Chemical and Biomolecular Engineering, 201 Gilman Hall, Berkeley, CA 94720 (United States); Hong, Rada; Peterson, Per F. [University of California Berkeley, Nuclear Engineering, 4118 Etcheverry Hall, Berkeley, CA 94720 (United States)

2012-10-15

This paper considers the safety analysis and licensing approach for co-locating a pebble bed modular reactor (PBMR) to provide process heat to an ethylene production unit. The PBMR is an advanced nuclear reactor design that provides 400 MW of thermal energy. Ethylene production is an energy intensive process that utilizes large gas furnaces to provide the heat for the process. Coupling a PBMR with an ethylene production plant would open a new market for nuclear power, and would provide the chemical industry with a cleaner power source, helping to achieve the Clean Air Act standards, and eliminating the 0.5 ton of CO{sub 2} emissions per ton of produced ethylene. Our analysis uses the Chevron Phillips chemical plant in Sweeney, TX as a prototypical site. The plant has four ethylene production trains, with a total power consumption of 2.4 GW, for an ethylene output of 3.7 million tons per year, 4% of the global ethylene production capacity. This paper proposes replacement of the gas furnaces by low-emission PBMR modules, and presents the safety concerns and risk mitigation and management options for this coupled system. Two coupling design options are proposed, and the necessary changes to the design basis events and severe accidents for the PBMR licensing application are discussed. A joint effort between the chemical and the nuclear entities to optimize the coupling design, establish preventive maintenance procedures, and develop emergency response plans for both of the units is recommended.

Skipping one or more dialysis sessions significantly increases mortality: measuring the impact of non-adherence

Directory of Open Access Journals (Sweden)

Eduardo Gottlieb

2014-06-01

Full Text Available Introduction: Non-adherence to the prescribed dialysis sessions frequency ranges from 2% to 50% of patients. The objective of this study was to evaluate the impact of detecting and measuring the non-adherence to the prescribed dialysis frequency and to determine the importance of a multidisciplinary approach with the aim of improving adherence. Methods: longitudinal cohort study including 8,164 prevalent hemodialysis patients in April 2010, with more than 90 days of treatment, in Fresenius Medical Care Argentina units that were monitored for 3 years. The survey evaluated: interruption of at least one dialysis session in a month or reduction at least 10 minutes of a dialysis session in a month, during 6 months prior to the survey. Relative mortality risks were evaluated among groups. Results: 648 patients (7.9% interrupted dialysis sessions: 320 (3.9% interrupted one session per month and 328 (4.01% interrupted more than one session per month. After 3 years monitoring, 349 patients (53.8 % remained active in hemodialysis and 299 were inactive due to different reasons: 206 deceased (31.8 %, 47 transfers or monitoring losses (7.25 %, 36 transplanted (5.55 %, 8 changes to PD modality (1.2% and 2 recovered their kidney function (0.3 %.Interrupting one session per month significantly increased the mortality risk comparing both groups (interrupters and non-interrupters: RR 2.65 (IC 95% 2.24 – 3.14. Interrupting more than one dialysis session also increased significantly mortality risk comparing to the non-interrupters: RR 2.8 (IC 95% 2.39 – 3.28. After 3 years monitoring, 41.6 % of interrupters at the beginning had improved their adherence through a multidisciplinary program of quality improvement. Conclusion: Global mortality was greater among patients who interrupted dialysis sessions. A considerable proportion of interrupter patients at the beginning modified their behavior through the implementation of a multidisciplinary program of quality

A Data Colocation Grid Framework for Big Data Medical Image Processing: Backend Design

Science.gov (United States)

Huo, Yuankai; Parvathaneni, Prasanna; Plassard, Andrew J.; Bermudez, Camilo; Yao, Yuang; Lyu, Ilwoo; Gokhale, Aniruddha; Landman, Bennett A.

2018-01-01

When processing large medical imaging studies, adopting high performance grid computing resources rapidly becomes important. We recently presented a "medical image processing-as-a-service" grid framework that offers promise in utilizing the Apache Hadoop ecosystem and HBase for data colocation by moving computation close to medical image storage. However, the framework has not yet proven to be easy to use in a heterogeneous hardware environment. Furthermore, the system has not yet validated when considering variety of multi-level analysis in medical imaging. Our target design criteria are (1) improving the framework’s performance in a heterogeneous cluster, (2) performing population based summary statistics on large datasets, and (3) introducing a table design scheme for rapid NoSQL query. In this paper, we present a heuristic backend interface application program interface (API) design for Hadoop & HBase for Medical Image Processing (HadoopBase-MIP). The API includes: Upload, Retrieve, Remove, Load balancer (for heterogeneous cluster) and MapReduce templates. A dataset summary statistic model is discussed and implemented by MapReduce paradigm. We introduce a HBase table scheme for fast data query to better utilize the MapReduce model. Briefly, 5153 T1 images were retrieved from a university secure, shared web database and used to empirically access an in-house grid with 224 heterogeneous CPU cores. Three empirical experiments results are presented and discussed: (1) load balancer wall-time improvement of 1.5-fold compared with a framework with built-in data allocation strategy, (2) a summary statistic model is empirically verified on grid framework and is compared with the cluster when deployed with a standard Sun Grid Engine (SGE), which reduces 8-fold of wall clock time and 14-fold of resource time, and (3) the proposed HBase table scheme improves MapReduce computation with 7 fold reduction of wall time compare with a naïve scheme when datasets are relative

[Significant increase in the colonisation of Staphylococcus aureus among medical students during their hospital practices].

Science.gov (United States)

Rodríguez-Avial, Carmen; Alvarez-Novoa, Andrea; Losa, Azucena; Picazo, Juan J

2013-10-01

Staphylococcus aureus is a pathogen of major concern. The emergence of methicillin-resistant S. aureus (MRSA) has increasingly complicated the therapeutic approach of hospital-acquired infections. Surveillance of MRSA and control measures must be implemented in different healthcare settings, including screening programs for carriers. Our first aim was to determine the prevalence of methicillin-susceptible S. aureus (MSSA) and MRSA nasal carriage in medical students from the Clínico San Carlos Hospital (Madrid). As the MRSA carrier rate in healthcare workers is higher than in the general population, we hypothesised that carrier rate could be increased during their clinical practice in their last three years. We performed an epidemiologic al study of the prevalence of S. aureus colonisation among a group of medical students, who were sampled in 2008 in their third-year, and in 2012 when this class was in its sixth year. We have found a significant increase in MSSA carriage, from 27% to 46%. There were no MRSA colonisations in the third-year, but one was found in the sixth-year group. The large majority of strains (89%) of strains were resistant to penicillin, and 27% to erythromycin and clindamycin. As 19 coagulase-negative Staphylococcus MR were also identified, a horizontal transfer of genes, such as mecA gene to S. aureus, could have occurred. Medical students are both, at risk for acquiring, and a potential source of nosocomial pathogens, mainly MSSA. Therefore, they should take special care for hygienic precautions, such as frequent and proper hand washing, while working in the hospital. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Increasing vaginal progesterone gel supplementation after frozen-thawed embryo transfer significantly increases the delivery rate

DEFF Research Database (Denmark)

Alsbjerg, Birgit; Polyzos, Nikolaos P; Elbaek, Helle Olesen

2013-01-01

The aim of this study was to evaluate the reproductive outcome in patients receiving frozen-thawed embryo transfer before and after doubling of the vaginal progesterone gel supplementation. The study was a retrospective study performed in The Fertility Clinic, Skive Regional Hospital, Denmark....... A total of 346 infertility patients with oligoamenorrhoea undergoing frozen-thawed embryo transfer after priming with oestradiol and vaginal progesterone gel were included. The vaginal progesterone dose was changed from 90mg (Crinone) once a day to twice a day and the reproductive outcome during the two...... rate (8.7% versus 20.5%, respectively; P=0.002). Doubling of the vaginal progesterone gel supplementation during frozen-thawed embryo transfer cycles decreased the early pregnancy loss rate, resulting in a significantly higher delivery rate. This study evaluated the reproductive outcome of 346 women...

One stone, two birds: silica nanospheres significantly increase photocatalytic activity and colloidal stability of photocatalysts

Science.gov (United States)

Rasamani, Kowsalya D.; Foley, Jonathan J., IV; Sun, Yugang

2018-03-01

Silver-doped silver chloride [AgCl(Ag)] nanoparticles represent a unique class of visible-light-driven photocatalysts, in which the silver dopants introduce electron-abundant mid-gap energy levels to lower the bandgap of AgCl. However, free-standing AgCl(Ag) nanoparticles, particularly those with small sizes and large surface areas, exhibit low colloidal stability and low compositional stability upon exposure to light irradiation, leading to easy aggregation and conversion to metallic silver and thus a loss of photocatalytic activity. These problems could be eliminated by attaching the small AgCl(Ag) nanoparticles to the surfaces of spherical dielectric silica particles with submicrometer sizes. The high optical transparency in the visible spectral region (400-800 nm), colloidal stability, and chemical/electronic inertness displayed by the silica spheres make them ideal for supporting photocatalysts and significantly improving their stability. The spherical morphology of the dielectric silica particles can support light scattering resonances to generate significantly enhanced electric fields near the silica particle surfaces, on which the optical absorption cross-section of the AgCl(Ag) nanoparticles is dramatically increased to promote their photocatalytic activity. The hybrid silica/AgCl(Ag) structures exhibit superior photocatalytic activity and stability, suitable for supporting photocatalysis sustainably; for instance, their efficiency in the photocatalytic decomposition of methylene blue decreases by only ˜9% even after ten cycles of operation.

The colocalization potential of HIV-specific CD8+ and CD4+ T-cells is mediated by integrin β7 but not CCR6 and regulated by retinoic acid.

Directory of Open Access Journals (Sweden)

Vanessa Sue Wacleche

Full Text Available CD4(+ T-cells from gut-associated lymphoid tissues (GALT are major targets for HIV-1 infection. Recruitment of excess effector CD8(+ T-cells in the proximity of target cells is critical for the control of viral replication. Here, we investigated the colocalization potential of HIV-specific CD8(+ and CD4(+ T-cells into the GALT and explored the role of retinoic acid (RA in regulating this process in a cohort of HIV-infected subjects with slow disease progression. The expression of the gut-homing molecules integrin β7, CCR6, and CXCR3 was identified as a "signature" for HIV-specific but not CMV-specific CD4(+ T-cells thus providing a new explanation for their enhanced permissiveness to infection in vivo. HIV-specific CD8(+ T-cells also expressed high levels of integrin β7 and CXCR3; however CCR6 was detected at superior levels on HIV-specific CD4(+ versus CD8(+ T-cells. All trans RA (ATRA upregulated the expression of integrin β7 but not CCR6 on HIV-specific T-cells. Together, these results suggest that HIV-specific CD8(+ T-cells may colocalize in excess with CD4(+ T-cells into the GALT via integrin β7 and CXCR3, but not via CCR6. Considering our previous findings that CCR6(+CD4(+ T-cells are major cellular targets for HIV-DNA integration in vivo, a limited ability of CD8(+ T-cells to migrate in the vicinity of CCR6(+CD4(+ T-cells may facilitate HIV replication and dissemination at mucosal sites.

Myriocin significantly increases the mortality of a non-mammalian model host during Candida pathogenesis.

Directory of Open Access Journals (Sweden)

Nadja Rodrigues de Melo

Full Text Available Candida albicans is a major human pathogen whose treatment is challenging due to antifungal drug toxicity, drug resistance and paucity of antifungal agents available. Myrocin (MYR inhibits sphingosine synthesis, a precursor of sphingolipids, an important cell membrane and signaling molecule component. MYR also has dual immune suppressive and antifungal properties, potentially modulating mammalian immunity and simultaneously reducing fungal infection risk. Wax moth (Galleria mellonella larvae, alternatives to mice, were used to establish if MYR suppressed insect immunity and increased survival of C. albicans-infected insects. MYR effects were studied in vivo and in vitro, and compared alone and combined with those of approved antifungal drugs, fluconazole (FLC and amphotericin B (AMPH. Insect immune defenses failed to inhibit C. albicans with high mortalities. In insects pretreated with the drug followed by C. albicans inoculation, MYR+C. albicans significantly increased mortality to 93% from 67% with C. albicans alone 48 h post-infection whilst AMPH+C. albicans and FLC+C. albicans only showed 26% and 0% mortalities, respectively. MYR combinations with other antifungal drugs in vivo also enhanced larval mortalities, contrasting the synergistic antifungal effect of the MYR+AMPH combination in vitro. MYR treatment influenced immunity and stress management gene expression during C. albicans pathogenesis, modulating transcripts putatively associated with signal transduction/regulation of cytokines, I-kappaB kinase/NF-kappaB cascade, G-protein coupled receptor and inflammation. In contrast, all stress management gene expression was down-regulated in FLC and AMPH pretreated C. albicans-infected insects. Results are discussed with their implications for clinical use of MYR to treat sphingolipid-associated disorders.

The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

International Nuclear Information System (INIS)

Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.

2010-01-01

Research highlights: → Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. → We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. → Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. → Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient-related hormones such as leptin

The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

Energy Technology Data Exchange (ETDEWEB)

Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); others, and

2010-09-24

Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

Time-Lapse Monitoring of DNA Damage Colocalized With Particle Tracks in Single Living Cells

Energy Technology Data Exchange (ETDEWEB)

McFadden, Conor H. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hallacy, Timothy M. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Physics and Astronomy, Rice University, Houston, Texas (United States); Flint, David B. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States); Granville, Dal A. [Department of Medical Physics, The Ottawa Hospital Cancer Centre, Ottawa, Ontario (Canada); Asaithamby, Aroumougame [Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Centre, Dallas, Texas (United States); Sahoo, Narayan [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Akselrod, Mark S. [Crystal Growth Division, Landauer, Inc, Stillwater, Oklahoma (United States); Sawakuchi, Gabriel O., E-mail: gsawakuchi@mdanderson.org [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States)

2016-09-01

Purpose: Understanding the DNA damage and repair induced by hadron therapy (HT) beams is crucial for developing novel strategies to maximize the use of HT beams to treat cancer patients. However, spatiotemporal studies of DNA damage and repair for beam energies relevant to HT have been challenging. We report a technique that enables spatiotemporal measurement of radiation-induced damage in live cells and colocalization of this damage with charged particle tracks over a broad range of clinically relevant beam energies. The technique uses novel fluorescence nuclear track detectors with fluorescence confocal laser scanning microscopy in the beam line to visualize particle track traversals within the subcellular compartments of live cells within seconds after injury. Methods and Materials: We designed and built a portable fluorescence confocal laser scanning microscope for use in the beam path, coated fluorescence nuclear track detectors with fluorescent-tagged live cells (HT1080 expressing enhanced green fluorescent protein tagged to XRCC1, a single-strand break repair protein), placed the entire assembly into a proton therapy beam line, and irradiated the cells with a fluence of ∼1 × 10{sup 6} protons/cm{sup 2}. Results: We successfully obtained confocal images of proton tracks and foci of DNA single-strand breaks immediately after irradiation. Conclusions: This technique represents an innovative method for analyzing biological responses in any HT beam line at energies and dose rates relevant to therapy. It allows precise determination of the number of tracks traversing a subcellular compartment and monitoring the cellular damage therein, and has the potential to measure the linear energy transfer of each track from therapeutic beams.

Big data integration shows Australian bush-fire frequency is increasing significantly.

Science.gov (United States)

Dutta, Ritaban; Das, Aruneema; Aryal, Jagannath

2016-02-01

Increasing Australian bush-fire frequencies over the last decade has indicated a major climatic change in coming future. Understanding such climatic change for Australian bush-fire is limited and there is an urgent need of scientific research, which is capable enough to contribute to Australian society. Frequency of bush-fire carries information on spatial, temporal and climatic aspects of bush-fire events and provides contextual information to model various climate data for accurately predicting future bush-fire hot spots. In this study, we develop an ensemble method based on a two-layered machine learning model to establish relationship between fire incidence and climatic data. In a 336 week data trial, we demonstrate that the model provides highly accurate bush-fire incidence hot-spot estimation (91% global accuracy) from the weekly climatic surfaces. Our analysis also indicates that Australian weekly bush-fire frequencies increased by 40% over the last 5 years, particularly during summer months, implicating a serious climatic shift.

Rabies virus co-localizes with early (Rab5) and late (Rab7) endosomal proteins in neuronal and SH-SY5Y cells.

Science.gov (United States)

Ahmad, Waqas; Li, Yingying; Guo, Yidi; Wang, Xinyu; Duan, Ming; Guan, Zhenhong; Liu, Zengshan; Zhang, Maolin

2017-06-01

Rabies virus (RABV) is a highly neurotropic virus that follows clathrin-mediated endocytosis and pH-dependent pathway for trafficking and invasion into endothelial cells. Early (Rab5, EEA1) and late (Rab7, LAMP1) endosomal proteins play critical roles in endosomal sorting, maturity and targeting various molecular cargoes, but their precise functions in the early stage of RABV neuronal infection remain elusive. In this study, the relationship between enigmatic entry of RABV with these endosomal proteins into neuronal and SH-SY5Y cells was investigated. Immunofluorescence, TCID 50 titers, electron microscopy and western blotting were carried out to determine the molecular interaction of the nucleoprotein (N) of RABV with early or late endosomal proteins in these cell lines. The expression of N was also determined by down-regulating Rab5 and Rab7 in both cell lines through RNA interference. The results were indicative that N proficiently colocalized with Rab5/EEA1 and Rab7/LAMP1 in both cell lines at 24 and 48 h post-infection, while N titers significantly decreased in early infection of RABV. Down-regulation of Rab5 and Rab7 did not inhibit N expression, but it prevented productive infection via blocking the normal trafficking of RABV in a low pH environment. Ultrathin sections of cells studied by electron microscope also verified the close association of RABV with Rab5 and Rab7 in neurons. From the data it was concluded that primary entry of RABV strongly correlates with the kinetics of Rab-proteins present on early and late vesicles, which provides helpful clues to explain the early events of RABV in nerve cells.

Significant yield increases from control of leaf diseases in maize - an overlooked problem?!

DEFF Research Database (Denmark)

Jørgensen, Lise Nistrup

2012-01-01

The area of maize has increased in several European countries in recent years. In Denmark, the area has increased from 10,000 ha in 1980 to 185,000 ha in 2011. Initially only silage maize was cultivated in Denmark, but in more recent years the area of grain maize has also increased. Farms growing...

Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

Energy Technology Data Exchange (ETDEWEB)

Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.; Shyamala, G.; Moses, Harold L.; Barcellos-Hoff, Mary Helen

2005-03-03

Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha} co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.

Co-encapsulation of paclitaxel and C6 ceramide in tributyrin-containing nanocarriers improve co-localization in the skin and potentiate cytotoxic effects in 2D and 3D models.

Science.gov (United States)

Carvalho, Vanessa F M; Migotto, Amanda; Giacone, Daniela V; de Lemos, Débora P; Zanoni, Thalita B; Maria-Engler, Silvya S; Costa-Lotufo, Leticia V; Lopes, Luciana B

2017-11-15

Considering that tumor development is generally multifactorial, therapy with a combination of agents capable of potentiating cytotoxic effects is promising. In this study, we co-encapsulated C6 ceramide (0.35%) and paclitaxel (0.50%) in micro and nanoemulsions containing tributyrin (a butyric acid pro-drug included for potentiation of cytotoxicity), and compared their ability to co-localize the drugs in viable skin layers. The nanoemulsion delivered 2- and 2.4-fold more paclitaxel into viable skin layers of porcine skin in vitro at 4 and 8h post-application than the microemulsion, and 1.9-fold more C6 ceramide at 8h. The drugs were co-localized mainly in the epidermis, suggesting the nanoemulsion ability for a targeted delivery. Based on this result, the nanoemulsion was selected for evaluation of the nanocarrier-mediated cytotoxicity against cells in culture (2D model) and histological changes in a 3D melanoma model. Encapsulation of the drugs individually decreased the concentration necessary to reduce melanoma cells viability to 50% (EC 50 ) by approximately 4- (paclitaxel) and 13-fold (ceramide), demonstrating an improved nanoemulsion-mediated drug delivery. Co-encapsulation of paclitaxel and ceramide further decreased EC 50 by 2.5-4.5-fold, and calculation of the combination index indicated a synergistic effect. Nanoemulsion topical administration on 3D bioengineered melanoma models for 48h promoted marked epidermis destruction, with only few cells remaining in this layer. This result demonstrates the efficacy of the nanoemulsion, but also suggests non-selective cytotoxic effects, which highlights the importance of localizing the drugs within cutaneous layers where the lesions develop to avoid adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Integrating Algae with Bioenergy Carbon Capture and Storage (ABECCS) Increases Sustainability

Science.gov (United States)

Beal, Colin M.; Archibald, Ian; Huntley, Mark E.; Greene, Charles H.; Johnson, Zackary I.

2018-03-01

Bioenergy carbon capture and storage (BECCS) has been proposed to reduce atmospheric CO2 concentrations, but concerns remain about competition for arable land and freshwater. The synergistic integration of algae production, which does not require arable land or freshwater, with BECCS (called "ABECCS") can reduce CO2 emissions without competing with agriculture. This study presents a technoeconomic and life-cycle assessment for colocating a 121-ha algae facility with a 2,680-ha eucalyptus forest for BECCS. The eucalyptus biomass fuels combined heat and power (CHP) generation with subsequent amine-based carbon capture and storage (CCS). A portion of the captured CO2 is used for growing algae and the remainder is sequestered. Biomass combustion supplies CO2, heat, and electricity, thus increasing the range of sites suitable for algae cultivation. Economic, energetic, and environmental impacts are considered. The system yields as much protein as soybeans while generating 61.5 TJ of electricity and sequestering 29,600 t of CO2 per year. More energy is generated than consumed and the freshwater footprint is roughly equal to that for soybeans. Financial break-even is achieved for product value combinations that include 1) algal biomass sold for 1,400/t (fishmeal replacement) with a 68/t carbon credit and 2) algal biomass sold for 600/t (soymeal replacement) with a 278/t carbon credit. Sensitivity analysis shows significant reductions to the cost of carbon sequestration are possible. The ABECCS system represents a unique technology for negative emissions without reducing protein production or increasing water demand, and should therefore be included in the suite of technologies being considered to address global sustainability.

Direction-of-arrival estimation for co-located multiple-input multiple-output radar using structural sparsity Bayesian learning

Science.gov (United States)

Wen, Fang-Qing; Zhang, Gong; Ben, De

2015-11-01

This paper addresses the direction of arrival (DOA) estimation problem for the co-located multiple-input multiple-output (MIMO) radar with random arrays. The spatially distributed sparsity of the targets in the background makes compressive sensing (CS) desirable for DOA estimation. A spatial CS framework is presented, which links the DOA estimation problem to support recovery from a known over-complete dictionary. A modified statistical model is developed to accurately represent the intra-block correlation of the received signal. A structural sparsity Bayesian learning algorithm is proposed for the sparse recovery problem. The proposed algorithm, which exploits intra-signal correlation, is capable being applied to limited data support and low signal-to-noise ratio (SNR) scene. Furthermore, the proposed algorithm has less computation load compared to the classical Bayesian algorithm. Simulation results show that the proposed algorithm has a more accurate DOA estimation than the traditional multiple signal classification (MUSIC) algorithm and other CS recovery algorithms. Project supported by the National Natural Science Foundation of China (Grant Nos. 61071163, 61271327, and 61471191), the Funding for Outstanding Doctoral Dissertation in Nanjing University of Aeronautics and Astronautics, China (Grant No. BCXJ14-08), the Funding of Innovation Program for Graduate Education of Jiangsu Province, China (Grant No. KYLX 0277), the Fundamental Research Funds for the Central Universities, China (Grant No. 3082015NP2015504), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PADA), China.

MRS/IS facility co-located with a repository: preconceptual design and life-cycle cost estimates

International Nuclear Information System (INIS)

Smith, R.I.; Nesbitt, J.F.

1982-11-01

A program is described to examine the various alternatives for monitored retrievable storage (MRS) and interim storage (IS) of spent nuclear fuel, solidified high-level waste (HLW), and transuranic (TRU) waste until appropriate geologic repository/repositories are available. The objectives of this study are: (1) to develop a preconceptual design for an MRS/IS facility that would become the principal surface facility for a deep geologic repository when the repository is opened, (2) to examine various issues such as transportation of wastes, licensing of the facility, and environmental concerns associated with operation of such a facility, and (3) to estimate the life cycle costs of the facility when operated in response to a set of scenarios which define the quantities and types of waste requiring storage in specific time periods, which generally span the years from 1990 until 2016. The life cycle costs estimated in this study include: the capital expenditures for structures, casks and/or drywells, storage areas and pads, and transfer equipment; the cost of staff labor, supplies, and services; and the incremental cost of transporting the waste materials from the site of origin to the MRS/IS facility. Three scenarios are examined to develop estimates of life cycle costs of the MRS/IS facility. In the first scenario, HLW canisters are stored, starting in 1990, until the co-located repository is opened in the year 1998. Additional reprocessing plants and repositories are placed in service at various intervals. In the second scenario, spent fuel is stored, starting in 1990, because the reprocessing plants are delayed in starting operations by 10 years, but no HLW is stored because the repositories open on schedule. In the third scenario, HLW is stored, starting in 1990, because the repositories are delayed 10 years, but the reprocessing plants open on schedule

Anti-Streptococcus IgM Antibodies Induce Repetitive Stereotyped Movements: Cell Activation and Co-Localization with Fcα/μ Receptors in the Striatum and Motor Cortex

Science.gov (United States)

Zhang, Danhui; Patel, Ankur; Zhu, Youhua; Siegel, Allan; Zalcman, Steven S.

2012-01-01

Group A beta-hemolytic streptococcus (GABHS) infections are implicated in neuropsychiatric disorders associated with an increased expression of repetitive stereotyped movements. Anti-streptococcus IgG presumably cross-reacts with elements on basal ganglia cells, modifies their function, and triggers symptoms. IgM may play a unique role in precipitating behavioral disturbances since variations in cortico-striatal activity occur in temporal congruity with peak IgM titers during an orchestrated immune response. We discovered in Balb/c mice that single subcutaneous injections of mouse monoclonal IgM antibodies to Streptococcus Group A bacteria induce marked dose-dependent increases in repetitive stereotyped movements, including head bobbing, sniffing, and intense grooming. Effects were antibody- and antigen-specific: anti-streptococcus IgG stimulated ambulatory activity and vertical activity but not these stereotypies, while anti-KLH IgM reduced activity. We suggest that anti-streptococcus IgM and IgG play unique roles in provoking GABHS-related behavioral disturbances. Paralleling its stereotypy-inducing effects, anti-streptococcus IgM stimulated Fos-like immunoreactivity in regions linked to cortico-striatal projections involved in motor control, including subregions of the caudate, nucleus accumbens, and motor cortex. This is the first evidence that anti-streptococcus IgM antibodies induce in vivo functional changes in these structures. Moreover, there was a striking similarity in the distributions of anti-streptococcus IgM deposits and Fos-like immunoreactivity in these regions. Of further importance, Fcα/μ receptors, which bind IgM, were present- and co-localized with anti-streptococcus IgM in these structures. We suggest that anti-streptococcus IgM-induced alterations of cell activity reflect local actions of IgM that involve Fcα/μ receptors. These findings support the use of anti-streptococcus monoclonal antibody administration in Balb/c mice to model GABHS

Application of Bioorganic Fertilizer Significantly Increased Apple Yields and Shaped Bacterial Community Structure in Orchard Soil.

Science.gov (United States)

Wang, Lei; Li, Jing; Yang, Fang; E, Yaoyao; Raza, Waseem; Huang, Qiwei; Shen, Qirong

2017-02-01

and Rhodospirillaceae, were found to be the significantly increased by the BOF addition and the genus Lysobacter may identify members of this group effective in biological control-based plant disease management and the members of family Rhodospirillaceae had an important role in fixing molecular nitrogen. These results strengthen the understanding of responses to the BOF and possible interactions within bacterial communities in soil that can be associated with disease suppression and the accumulation of carbon and nitrogen. The increase of apple yields after the application of BOF might be attributed to the fact that the application of BOF increased SOM, and soil total nitrogen, and changed the bacterial community by enriching Rhodospirillaceae, Alphaprotreobateria, and Proteobacteria.

Increased susceptibility to collagen-induced arthritis in female mice carrying congenic Cia40/Pregq2 fragments

DEFF Research Database (Denmark)

Liljander, Maria; Andersson, Åsa Inga Maria; Holmdahl, Rikard

2008-01-01

ABSTRACT: INTRODUCTION: Collagen-induced arthritis (CIA) in mice is a commonly used experimental model for rheumatoid arthritis (RA). We have previously identified a significant quantitative trait locus denoted Cia40 on chromosome 11 that affects CIA in older female mice. This locus colocalizes...... with another locus, denoted Pregq2, known to affect reproductive success. The present study was performed to evaluate the role of the Cia40 locus in congenic B10.Q mice and to identify possible polymorphic candidate genes, which may also be relevant in the context of RA. METHODS: Congenic B10.Q mice carrying...... an NFR/N fragment surrounding the Cia40/Pregq2 loci were created by 10 generations of backcrossing (N10). The congenic mice were investigated in the CIA model, and the incidence and severity of arthritis as well as the serum levels of anti-collagen II (CII) antibodies were recorded. RESULTS: Significant...

Transabdominal cerclage: the significance of dual pathology and increased preterm delivery.

Science.gov (United States)

Farquharson, Roy G; Topping, Joanne; Quenby, Siobhan M

2005-10-01

Transabdominal cerclage is a recognised treatment for cervical weakness with a history of recurrent mid-trimester loss and a failed elective vaginal suture. The emergence of dual pathology, such as antiphospholipid syndrome and bacterial vaginosis, is associated with an increased risk of preterm delivery (RR 2.34, 95% CI 1.15-5.8). The first 40 cases are described where strict adherence to an investigation protocol and consistent treatment plan has been implemented.

Angiopoietin-like protein 2 increases renal fibrosis by accelerating transforming growth factor-β signaling in chronic kidney disease.

Science.gov (United States)

Morinaga, Jun; Kadomatsu, Tsuyoshi; Miyata, Keishi; Endo, Motoyoshi; Terada, Kazutoyo; Tian, Zhe; Sugizaki, Taichi; Tanigawa, Hiroki; Zhao, Jiabin; Zhu, Shunshun; Sato, Michio; Araki, Kimi; Iyama, Ken-ichi; Tomita, Kengo; Mukoyama, Masashi; Tomita, Kimio; Kitamura, Kenichiro; Oike, Yuichi

2016-02-01

Renal fibrosis is a common pathological consequence of chronic kidney disease (CKD) with tissue fibrosis closely associated with chronic inflammation in numerous pathologies. However, molecular mechanisms underlying that association, particularly in the kidney, remain unclear. Here, we determine whether there is a molecular link between chronic inflammation and tissue fibrosis in CKD progression. Histological analysis of human kidneys indicated abundant expression of angiopoietin-like protein 2 (ANGPTL2) in renal tubule epithelial cells during progression of renal fibrosis. Numerous ANGPTL2-positive renal tubule epithelial cells colocalized with cells positive for transforming growth factor (TGF)-β1, a critical mediator of tissue fibrosis. Analysis of M1 collecting duct cells in culture showed that TGF-β1 increases ANGPTL2 expression by attenuating its repression through microRNA-221. Conversely, ANGPTL2 increased TGF-β1 expression through α5β1 integrin-mediated activation of extracellular signal-regulated kinase. Furthermore, ANGPTL2 deficiency in a mouse unilateral ureteral obstruction model significantly reduced renal fibrosis by decreasing TGF-β1 signal amplification in kidney. Thus, ANGPTL2 and TGF-β1 positively regulate each other as renal fibrosis progresses. Our study provides insight into molecular mechanisms underlying chronic inflammation and tissue fibrosis and identifies potential therapeutic targets for CKD treatment. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

International Nuclear Information System (INIS)

Hsieh, Yi-Chen; Lien, Li-Ming; Chung, Wen-Ting; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

2011-01-01

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 μg/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 μg/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 μg/l). - Highlights: →Arsenic metabolic genes might be associated with carotid atherosclerosis. → A case

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

Energy Technology Data Exchange (ETDEWEB)

Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

2011-08-15

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

Metrology of ground-based satellite validation: co-location mismatch and smoothing issues of total ozone comparisons

Directory of Open Access Journals (Sweden)

T. Verhoelst

2015-12-01

Full Text Available Comparisons with ground-based correlative measurements constitute a key component in the validation of satellite data on atmospheric composition. The error budget of these comparisons contains not only the measurement errors but also several terms related to differences in sampling and smoothing of the inhomogeneous and variable atmospheric field. A versatile system for Observing System Simulation Experiments (OSSEs, named OSSSMOSE, is used here to quantify these terms. Based on the application of pragmatic observation operators onto high-resolution atmospheric fields, it allows a simulation of each individual measurement, and consequently, also of the differences to be expected from spatial and temporal field variations between both measurements making up a comparison pair. As a topical case study, the system is used to evaluate the error budget of total ozone column (TOC comparisons between GOME-type direct fitting (GODFITv3 satellite retrievals from GOME/ERS2, SCIAMACHY/Envisat, and GOME-2/MetOp-A, and ground-based direct-sun and zenith–sky reference measurements such as those from Dobsons, Brewers, and zenith-scattered light (ZSL-DOAS instruments, respectively. In particular, the focus is placed on the GODFITv3 reprocessed GOME-2A data record vs. the ground-based instruments contributing to the Network for the Detection of Atmospheric Composition Change (NDACC. The simulations are found to reproduce the actual measurements almost to within the measurement uncertainties, confirming that the OSSE approach and its technical implementation are appropriate. This work reveals that many features of the comparison spread and median difference can be understood as due to metrological differences, even when using strict co-location criteria. In particular, sampling difference errors exceed measurement uncertainties regularly at most mid- and high-latitude stations, with values up to 10 % and more in extreme cases. Smoothing difference errors only

Sugar Lego: gene composition of bacterial carbohydrate metabolism genomic loci.

Science.gov (United States)

Kaznadzey, Anna; Shelyakin, Pavel; Gelfand, Mikhail S

2017-11-25

Bacterial carbohydrate metabolism is extremely diverse, since carbohydrates serve as a major energy source and are involved in a variety of cellular processes. Bacterial genes belonging to same metabolic pathway are often co-localized in the chromosome, but it is not a strict rule. Gene co-localization in linked to co-evolution and co-regulation. This study focuses on a large-scale analysis of bacterial genomic loci related to the carbohydrate metabolism. We demonstrate that only 53% of 148,000 studied genes from over six hundred bacterial genomes are co-localized in bacterial genomes with other carbohydrate metabolism genes, which points to a significant role of singleton genes. Co-localized genes form cassettes, ranging in size from two to fifteen genes. Two major factors influencing the cassette-forming tendency are gene function and bacterial phylogeny. We have obtained a comprehensive picture of co-localization preferences of genes for nineteen major carbohydrate metabolism functional classes, over two hundred gene orthologous clusters, and thirty bacterial classes, and characterized the cassette variety in size and content among different species, highlighting a significant role of short cassettes. The preference towards co-localization of carbohydrate metabolism genes varies between 40 and 76% for bacterial taxa. Analysis of frequently co-localized genes yielded forty-five significant pairwise links between genes belonging to different functional classes. The number of such links per class range from zero to eight, demonstrating varying preferences of respective genes towards a specific chromosomal neighborhood. Genes from eleven functional classes tend to co-localize with genes from the same class, indicating an important role of clustering of genes with similar functions. At that, in most cases such co-localization does not originate from local duplication events. Overall, we describe a complex web formed by evolutionary relationships of bacterial

Cellular senescence of human mammary epithelial cells (HMEC) is associated with an altered MMP-7/HB-EGF signaling and increased formation of elastin-like structures.

Science.gov (United States)

Bertram, Catharina; Hass, Ralf

2009-10-01

The extracellular matrix (ECM) and a complex interplay of cell-to-cell and cell-to-matrix (ECM) interactions provide important platforms to determine cellular senescence and a potentially tumorigenic transformation of normal human mammary epithelial cells (HMEC). An enhanced formation of extracellular filaments, consisting of elastin-like structures, in senescent post-selection HMEC populations was paralleled by a significantly increased expression of its precursor protein tropoelastin and matched with a markedly elevated activity of the cross-linking enzyme family of lysyl oxidases (LOX). RNAi experiments revealed both the ECM metalloproteinase MMP-7 and the growth factor HB-EGF as potential effectors of an increased tropoelastin expression. Moreover, co-localization of MMP-7 and HB-EGF as well as a concomittant downstream signaling via Fra-1 indicated a possible association between the reduced MMP-7 enzyme activity and an impaired HB-EGF processing, resulting in an enhanced tropoelastin synthesis during senescence of HMEC. In agreement with previous work, these findings suggested an important influence of the extracellular proteinase MMP-7 on the aging process of HMEC, affecting both extracellular remodeling as well as intracellular signaling pathways.

Increased synaptophysin is involved in inflammation-induced heat hyperalgesia mediated by cyclin-dependent kinase 5 in rats.

Directory of Open Access Journals (Sweden)

Hong-Hai Zhang

Full Text Available Mechanisms associated with cyclin-dependent kinase 5 (Cdk5-mediated heat hyperalgesia induced by inflammation remain undefined. This study was designed to examine whether Cdk5 mediates heat hyperalgesia resulting from peripheral injection of complete Freund's adjuvant (CFA in the spinal dorsal horns of rats by interacting with synaptophysin, a well known membrane protein mediating the endocytosis-exocytosis cycle of synaptic vesicles as a molecular marker associated with presynaptic vesicle membranes. The role of Cdk5 in mediating synaptophysin was examined through the combined use of behavioral approaches, imaging studies, and immunoprecipitation following CFA-induced inflammatory pain. Results showed that Cdk5 colocalized with both synaptophysin and soluble N-ethylmaleimide-sensitive factor (NSF attachment protein receptors (SNAREs consisting of VAMP-2, SNAP-25, and syntaxin 1A in spinal dorsal horn of rats. Increased synaptophysin expression of spinal cord horn neurons post intraplantar injection of CFA coincided with increased duration of heat hyperalgesia lasting from 6 h to 3 d. Intrathecal administration of roscovitine, a Cdk5 specific inhibitor, significantly depressed synaptophysin expression during peak heat hyperalgesia and heat hyperalgesia induced by peripheral injection of CFA. Data presented in this report indicated that calpain activity was transiently upregulated 6 h post CFA-treatment despite previous reports suggesting that calpain was capable of cleaving p35 into p25. Results from previous studies obtained by other laboratories demonstrated that significant changes in p35 expression levels within spinal cord horn neurons were not observed in the CFA-treated inflammatory pain model although significant upregulation of Cdk5 kinase was observed between 2 h to 7 d. Therefore, generation of p25 occurred in a calpain-independent fashion in a CFA-treated inflammatory pain model. Our results demonstrated that increased synaptophysin

Microspectroscopy (μFTIR) reveals co-localization of lipid oxidation and amyloid plaques in human Alzheimer disease brains.

Science.gov (United States)

Benseny-Cases, Núria; Klementieva, Oxana; Cotte, Marine; Ferrer, Isidre; Cladera, Josep

2014-12-16

Amyloid peptides are the main component of one of the characteristic pathological hallmarks of Alzheimer's disease (AD): senile plaques. According to the amyloid cascade hypothesis, amyloid peptides may play a central role in the sequence of events that leads to neurodegeneration. However, there are other factors, such as oxidative stress, that may be crucial for the development of the disease. In the present paper, we show that it is possible, by using Fourier tranform infrared (FTIR) microscopy, to co-localize amyloid deposits and lipid peroxidation in tissue slides from patients affected by Alzheimer's disease. Plaques and lipids can be analyzed in the same sample, making use of the characteristic infrared bands for peptide aggregation and lipid oxidation. The results show that, in samples from patients diagnosed with AD, the plaques and their immediate surroundings are always characterized by the presence of oxidized lipids. As for samples from non-AD individuals, those without amyloid plaques show a lower level of lipid oxidation than AD individuals. However, it is known that plaques can be detected in the brains of some non-AD individuals. Our results show that, in such cases, the lipid in the plaques and their surroundings display oxidation levels that are similar to those of tissues with no plaques. These results point to lipid oxidation as a possible key factor in the path that goes from showing the typical neurophatological hallmarks to suffering from dementia. In this process, the oxidative power of the amyloid peptide, possibly in the form of nonfibrillar aggregates, could play a central role.

Neurite outgrowth is significantly increased by the simultaneous presentation of Schwann cells and moderate exogenous electric fields

Science.gov (United States)

Koppes, Abigail N.; Seggio, Angela M.; Thompson, Deanna M.

2011-08-01

Axonal extension is influenced by a variety of external guidance cues; therefore, the development and optimization of a multi-faceted approach is probably necessary to address the intricacy of functional regeneration following nerve injury. In this study, primary dissociated neonatal rat dorsal root ganglia neurons and Schwann cells were examined in response to an 8 h dc electrical stimulation (0-100 mV mm-1). Stimulated samples were then fixed immediately, immunostained, imaged and analyzed to determine Schwann cell orientation and characterize neurite outgrowth relative to electric field strength and direction. Results indicate that Schwann cells are viable following electrical stimulation with 10-100 mV mm-1, and retain a normal morphology relative to unstimulated cells; however, no directional bias is observed. Neurite outgrowth was significantly enhanced by twofold following exposure to either a 50 mV mm-1 electric field (EF) or co-culture with unstimulated Schwann cells by comparison to neurons cultured alone. Neurite outgrowth was further increased in the presence of simultaneously applied cues (Schwann cells + 50 mV mm-1 dc EF), exhibiting a 3.2-fold increase over unstimulated control neurons, and a 1.2-fold increase over either neurons cultured with unstimulated Schwann cells or the electrical stimulus alone. These results indicate that dc electric stimulation in combination with Schwann cells may provide synergistic guidance cues for improved axonal growth relevant to nerve injuries in the peripheral nervous system.

Phospho-Rb mediating cell cycle reentry induces early apoptosis following oxygen-glucose deprivation in rat cortical neurons.

Science.gov (United States)

Yu, Ying; Ren, Qing-Guo; Zhang, Zhao-Hui; Zhou, Ke; Yu, Zhi-Yuan; Luo, Xiang; Wang, Wei

2012-03-01

The aim of this study was to investigate the relationship between cell cycle reentry and apoptosis in cultured cortical neurons following oxygen-glucose deprivation (OGD). We found that the percentage of neurons with BrdU uptake, TUNEL staining, and colocalized BrdU uptake and TUNEL staining was increased relative to control 6, 12 and 24 h after 1 h of OGD. The number of neurons with colocalized BrdU and TUNEL staining was decreased relative to the number of TUNEL-positive neurons at 24 h. The expression of phosphorylated retinoblastoma protein (phospho-Rb) was significantly increased 6, 12 and 24 h after OGD, parallel with the changes in BrdU uptake. Phospho-Rb and TUNEL staining were colocalized in neurons 6 and 12 h after OGD. This colocalization was strikingly decreased 24 h after OGD. Treatment with the cyclin-dependent kinase inhibitor roscovitine (100 μM) decreased the expression of phospho-Rb and reduced neuronal apoptosis in vitro. These results demonstrated that attempted cell cycle reentry with phosphorylation of Rb induce early apoptosis in neurons after OGD and there must be other mechanisms involved in the later stages of neuronal apoptosis besides cell cycle reentry. Phosphoralated Rb may be an important factor which closely associates aberrant cell cycle reentry with the early stages of neuronal apoptosis following ischemia/hypoxia in vitro, and pharmacological interventions for neuroprotection may be useful directed at this keypoint.

Rain-Induced Increase in Background Radiation Detected by Radiation Portal Monitors

Energy Technology Data Exchange (ETDEWEB)

Hausladen, Paul [ORNL; Blessinger, Christopher S [ORNL; Guzzardo, Tyler [ORNL; Livesay, Jake [ORNL

2012-07-01

A complete understanding of both the steady state and transient background measured by Radiation Portal Monitors (RPMs) is essential to predictable system performance, as well as maximization of detection sensitivity. To facilitate this understanding, a test bed for the study of natural background in RPMs has been established at the Oak Ridge National Laboratory. This work was performed in support of the Second Line of Defense Program's mission to detect the illicit movement of nuclear material. In the present work, transient increases in gamma ray counting rates in RPMs due to rain are investigated. The increase in background activity associated with rain, which has been well documented in the field of environmental radioactivity, originates from the atmospheric deposition of two radioactive daughters of radon-222, namely lead-214 and bismuth-214 (henceforth {sup 222}Rn, {sup 214}Pb and {sup 214}Bi). In this study, rainfall rates recorded by a co-located weather station are compared with RPM count rates and High Purity Germanium spectra. The data verifies these radionuclides are responsible for the dominant transient natural background fluctuations in RPMs. Effects on system performance and potential mitigation strategies are discussed.

Corruption Significantly Increases the Capital Cost of Power Plants in Developing Contexts

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Kumar Biswajit Debnath

2018-03-01

Full Text Available Emerging economies with rapidly growing population and energy demand, own some of the most expensive power plants in the world. We hypothesized that corruption has a relationship with the capital cost of power plants in developing countries such as Bangladesh. For this study, we analyzed the capital cost of 61 operational and planned power plants in Bangladesh. Initial comparison study revealed that the mean capital cost of a power plant in Bangladesh is twice than that of the global average. Then, the statistical analysis revealed a significant correlation between corruption and the cost of power plants, indicating that higher corruption leads to greater capital cost. The high up-front cost can be a significant burden on the economy, at present and in the future, as most are financed through international loans with extended repayment terms. There is, therefore, an urgent need for the review of the procurement and due diligence process of establishing power plants, and for the implementation of a more transparent system to mitigate adverse effects of corruption on megaprojects.

Major Co-localized QTL for Plant Height, Branch Initiation Height, Stem Diameter, and Flowering Time in an Alien Introgression Derived Brassica napus DH Population

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Yusen Shen

2018-03-01

Full Text Available Plant height (PH, branch initiation height (BIH, and stem diameter (SD are three stem-related traits that play crucial roles in plant architecture and lodging resistance. Herein, we show one doubled haploid (DH population obtained from a cross between Y689 (one Capsella bursa-pastoris derived Brassica napus intertribal introgression and Westar (B. napus cultivar that these traits were significantly positively correlated with one another and with flowering time (FT. Based on a high-density SNP map, a total of 102 additive quantitative trait loci (QTL were identified across six environments. Seventy-two consensus QTL and 49 unique QTL were identified using a two-round strategy of QTL meta-analysis. Notably, a total of 19 major QTL, including 11 novel ones, were detected for these traits, which comprised two QTL clusters on chromosomes A02 and A07. Conditional QTL mapping was performed to preliminarily evaluate the genetic basis (pleiotropy or tight linkage of the co-localized QTL. In addition, QTL by environment interactions (QEI mapping was performed to verify the additive QTL and estimate the QEI effect. In the genomic regions of all major QTL, orthologs of the genes involved in phytohormone biosynthesis, phytohormone signaling, flower development, and cell differentiation in Arabidopsis were proposed as candidate genes. Of these, BnaA02g02560, an ortholog of Arabidopsis GASA4, was suggested as a candidate gene for PH, SD, and FT; and BnaA02g08490, an ortholog of Arabidopsis GNL, was associated with PH, BIH and FT. These results provide useful information for further genetic studies on stem-related traits and plant growth adaptation.

Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance

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Hoogsteen, Ilse J., E-mail: i.hoogsteen@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Marres, Henri A.M.; Hoogen, Franciscus J.A. van den [Department of Otorhinolaryngology/Head-Neck Surgery, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Rijken, Paul F.J.W.; Lok, Jasper; Bussink, Johan; Kaanders, Johannes H.A.M. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

2012-11-01

Purpose: Overexpression of epidermal growth factor receptor (EGFR) and tumor hypoxia have been shown to correlate with worse outcome in several types of cancer including head-and-neck squamous cell carcinoma. Little is known about the combination and possible interactions between the two phenomena. Methods and Materials: In this study, 45 cases of histologically confirmed squamous cell carcinomas of the head and neck were analyzed. All patients received intravenous infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia were examined using immunohistochemistry. Results: Of all biopsies examined, respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A weak but significant association was found between the hypoxic fractions of pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative vascular area. Various degrees of colocalization between hypoxia and EGFR were found, increasing with distance from the vasculature. A high fraction of EGFR was correlated with better disease-free and metastasis-free survival, whereas a high degree of colocalization correlated with poor outcome. Conclusions: Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous cell carcinomas, predominantly at longer distances from vessels. A large amount of colocalization was associated with poor outcome, which points to a survival advantage of hypoxic cells that are also able to express EGFR. This subpopulation of tumor cells might be indicative of tumor aggressiveness and be partly responsible for treatment resistance.

Apoptosis in response to heat stress is positively associated with heat-shock protein 90 expression in chicken myocardial cells in vitro.

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Zhang, Xiao-Hui; Wu, Hong; Tang, Shu; Li, Qiao-Ning; Xu, Jiao; Zhang, Miao; Su, Ya-Nan; Yin, Bin; Zhao, Qi-Ling; Kemper, Nicole; Hartung, Joerg; Bao, En-Dong

2017-06-30

To determine heat-shock protein (Hsp)90 expression is connected with cellular apoptotic response to heat stress and its mechanism, chicken ( Gallus gallus ) primary myocardial cells were treated with the Hsp90 promoter, aspirin, and its inhibitor, geldanamycin (GA), before heat stress. Cellular viability, heat-stressed apoptosis and reactive oxygen species level under different treatments were measured, and the expression of key proteins of the signaling pathway related to Hsp90 and their colocalization with Hsp90 were detected. The results showed that aspirin treatment increased the expression of protein kinase B (Akt), the signal transducer and activator of transcription (STAT)-3 and p-IKKα/β and the colocalization of Akt and STAT-3 with Hsp90 during heat stress, which was accompanied by improved viability and low apoptosis. GA significantly inhibited Akt expression and p-IKKα/β level, but not STAT-3 quantity, while the colocalization of Akt and STAT-3 with Hsp90 was weakened, followed by lower cell viability and higher apoptosis. Aspirin after GA treatment partially improved the stress response and apoptosis rate of tested cells caused by the recovery of Akt expression and colocalization, rather than the level of STAT-3 (including its co-localization with Hsp90) and p-IKKα/β. Therefore, Hsp90 expression has a positive effect on cellular capacity to resist heat-stressed injury and apoptosis. Moreover, inhibition of Hsp90 before stress partially attenuated its positive effects.

Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits.

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Downey, Luke A; Sands, Helen; Jones, Lewis; Clow, Angela; Evans, Phil; Stalder, Tobias; Parrott, Andrew C

2015-05-01

The goals of this study were to measure the neurocognitive performance of recent users of recreational Ecstasy and investigate whether it was associated with the stress hormone cortisol. The 101 participants included 27 recent light users of Ecstasy (one to four times in the last 3 months), 23 recent heavier Ecstasy users (five or more times) and 51 non-users. Rivermead paragraph recall provided an objective measure for immediate and delayed recall. The prospective and retrospective memory questionnaire provided a subjective index of memory deficits. Cortisol levels were taken from near-scalp 3-month hair samples. Cortisol was significantly raised in recent heavy Ecstasy users compared with controls, whereas hair cortisol in light Ecstasy users was not raised. Both Ecstasy groups were significantly impaired on the Rivermead delayed word recall, and both groups reported significantly more retrospective and prospective memory problems. Stepwise regression confirmed that lifetime Ecstasy predicted the extent of these memory deficits. Recreational Ecstasy is associated with increased levels of the bio-energetic stress hormone cortisol and significant memory impairments. No significant relationship between cortisol and the cognitive deficits was observed. Ecstasy users did display evidence of a metacognitive deficit, with the strength of the correlations between objective and subjective memory performances being significantly lower in the Ecstasy users. Copyright © 2015 John Wiley & Sons, Ltd.

Balance disorder and increased risk of falls in osteoporosis and kyphosis: significance of kyphotic posture and muscle strength.

Science.gov (United States)

Sinaki, Mehrsheed; Brey, Robert H; Hughes, Christine A; Larson, Dirk R; Kaufman, Kenton R

2005-08-01

This controlled trial was designed to investigate the influence of osteoporosis-related kyphosis (O-K) on falls. Twelve community-dwelling women with O-K (Cobb angle, 50-65 degrees measured from spine radiographs) and 13 healthy women serving as controls were enrolled. Mean age of the O-K group was 76 years (+/-5.1), height 158 cm (+/-5), and weight 61 kg (+/-7.9), and mean age of the control group was 71 years (+/-4.6), height 161 cm (+/-3.8), and weight 66 kg (+/-11.7). Quantitative isometric strength data were collected. Gait was monitored during unobstructed level walking and during stepping over an obstacle of four different heights randomly assigned (2.5%, 5%, 10%, and 15% of the subject's height). Balance was objectively assessed with computerized dynamic posturography consisting of the sensory organization test. Back extensor strength, grip strength, and all lower extremity muscle groups were significantly weaker in the O-K group than the control group (P controls for all conditions of unobstructed and obstructed level walking. Obstacle height had a significant effect on all center-of-mass variables. The O-K subjects had significantly greater balance abnormalities on computerized dynamic posturography than the control group (P =0.002). Data show that thoracic hyperkyphosis on a background of reduced muscle strength plays an important role in increasing body sway, gait unsteadiness, and risk of falls in osteoporosis.

Cardioprotective adaptation of rats to intermittent hypobaric hypoxia is accompanied by the increased association of hexokinase with mitochondria

Czech Academy of Sciences Publication Activity Database

Wasková-Arnoštová, P.; Elsnicová, B.; Kašparová, D.; Horníková, D.; Kolář, František; Novotný, J.; Žurmanová, J.

2015-01-01

Roč. 119, č. 12 (2015), s. 1487-1493 ISSN 8750-7587 Institutional support: RVO:67985823 Keywords : hexokinase * mitochondrial colocalization * cardioprotection * chronic hypoxia * rat heart Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.004, year: 2015

MPL-Net Measurements of Aerosol and Cloud Vertical Distributions at Co-Located AERONET Sites

Science.gov (United States)

Welton, Ellsworth J.; Campbell, James R.; Berkoff, Timothy A.; Spinhirne, James D.; Tsay, Si-Chee; Holben, Brent; Starr, David OC. (Technical Monitor)

2002-01-01

In the early 1990s, the first small, eye-safe, and autonomous lidar system was developed, the Micropulse Lidar (MPL). The MPL acquires signal profiles of backscattered laser light from aerosols and clouds. The signals are analyzed to yield multiple layer heights, optical depths of each layer, average extinction-to-backscatter ratios for each layer, and profiles of extinction in each layer. In 2000, several MPL sites were organized into a coordinated network, called MPL-Net, by the Cloud and Aerosol Lidar Group at NASA Goddard Space Flight Center (GSFC) using funding provided by the NASA Earth Observing System. tn addition to the funding provided by NASA EOS, the NASA CERES Ground Validation Group supplied four MPL systems to the project, and the NASA TOMS group contributed their MPL for work at GSFC. The Atmospheric Radiation Measurement Program (ARM) also agreed to make their data available to the MPL-Net project for processing. In addition to the initial NASA and ARM operated sites, several other independent research groups have also expressed interest in joining the network using their own instruments. Finally, a limited amount of EOS funding was set aside to participate in various field experiments each year. The NASA Sensor Intercomparison and Merger for Biological and Interdisciplinary Oceanic Studies (SIMBIOS) project also provides funds to deploy their MPL during ocean research cruises. All together, the MPL-Net project has participated in four major field experiments since 2000. Most MPL-Net sites and field experiment locations are also co-located with sunphotometers in the NASA Aerosol Robotic Network. (AERONET). Therefore, at these locations data is collected on both aerosol and cloud vertical structure as well as column optical depth and sky radiance. Real-time data products are now available from most MPL-Net sites. Our real-time products are generated at times of AERONET aerosol optical depth (AOD) measurements. The AERONET AOD is used as input to our

Co-localization and regulation of basic fibroblast growth factor and arginine vasopressin in neuroendocrine cells of the rat and human brain

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Gonzalez Ana M

2010-08-01

Full Text Available Abstract Background Adult rat hypothalamo-pituitary axis and choroid plexus are rich in basic fibroblast growth factor (FGF2 which likely has a role in fluid homeostasis. Towards this end, we characterized the distribution and modulation of FGF2 in the human and rat central nervous system. To ascertain a functional link between arginine vasopressin (AVP and FGF2, a rat model of chronic dehydration was used to test the hypothesis that FGF2 expression, like that of AVP, is altered by perturbed fluid balance. Methods Immunohistochemistry and confocal microscopy were used to examine the distribution of FGF2 and AVP neuropeptides in the normal human brain. In order to assess effects of chronic dehydration, Sprague-Dawley rats were water deprived for 3 days. AVP neuropeptide expression and changes in FGF2 distribution in the brain, neural lobe of the pituitary and kidney were assessed by immunohistochemistry, and western blotting (FGF2 isoforms. Results In human hypothalamus, FGF2 and AVP were co-localized in the cytoplasm of supraoptic and paraventricular magnocellular neurons and axonal processes. Immunoreactive FGF2 was associated with small granular structures distributed throughout neuronal cytoplasm. Neurohypophysial FGF2 immunostaining was found in axonal processes, pituicytes and Herring bodies. Following chronic dehydration in rats, there was substantially-enhanced FGF2 staining in basement membranes underlying blood vessels, pituicytes and other glia. This accompanied remodeling of extracellular matrix. Western blot data revealed that dehydration increased expression of the hypothalamic FGF2 isoforms of ca. 18, 23 and 24 kDa. In lateral ventricle choroid plexus of dehydrated rats, FGF2 expression was augmented in the epithelium (Ab773 as immunomarker but reduced interstitially (Ab106 immunostaining. Conclusions Dehydration altered FGF2 expression patterns in AVP-containing magnocellular neurons and neurohypophysis, as well as in choroid

Induction of expression and co-localization of heat shock polypeptides with the polyalanine expansion mutant of poly(A)-binding protein N1 after chemical stress

International Nuclear Information System (INIS)

Wang Qishan; Bag, Jnanankur

2008-01-01

Formation of nuclear inclusions consisting of aggregates of a polyalanine expansion mutant of nuclear poly(A)-binding protein (PABPN1) is the hallmark of oculopharyngeal muscular dystrophy (OPMD). OPMD is a late onset autosomal dominant disease. Patients with this disorder exhibit progressive swallowing difficulty and drooping of their eye lids, which starts around the age of 50. Previously we have shown that treatment of cells expressing the mutant PABPN1 with a number of chemicals such as ibuprofen, indomethacin, ZnSO 4 , and 8-hydroxy-quinoline induces HSP70 expression and reduces PABPN1 aggregation. In these studies we have shown that expression of additional HSPs including HSP27, HSP40, and HSP105 were induced in mutant PABPN1 expressing cells following exposure to the chemicals mentioned above. Furthermore, all three additional HSPs were translocated to the nucleus and probably helped to properly fold the mutant PABPN1 by co-localizing with this protein

Constrained parameterisation of photosynthetic capacity causes significant increase of modelled tropical vegetation surface temperature

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Kattge, J.; Knorr, W.; Raddatz, T.; Wirth, C.

2009-04-01

Photosynthetic capacity is one of the most sensitive parameters of terrestrial biosphere models whose representation in global scale simulations has been severely hampered by a lack of systematic analyses using a sufficiently broad database. Due to its coupling to stomatal conductance changes in the parameterisation of photosynthetic capacity may potentially influence transpiration rates and vegetation surface temperature. Here, we provide a constrained parameterisation of photosynthetic capacity for different plant functional types in the context of the photosynthesis model proposed by Farquhar et al. (1980), based on a comprehensive compilation of leaf photosynthesis rates and leaf nitrogen content. Mean values of photosynthetic capacity were implemented into the coupled climate-vegetation model ECHAM5/JSBACH and modelled gross primary production (GPP) is compared to a compilation of independent observations on stand scale. Compared to the current standard parameterisation the root-mean-squared difference between modelled and observed GPP is substantially reduced for almost all PFTs by the new parameterisation of photosynthetic capacity. We find a systematic depression of NUE (photosynthetic capacity divided by leaf nitrogen content) on certain tropical soils that are known to be deficient in phosphorus. Photosynthetic capacity of tropical trees derived by this study is substantially lower than standard estimates currently used in terrestrial biosphere models. This causes a decrease of modelled GPP while it significantly increases modelled tropical vegetation surface temperatures, up to 0.8°C. These results emphasise the importance of a constrained parameterisation of photosynthetic capacity not only for the carbon cycle, but also for the climate system.

Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance

International Nuclear Information System (INIS)

Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

2015-01-01

Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80–11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density

SSX and the synovial-sarcoma-specific chimaeric protein SYT-SSX co-localize with the human Polycomb group complex.

Science.gov (United States)

Soulez, M; Saurin, A J; Freemont, P S; Knight, J C

1999-04-29

Chromosome translocation t(X;18)(p11.2;q11.2) is unique to synovial sarcomas and results in an 'in frame' fusion of the SYT gene with the SSX1 or closely-related SSX2 gene. Wild-type SYT and SSX proteins, and the SYT-SSX chimaeric proteins, can modulate transcription in gene reporter assays. To help elucidate the role of these proteins in cell function and neoplasia we have performed immunolabelling experiments to determine their subcellular localization in three cell types. Transient expression of epitope-tagged proteins produced distinctive nuclear staining patterns. The punctate staining of SYT and SYT-SSX proteins showed some similarities. We immunolabelled a series of endogenous nuclear antigens and excluded the SYT and SYT-SSX focal staining from association with these domains (e.g. sites of active transcription, snRNPs). In further experiments we immunolabelled the Polycomb group (PcG) proteins RING1 or BMI-1 and showed that SSX and SYT-SSX proteins, but not SYT, co-localized with these markers. Consistent with this we show that SSX and SYT-SSX associate with chromatin, and also associate with condensed chromatin at metaphase. Noteably, SSX produced a dense signal over the surface of metaphase chromosomes whereas SYT-SSX produced discrete focal staining. Our data indicate that SSX and SYT-SSX proteins are recruited to nuclear domains occupied by PcG complexes, and this provides us with a new insight into the possible function of wild-type SSX and the mechanism by which the aberrant SYT-SSX protein might disrupt fundamental mechanisms controlling cell division and cell fate.

A Prolonged Time Interval Between Trauma and Prophylactic Radiation Therapy Significantly Increases the Risk of Heterotopic Ossification

Energy Technology Data Exchange (ETDEWEB)

Mourad, Waleed F., E-mail: Waleed246@gmail.com [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Department of Radiation Oncology, Beth Israel Medical Center, New York, NY (Israel); Packianathan, Satyaseelan [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Shourbaji, Rania A. [Department of Epidemiology and Biostatistics, Jackson State University, Jackson, MS (United States); Zhang Zhen; Graves, Mathew [Department of Orthopedic Surgery, University of Mississippi Medical Center, Jackson, MS (United States); Khan, Majid A. [Department of Radiology, University of Mississippi Medical Center, Jackson, MS (United States); Baird, Michael C. [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Russell, George [Department of Orthopedic Surgery, University of Mississippi Medical Center, Jackson, MS (United States); Vijayakumar, Srinivasan [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States)

2012-03-01

Purpose: To ascertain whether the time from injury to prophylactic radiation therapy (RT) influences the rate of heterotopic ossification (HO) after operative treatment of displaced acetabular fractures. Methods and Materials: This is a single-institution, retrospective analysis of patients referred for RT for the prevention of HO. Between January 2000 and January 2009, 585 patients with displaced acetabular fractures were treated surgically followed by RT for HO prevention. We analyzed the effect of time from injury on prevention of HO by RT. In all patients, 700 cGy was prescribed in a single fraction and delivered within 72 hours postsurgery. The patients were stratified into five groups according to time interval (in days) from the date of their accident to the date of RT: Groups A {<=}3, B {<=}7, C {<=}14, D {<=}21, and E >21days. Results: Of the 585 patients with displaced acetabular fractures treated with RT, (18%) 106 patients developed HO within the irradiated field. The risk of HO after RT increased from 10% for RT delivered {<=}3 days to 92% for treatment delivered >21 days after the initial injury. Wilcoxon test showed a significant correlation between the risk of HO and the length of time from injury to RT (p < 0.0001). Chi-square test and multiple logistic regression analysis showed no significant association between all other factors and the risk of HO (race, gender, cause and type of fracture, surgical approach, or the use of indomethacin). Conclusions: Our data suggest that there is higher incidence and risk of HO if prophylactic RT is significantly delayed after a displaced acetabular fracture. Thus, RT should be administered as early as clinically possible after the trauma. Patients undergoing RT >3 weeks from their displaced acetabular fracture should be informed of the higher risk (>90%) of developing HO despite prophylaxis.

Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients.

Science.gov (United States)

Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

2016-02-28

To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers.

Plucking the Golden Goose: Higher Royalty Rates on the Oil Sands Generate Significant Increases in Government Revenue

Directory of Open Access Journals (Sweden)

Kenneth J. McKenzie

2011-09-01

Full Text Available The Alberta government’s 2009 New Royalty Framework elicited resistance on the part of the energy industry, leading to subsequent reductions in the royalties imposed on natural gas and conventional oil. However, the oil sands sector, subject to different terms, quickly accepted the new arrangement with little complaint, recognizing it as win-win situation for industry and the government. Under the framework, Alberta recoups much more money in royalties — about $1 billion over the two year period of 2009 and 2010 — without impinging significantly on investment in the oil sands. This brief paper demonstrates that by spreading the financial risks and benefits to everyone involved, the new framework proves it’s possible to generate increased revenue without frightening off future investment. The same model could conceivably be applied to the conventional oil and natural gas sectors.

Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and Prenatally Androgenized Female Mice.

Science.gov (United States)

Marshall, Christopher J; Desroziers, Elodie; McLennan, Timothy; Campbell, Rebecca E

2017-01-01

Arcuate nucleus (ARN) γ-aminobutyric acid (GABA) neurons are implicated in many critical homeostatic mechanisms, from food intake to fertility. To determine the functional relevance of ARN GABA neurons, it is essential to define the neurotransmitters co-expressed with and potentially co-released from ARN GABA neurons. The present study investigated the expression of markers of specific signaling molecules by ARN GABA neurons in brain sections from male, female, and, in some cases, prenatally androgen-treated (PNA) female, vesicular GABA transporter (VGaT)-ires-Cre/tdTomato reporter mice. Immunofluorescence for kisspeptin, β-endorphin, neuropeptide Y (NPY), tyrosine hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) was detected by confocal microscopy, and co-localization with tdTomato VGaT reporter expression throughout the ARN was quantified. GABA neurons rarely co-localized with kisspeptin (95%) co-localized with VGaT across groups. Both TH and nNOS labeling was co-localized with ∼10% of ARN GABA neurons. The proportion of TH neurons co-localized with VGaT was significantly greater in males than either control or PNA females, and the proportion of nNOS neurons co-localizing VGaT was higher in control and PNA females compared with males. These data highlight NPY as a significant subpopulation of ARN GABA neurons, demonstrate no significant impact of PNA on signal co-expression, and, for the first time, show sexually dimorphic co-expression patterns of TH and nNOS with ARN GABA neurons. © 2016 S. Karger AG, Basel.

2,2'-Bis(monoacylglycero) PO4 (BMP), but Not 3,1'-BMP, increases membrane curvature stress to enhance α-tocopherol transfer protein binding to membranes.

Science.gov (United States)

Baptist, Matilda; Panagabko, Candace; Nickels, Jonathan D; Katsaras, John; Atkinson, Jeffrey

2015-03-01

Previous work revealed that α-tocopherol transfer protein (α-TTP) co-localizes with bis(monoacylglycero)phosphate (BMP) in late endosomes. BMP is a lipid unique to late endosomes and is believed to induce membrane curvature and support the multivesicular nature of this organelle. We examined the effect of BMP on α-TTP binding to membranes using dual polarization interferometry and vesicle-binding assay. α-TTP binding to membranes is increased by the curvature-inducing lipid BMP. α-TTP binds to membranes with greater affinity when they contain the 2,2'-BMP versus 3,1'-BMP isomers.

Significance of increased lung thallium-201 activity on serial cardiac images after dipyridamole treatment in coronary heart disease

International Nuclear Information System (INIS)

Okada, R.D.; Dai, Y.H.; Boucher, C.A.; Pohost, G.M.

1984-01-01

Increased lung thallium-201 (Tl-201) activity occurs in patients with severe coronary artery disease (CAD) on initial postexercise images. To determine the significance of assessing lung Tl-201 on serial imaging after dipyridamole therapy, initial and delayed (2 to 3 hours) Tl-201 imaging was performed in 40 patients with CAD and 26 normal control subjects. Lung Tl-201 activity was quantitated as a percentage of maximal myocardial activity for each imaging time (lung Tl-201 index). The mean initial lung Tl-201 activity was 42 +/- 2% (+/- standard error of the mean) in 26 control subjects, 56 +/- 2% in 25 patients with 2- or 3-vessel CAD (p less than 0.001) and 53 +/- 2% in 15 patients with 1-vessel CAD (p less than 0.005 compared with control subjects) (difference not significant between 1-vessel and multivessel CAD). Dipyridamole lung Tl-201 activity decreased relative to the myocardium from initial to delayed images (p less than 0.001) in patients with CAD but not in control subjects. When a dipyridamole lung Tl-201 index of 58% (mean +/- 2 standard deviations for control subjects) was chosen as the upper limit of normal, 14 of 40 of the CAD patients (35%) had abnormal values and all control patients had values within normal limits. These 14 patients with CAD and abnormal initial lung Tl-201 indexes had rest ejection fractions that were not significantly different from those in patients with CAD, and normal initial dipyridamole lung Tl-201 index (58 +/- 4% and 63 +/- 2%, respectively)

Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat expanded C9orf72 amyotrophic lateral sclerosis

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Saberi, Shahram; Stauffer, Jennifer E.; Jiang, Jie; Garcia, Sandra Diaz; Taylor, Amy E; Schulte, Derek; Ohkubo, Takuya; Schloffman, Cheyenne L.; Maldonado, Marcus; Baughn, Michael; Rodriguez, Maria J; Pizzo, Don; Cleveland, Don; Ravits, John

2018-01-01

Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models. We quantitatively studied and compared DPRs, nuclear pore proteins and C9orf72 protein in clinically-related and clinically-unrelated regions of the central nervous system, and compared them to phosphorylated TDP-43 (pTDP-43), the hallmark protein of ALS. Of the five DPRs, only poly-GR was significantly abundant in clinically-related areas compared to unrelated areas (p<0.001), and formed dendritic-like aggregates in the motor cortex that co-localized with pTDP-43 (p<0.0001). While most poly-GR dendritic inclusions were pTDP-43-positive, only 4% of pTDP-43 dendritic inclusions were poly-GR-positive. Staining for arginine-containing poly-GR and poly-PR in nuclei of neurons produced signals that were not specific to C9 ALS. We could not detect significant differences of nuclear markers RanGap, Lamin B1, and Importin β1 in C9 ALS, although we observed subtle nuclear changes in ALS, both C9 and non-C9, compared to control. The C9orf72 protein itself was diffusely expressed in cytoplasm of large neurons and glia, and nearly 50% reduced, in both clinically-related frontal cortex and unrelated occipital cortex, but not in cerebellum. In summary, sense-encoded poly-GR DPR was unique, and localized to neurites and pTDP43 in motor regions of C9 ALS CNS. This is consistent with new emerging ideas about TDP-43 functions in dendrites. PMID:29196813

Final report of a randomized trial on altered-fractionated radiotherapy in nasopharyngeal carcinoma prematurely terminated by significant increase in neurologic complications

International Nuclear Information System (INIS)

Teo, Peter Man Lung; Leung, Sing Fai; Chan, Anthony Tak Cheung; Leung, Thomas Wai Tong; Choi, Peter Ho Keung; Kwan, Wing Hong; Lee, Wai Yee; Chau, Ricky Ming Chun; Yu, Peter Kau Wing; Johnson, Philip James

2000-01-01

Purpose: The aim of the present study was to compare the survival, local control and complications of conventional/accelerated-hyperfractionated radiotherapy and conventional radiotherapy in nonmetastatic nasopharyngeal carcinoma (NPC). Methods and Materials: From February 1993 to October 1995, 159 patients with newly diagnosed nonmetastatic (M0) NPC with N0 or 4 cm or less N1 disease (Ho's N-stage classification, 1978) were randomized to receive either conventional radiotherapy (Arm I, n = 82) or conventional/accelerated-hyperfractionated radiotherapy (Arm II, n = 77). Stratification was according to the T stage. The biologic effective dose (10 Grays) to the primary and the upper cervical lymphatics were 75.0 and 73.1 for Arm I and 84.4 and 77.2 for Arm II, respectively. Results: With comparable distribution among the T stages between the two arms, the free from local failure rate at 5 years after radiotherapy was not significantly different between the two arms (85.3%; 95% confidence interval, 77.2-93.4% for Arm I; and 88.9%; 95% confidence interval, 81.7-96.2% for Arm II). The two arms were also comparable in overall survival, relapse-free survival, and rates of distant metastasis and regional relapse. Conventional/accelerated-hyperfractionated radiotherapy was associated with significantly increased radiation-induced damage to the central nervous system (including temporal lobe, cranial nerves, optic nerve/chiasma, and brainstem/spinal cord) in Arm II. Although insignificant, radiation-induced cranial nerve(s) palsy (typically involving VIII-XII), trismus, neck soft tissue fibrosis, and hypopituiturism and hypothyroidism occurred more often in Arm II. In addition, the complications occurred at significantly shorter intervals after radiotherapy in Arm II. Conclusion: Accelerated hyperfractionation when used in conjunction with a two-dimensional radiotherapy planning technique, in this case the Ho's technique, resulted in increased radiation damage to the central

Increased expression of EMMPRIN and VEGF in the rat brain after gamma irradiation.

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Wei, Ming; Li, Hong; Huang, Huiling; Xu, Desheng; Zhi, Dashi; Liu, Dong; Zhang, Yipei

2012-03-01

The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to play a key regulatory role in pathological angiogenesis. A elevated activation of vascular endothelial growth factor (VEGF) following radiation injury has been shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes in a rat model of radiation injury following GKS and examined potential associations between EMMPRIN and VEGF expression. Adult male rats were subjected to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and VEGF expression were markedly upregulated in the target area at 8-12 weeks after GKS compared with the control group by western blot, immunohistochemistry, and RT-PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated that increased EMMPRIN expression was correlated with increased VEGF levels in a temporal manner. This is the first study to show that EMMPRIN and VEGF may play a role in radiation injuries of the central nervous system after GKS.

Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring.

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Angelica B Bernal

Full Text Available BACKGROUND: We have shown recently that maternal undernutrition (UN advanced female pubertal onset in a manner that is dependent upon the timing of UN. The long-term consequence of this accelerated puberty on ovarian function is unknown. Recent findings suggest that oxidative stress may be one mechanism whereby early life events impact on later physiological functioning. Therefore, using an established rodent model of maternal UN at critical windows of development, we examined maternal UN-induced changes in offspring ovarian function and determined whether these changes were underpinned by ovarian oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: Our study is the first to show that maternal UN significantly reduced primordial and secondary follicle number in offspring in a manner that was dependent upon the timing of maternal UN. Specifically, a reduction in these early stage follicles was observed in offspring born to mothers undernourished throughout both pregnancy and lactation. Additionally, antral follicle number was reduced in offspring born to all mothers that were UN regardless of whether the period of UN was restricted to pregnancy or lactation or both. These reductions were associated with decreased mRNA levels of genes critical for follicle maturation and ovulation. Increased ovarian protein carbonyls were observed in offspring born to mothers UN during pregnancy and/or lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced mRNA levels; suggesting compromised antioxidant defence. This was not observed in offspring of mothers UN during lactation alone. CONCLUSIONS: We propose that maternal UN, particularly at a time-point that includes pregnancy, results in reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes and may be mediated by increased ovarian oxidative stress coupled with a decreased ability to repair the resultant oxidative damage. Together these data are suggestive of

Prognostic significance of increased bone marrow microcirculation in newly diagnosed multiple myeloma: results of a prospective DCE-MRI study

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Merz, Maximilian; Hillengass, Jens [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Moehler, Thomas M.; Ritsch, Judith; Delorme, Stefan [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); Baeuerle, Tobias [University of Erlangen-Nuremberg, Department of Radiology, Erlangen (Germany); Zechmann, Christian M. [Rinecker Proton Therapy, Muenchen (Germany); Wagner, Barbara; Hose, Dirk [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Jauch, Anna [University of Heidelberg, Institute of Human Genetics, Heidelberg (Germany); Kunz, Christina; Hielscher, Thomas [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Laue, Hendrik [Fraunhofer MEVIS, Bremen (Germany); Goldschmidt, Hartmut [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); National Center for Tumor Diseases, Heidelberg (Germany)

2016-05-15

Aim of this prospective study was to investigate prognostic significance of increased bone marrow microcirculation as detected by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for survival and local complications in patients with multiple myeloma (MM). We performed DCE-MRI of the lumbar spine in 131 patients with newly diagnosed MM and analysed data according to the Brix model to acquire amplitude A and exchange rate constant k{sub ep}. In 61 patients a second MRI performed after therapy was evaluated to assess changes in vertebral height and identify vertebral fractures. Correlation analysis revealed significant positive association between beta2-microglobulin as well as immunoparesis with DCE-MRI parameters A and k{sub ep}. Additionally, A was negatively correlated with haemoglobin levels and k{sub ep} was positively correlated with LDH levels. Higher baseline k{sub ep} values were associated with decreased vertebral height in a second MRI (P = 0.007) and A values were associated with new vertebral fractures in the lower lumbar spine (P = 0.03 for L4). Pre-existing lytic bone lesions or remission after therapy had no impact on the occurrence of vertebral fractures. Multivariate analysis revealed that amplitude A is an independent adverse risk factor for overall survival. DCE-MRI is a non-invasive tool with significance for systemic prognosis and vertebral complications. (orig.)

Expression of a bacterial catalase in a strictly anaerobic methanogen significantly increases tolerance to hydrogen peroxide but not oxygen

Science.gov (United States)

Jennings, Matthew E.; Schaff, Cody W.; Horne, Alexandra J.; Lessner, Faith H.

2014-01-01

Haem-dependent catalase is an antioxidant enzyme that degrades H2O2, producing H2O and O2, and is common in aerobes. Catalase is present in some strictly anaerobic methane-producing archaea (methanogens), but the importance of catalase to the antioxidant system of methanogens is poorly understood. We report here that a survey of the sequenced genomes of methanogens revealed that the majority of species lack genes encoding catalase. Moreover, Methanosarcina acetivorans is a methanogen capable of synthesizing haem and encodes haem-dependent catalase in its genome; yet, Methanosarcina acetivorans cells lack detectable catalase activity. However, inducible expression of the haem-dependent catalase from Escherichia coli (EcKatG) in the chromosome of Methanosarcina acetivorans resulted in a 100-fold increase in the endogenous catalase activity compared with uninduced cells. The increased catalase activity conferred a 10-fold increase in the resistance of EcKatG-induced cells to H2O2 compared with uninduced cells. The EcKatG-induced cells were also able to grow when exposed to levels of H2O2 that inhibited or killed uninduced cells. However, despite the significant increase in catalase activity, growth studies revealed that EcKatG-induced cells did not exhibit increased tolerance to O2 compared with uninduced cells. These results support the lack of catalase in the majority of methanogens, since methanogens are more likely to encounter O2 rather than high concentrations of H2O2 in the natural environment. Catalase appears to be a minor component of the antioxidant system in methanogens, even those that are aerotolerant, including Methanosarcina acetivorans. Importantly, the experimental approach used here demonstrated the feasibility of engineering beneficial traits, such as H2O2 tolerance, in methanogens. PMID:24222618

Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.

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Heidi O Nousiainen

Full Text Available Prostatic acid phosphatase (PAP, the first diagnostic marker and present therapeutic target for prostate cancer, modulates nociception at the dorsal root ganglia (DRG, but its function in the central nervous system has remained unknown. We studied expression and function of TMPAP (the transmembrane isoform of PAP in the brain by utilizing mice deficient in TMPAP (PAP-/- mice. Here we report that TMPAP is expressed in a subpopulation of cerebral GABAergic neurons, and mice deficient in TMPAP show multiple behavioral and neurochemical features linked to hyperdopaminergic dysregulation and altered GABAergic transmission. In addition to increased anxiety, disturbed prepulse inhibition, increased synthesis of striatal dopamine, and augmented response to amphetamine, PAP-deficient mice have enlarged lateral ventricles, reduced diazepam-induced loss of righting reflex, and increased GABAergic tone in the hippocampus. TMPAP in the mouse brain is localized presynaptically, and colocalized with SNARE-associated protein snapin, a protein involved in synaptic vesicle docking and fusion, and PAP-deficient mice display altered subcellular distribution of snapin. We have previously shown TMPAP to reside in prostatic exosomes and we propose that TMPAP is involved in the control of GABAergic tone in the brain also through exocytosis, and that PAP deficiency produces a distinct neurological phenotype.

Exposure to Tumescent Solution Significantly Increases Phosphorylation of Perilipin in Adipocytes.

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Keskin, Ilknur; Sutcu, Mustafa; Eren, Hilal; Keskin, Mustafa

2017-02-01

Lidocaine and epinephrine could potentially decrease adipocyte viability, but these effects have not been substantiated. The phosphorylation status of perilipin in adipocytes may be predictive of cell viability. Perilipin coats lipid droplets and restricts access of lipases; phospho-perilipin lacks this protective function. The authors investigated the effects of tumescent solution containing lidocaine and epinephrine on the phosphorylation status of perilipin in adipocytes. In this in vitro study, lipoaspirates were collected before and after tumescence from 15 women who underwent abdominoplasty. Fat samples were fixed, sectioned, and stained for histologic and immunohistochemical analyses. Relative phosphorylation of perilipin was inferred from pixel intensities of immunostained adipocytes observed with confocal microscopy. For adipocytes collected before tumescent infiltration, 10.08% of total perilipin was phosphorylated. In contrast, 30.62% of total perilipin was phosphorylated for adipocytes collected from tumescent tissue (P < .01). The tumescent technique increases the relative phosphorylation of perilipin in adipocytes, making these cells more vulnerable to lipolysis. Tumescent solution applied for analgesia or hemostasis of the donor site should contain the lowest possible concentrations of lidocaine and epinephrine. LEVEL OF EVIDENCE 5. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Pressure sores significantly increase the risk of developing a Fournier's gangrene in patients with spinal cord injury.

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Backhaus, M; Citak, M; Tilkorn, D-J; Meindl, R; Schildhauer, T A; Fehmer, T

2011-11-01

Retrospective chart review. The aim of our study was to evaluate the mortality rate and further specific risk factors for Fournier's gangrene in patients with spinal cord injury (SCI). Division of Spinal Cord Injury, BG-University Hospital Bergmannsheil Bochum, Ruhr-University Bochum, Germany. All patients with a SCI and a Fournier's gangrene treated in our hospital were enrolled in this study. Following parameters were taken form patients medical records: age, type of SCI, cause of Fournier's gangrene, number of surgical debridements, length of hospital and intensive care unit stay, co morbidity factors and mortality rate. In addition, laboratory parameter including the laboratory risk indicator for necrotizing fasciitis (LRINEC) score and microbiological findings were analyzed. Clinical diagnosis was made via histological examination. A total of 16 male patients (15 paraplegic and one tetraplegic) were included in the study. In 81% of all cases, the origin of Fournier's gangrene was a pressure sore. The median LRINEC score on admission was 6.5. In the vast majority of cases, a polybacterial infection was found. No patient died during the hospital stay. The mean number of surgical debridements before soft tissue closure was 1.9 and after a mean time interval of 39.1 days wound closure was performed in all patients. Pressure sores significantly increase the risk of developing Fournier's gangrene in patients with SCI. We reported the results of our patients to increase awareness among physicians and training staff working with patients with a SCI in order to expedite the diagnosis.

Light fractionation increases the efficacy of ALA-PDT but not of MAL-PDT: What is the role of (vascular) endothelial cells?

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de Bruijn, H. S.; de Vijlder, H. C.; de Haas, E. R. M.; van der Ploeg-van den Heuvel, A.; Kruijt, B.; Poel-Dirks, D.; Sterenborg, H. J. C. M.; ten Hagen, T. L. M.; Robinson, D. J.

2009-06-01

Photodynamic therapy (PDT) using protoporpyrin IX (PpIX) precursors like 5-aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL) has shown to be effective in the treatment of various skin diseases. Using ALA we have shown in numerous studies a significantly improved efficacy by applying light fractionation with a long dark interval. In contrast, in the hairless mouse model, the PDT efficacy using MAL is unaffected by adopting this approach. More acute edema is found after ALA-PDT suggesting a difference in response of endothelial cells to PDT. To investigate the role of endothelial cells, cryo-sections of hairless mouse skin after 4 hours of topical MAL or ALA application were stained with a fluorescent endothelial cell marker (CD31). Co-localization of this marker with the PpIX fluorescence was performed using the spectral imaging function of the confocal microscope. We have also used intra-vital confocal microscopy to image the PpIX fluorescence distribution in correlation with the vasculature of live mouse skin. Our results show PpIX fluorescence at depth in cryo-sections of mouse skin after 4 hours of topical application. Co-localization has shown to be difficult due to the changes in tissue organization caused by the staining procedure. As expected we found high PpIX fluorescence levels in the epidermis after both MAL and ALA application using intra-vital microscopy. After ALA application more PpIX fluorescence was found deep in the dermal layer of the skin than after MAL. Furthermore we detected localized fluorescence in unidentified structures that could not be correlated to blood vessels or nerves.

Oxytocin mechanisms of stress response and aggression in a territorial finch.

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Goodson, James L; Schrock, Sara E; Kingsbury, Marcy A

2015-03-15

All jawed vertebrates produce a form of oxytocin (OT), and in birds, mammals and fish, OT is strongly associated with affiliation. However, remarkably few data are available on the roles of OT and OT receptors (OTRs) in aggression. Because OT and OTRs exert anxiolytic effects in mammals (although context-specific) and modulate stress coping, we hypothesized that OTR activation is at least permissive for territorial aggression. Indeed, we find that peripheral injections of an OTR antagonist significantly reduce male-male and female-female aggression in a highly territorial finch. This finding suggests the hypothesis that aggression is accompanied by an increase in transcriptional (Fos) activity of OT neurons, but contrary to this hypothesis, we find that dominant male residents do not elevate OT-Fos colocalization following an aggressive encounter and that OT-Fos colocalization in the preoptic area and hypothalamus correlates negatively with aggression. Furthermore, OT-Fos colocalization increases dramatically in males that were aggressively subjugated or pursued by a human hand, likely reflecting OT modulation of stress response. Because OT inhibits the hypothalamo-pituitary-adrenal axis, the antagonist effects may reflect the fact that aggressive birds and mammals tend to be hyporesponsive to stress. If this is correct, then 1) the observed effects of OTR antagonism may reflect alterations in corticosterone feedback to the brain rather than centrally mediated OTR effects, and 2) the negative correlation between OT-Fos colocalization and aggression may reflect the fact that more aggressive, stress hyporesponsive males require less inhibition of the hypothalamo-pituitary-adrenal axis than do less aggressive males, despite the requirement of that inhibition for the normal display of aggression. Copyright © 2015 Elsevier Inc. All rights reserved.

Integrating non-colocated well and geophysical data to capture subsurface heterogeneity at an aquifer recharge and recovery site

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Gottschalk, Ian P.; Hermans, Thomas; Knight, Rosemary; Caers, Jef; Cameron, David A.; Regnery, Julia; McCray, John E.

2017-12-01

Geophysical data have proven to be very useful for lithological characterization. However, quantitatively integrating the information gained from acquiring geophysical data generally requires colocated lithological and geophysical data for constructing a rock-physics relationship. In this contribution, the issue of integrating noncolocated geophysical and lithological data is addressed, and the results are applied to simulate groundwater flow in a heterogeneous aquifer in the Prairie Waters Project North Campus aquifer recharge site, Colorado. Two methods of constructing a rock-physics transform between electrical resistivity tomography (ERT) data and lithology measurements are assessed. In the first approach, a maximum likelihood estimation (MLE) is used to fit a bimodal lognormal distribution to horizontal crosssections of the ERT resistivity histogram. In the second approach, a spatial bootstrap is applied to approximate the rock-physics relationship. The rock-physics transforms provide soft data for multiple point statistics (MPS) simulations. Subsurface models are used to run groundwater flow and tracer test simulations. Each model's uncalibrated, predicted breakthrough time is evaluated based on its agreement with measured subsurface travel time values from infiltration basins to selected groundwater recovery wells. We find that incorporating geophysical information into uncalibrated flow models reduces the difference with observed values, as compared to flow models without geophysical information incorporated. The integration of geophysical data also narrows the variance of predicted tracer breakthrough times substantially. Accuracy is highest and variance is lowest in breakthrough predictions generated by the MLE-based rock-physics transform. Calibrating the ensemble of geophysically constrained models would help produce a suite of realistic flow models for predictive purposes at the site. We find that the success of breakthrough predictions is highly

The contribution of human agricultural activities to increasing evapotranspiration is significantly greater than climate change effect over Heihe agricultural region.

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Zou, Minzhong; Niu, Jun; Kang, Shaozhong; Li, Xiaolin; Lu, Hongna

2017-08-18

Evapotranspiration (ET) is a major component linking the water, energy, and carbon cycles. Understanding changes in ET and the relative contribution rates of human activity and of climate change at the basin scale is important for sound water resources management. In this study, changes in ET in the Heihe agricultural region in northwest China during 1984-2014 were examined using remotely-sensed ET data with the Soil and Water Assessment Tool (SWAT). Correlation analysis identified the dominant factors that influence change in ET per unit area and those that influence change in total ET. Factor analysis identified the relative contribution rates of the dominant factors in each case. The results show that human activity, which includes factors for agronomy and irrigation, and climate change, including factors for precipitation and relative humidity, both contribute to increases in ET per unit area at rates of 60.93% and 28.01%, respectively. Human activity, including the same factors, and climate change, including factors for relative humidity and wind speed, contribute to increases in total ET at rates of 53.86% and 35.68%, respectively. Overall, in the Heihe agricultural region, the contribution of human agricultural activities to increased ET was significantly greater than that of climate change.

Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats

DEFF Research Database (Denmark)

Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir

2013-01-01

Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during...... the perinatal period. Pregnant Wistar rats were administered a 200mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND...

COPS5 (Jab1) protein increases β site processing of amyloid precursor protein and amyloid β peptide generation by stabilizing RanBP9 protein levels.

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Wang, Hongjie; Dey, Debleena; Carrera, Ivan; Minond, Dmitriy; Bianchi, Elisabetta; Xu, Shaohua; Lakshmana, Madepalli K

2013-09-13

Increased processing of amyloid precursor protein (APP) and accumulation of neurotoxic amyloid β peptide (Aβ) in the brain is central to the pathogenesis of Alzheimer's disease (AD). Therefore, the identification of molecules that regulate Aβ generation is crucial for future therapeutic approaches for AD. We demonstrated previously that RanBP9 regulates Aβ generation in a number of cell lines and primary neuronal cultures by forming tripartite protein complexes with APP, low-density lipoprotein-related protein, and BACE1, consequently leading to increased amyloid plaque burden in the brain. RanBP9 is a scaffold protein that exists and functions in multiprotein complexes. To identify other proteins that may bind RanBP9 and regulate Aβ levels, we used a two-hybrid analysis against a human brain cDNA library and identified COPS5 as a novel RanBP9-interacting protein. This interaction was confirmed by coimmunoprecipitation experiments in both neuronal and non-neuronal cells and mouse brain. Colocalization of COPS5 and RanBP9 in the same subcellular compartments further supported the interaction of both proteins. Furthermore, like RanBP9, COPS5 robustly increased Aβ generation, followed by increased soluble APP-β (sAPP-β) and decreased soluble-APP-α (sAPP-α) levels. Most importantly, down-regulation of COPS5 by siRNAs reduced Aβ generation, implying that endogenous COPS5 regulates Aβ generation. Finally, COPS5 levels were increased significantly in AD brains and APΔE9 transgenic mice, and overexpression of COPS5 strongly increased RanBP9 protein levels by increasing its half-life. Taken together, these results suggest that COPS5 increases Aβ generation by increasing RanBP9 levels. Thus, COPS5 is a novel RanBP9-binding protein that increases APP processing and Aβ generation by stabilizing RanBP9 protein levels.

Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia.

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Zhong, Xiao Yan; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Holzgreve, Wolfgang; Hahn, Sinuhe

2005-08-01

Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder. Copyright 2005 John Wiley & Sons, Ltd.

Fatigue load reductions in co-located wind-wave arrays

DEFF Research Database (Denmark)

Clark, Caitlyn; Velarde, Joey; Nielsen, Jannie Sønderkær

2018-01-01

As offshore wind turbines (OWTs) increase in size and are placed farther offshore, hydrodynamic loads have increased contribution to total load, resulting in fatigue limit states becoming more important to consider in structural design. Previous literature shows that placing wave energy converters...... is investigated. A method for quantifying relative sea state reductions from WECs are applied, and fully-coupled time-domain fatigue analyses are performed for a 10 MW reference offshore wind turbine. Results indicate that a single WEC and a WEC array can lead to 8% and 10% fatigue load reduction, respectively....

ApoER2 expression increases Aβ production while decreasing Amyloid Precursor Protein (APP endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of γ-secretase activity

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Bu Guojun

2007-07-01

Full Text Available Abstract Background The generation of the amyloid-β peptide (Aβ through the proteolytic processing of the amyloid precursor protein (APP is a central event in the pathogenesis of Alzheimer's disease (AD. Recent studies highlight APP endocytosis and localization to lipid rafts as important events favoring amyloidogenic processing. However, the precise mechanisms underlying these events are poorly understood. ApoER2 is a member of the low density lipoprotein receptor (LDL-R family exhibiting slow endocytosis rate and a significant association with lipid rafts. Despite the important neurophysiological roles described for ApoER2, little is known regarding how ApoER2 regulates APP trafficking and processing. Results Here, we demonstrate that ApoER2 physically interacts and co-localizes with APP. Remarkably, we found that ApoER2 increases cell surface APP levels and APP association with lipid rafts. The increase of cell surface APP requires the presence of ApoER2 cytoplasmic domain and is a result of decreased APP internalization rate. Unexpectedly, ApoER2 expression correlated with a significant increase in Aβ production and reduced levels of APP-CTFs. The increased Aβ production was dependent on the integrity of the NPxY endocytosis motif of ApoER2. We also found that expression of ApoER2 increased APP association with lipid rafts and increased γ-secretase activity, both of which might contribute to increased Aβ production. Conclusion These findings show that ApoER2 negatively affects APP internalization. However, ApoER2 expression stimulates Aβ production by shifting the proportion of APP from the non-rafts to the raft membrane domains, thereby promoting β-secretase and γ-secretase mediated amyloidogenic processing and also by incrementing the activity of γ-secretase.

Carotenoids co-localize with hydroxyapatite, cholesterol, and other lipids in calcified stenotic aortic valves. Ex vivo Raman maps compared to histological patterns

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A. Bonetti

2015-04-01

Full Text Available Unlike its application for atherosclerotic plaque analysis, Raman microspectroscopy was sporadically used to check the sole nature of bioapatite deposits in stenotic aortic valves, neglecting the involvement of accumulated lipids/lipoproteins in the calcific process. Here, Raman microspectroscopy was employed for examination of stenotic aortic valve leaflets to add information on nature and distribution of accumulated lipids and their correlation with mineralization in the light of its potential precocious diagnostic use. Cryosections from surgically explanted stenotic aortic valves (n=4 were studied matching Raman maps against specific histological patterns. Raman maps revealed the presence of phospholipids/triglycerides and cholesterol, which showed spatial overlapping with one another and Raman-identified hydroxyapatite. Moreover, the Raman patterns correlated with those displayed by both von-Kossa-calcium- and Nile-blue-stained serial cryosections. Raman analysis also provided the first identification of carotenoids, which co-localized with the identified lipid moieties. Additional fit concerned the distribution of collagen and elastin. The good correlation of Raman maps with high-affinity staining patterns proved that Raman microspectroscopy is a reliable tool in evaluating calcification degree, alteration/displacement of extracellular matrix components, and accumulation rate of different lipid forms in calcified heart valves. In addition, the novel identification of carotenoids supports the concept that valve stenosis is an atherosclerosis-like valve lesion, consistently with their previous Raman microspectroscopical identification inside atherosclerotic plaques.

Carotenoids co-localize with hydroxyapatite, cholesterol, and other lipids in calcified stenotic aortic valves. Ex vivo Raman maps compared to histological patterns.

Science.gov (United States)

Bonetti, A; Bonifacio, A; Della Mora, A; Livi, U; Marchini, M; Ortolani, F

2015-04-20

Unlike its application for atherosclerotic plaque analysis, Raman microspectroscopy was sporadically used to check the sole nature of bioapatite deposits in stenotic aortic valves, neglecting the involvement of accumulated lipids/lipoproteins in the calcific process. Here, Raman microspectroscopy was employed for examination of stenotic aortic valve leaflets to add information on nature and distribution of accumulated lipids and their correlation with mineralization in the light of its potential precocious diagnostic use. Cryosections from surgically explanted stenotic aortic valves (n=4) were studied matching Raman maps against specific histological patterns. Raman maps revealed the presence of phospholipids/triglycerides and cholesterol, which showed spatial overlapping with one another and Raman-identified hydroxyapatite. Moreover, the Raman patterns correlated with those displayed by both von-Kossa-calcium- and Nile-blue-stained serial cryosections. Raman analysis also provided the first identification of carotenoids, which co-localized with the identified lipid moieties. Additional fit concerned the distribution of collagen and elastin. The good correlation of Raman maps with high-affinity staining patterns proved that Raman microspectroscopy is a reliable tool in evaluating calcification degree, alteration/displacement of extracellular matrix components, and accumulation rate of different lipid forms in calcified heart valves. In addition, the novel identification of carotenoids supports the concept that valve stenosis is an atherosclerosis-like valve lesion, consistently with their previous Raman microspectroscopical identification inside atherosclerotic plaques.

Increased membrane cholesterol in lymphocytes diverts T-cells toward an inflammatory response.

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Jacqueline Surls

Full Text Available Cell signaling for T-cell growth, differentiation, and apoptosis is initiated in the cholesterol-rich microdomains of the plasma membrane known as lipid rafts. Herein, we investigated whether enrichment of membrane cholesterol in lipid rafts affects antigen-specific CD4 T-helper cell functions. Enrichment of membrane cholesterol by 40-50% following squalene administration in mice was paralleled by an increased number of resting CD4 T helper cells in periphery. We also observed sensitization of the Th1 differentiation machinery through co-localization of IL-2Rα, IL-4Rα, and IL-12Rβ2 subunits with GM1 positive lipid rafts, and increased STAT-4 and STAT-5 phosphorylation following membrane cholesterol enrichment. Antigen stimulation or CD3/CD28 polyclonal stimulation of membrane cholesterol-enriched, resting CD4 T-cells followed a path of Th1 differentiation, which was more vigorous in the presence of increased IL-12 secretion by APCs enriched in membrane cholesterol. Enrichment of membrane cholesterol in antigen-specific, autoimmune Th1 cells fostered their organ-specific reactivity, as confirmed in an autoimmune mouse model for diabetes. However, membrane cholesterol enrichment in CD4(+Foxp3(+ T-reg cells did not alter their suppressogenic function. These findings revealed a differential regulatory effect of membrane cholesterol on the function of CD4 T-cell subsets. This first suggests that membrane cholesterol could be a new therapeutic target to modulate the immune functions, and second that increased membrane cholesterol in various physiopathological conditions may bias the immune system toward an inflammatory Th1 type response.

Communication and proximity effects on outcomes attributable to sense of presence in distance bioinformatics education

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Maisiak Richard

2011-03-01

Full Text Available Abstract Background Online learning is increasingly popular in medical education and sense of presence has been posited as a factor contributing to its success. Communication media influences on sense of presence and learning outcomes were explored in this study. Test performance and ratings of instruction and technology, factors influenced by sense of presence, are compared under four conditions involving different media and degrees of student physical presence: 1 videoconference co-located, 2 webcast co-located, 3 videoconference dispersed, and 4 webcast dispersed. Methods Eighty one first to forth year medical students heard a lecture on telemedicine and were asked to collaboratively search a telemedicine website under conditions where the lecture was delivered by videoconference or one way streaming (webcast and where students were either co-located or dispersed. In the videoconference conditions, co-located students could use the technology to interact with the instructor and could interact with each other face to face, while the dispersed students could use the technology to interact with both the instructor and each other. In the webcast conditions, all students could use chat to communicate with the instructor or each other, although the co-located students also could interact orally. After hearing the lecture, students collaboratively searched a telemedicine website, took a test on lecture-website content and rated the instruction and the technology they used. Test scores on lecture and website content and ratings of instruction and technology for the four conditions were compared with analysis of variance and chi-square tests. Results There were no significant differences in overall measures, although there were on selected ratings of instruction. Students in both webcast conditions indicated they were encouraged more to follow up on their own and felt instruction was more interactive than co-located videoconferencing students

Communication and proximity effects on outcomes attributable to sense of presence in distance bioinformatics education.

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Locatis, Craig; Berner, Eta S; Hammack, Glenn; Smith, Steve; Maisiak, Richard; Ackerman, Michael

2011-03-14

Online learning is increasingly popular in medical education and sense of presence has been posited as a factor contributing to its success. Communication media influences on sense of presence and learning outcomes were explored in this study. Test performance and ratings of instruction and technology, factors influenced by sense of presence, are compared under four conditions involving different media and degrees of student physical presence: 1) videoconference co-located, 2) webcast co-located, 3) videoconference dispersed, and 4) webcast dispersed. Eighty one first to forth year medical students heard a lecture on telemedicine and were asked to collaboratively search a telemedicine website under conditions where the lecture was delivered by videoconference or one way streaming (webcast) and where students were either co-located or dispersed. In the videoconference conditions, co-located students could use the technology to interact with the instructor and could interact with each other face to face, while the dispersed students could use the technology to interact with both the instructor and each other. In the webcast conditions, all students could use chat to communicate with the instructor or each other, although the co-located students also could interact orally. After hearing the lecture, students collaboratively searched a telemedicine website, took a test on lecture-website content and rated the instruction and the technology they used. Test scores on lecture and website content and ratings of instruction and technology for the four conditions were compared with analysis of variance and chi-square tests. There were no significant differences in overall measures, although there were on selected ratings of instruction. Students in both webcast conditions indicated they were encouraged more to follow up on their own and felt instruction was more interactive than co-located videoconferencing students. Dispersed videoconferencing students indicated the highest

Modern environmental health hazards: a public health issue of increasing significance in Africa.

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Nweke, Onyemaechi C; Sanders, William H

2009-06-01

Traditional hazards such as poor sanitation currently account for most of Africa's environmentally related disease burden. However, with rapid development absent appropriate safeguards for environment and health, modern environmental health hazards (MEHHs) may emerge as critical contributors to the continent's disease burden. We review recent evidence of human exposure to and health effects from MEHHs, and their occurrence in environmental media and consumer products. Our purpose is to highlight the growing significance of these hazards as African countries experience urbanization, industrial growth, and development. We reviewed published epidemiologic, exposure, and environmental studies of chemical agents such as heavy metals and pesticides. The body of evidence demonstrates ongoing environmental releases of MEHHs and human exposures sometimes at toxicologically relevant levels. Several sources of MEHHs in environmental media have been identified, including natural resource mining and processing and automobile exhaust. Biomonitoring studies provided direct evidence of human exposure to metals such as mercury and lead and pesticides such as p,p'-dichlorodiphenyltrichloroethane (DDT) and organophosphates. Land and water resource pollution and industrial air toxics are areas of significant data gaps, notwithstanding the presence of several emitting sources. Unmitigated MEHH releases and human exposure have implications for Africa's disease burden. For Africans encumbered by conditions such as malnutrition that impair resilience to toxicologic challenges, the burden may be higher. A shift in public health policy toward accommodating the emerging diversity in Africa's environmental health issues is necessary to successfully alleviate the burden of avoidable ill health and premature death for all its communities now and in the future.

Clinical significance of increased lung/heart ratio in 210Tl stress myocardial image

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Liu Zaoli; Chang Fengqin; Zhang Fengge; Wang Xiaoyuan; Liu Liuhua

1990-01-01

230 cases were studied with 201 Tl stress image. The results showed that the lung/heart ratio closely correlated with the presence and severity of coronary heart disease (CHD). Among them, 18 cases (7.8%) showed significantly elevated lung/heart ratio (> 0.50). It was confirmed that all of the 18 cases have severe CHD with left ventricular insufficiency. The author emphasizes that measurement of the lung/heart ratio during 201 Tl stress myocardial image may be useful for the assessment of the severity, evalation of the left ventricular function and judgement of prognosis in CHD

Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice

International Nuclear Information System (INIS)

Chang Mengya; Chen Yuhung; Chang Chihjui; Chen Helen H-W; Wu Chaoliang; Shiau Aili

2008-01-01

High atomic number material, such as gold, may be used in conjunction with radiation to provide dose enhancement in tumors. In the current study, we investigated the dose-enhancing effect and apoptotic potential of gold nanoparticles in combination with single-dose clinical electron beams on B16F10 melanoma tumor-bearing mice. We revealed that the accumulation of gold nanoparticles was detected inside B16F10 culture cells after 18 h of incubation, and moreover, the gold nanoparticles were shown to be colocalized with endoplasmic reticulum and Golgi apparatus in cells. Furthermore, gold nanoparticles radiosensitized melanoma cells in the colony formation assay (P=0.02). Using a B16F10 tumor-bearing mouse model, we further demonstrated that gold nanoparticles in conjunction with ionizing radiation significantly retarded tumor growth and prolonged survival compared to the radiation alone controls (P<0.05). Importantly, an increase of apoptotic signals was detected inside tumors in the combined treatment group (P<0.05). Knowing that radiation-induced apoptosis has been considered a determinant of tumor responses to radiation therapy, and the length of tumor regrowth delay correlated with the extent of apoptosis after single-dose radiotherapy, these results may suggest the clinical potential of gold nanoparticles in improving the outcome of melanoma radiotherapy. (author)

Presence of gingivitis and periodontitis significantly increases hospital charges in patients undergoing heart valve surgery.

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Allareddy, Veerasathpurush; Elangovan, Satheesh; Rampa, Sankeerth; Shin, Kyungsup; Nalliah, Romesh P; Allareddy, Veerajalandhar

2015-01-01

To examine the prevalence and impact of gingivitis and periodontitis in patients having heart valve surgical procedures. Nationwide Inpatient Sample for the years 2004-2010 was used. All patients who had heart valve surgical procedures were selected. Prevalence of gingivitis/periodontitis was examined in these patients. Impact of gingivitis/periodontitis on hospital charges, length of stay, and infectious complications was examined. 596,190 patients had heart valve surgical procedures. Gingivitis/periodontitis was present in 0.2 percent. Outcomes included: median hospital charges ($175,418 with gingivitis/ periodontitis versus $149,353 without gingivitis/periodontitis) and median length of stay (14 days with gingivitis/periodontitis versus 8 days without gingivitis/periodontitis). After adjusting for the effects of patient- and hospital-level confounding factors, hospital charges and length of stay were significantly higher (p gingivitis/periodontitis compared to their counterparts. Further, patients with gingivitis/periodontitis had significantly higher odds for having bacterial infections (OR = 3.41, 95% CI = 2.33-4.98, p gingivitis/periodontitis. Presence of gingivitis and periodontitis is associated with higher risk for bacterial infections and significant hospital resource utilization.

Aplicação do processamento de imagens por computador na quantificação das variáveis histopatológicas da reparação tecidual de anastomoses colocólicas em cães

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Novelli M.D.

1997-01-01

Full Text Available OBJETIVO. Os autores apresentam a metodologia de quantificação, através do processamento de imagens, de estruturas teciduais microscópicas envolvidas no processo de reparação de anastomoses colocólicas, feitas por meio de sutura manual e por anel biofragmentável. As variáveis quantificadas neste trabalho foram líquido de edema, tecido fibromuscular, vasos e núcleos celulares. MATERIAL E MÉTODOS. Para esta análise, foi utilizado programa de processamento de imagens desenvolvido no Laboratório de Informática Dedicado à Odontologia (LIDO da Universidade de São Paulo, com a finalidade de quantificar as alterações patognomônicas do processo inflamatório em anastomoses colocólicas em 14 cães. Os resultados foram comparados, como contraprova, aos obtidos através de leituras convencionais feitas por dois patologistas. A gradação de alterações ausentes, leves, moderadas e intensas foi utilizada nesta leitura para que se semiquantificassem as mesmas variáveis lidas pelo computador. RESULTADOS. Houve diferença significativa entre as duas técnicas, com a de anel biofragmentável apresentando menor quantidade de edema, fibras organizadas e prevalência de núcleos celulares alongados em relação aos esféricos, sinal evidente de organização tecidual. CONCLUSÃO. Os resultados permitiram concluir que a histometria por processamento de imagem computacional mostrou-se eficiente na quantificação das principais estruturas teciduais envolvidas no processo inflamatório e reparativo.

Estradiol upregulates progesterone receptor and orphanin FQ colocalization in arcuate nucleus neurons and opioid receptor-like receptor-1 expression in proopiomelanocortin neurons that project to the medial preoptic nucleus in the female rat

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Sanathara, Nayna M.; Moreas, Justine; Mahavongtrakul, Matthew; Sinchak, Kevin

2014-01-01

Background Ovarian steroids regulate sexual receptivity in the female rat by acting on neurons that converge on proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH) that project to the medial preoptic nucleus (MPN). Estradiol rapidly activates these neurons to release β-endorphin that activates MPN μ-opioid receptors (MOP) to inhibit lordosis. Lordosis is facilitated by the subsequent action of progesterone that deactivates the estradiol-induced MPN MOP activation. Orphanin FQ (OFQ/N; aka nociceptin) infusions into the ARH, like progesterone, deactivate MPN MOP and facilitate lordosis in estradiol-primed rats. OFQ/N reduces the activity of ARH β-endorphin neurons through post- and presynaptic mechanisms via its cognate receptor, ORL-1. Methods We tested the hypotheses that progesterone receptors (PR) are expressed in ARH OFQ/N neurons by immunohistochemistry and ORL-1 is expressed in POMC neurons that project to the MPN by combining Fluoro-Gold injection into the MPN and double-label fluorescent in situ hybridization (FISH). We also hypothesized that estradiol increases coexpression of PR-OFQ/N and ORL-1-POMC in ARH neurons of ovariectomized rats. Results The number of PR and OFQ/N immunopositive ARH neurons was increased as was their colocalization by estradiol treatment. FISH for ORL-1 and POMC mRNA revealed a subpopulation of ARH neurons that was triple-labeled indicating these neurons project to the MPN and coexpress ORL-1 and POMC mRNA. Estradiol was shown to upregulate ORL-1 and POMC expression in MPN-projecting ARH neurons. Conclusion Estradiol upregulates the ARH OFQ/N-ORL-1 system projecting to the MPN that regulates lordosis. PMID:24821192

Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells.

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Chinchar, Edmund; Makey, Kristina L; Gibson, John; Chen, Fang; Cole, Shelby A; Megason, Gail C; Vijayakumar, Srinivassan; Miele, Lucio; Gu, Jian-Wei

2014-01-01

The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an

Significantly Increased Extreme Precipitation Expected in Europe and North America from Extratropical Storms

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Hawcroft, M.; Hodges, K.; Walsh, E.; Zappa, G.

2017-12-01

For the Northern Hemisphere extratropics, changes in circulation are key to determining the impacts of climate warming. The mechanisms governing these circulation changes are complex, leading to the well documented uncertainty in projections of the future location of the mid-latitude storm tracks simulated by climate models. These storms are the primary source of precipitation for North America and Europe and generate many of the large-scale precipitation extremes associated with flooding and severe economic loss. Here, we show that in spite of the uncertainty in circulation changes, by analysing the behaviour of the storms themselves, we find entirely consistent and robust projections across an ensemble of climate models. In particular, we find that projections of change in the most intensely precipitating storms (above the present day 99th percentile) in the Northern Hemisphere are substantial and consistent across models, with large increases in the frequency of both summer (June-August, +226±68%) and winter (December-February, +186±34%) extreme storms by the end of the century. Regionally, both North America (summer +202±129%, winter +232±135%) and Europe (summer +390±148%, winter +318±114%) are projected to experience large increases in the frequency of intensely precipitating storms. These changes are thermodynamic and driven by surface warming, rather than by changes in the dynamical behaviour of the storms. Such changes in storm behaviour have the potential to have major impacts on society given intensely precipitating storms are responsible for many large-scale flooding events.

Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury.

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Jung, J; Uesugi, N; Jeong, N Y; Park, B S; Konishi, H; Kiyama, H

2016-01-28

In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. Recent in vitro study revealed that an ATP marker, quinacrine, in lysosomes was released from neurite terminal of dorsal root ganglion (DRG) neurons to extracellular space via lysosomal exocytosis. Here, we demonstrate a possibility that the lysosomal ingredient including ATP released from DRG neurons by lysosomal-exocytosis is an additional source of the glial activation in DH after nerve injury. After rat L5 spinal nerve ligation (SNL), mRNA for transcription factor EB (TFEB), a transcription factor controlling lysosomal activation and exocytosis, was induced in the DRG. Simultaneously both lysosomal protein, LAMP1- and vesicular nuclear transporter (VNUT)-positive vesicles were increased in L5 DRG neurons and ipsilateral DH. The quinacrine staining in DH was increased and co-localized with LAMP1 immunoreactivity after nerve injury. In DH, LAMP1-positive vesicles were also co-localized with a peripheral nerve marker, Isolectin B4 (IB4) lectin. Injection of the adenovirus encoding mCherry-LAMP1 into DRG showed that mCherry-positive lysosomes are transported to the central nerve terminal in DH. These findings suggest that activation of lysosome synthesis including ATP packaging in DRG, the central transportation of the lysosome, and subsequent its exocytosis from the central nerve terminal of DRG neurons in response to nerve injury could be a partial mechanism for activation of microglia in DH. This lysosome-mediated microglia activation mechanism may provide another clue to control nociception and pain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Unequivocal detection of ozone recovery in the Antarctic Ozone Hole through significant increases in atmospheric layers with minimum ozone

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de Laat, Jos; van Weele, Michiel; van der A, Ronald

2015-04-01

An important new landmark in present day ozone research is presented through MLS satellite observations of significant ozone increases during the ozone hole season that are attributed unequivocally to declining ozone depleting substances. For many decades the Antarctic ozone hole has been the prime example of both the detrimental effects of human activities on our environment as well as how to construct effective and successful environmental policies. Nowadays atmospheric concentrations of ozone depleting substances are on the decline and first signs of recovery of stratospheric ozone and ozone in the Antarctic ozone hole have been observed. The claimed detection of significant recovery, however, is still subject of debate. In this talk we will discuss first current uncertainties in the assessment of ozone recovery in the Antarctic ozone hole by using multi-variate regression methods, and, secondly present an alternative approach to identify ozone hole recovery unequivocally. Even though multi-variate regression methods help to reduce uncertainties in estimates of ozone recovery, great care has to be taken in their application due to the existence of uncertainties and degrees of freedom in the choice of independent variables. We show that taking all uncertainties into account in the regressions the formal recovery of ozone in the Antarctic ozone hole cannot be established yet, though is likely before the end of the decade (before 2020). Rather than focusing on time and area averages of total ozone columns or ozone profiles, we argue that the time evolution of the probability distribution of vertically resolved ozone in the Antarctic ozone hole contains a better fingerprint for the detection of ozone recovery in the Antarctic ozone hole. The advantages of this method over more tradition methods of trend analyses based on spatio-temporal average ozone are discussed. The 10-year record of MLS satellite measurements of ozone in the Antarctic ozone hole shows a

Co-localization of glycine and gaba immunoreactivity in interneurons in Macaca monkey cerebellar cortex.

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Crook, J; Hendrickson, A; Robinson, F R

2006-09-15

Previous work demonstrates that the cerebellum uses glycine as a fast inhibitory neurotransmitter [Ottersen OP, Davanger S, Storm-Mathisen J (1987) Glycine-like immunoreactivity in the cerebellum of rat and Senegalese baboon, Papio papio: a comparison with the distribution of GABA-like immunoreactivity and with [3H]glycine and [3H]GABA uptake. Exp Brain Res 66(1):211-221; Ottersen OP, Storm-Mathisen J, Somogyi P (1988) Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: a postembedding light and electron microscopic study. Brain Res 450(1-2):342-353; Dieudonne S (1995) Glycinergic synaptic currents in Golgi cells of the rat cerebellum. Proc Natl Acad Sci U S A 92:1441-1445; Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057; Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498; Zeilhofer HU, Studler B, Arabadzisz D, Schweizer C, Ahmadi S, Layh B, Bosl MR, Fritschy JM (2005) Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice. J Comp Neurol 482(2):123-141]. In the rat cerebellum glycine is not released by itself but is released together with GABA by Lugaro cells onto Golgi cells [Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057] and by Golgi cells onto unipolar brush and granule cells [Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498]. Here we report, from immunolabeling evidence in Macaca cerebellum, that interneurons in the granular cell layer are glycine+ at a density

Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein.

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Aditi Gupta

2016-03-01

Full Text Available Epistatic interactions between residues determine a protein's adaptability and shape its evolutionary trajectory. When a protein experiences a changed environment, it is under strong selection to find a peak in the new fitness landscape. It has been shown that strong selection increases epistatic interactions as well as the ruggedness of the fitness landscape, but little is known about how the epistatic interactions change under selection in the long-term evolution of a protein. Here we analyze the evolution of epistasis in the protease of the human immunodeficiency virus type 1 (HIV-1 using protease sequences collected for almost a decade from both treated and untreated patients, to understand how epistasis changes and how those changes impact the long-term evolvability of a protein. We use an information-theoretic proxy for epistasis that quantifies the co-variation between sites, and show that positive information is a necessary (but not sufficient condition that detects epistasis in most cases. We analyze the "fossils" of the evolutionary trajectories of the protein contained in the sequence data, and show that epistasis continues to enrich under strong selection, but not for proteins whose environment is unchanged. The increase in epistasis compensates for the information loss due to sequence variability brought about by treatment, and facilitates adaptation in the increasingly rugged fitness landscape of treatment. While epistasis is thought to enhance evolvability via valley-crossing early-on in adaptation, it can hinder adaptation later when the landscape has turned rugged. However, we find no evidence that the HIV-1 protease has reached its potential for evolution after 9 years of adapting to a drug environment that itself is constantly changing. We suggest that the mechanism of encoding new information into pairwise interactions is central to protein evolution not just in HIV-1 protease, but for any protein adapting to a changing

Significance of Increasing n-3 PUFA Content in Pork on Human Health.

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Ma, Xianyong; Jiang, Zongyong; Lai, Chaoqiang

2016-01-01

Evidence for the health-promoting effects of food rich in n-3 polyunsaturated fatty acids (n-3 PUFA) is reviewed. Pork is an important meat source for humans. According to a report by the US Department of Agriculture ( http://www.ers.usda.gov/topics ), the pork consumption worldwide in 2011 was about 79.3 million tons, much higher than that of beef (48.2 million tons). Pork also contains high levels of unsaturated fatty acids relative to ruminant meats (Enser, M., Hallett, K., Hewett, B., Fursey, G. A. J. and Wood, J. D. (1996) . Fatty acid content and composition of English beef, lamb, and pork at retail. Meat Sci. 44:443-458). The available literature indicates that the levels of eicosatetraenoic and docosahexaenoic in pork may be increased by fish-derived or linseed products, the extent of which being dependent on the nature of the supplementation. Transgenic pigs and plants show promise with high content of n-3 PUFA and low ratio of n-6/n-3 fatty acids in their tissues. The approaches mentioned for decreasing n-6/n-3 ratios have both advantages and disadvantages. Selected articles are critically reviewed and summarized.

Significantly increased lifetime of recent microchannel-plate photomultipliers

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Britting, Alexander; Eyrich, Wolfgang; Lehmann, Albert; Uhlig, Fred [Physikalisches Institut, Universitaet Erlangen-Nuernberg (Germany)

2013-07-01

Micro-channel plate photo multipliers (MCP-PMT) are the favored sensors for the DIRC detectors (Detection of Internally Reflected Cherenkov Light) of the PANDA experiment. The main reasons for this are their usability in high magnetic fields of up to 2 T, a time resolution of better than σ = 50 ps and a rate capability high enough to withstand a detected photon rate of about 200 kHz cm{sup -2} at the MCP-PMTs surface, which is anticipated at the average luminosity of 2 . 10{sup 32} cm{sup -2}s{sup -1} in PANDA. Moreover, for the reconstruction of the Cherenkov angle using the planned optics for the barrel DIRC a spatial resolution of about 5 mm at the focal plane is needed. Until recently the major drawback of MCP-PMTs was their limited lifetime which was by far not sufficient to stand the integrated anode charge, which is ∼ 5 C/cm{sup 2} for the Barrel-DIRC and even more for the Disc-DIRC. However, the latest MCP prototype devices show a hugh step forward in this respect. The results of these lifetime measurements are presented. The achieved values are meanwhile close to the PANDA requirements for the Barrel-DIRC.

Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats.

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Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir; Bock, Elisabeth

2013-07-01

Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during the perinatal period. Pregnant Wistar rats were administered a 200 mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND40 but no effect of prenatal prochloraz exposure on social investigation or acquisition of social-olfactory memory. Copyright © 2012 Elsevier GmbH. All rights reserved.

Ground motion response to an ML 4.3 earthquake using co-located distributed acoustic sensing and seismometer arrays

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Wang, Herbert F.; Zeng, Xiangfang; Miller, Douglas E.; Fratta, Dante; Feigl, Kurt L.; Thurber, Clifford H.; Mellors, Robert J.

2018-06-01

The PoroTomo research team deployed two arrays of seismic sensors in a natural laboratory at Brady Hot Springs, Nevada in March 2016. The 1500 m (length) × 500 m (width) × 400 m (depth) volume of the laboratory overlies a geothermal reservoir. The distributed acoustic sensing (DAS) array consisted of about 8400 m of fiber-optic cable in a shallow trench and 360 m in a well. The conventional seismometer array consisted of 238 shallowly buried three-component geophones. The DAS cable was laid out in three parallel zig-zag lines with line segments approximately 100 m in length and geophones were spaced at approximately 60 m intervals. Both DAS and conventional geophones recorded continuously over 15 d during which a moderate-sized earthquake with a local magnitude of 4.3 was recorded on 2016 March 21. Its epicentre was approximately 150 km south-southeast of the laboratory. Several DAS line segments with co-located geophone stations were used to compare signal-to-noise ratios (SNRs) in both time and frequency domains and to test relationships between DAS and geophone data. The ratios were typically within a factor of five of each other with DAS SNR often greater for P-wave but smaller for S-wave relative to geophone SNR. The SNRs measured for an earthquake can be better than for active sources because the earthquake signal contains more low-frequency energy and the noise level is also lower at those lower frequencies. Amplitudes of the sum of several DAS strain-rate waveforms matched the finite difference of two geophone waveforms reasonably well, as did the amplitudes of DAS strain waveforms with particle-velocity waveforms recorded by geophones. Similar agreement was found between DAS and geophone observations and synthetic strain seismograms. The combination of good SNR in the seismic frequency band, high-spatial density, large N and highly accurate time control among individual sensors suggests that DAS arrays have potential to assume a role in earthquake

Increased Risk of Clinically Significant Gallstones following an Appendectomy: A Five-Year Follow-Up Study.

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Shiu-Dong Chung

Full Text Available Although the vermiform appendix is commonly considered a vestigial organ, adverse health consequences after an appendectomy have garnered increasing attention. In this study, we investigated the risks of gallstone occurrence during a 5-year follow-up period after an appendectomy, using a population-based dataset. We used data from the Taiwan Longitudinal Health Insurance Database 2005. The exposed cohort included 4916 patients who underwent an appendectomy. The unexposed cohort was retrieved by randomly selecting 4916 patients matched with the exposed cohort in terms of sex, age, and year. We individually tracked each patient for a 5-year period to identify those who received a diagnosis of gallstones during the follow-up period. Cox proportional hazard regressions were performed for the analysis. During the 5-year follow-up period, the incidence rate per 1000 person-years was 4.71 for patients who had undergone an appendectomy, compared to a rate of 2.59 for patients in the unexposed cohort (p<0.001. Patients who had undergone an appendectomy were independently associated with a 1.79 (95% CI = 1.29~2.48-fold increased risk of being diagnosed with gallstones during the 5-year follow-up period. We found that among female patients, the adjusted hazard ratio of gallstones was 2.25 (95% CI = 1.41~3.59 for patients who underwent an appendectomy compared to unexposed patients. However, for male patients, we failed to observe an increased hazard for gallstones among patients who underwent an appendectomy compared to unexposed patients. We found an increased risk of a subsequent gallstone diagnosis within 5 years after an appendectomy.

Continues administration of Nano-PSO significantly increased survival of genetic CJD mice.

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Binyamin, Orli; Keller, Guy; Frid, Kati; Larush, Liraz; Magdassi, Shlomo; Gabizon, Ruth

2017-12-01

We have shown previously that Nano-PSO, a nanodroplet formulation of pomegranate seed oil, delayed progression of neurodegeneration signs when administered for a designated period of time to TgMHu2ME199K mice, modeling for genetic prion disease. In the present work, we treated these mice with a self-emulsion formulation of Nano-PSO or a parallel Soybean oil formulation from their day of birth until a terminal disease stage. We found that long term Nano-PSO administration resulted in increased survival of TgMHu2ME199K lines by several months. Interestingly, initiation of treatment at day 1 had no clinical advantage over initiation at day 70, however cessation of treatment at 9months of age resulted in the rapid loss of the beneficial clinical effect. Pathological studies revealed that treatment with Nano-PSO resulted in the reduction of GAG accumulation and lipid oxidation, indicating a strong neuroprotective effect. Contrarily, the clinical effect of Nano-PSO did not correlate with reduction in the levels of disease related PrP, the main prion marker. We conclude that long term administration of Nano-PSO is safe and may be effective in the prevention/delay of onset of neurodegenerative conditions such as genetic CJD. Copyright © 2017. Published by Elsevier Inc.

Increased GABA(A receptor ε-subunit expression on ventral respiratory column neurons protects breathing during pregnancy.

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Keith B Hengen

Full Text Available GABAergic signaling is essential for proper respiratory function. Potentiation of this signaling with allosteric modulators such as anesthetics, barbiturates, and neurosteroids can lead to respiratory arrest. Paradoxically, pregnant animals continue to breathe normally despite nearly 100-fold increases in circulating neurosteroids. ε subunit-containing GABA(ARs are insensitive to positive allosteric modulation, thus we hypothesized that pregnant rats increase ε subunit-containing GABA(AR expression on brainstem neurons of the ventral respiratory column (VRC. In vivo, pregnancy rendered respiratory motor output insensitive to otherwise lethal doses of pentobarbital, a barbiturate previously used to categorize the ε subunit. Using electrode array recordings in vitro, we demonstrated that putative respiratory neurons of the preBötzinger Complex (preBötC were also rendered insensitive to the effects of pentobarbital during pregnancy, but unit activity in the VRC was rapidly inhibited by the GABA(AR agonist, muscimol. VRC unit activity from virgin and post-partum females was potently inhibited by both pentobarbital and muscimol. Brainstem ε subunit mRNA and protein levels were increased in pregnant rats, and GABA(AR ε subunit expression co-localized with a marker of rhythm generating neurons (neurokinin 1 receptors in the preBötC. These data support the hypothesis that pregnancy renders respiratory motor output and respiratory neuron activity insensitive to barbiturates, most likely via increased ε subunit-containing GABA(AR expression on respiratory rhythm-generating neurons. Increased ε subunit expression may be critical to preserve respiratory function (and life despite increased neurosteroid levels during pregnancy.

Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis.

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Nielsen, C T; Østergaard, O; Rekvig, O P; Sturfelt, G; Jacobsen, S; Heegaard, N H H

2015-10-01

A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow cytometry. Quantitation of microparticle-associated G3BP, C1q and immunoglobulins was obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS). Correlations between microparticle-G3BP data and clinical parameters were analyzed. Co-localization of G3BP with in vivo-bound IgG was examined in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P microparticle populations could be discerned by flow cytometry, including two subpopulations that were significantly increased in SLE samples (P = 0.01 and P = 0.0002, respectively). No associations of G3BP-positive microparticles with clinical manifestations or disease activity were found. Immune electron microscopy showed co-localization of G3BP with in vivo-bound IgG in glomerular electron dense immune complex deposits in all lupus nephritis biopsies. Both circulating microparticle-G3BP numbers as well as G3BP expression are increased in SLE patients corroborating G3BP being a feature of SLE microparticles. By demonstrating G3BP co-localized with deposited immune complexes in lupus nephritis, the study supports cell-derived microparticles as a major autoantigen source and provides a new understanding of the origin of

Co-localized or randomly distributed? Pair cross correlation of in vivo grown subgingival biofilm bacteria quantified by digital image analysis.

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Claudia Schillinger

Full Text Available The polymicrobial nature of periodontal diseases is reflected by the diversity of phylotypes detected in subgingival plaque and the finding that consortia of suspected pathogens rather than single species are associated with disease development. A number of these microorganisms have been demonstrated in vitro to interact and enhance biofilm integration, survival or even pathogenic features. To examine the in vivo relevance of these proposed interactions, we extended the spatial arrangement analysis tool of the software daime (digital image analysis in microbial ecology. This modification enabled the quantitative analysis of microbial co-localization in images of subgingival biofilm species, where the biomass was confined to fractions of the whole-image area, a situation common for medical samples. Selected representatives of the disease-associated red and orange complexes that were previously suggested to interact with each other in vitro (Tannerella forsythia with Fusobacterium nucleatum and Porphyromonas gingivalis with Prevotella intermedia were chosen for analysis and labeled with specific fluorescent probes via fluorescence in situ hybridization. Pair cross-correlation analysis of in vivo grown biofilms revealed tight clustering of F. nucleatum/periodonticum and T. forsythia at short distances (up to 6 µm with a pronounced peak at 1.5 µm. While these results confirmed previous in vitro observations for F. nucleatum and T. forsythia, random spatial distribution was detected between P. gingivalis and P. intermedia in the in vivo samples. In conclusion, we successfully employed spatial arrangement analysis on the single cell level in clinically relevant medical samples and demonstrated the utility of this approach for the in vivo validation of in vitro observations by analyzing statistically relevant numbers of different patients. More importantly, the culture-independent nature of this approach enables similar quantitative analyses for "as

The Coexpression of Reelin and Neuronal Nitric Oxide Synthase in a Subpopulation of Dentate Gyrus Neurons Is Downregulated in Heterozygous Reeler Mice

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Raquel Romay-Tallón

2010-01-01

Full Text Available Reelin is an extracellular matrix protein expressed in several interneuron subtypes in the hippocampus and dentate gyrus. Neuronal nitric oxide synthase (nNOS is also expressed by interneurons in these areas. We investigated whether reelin and nNOS are co-localized in the same population of hippocampal interneurons, and whether this colocalization is altered in the heterozygous reeler mouse. We found colocalization of nNOS in reelin-positive cells in the CA1 stratum radiatum and lacunosum moleculare, the CA3 stratum radiatum, and the dentate gyrus subgranular zone, molecular layer, and hilus. In heterozygous reeler mice, the colocalization of nNOS in reelin-positive cells was significantly decreased only in the subgranular zone and molecular layer. The coexpression of reelin and nNOS in several hippocampal regions suggests that reelin and nNOS may work synergistically to promote glutamatergic function, and the loss of this coexpression in heterozygous reeler mice may underlie some of the behavioral deficits observed in these animals.

Clinical significance of anismus in encopresis.

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Catto-Smith, A G; Nolan, T M; Coffey, C M

1998-09-01

Treatments designed to relieve paradoxical contraction of the anal sphincters during defecation (anismus) have had limited success in children with encopresis. This has raised doubts as to the clinical relevance of this diagnosis in childhood as anorectal dysfunction. Our aim was to determine whether, in patients who had treatment-resistant encopresis, the presence of electromyographic anismus was associated with increased faecal retention. Sixty-eight children with soiling (mean age 8.7+/-2.06 years) were assessed by clinical examination, abdominal radiography and then with anorectal manometry. Patients with electromyographic anismus (n=32; 47%) had significantly increased radiographic rectal faecal retention and were significantly less likely to be able to defecate water-filled balloons. There were no significant differences in response to prior therapy, history of primary encopresis, behavioural adjustment or in sociodemographic data. Our results suggest that electromyographic anismus is associated with obstructed defecation and faecal retention.

The In Vitro Mass-Produced Model Mycorrhizal Fungus, Rhizophagus irregularis, Significantly Increases Yields of the Globally Important Food Security Crop Cassava

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Ceballos, Isabel; Ruiz, Michael; Fernández, Cristhian; Peña, Ricardo

2013-01-01

The arbuscular mycorrhizal symbiosis is formed between arbuscular mycorrhizal fungi (AMF) and plant roots. The fungi provide the plant with inorganic phosphate (P). The symbiosis can result in increased plant growth. Although most global food crops naturally form this symbiosis, very few studies have shown that their practical application can lead to large-scale increases in food production. Application of AMF to crops in the tropics is potentially effective for improving yields. However, a main problem of using AMF on a large-scale is producing cheap inoculum in a clean sterile carrier and sufficiently concentrated to cheaply transport. Recently, mass-produced in vitro inoculum of the model mycorrhizal fungus Rhizophagus irregularis became available, potentially making its use viable in tropical agriculture. One of the most globally important food plants in the tropics is cassava. We evaluated the effect of in vitro mass-produced R. irregularis inoculum on the yield of cassava crops at two locations in Colombia. A significant effect of R. irregularis inoculation on yield occurred at both sites. At one site, yield increases were observed irrespective of P fertilization. At the other site, inoculation with AMF and 50% of the normally applied P gave the highest yield. Despite that AMF inoculation resulted in greater food production, economic analyses revealed that AMF inoculation did not give greater return on investment than with conventional cultivation. However, the amount of AMF inoculum used was double the recommended dose and was calculated with European, not Colombian, inoculum prices. R. irregularis can also be manipulated genetically in vitro, leading to improved plant growth. We conclude that application of in vitro R. irregularis is currently a way of increasing cassava yields, that there is a strong potential for it to be economically profitable and that there is enormous potential to improve this efficiency further in the future. PMID:23950975

The in vitro mass-produced model mycorrhizal fungus, Rhizophagus irregularis, significantly increases yields of the globally important food security crop cassava.

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Isabel Ceballos

Full Text Available The arbuscular mycorrhizal symbiosis is formed between arbuscular mycorrhizal fungi (AMF and plant roots. The fungi provide the plant with inorganic phosphate (P. The symbiosis can result in increased plant growth. Although most global food crops naturally form this symbiosis, very few studies have shown that their practical application can lead to large-scale increases in food production. Application of AMF to crops in the tropics is potentially effective for improving yields. However, a main problem of using AMF on a large-scale is producing cheap inoculum in a clean sterile carrier and sufficiently concentrated to cheaply transport. Recently, mass-produced in vitro inoculum of the model mycorrhizal fungus Rhizophagus irregularis became available, potentially making its use viable in tropical agriculture. One of the most globally important food plants in the tropics is cassava. We evaluated the effect of in vitro mass-produced R. irregularis inoculum on the yield of cassava crops at two locations in Colombia. A significant effect of R. irregularis inoculation on yield occurred at both sites. At one site, yield increases were observed irrespective of P fertilization. At the other site, inoculation with AMF and 50% of the normally applied P gave the highest yield. Despite that AMF inoculation resulted in greater food production, economic analyses revealed that AMF inoculation did not give greater return on investment than with conventional cultivation. However, the amount of AMF inoculum used was double the recommended dose and was calculated with European, not Colombian, inoculum prices. R. irregularis can also be manipulated genetically in vitro, leading to improved plant growth. We conclude that application of in vitro R. irregularis is currently a way of increasing cassava yields, that there is a strong potential for it to be economically profitable and that there is enormous potential to improve this efficiency further in the future.

Karyotype characterization of Mugil incilis Hancock, 1830 (Mugiliformes: Mugilidae, including a description of an unusual co-localization of major and minor ribosomal genes in the family

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Anne Kathrin Hett

Full Text Available This study reports the description of the karyotype of Mugil incilis from Venezuela. The chromosome complement is composed of 48 acrocentric chromosomes, which uniformly decrease in size. Therefore, the homologues can not be clearly identified, with the exception of one of the largest chromosome pairs, classified as number 1, whose homologues may show a subcentromeric secondary constriction, and of chromosome pair number 24, which is considerably smaller than the others. C-banding showed heterochromatic blocks at the centromeric/pericentromeric regions of all chromosomes, which were more conspicuous on chromosomes 1, given the C-positive signals include the secondary constrictions. AgNO3 and fluorescent in situ hybridization (FISH with 45S rDNA demonstrated that the nucleolus organizer regions are indeed located on the secondary constrictions of chromosome pair number 1. FISH with 5S rDNA revealed that the minor ribosomal genes are located on this same chromosome pair, near the NORs, though signals are closer to the centromeres and of smaller size, compared to those of the major ribosomal gene clusters. This is the first description of co-localization of major and minor ribosomal genes in the family. Data are discussed from a cytotaxonomic and phylogenetic perspective.

Marrying Step Feed with Secondary Clarifier Improvements to Significantly Increase Peak Wet Weather Treatment Capacity: An Integrated Methodology.

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Daigger, Glen T; Siczka, John S; Smith, Thomas F; Frank, David A; McCorquodale, J A

2017-08-01

  The need to increase the peak wet weather secondary treatment capacity of the City of Akron, Ohio, Water Reclamation Facility (WRF) provided the opportunity to test an integrated methodology for maximizing the peak wet weather secondary treatment capacity of activated sludge systems. An initial investigation, consisting of process modeling of the secondary treatment system and computational fluid dynamics (CFD) analysis of the existing relatively shallow secondary clarifiers (3.3 and 3.7 m sidewater depth in 30.5 m diameter units), indicated that a significant increase in capacity from 416 000 to 684 000 m3/d or more was possible by adding step feed capabilities to the existing bioreactors and upgrading the existing secondary clarifiers. One of the six treatment units at the WRF was modified, and an extensive 2-year testing program was conducted to determine the total peak wet weather secondary treatment capacity achievable. The results demonstrated that a peak wet weather secondary treatment capacity approaching 974 000 m3/d is possible as long as secondary clarifier solids and hydraulic loadings could be separately controlled using the step feed capability provided. Excellent sludge settling characteristics are routinely experienced at the City of Akron WRF, raising concerns that the identified peak wet weather secondary treatment capacity could not be maintained should sludge settling characteristics deteriorate for some reason. Computational fluid dynamics analysis indicated that the impact of the deterioration of sludge settling characteristics could be mitigated and the identified peak wet weather secondary treatment capacity maintained by further use of the step feed capability provided to further reduce secondary clarifier solids loading rates at the identified high surface overflow rates. The results also demonstrated that effluent limits not only for total suspended solids (TSS) and five-day carbonaceous biochemical oxygen demand (cBOD5) could be

The PTI1-like kinase ZmPti1a from maize (Zea mays L.) co-localizes with callose at the plasma membrane of pollen and facilitates a competitive advantage to the male gametophyte.

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Herrmann, Markus M; Pinto, Sheena; Kluth, Jantjeline; Wienand, Udo; Lorbiecke, René

2006-10-06

The tomato kinase Pto confers resistance to bacterial speck disease caused by Pseudomonas syringae pv. tomato in a gene for gene manner. Upon recognition of specific avirulence factors the Pto kinase activates multiple signal transduction pathways culminating in induction of pathogen defense. The soluble cytoplasmic serine/threonine kinase Pti1 is one target of Pto phosphorylation and is involved in the hypersensitive response (HR) reaction. However, a clear role of Pti1 in plant pathogen resistance is uncertain. So far, no Pti1 homologues from monocotyledonous species have been studied. Here we report the identification and molecular analysis of four Pti1-like kinases from maize (ZmPti1a, -b, -c, -d). These kinase genes showed tissue-specific expression and their corresponding proteins were targeted to different cellular compartments. Sequence similarity, expression pattern and cellular localization of ZmPti1b suggested that this gene is a putative orthologue of Pti1 from tomato. In contrast, ZmPti1a was specifically expressed in pollen and sequestered to the plasma membrane, evidently owing to N-terminal modification by myristoylation and/or S-acylation. The ZmPti1a:GFP fusion protein was not evenly distributed at the pollen plasma membrane but accumulated as an annulus-like structure which co-localized with callose (1,3-beta-glucan) deposition. In addition, co-localization of ZmPti1a and callose was observed during stages of pollen mitosis I and pollen tube germination. Maize plants in which ZmPti1a expression was silenced by RNA interference (RNAi) produced pollen with decreased competitive ability. Hence, our data provide evidence that ZmPti1a plays an important part in a signalling pathway that accelerates pollen performance and male fitness. ZmPti1a from maize is involved in pollen-specific processes during the progamic phase of reproduction, probably in crucial signalling processes associated with regions of callose deposition. Pollen

Hydrocephalus induces dynamic spatiotemporal regulation of aquaporin-4 expression in the rat brain

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Praetorius Jeppe

2010-11-01

Full Text Available Abstract Background The water channel protein aquaporin-4 (AQP4 is reported to be of possible major importance for accessory cerebrospinal fluid (CSF circulation pathways. We hypothesized that changes in AQP4 expression in specific brain regions correspond to the severity and duration of hydrocephalus. Methods Hydrocephalus was induced in adult rats (~8 weeks by intracisternal kaolin injection and evaluated after two days, one week and two weeks. Using magnetic resonance imaging (MRI we quantified lateral ventricular volume, water diffusion and blood-brain barrier properties in hydrocephalic and control animals. The brains were analysed for AQP4 density by western blotting and localisation by immunohistochemistry. Double fluorescence labelling was used to study cell specific origin of AQP4. Results Lateral ventricular volume was significantly increased over control at all time points after induction and the periventricular apparent diffusion coefficient (ADC value significantly increased after one and two weeks of hydrocephalus. Relative AQP4 density was significantly decreased in both cortex and periventricular region after two days and normalized after one week. After two weeks, periventricular AQP4 expression was significantly increased. Relative periventricular AQP4 density was significantly correlated to lateral ventricular volume. AQP4 immunohistochemical analysis demonstrated the morphological expression pattern of AQP4 in hydrocephalus in astrocytes and ventricular ependyma. AQP4 co-localized with astrocytic glial fibrillary acidic protein (GFAP in glia limitans. In vascular structures, AQP4 co-localized to astroglia but not to microglia or endothelial cells. Conclusions AQP4 levels are significantly altered in a time and region dependent manner in kaolin-induced hydrocephalus. The presented data suggest that AQP4 could play an important neurodefensive role, and may be a promising future pharmaceutical target in hydrocephalus and CSF

Cell-specific expression of calcineurin immunoreactivity within the rat basolateral amygdala complex and colocalization with the neuropeptide Y Y1 receptor.

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Leitermann, Randy J; Sajdyk, Tammy J; Urban, Janice H

2012-10-01

Neuropeptide Y (NPY) produces potent anxiolytic effects via activation of NPY Y1 receptors (Y1r) within the basolateral amygdaloid complex (BLA). The role of NPY in the BLA was recently expanded to include the ability to produce stress resilience and long-lasting reductions in anxiety-like behavior. These persistent behavioral effects are dependent upon activity of the protein phosphatase, calcineurin (CaN), which has long been associated with shaping long-term synaptic signaling. Furthermore, NPY-induced reductions in anxiety-like behavior persist months after intra-BLA delivery, which together indicate a form of neuronal plasticity had likely occurred. To define a site of action for NPY-induced CaN signaling within the BLA, we employed multi-label immunohistochemistry to determine which cell types express CaN and if CaN colocalizes with the Y1r. We have previously reported that both major neuronal cell populations in the BLA, pyramidal projection neurons and GABAergic interneurons, express the Y1r. Therefore, this current study evaluated CaN immunoreactivity in these cell types, along with Y1r immunoreactivity. Antibodies against calcium-calmodulin kinase II (CaMKII) and GABA were used to identify pyramidal neurons and GABAergic interneurons, respectively. A large population of CaN immunoreactive cells displayed Y1r immunoreactivity (90%). Nearly all (98%) pyramidal neurons displayed CaN immunoreactivity, while only a small percentage of interneurons (10%) contained CaN immunoreactivity. Overall, these anatomical findings provide a model whereby NPY could directly regulate CaN activity in the BLA via activation of the Y1r on CaN-expressing, pyramidal neurons. Importantly, they support BLA pyramidal neurons as prime targets for neuronal plasticity associated with the long-term reductions in anxiety-like behavior produced by NPY injections into the BLA. Copyright © 2012 Elsevier B.V. All rights reserved.

Mas-allatotropin in the developing antennal lobe of the sphinx moth Manduca sexta: distribution, time course, developmental regulation, and colocalization with other neuropeptides.

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Utz, Sandra; Huetteroth, Wolf; Vömel, Matthias; Schachtner, Joachim

2008-01-01

The paired antennal lobes (ALs) of the sphinx moth Manduca sexta serve as a well-established model for studying development of the primary integration centers for odor information in the brain. To further reveal the role of neuropeptides during AL development, we have analyzed cellular distribution, developmental time course, and regulation of the neuropeptide M. sexta allatotropin (Mas-AT). On the basis of morphology and appearance during AL formation, seven major types of Mas-AT-immunoreactive (ir) cells could be distinguished. Mas-AT-ir cells are identified as local, projection, and centrifugal neurons, which are either persisting larval or newly added adult-specific neurons. Complementary immunostaining with antisera against two other neuropeptide families (A-type allatostatins, RFamides) revealed colocalization within three of the Mas-AT-ir cell types. On the basis of this neurochemistry, the most prominent type of Mas-AT-ir neurons, the local AT neurons (LATn), could be divided in three subpopulations. The appearance of the Mas-AT-ir cell types occurring during metamorphosis parallels the rising titer of the developmental hormone 20-hydroxyecdysone (20E). Artificially shifting the 20E titer to an earlier developmental time point resulted in the precocious occurrence of Mas-AT immunostaining. This result supports the hypothesis that the pupal rise of 20E is causative for Mas-AT expression during AL development. Comparing localization and developmental time course of Mas-AT and other neuropeptides with the time course of AL formation suggests various functions for these neuropeptides during development, including an involvement in the formation of the olfactory glomeruli.

MaquiBright™ standardized maqui berry extract significantly increases tear fluid production and ameliorates dry eye-related symptoms in a clinical pilot trial.

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Hitoe, S; Tanaka, J; Shimoda, H

2014-09-01

Dry eye symptoms, resulting from insufficient tear fluid generation, represent a considerable burden for a largely underestimated number of people. We concluded from earlier pre-clinical investigations that the etiology of dry eyes encompasses oxidative stress burden to lachrymal glands and that antioxidant MaquiBright™ Aristotelia chilensis berry extract helps restore glandular activity. In this pilot trial we investigated 13 healthy volunteers with moderately dry eyes using Schirmer test, as well as a questionnaire which allows for estimating the impact of dry eyes on daily routines. Study participants were assigned to one of two groups, receiving MaquiBright™ at daily dosage of either 30 mg (N.=7) or 60 mg (N.=6) over a period of 60 days. Both groups presented with significantly (Peye dryness on daily routines was evaluated employing the "Dry Eye-related Quality of life Score" (DEQS), with values spanning from zero (impact) to a maximum score of 60. Participants had comparable baseline values of 41.0±7.7 (30 mg) and 40.2±6.3 (60 mg). With 30 mg treatment the score significantly decreased to 21.8±3.9 and 18.9±3.9, after 30 and 60 days, respectively. With 60 mg treatment the DEQS significantly decreased to 26.9±5.3 and 11.1±2.7, after 30 and 60 days, respectively. Blood was drawn for safety analyses (complete blood rheology and -chemistry) at all three investigative time points without negative findings. In conclusion, while daily supplementation with 30 mg MaquiBright™ is effective, the dosage of 60 significantly increased tear fluid volume at all investigative time points and decreased dry eye symptoms to almost a quarter from initial values after two months treatment.

Human Homolog of Drosophila Ariadne (HHARI) is a marker of cellular proliferation associated with nuclear bodies

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Elmehdawi, Fatima; Wheway, Gabrielle; Szymanska, Katarzyna [Division of Clinical Sciences, Leeds Institute of Molecular Medicine, Level 8, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom); Adams, Matthew [BioScreening Technology Group, Biomedical Health Research Center, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom); High, Alec S. [Department of Histopathology, Bexley Wing, St. James' s University Hospital, Beckett Street, Leeds, LS9 7TF West Yorkshire (United Kingdom); Johnson, Colin A., E-mail: c.johnson@leeds.ac.uk [Division of Clinical Sciences, Leeds Institute of Molecular Medicine, Level 8, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom); Robinson, Philip A. [Division of Clinical Sciences, Leeds Institute of Molecular Medicine, Level 8, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF West Yorkshire (United Kingdom)

2013-02-01

HHARI (also known as ARIH1) is an ubiquitin-protein ligase and is the cognate of the E2, UbcH7 (UBE2L3). To establish a functional role for HHARI in cellular proliferation processes, we performed a reverse genetics screen that identified n=86/522 (16.5%) ubiquitin conjugation components that have a statistically significant effect on cell proliferation, which included HHARI as a strong hit. We then produced and validated a panel of specific antibodies that establish HHARI as both a nuclear and cytoplasmic protein that is expressed in all cell types studied. HHARI was expressed at higher levels in nuclei, and co-localized with nuclear bodies including Cajal bodies (p80 coilin, NOPP140), PML and SC35 bodies. We confirmed reduced cellular proliferation after ARIH1 knockdown with individual siRNA duplexes, in addition to significantly increased levels of apoptosis, an increased proportion of cells in G2 phase of the cell cycle, and significant reductions in total cellular RNA levels. In head and neck squamous cell carcinoma biopsies, there are higher levels of HHARI expression associated with increased levels of proliferation, compared to healthy control tissues. We demonstrate that HHARI is associated with cellular proliferation, which may be mediated through its interaction with UbcH7 and modification of proteins in nuclear bodies. -- Highlights: ► We produce and validate new antibody reagents for the ubiquitin-protein ligase HHARI. ► HHARI colocalizes with nuclear bodies including Cajal, PML and SC35 bodies. ► We establish new functions in cell proliferation regulation for HHARI. ► Increased HHARI expression associates with squamous cell carcinoma and proliferation.

Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice

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Keshavarzian Ali

2011-06-01

Full Text Available Abstract Background Exposure to particulate matter (PM air pollution may be an important environmental factor leading to exacerbations of inflammatory illnesses in the GI tract. PM can gain access to the gastrointestinal (GI tract via swallowing of air or secretions from the upper airways or mucociliary clearance of inhaled particles. Methods We measured PM-induced cell death and mitochondrial ROS generation in Caco-2 cells stably expressing oxidant sensitive GFP localized to mitochondria in the absence or presence of an antioxidant. C57BL/6 mice were exposed to a very high dose of urban PM from Washington, DC (200 μg/mouse or saline via gastric gavage and small bowel and colonic tissue were harvested for histologic evaluation, and RNA isolation up to 48 hours. Permeability to 4kD dextran was measured at 48 hours. Results PM induced mitochondrial ROS generation and cell death in Caco-2 cells. PM also caused oxidant-dependent NF-κB activation, disruption of tight junctions and increased permeability of Caco-2 monolayers. Mice exposed to PM had increased intestinal permeability compared with PBS treated mice. In the small bowel, colocalization of the tight junction protein, ZO-1 was lower in the PM treated animals. In the small bowel and colon, PM exposed mice had higher levels of IL-6 mRNA and reduced levels of ZO-1 mRNA. Increased apoptosis was observed in the colon of PM exposed mice. Conclusions Exposure to high doses of urban PM causes oxidant dependent GI epithelial cell death, disruption of tight junction proteins, inflammation and increased permeability in the gut in vitro and in vivo. These PM-induced changes may contribute to exacerbations of inflammatory disorders of the gut.

The effect of IT and Co-location on knowledge dissemination

NARCIS (Netherlands)

Song, Michael; Berends, Hans; van der Bij, Hans; Weggeman, Mathieu

Due to the increasing globalization of businesses, new ideas for innovation need to be disseminated rapidly both within and across different departments and divisions. Frequently, ideas and information are dispersed over globally distributed organizations or team members. As a result, the exchange

The effect of IT and co-location on knowledge dissemination

NARCIS (Netherlands)

Song, X.M.; Berends, J.J.; Bij, van der J.D.; Weggeman, M.C.D.P.

2007-01-01

Due to the increasing globalization of businesses, new ideas for innovation need to be disseminated rapidly both within and across different departments and divisions. Frequently, ideas and information are dispersed over globally distributed organizations or team members. As a result, the exchange

Prognostic significance of repeat biopsy in lupus nephritis: Histopathologic worsening and a short time between biopsies is associated with significantly increased risk for end stage renal disease and death.

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Arriens, Cristina; Chen, Sixia; Karp, David R; Saxena, Ramesh; Sambandam, Kamalanathan; Chakravarty, Eliza; James, Judith A; Merrill, Joan T

2017-12-01

histopathology had died compared to 2 (3.2%) of non-worsening patients. Biopsy worsening was associated with a significantly greater 15-year risk of ESRD (Hazard Ratio 4.2, p=0.0001) and death (Hazard Ratio 4.3, p=0.022), adjusting for age, gender, race, biopsy class, and treatment. Time between first and second biopsies was 5years in 28. Over a 15-year period, those with <1year between first and second biopsies (presumably enriched for patients with early clinical signs of progression) had a significantly greater risk of ESRD (Hazard Ratio 13.7, p<0.0001) and death (Hazard Ratio 16.9, p=0.0022) after adjusting for age, gender, race, biopsy class, and treatment. A repeat renal biopsy demonstrating worsening pathology increases the risk of ESRD and death more than four-fold compared to non-worsening patients. Given known potential mismatch between biopsy and clinical data, repeat biopsies may add important information and justify changes in treatment not considered on clinical grounds. Earlier detection of poor prognostic signs in those without early clinical deterioration might improve outcomes in enough patients to reconsider cost effectiveness of routine repeat biopsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Editorial Commentary: Big Data Suggest That Because of a Significant Increased Risk of Postoperative Infection, Steroid Injection Is Not Recommended After Ankle Arthroscopy.

Science.gov (United States)

Brand, Jefferson C

2016-02-01

A recent study addressing infection rate after intra-articular steroid injection during ankle arthroscopy gives pause to this practice, with an odds ratio of 2.2 in the entire population that was injected with a steroid simultaneously with ankle arthroscopy compared with patients who did not receive an ankle injection. Big data, used in the study upon which the Editor comments here, suggest that because of a significant increased risk of postoperative infection, steroid injection is not recommended after ankle arthroscopy. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Increased expression of p62/SQSTM1 in prion diseases and its association with pathogenic prion protein.

Science.gov (United States)

Homma, Takujiro; Ishibashi, Daisuke; Nakagaki, Takehiro; Satoh, Katsuya; Sano, Kazunori; Atarashi, Ryuichiro; Nishida, Noriyuki

2014-03-28

Prion diseases are neurodegenerative disorders characterized by the aggregation of abnormally folded prion protein (PrP(Sc)). In this study, we focused on the mechanism of clearance of PrP(Sc), which remains unclear. p62 is a cytosolic protein known to mediate both the formation and degradation of aggregates of abnormal proteins. The levels of p62 protein increased in prion-infected brains and persistently infected cell cultures. Upon proteasome inhibition, p62 co-localized with PrP(Sc), forming a large aggregate in the perinuclear region, hereafter referred to as PrP(Sc)-aggresome. These aggregates were surrounded with autophagosome marker LC3 and lysosomes in prion-infected cells. Moreover, transient expression of the phosphomimic form of p62, which has enhanced ubiquitin-binding activity, reduced the amount of PrP(Sc) in prion-infected cells, indicating that the activation of p62 could accelerate the clearance of PrP(Sc). Our findings would thus suggest that p62 could be a target for the therapeutic control of prion diseases.

Strain selection, biomass to biofuel conversion, and resource colocation have strong impacts on the economic performance of algae cultivation sites

Directory of Open Access Journals (Sweden)

Erik R. Venteris

2014-09-01

Full Text Available Decisions involving strain selection, biomass to biofuel technology, and the location of cultivation facilities can strongly influence the economic viability of an algae-based biofuel enterprise. We summarize our past results in a new analysis to explore the relative economic impact of these design choices. Our growth model is used to predict average biomass production for two saline strains (Nannocloropsis salina, Arthrospira sp., one fresh to brackish strain (Chlorella sp., DOE strain 1412, and one freshwater strain (order Sphaeropleales. Biomass to biofuel conversion is compared between lipid extraction (LE and hydrothermal liquefaction (HTL technologies. National-scale models of water, CO2 (as flue gas, land acquisition, site leveling, construction of connecting roads, and transport of HTL oil to existing refineries are used in conjunction with estimates of fuel value (from HTL to prioritize and select from 88,692 unit farms (UF, 405 ha in pond area, a number sufficient to produce 136E+9 L yr-1 of renewable diesel (36 billion gallons yr-1. Strain selection and choice of conversion technology have large economic impacts, with differences between combinations of strains and biomass to biofuel technologies being up to $10 million dollars yr-1 UF-1. Results based on the most productive strain, HTL-based fuel conversion, and resource costs show that the economic potential between geographic locations within the selection can differ by up to $4 million yr-1 UF-1, with 1.8 BGY of production possible from the most cost-effective sites. The local spatial variability in site rank is extreme, with very high and low sites within 10s of km of each other. Colocation with flue gas sources has a strong influence on rank, but the most costly resource component varies from site to site. The highest rank UFs are located predominantly in Florida and Texas, but most states south of 37°N latitude contain promising locations.

Strain selection, biomass to biofuel conversion, and resource colocation have strong impacts on the economic performance of algae cultivation sites

Energy Technology Data Exchange (ETDEWEB)

Venteris, Erik R.; Wigmosta, Mark S.; Coleman, Andre M.; Skaggs, Richard

2014-09-16

Decisions involving strain selection, biomass to biofuel technology, and the location of cultivation facilities can strongly influence the economic viability of an algae-based biofuel enterprise. In this contribution we summarize our past results in a new analysis to explore the relative economic impact of these design choices. We present strain-specific growth model results from two saline strains (Nannocloropsis salina, Arthrospira sp.), a fresh to brackish strain (Chlorella sp., DOE strain 1412), and a freshwater strain of the order Sphaeropleales. Biomass to biofuel conversion is compared between lipid extraction (LE) and hydrothermal liquefaction (HTL) technologies. National-scale models of water, CO2 (as flue gas), land acquisition, site leveling, construction of connecting roads, and transport of HTL oil to existing refineries are used in conjunction with estimates of fuel value (from HTL) to prioritize and select from 88,692 unit farms (UF, 405 ha in pond area), a number sufficient to produce 136E+9 L yr-1 of renewable diesel (36 billion gallons yr-1, BGY). Strain selection and choice of conversion technology have large economic impacts, with differences between combinations of strains and biomass to biofuel technologies being up to $10 million dollars yr-1 UF-1. Results based on the most productive species, HTL-based fuel conversion, and resource costs show that the economic potential between geographic locations within the selection can differ by up to $4 million yr-1 UF-1, with 2.0 BGY of production possible from the most cost-effective sites. The local spatial variability in site rank is extreme, with very high and low rank sites within 10s of km of each other. Colocation with flue gas sources has a strong influence on site rank, but the most costly resource component varies from site to site. The highest rank sites are located predominantly in Florida and Texas, but most states south of 37°N latitude contain promising locations. Keywords: algae

Strain Selection, Biomass to Biofuel Conversion, and Resource Colocation have Strong Impacts on the Economic Performance of Algae Cultivation Sites

Energy Technology Data Exchange (ETDEWEB)

Venteris, Erik R., E-mail: erik.venteris@pnl.gov; Wigmosta, Mark S.; Coleman, Andre M.; Skaggs, Richard L. [Pacific Northwest National Laboratory, Richland, WA (United States)

2014-09-16

Decisions involving strain selection, biomass to biofuel technology, and the location of cultivation facilities can strongly influence the economic viability of an algae-based biofuel enterprise. We summarize our past results in a new analysis to explore the relative economic impact of these design choices. Our growth model is used to predict average biomass production for two saline strains (Nannochloropsis salina and Arthrospira sp.), one fresh to brackish strain (Chlorella sp., DOE strain 1412), and one freshwater strain (order Sphaeropleales). Biomass to biofuel conversion is compared between lipid extraction and hydrothermal liquefaction (HTL) technologies. National-scale models of water, CO{sub 2} (as flue gas), land acquisition, site leveling, construction of connecting roads, and transport of HTL oil to existing refineries are used in conjunction with estimates of fuel value (from HTL) to prioritize and select from 88,692 unit farms (UF, 405 ha in pond area), a number sufficient to produce 136E + 9 L year{sup −1} of renewable diesel [36 billion gallons year{sup −1} (BGY)]. Strain selection and choice of conversion technology have large economic impacts, with differences between combinations of strains and biomass to biofuel technologies being up to $10 million year{sup −1} UF{sup −1}. Results based on the most productive strain, HTL-based fuel conversion, and resource costs show that the economic potential between geographic locations within the selection can differ by up to 4 million year{sup −1} UF{sup −1}, with 1.8 BGY of production possible from the most cost-effective sites. The local spatial variability in site rank is extreme, with very high and low sites within 10 kms of each other. Colocation with flue gas sources has a strong influence on rank, but the most costly resource component varies from site to site. The highest rank UFs are located predominantly in Florida and Texas, but most states south of 37°N latitude contain promising

Increased CD147 and MMP-9 expression in the normal rat brain after gamma irradiation

International Nuclear Information System (INIS)

Li Hong; Wei Ming; Li Shenghui; Zhou Ziwei; Xu Desheng

2013-01-01

Radiation-induced vascular injury is a major complication of Gamma knife surgery (GKS). Previous studies have shown that CD147 and MMP-9 are closely associated with vascular remodeling and pathological angiogenesis. Thus, we analysed changes in CD147 and MMP-9 expression in the cerebral cortex to investigate the correlation between CD147 and MMP-9 in the rat following GKS. Adult male Wistar rats were subjected to GKS at a maximum dose of 75 Gy and then euthanized 1 to 12 weeks later. Using immunohistochemistry and western blot analysis, we found that CD147 and MMP-9 expression were markedly upregulated in the target area 8-12 weeks after GKS when compared with the control group. Immunofluorescent double staining demonstrated that CD147 signals colocalized with CD31, GFAP and MMP-9-positive cells. Importantly, CD147 levels correlated with increased MMP-9 expression in irradiated brain tissue. For the first time, these data demonstrate a potential relationship between CD147 and MMP-9 following GKS. In addition, our study also suggests that CD147 and MMP-9 may play a role in vascular injury after GKS. (author)

Software Tool for Significantly Increasing Airport Throughput, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — NASA's Next Generation Air Transportation System (NextGen) Airportal effort seeks to optimize aircraft surface movements through approaches that could double or...

Modeling of enhanced catalysis in multienzyme nanostructures: effect of molecular scaffolds, spatial organization, and concentration.

Science.gov (United States)

Roberts, Christopher C; Chang, Chia-en A

2015-01-13

Colocalized multistep enzymatic reaction pathways within biological catabolic and metabolic processes occur with high yield and specificity. Spatial organization on membranes or surfaces may be associated with increased efficiency of intermediate substrate transfer. Using a new Brownian dynamics package, GeomBD, we explored the geometric features of a surface-anchored enzyme system by parallel coarse-grained Brownian dynamics simulations of substrate diffusion over microsecond (μs) to millisecond (ms) time scales. We focused on a recently developed glucose oxidase (GOx), horseradish peroxidase (HRP), and DNA origami-scaffold enzyme system, where the H2O2 substrate of HRP is produced by GOx. The results revealed and explained a significant advantage in catalytic enhancement by optimizing interenzyme distance and orientation in the presence of the scaffold model. The planar scaffold colocalized the enzymes and provided a diffusive barrier that enhanced substrate transfer probability, becoming more relevant with increasing interenzyme distance. The results highlight the importance of protein geometry in the proper assessment of distance and orientation dependence on the probability of substrate transfer. They shed light on strategies for engineering multienzyme complexes and further investigation of enhanced catalytic efficiency for substrate diffusion between membrane-anchoring proteins.

Colocalization properties of elementary Ca(2+) release signals with structures specific to the contractile filaments and the tubular system of intact mouse skeletal muscle fibers.

Science.gov (United States)

Georgiev, Tihomir; Zapiec, Bolek; Förderer, Moritz; Fink, Rainer H A; Vogel, Martin

2015-12-01

Ca(2+) regulates several important intracellular processes. We combined second harmonic generation (SHG) and two photon excited fluorescence microscopy (2PFM) to simultaneously record the SHG signal of the myosin filaments and localized elementary Ca(2+) release signals (LCSs). We found LCSs associated with Y-shaped structures of the myosin filament pattern (YMs), so called verniers, in intact mouse skeletal muscle fibers under hypertonic treatment. Ion channels crucial for the Ca(2+) regulation are located in the tubular system, a system that is important for Ca(2+) regulation and excitation-contraction coupling. We investigated the tubular system of intact, living mouse skeletal muscle fibers using 2PFM and the fluorescent Ca(2+) indicator Fluo-4 dissolved in the external solution or the membrane dye di-8-ANEPPS. We simultaneously measured the SHG signal from the myosin filaments of the skeletal muscle fibers. We found that at least a subset of the YMs observed in SHG images are closely juxtaposed with Y-shaped structures of the transverse tubules (YTs). The distances of corresponding YMs and YTs yield values between 1.3 μm and 4.1 μm including pixel uncertainty with a mean distance of 2.52±0.10 μm (S.E.M., n=41). Additionally, we observed that some of the linear-shaped areas in the tubular system are colocalized with linear-shaped areas in the SHG images. Copyright © 2015 Elsevier Inc. All rights reserved.

Scope and Significance of Eating Disorders.

Science.gov (United States)

Mitchell, James E.; Eckert, Elke D.

1987-01-01

Describes the increasing prevalence of anorexia nervosa and bulimia in many industrialized societies, and their association with significant morbidity and mortality. Discusses the genetic risks for the development of anorexia nervosa, and treatment strategies. Of these, pharmacotherapy and psychotherapy, particularly those incorporating…

In vivo topical application of acetyl aspartic acid increases fibrillin-1 and collagen IV deposition leading to a significant improvement of skin firmness.

Science.gov (United States)

Gillbro, J M; Merinville, E; Cattley, K; Al-Bader, T; Hagforsen, E; Nilsson, M; Mavon, A

2015-10-01

Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A-A-A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F-actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in-use trial demonstrated that 1% A-A-A was well tolerated. In this study, the aim was to investigate whether A-A-A could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study. Two separate double-blind vehicle-controlled in vivo studies were conducted using a 1% A-A-A containing oil-in-water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12-day treatment of A-A-A on collagen IV (COLIV) and fibrillin-1. In a subsequent pilot study, 0.1% retinol was used for comparison to A-A-A (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness. Twelve-day topical application of 1% A-A-A significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% A-A-A and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and A-A-A. However, only A-A-A exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of A-A-A as a skin

Immense random colocalization, revealed by automated high content image cytometry, seriously questions FISH as gold standard for detecting EML4-ALK fusion.

Science.gov (United States)

Smuk, Gábor; Tornóczky, Tamás; Pajor, László; Chudoba, Ilse; Kajtár, Béla; Sárosi, Veronika; Pajor, Gábor

2018-05-19

EML4-ALK gene fusion (inv2(p21p23)) of non-small cell lung cancer (NSCLC) predisposes to tyrosine kinase inhibitor treatment. One of the gold standard diagnostics is the dual color (DC) break-apart (BA) FISH technique, however, the unusual closeness of the involved genes has been suggested to raise likelihood of random co-localization (RCL) of signals. Although this is suspected to decrease sensitivity (often to as low as 40-70%), the exact level and effect of RCL has not been revealed thus far. Signal distances were analyzed to the 0.1 µm precision in more than 25,000 nuclei, via automated high content-image cytometry. Negative and positive controls were created using conventional DC BA-, and inv2(p21p23) mimicking probe-sets, respectively. Average distance between red and green signals was 9.72 pixels (px) (±5.14px) and 3.28px (±2.44px), in positives and negatives, respectively; overlap in distribution being 41%. Specificity and sensitivity of correctly determining ALK status was 97% and 29%, respectively. When investigating inv2(p21p23) with DC BA FISH, specificity is high, but seven out of ten aberrant nuclei are inevitably falsely classified as negative, due to the extreme level of RCL. Together with genetic heterogeneity and dilution effect of non-tumor cells in NSCLC, this immense analytical false negativity is the primary cause behind the often described low diagnostic sensitivity. These results convincingly suggest that if FISH is to remain a gold standard for detecting the therapy relevant inv(2), either a modified evaluation protocol, or a more reliable probe-design should be considered than the current DC BA one. © 2018 International Society for Advancement of Cytometry. © 2018 International Society for Advancement of Cytometry.

TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

Science.gov (United States)

Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

2016-07-07

Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. © 2016 by The American Society of Hematology.

Loading of the knee during 3.0 T MRI is associated with significantly increased medial meniscus extrusion in mild and moderate osteoarthritis

Energy Technology Data Exchange (ETDEWEB)

Stehling, Christoph, E-mail: christoph.stehling@radiology.ucsf.edu [Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA (United States); Department of Clinical Radiology, University of Muenster, Muenster (Germany); Souza, Richard B. [Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA (United States); Graverand, Marie-Pierre Hellio Le; Wyman, Bradley T. [Pfizer Inc. New London, CT (United States); Li, Xiaojuan; Majumdar, Sharmila; Link, Thomas M. [Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA (United States)

2012-08-15

Purpose: Standard knee MRI is performed under unloading (ULC) conditions and not much is known about changes of the meniscus, ligaments or cartilage under loading conditions (LC). The aim is to study the influence of loading of different knee structures at 3 Tesla (T) in subjects with osteoarthritis (OA) and normal controls. Materials and methods: 30 subjects, 10 healthy and 20 with radiographic evidence of OA (10 mild and 10 moderate) underwent 3 T MRI under ULC and LC at 50% body weight. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous abnormalities. The changes between ULC and LC were assessed. For meniscus, cartilage and ligaments the changes of lesions, signal and shape were evaluated. In addition, for the meniscus changes in extrusion were examined. A multivariate regression model was used for correlations to correct the data for the impact of age, gender, BMI. A paired T-Test was performed to calculate the differences in meniscus extrusion. Results: Subjects with degenerative knee abnormalities demonstrated significantly increased meniscus extrusion under LC when compared to normal subjects (p = 0.0008-0.0027). Subjects with knee abnormalities and higher KL scores showed significantly more changes in lesion, signal and shape of the meniscus (80% (16/20) vs. 20% (2/10); p = 0.0025), ligaments and cartilage during LC. Conclusion: The study demonstrates that axial loading has an effect on articular cartilage, ligament, and meniscus morphology, which is more significant in subjects with degenerative disease and may serve as an additional diagnostic tool for disease diagnosis and assessing progression in subjects with knee OA.

Loading of the knee during 3.0 T MRI is associated with significantly increased medial meniscus extrusion in mild and moderate osteoarthritis

International Nuclear Information System (INIS)

Stehling, Christoph; Souza, Richard B.; Graverand, Marie-Pierre Hellio Le; Wyman, Bradley T.; Li, Xiaojuan; Majumdar, Sharmila; Link, Thomas M.

2012-01-01

Purpose: Standard knee MRI is performed under unloading (ULC) conditions and not much is known about changes of the meniscus, ligaments or cartilage under loading conditions (LC). The aim is to study the influence of loading of different knee structures at 3 Tesla (T) in subjects with osteoarthritis (OA) and normal controls. Materials and methods: 30 subjects, 10 healthy and 20 with radiographic evidence of OA (10 mild and 10 moderate) underwent 3 T MRI under ULC and LC at 50% body weight. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous abnormalities. The changes between ULC and LC were assessed. For meniscus, cartilage and ligaments the changes of lesions, signal and shape were evaluated. In addition, for the meniscus changes in extrusion were examined. A multivariate regression model was used for correlations to correct the data for the impact of age, gender, BMI. A paired T-Test was performed to calculate the differences in meniscus extrusion. Results: Subjects with degenerative knee abnormalities demonstrated significantly increased meniscus extrusion under LC when compared to normal subjects (p = 0.0008–0.0027). Subjects with knee abnormalities and higher KL scores showed significantly more changes in lesion, signal and shape of the meniscus (80% (16/20) vs. 20% (2/10); p = 0.0025), ligaments and cartilage during LC. Conclusion: The study demonstrates that axial loading has an effect on articular cartilage, ligament, and meniscus morphology, which is more significant in subjects with degenerative disease and may serve as an additional diagnostic tool for disease diagnosis and assessing progression in subjects with knee OA.

The PTI1-like kinase ZmPti1a from maize (Zea mays L. co-localizes with callose at the plasma membrane of pollen and facilitates a competitive advantage to the male gametophyte

Directory of Open Access Journals (Sweden)

Wienand Udo

2006-10-01

Full Text Available Abstract Background The tomato kinase Pto confers resistance to bacterial speck disease caused by Pseudomonas syringae pv. tomato in a gene for gene manner. Upon recognition of specific avirulence factors the Pto kinase activates multiple signal transduction pathways culminating in induction of pathogen defense. The soluble cytoplasmic serine/threonine kinase Pti1 is one target of Pto phosphorylation and is involved in the hypersensitive response (HR reaction. However, a clear role of Pti1 in plant pathogen resistance is uncertain. So far, no Pti1 homologues from monocotyledonous species have been studied. Results Here we report the identification and molecular analysis of four Pti1-like kinases from maize (ZmPti1a, -b, -c, -d. These kinase genes showed tissue-specific expression and their corresponding proteins were targeted to different cellular compartments. Sequence similarity, expression pattern and cellular localization of ZmPti1b suggested that this gene is a putative orthologue of Pti1 from tomato. In contrast, ZmPti1a was specifically expressed in pollen and sequestered to the plasma membrane, evidently owing to N-terminal modification by myristoylation and/or S-acylation. The ZmPti1a:GFP fusion protein was not evenly distributed at the pollen plasma membrane but accumulated as an annulus-like structure which co-localized with callose (1,3-β-glucan deposition. In addition, co-localization of ZmPti1a and callose was observed during stages of pollen mitosis I and pollen tube germination. Maize plants in which ZmPti1a expression was silenced by RNA interference (RNAi produced pollen with decreased competitive ability. Hence, our data provide evidence that ZmPti1a plays an important part in a signalling pathway that accelerates pollen performance and male fitness. Conclusion ZmPti1a from maize is involved in pollen-specific processes during the progamic phase of reproduction, probably in crucial signalling processes associated with regions

Prognostic Significance of Creatinine Increases During an Acute Heart Failure Admission in Patients With and Without Residual Congestion: A Post Hoc Analysis of the PROTECT Data.

Science.gov (United States)

Metra, Marco; Cotter, Gad; Senger, Stefanie; Edwards, Christopher; Cleland, John G; Ponikowski, Piotr; Cursack, Guillermo C; Milo, Olga; Teerlink, John R; Givertz, Michael M; O'Connor, Christopher M; Dittrich, Howard C; Bloomfield, Daniel M; Voors, Adriaan A; Davison, Beth A

2018-05-01

The importance of a serum creatinine increase, traditionally considered worsening renal function (WRF), during admission for acute heart failure has been recently debated, with data suggesting an interaction between congestion and creatinine changes. In post hoc analyses, we analyzed the association of WRF with length of hospital stay, 30-day death or cardiovascular/renal readmission and 90-day mortality in the PROTECT study (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). Daily creatinine changes from baseline were categorized as WRF (an increase of 0.3 mg/dL or more) or not. Daily congestion scores were computed by summing scores for orthopnea, edema, and jugular venous pressure. Of the 2033 total patients randomized, 1537 patients had both available at study day 14. Length of hospital stay was longer and 30-day cardiovascular/renal readmission or death more common in patients with WRF. However, these were driven by significant associations in patients with concomitant congestion at the time of assessment of renal function. The mean difference in length of hospital stay because of WRF was 3.51 (95% confidence interval, 1.29-5.73) more days ( P =0.0019), and the hazard ratio for WRF on 30-day death or heart failure hospitalization was 1.49 (95% confidence interval, 1.06-2.09) times higher ( P =0.0205), in significantly congested than nonsignificantly congested patients. A similar trend was observed with 90-day mortality although not statistically significant. In patients admitted for acute heart failure, WRF defined as a creatinine increase of ≥0.3 mg/dL was associated with longer length of hospital stay, and worse 30- and 90-day outcomes. However, effects were largely driven by patients who had residual congestion at the time of renal function assessment. URL: https

Significant Lactic Acidosis from Albuterol

Directory of Open Access Journals (Sweden)

Deborah Diercks

2018-03-01

Full Text Available Lactic acidosis is a clinical entity that demands rapid assessment and treatment to prevent significant morbidity and mortality. With increased lactate use across many clinical scenarios, lactate values themselves cannot be interpreted apart from their appropriate clinical picture. The significance of Type B lactic acidosis is likely understated in the emergency department (ED. Given the mortality that sepsis confers, a serum lactate is an important screening study. That said, it is with extreme caution that we should interpret and react to the resultant elevated value. We report a patient with a significant lactic acidosis. Though he had a high lactate value, he did not require aggressive resuscitation. A different classification scheme for lactic acidosis that focuses on the bifurcation of the “dangerous” and “not dangerous” causes of lactic acidosis may be of benefit. In addition, this case is demonstrative of the potential overuse of lactates in the ED.

Symmetric dimeric bisbenzimidazoles DBP(n reduce methylation of RARB and PTEN while significantly increase methylation of rRNA genes in MCF-7 cancer cells.

Directory of Open Access Journals (Sweden)

Svetlana V Kostyuk

Full Text Available Hypermethylation is observed in the promoter regions of suppressor genes in the tumor cancer cells. Reactivation of these genes by demethylation of their promoters is a prospective strategy of the anticancer therapy. Previous experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n are able to block DNA methyltransferase activities. It was also found that DBP(n produces a moderate effect on the activation of total gene expression in HeLa-TI population containing epigenetically repressed avian sarcoma genome.It is shown that DBP(n are able to penetrate the cellular membranes and accumulate in breast carcinoma cell MCF-7, mainly in the mitochondria and in the nucleus, excluding the nucleolus. The DBP(n are non-toxic to the cells and have a weak overall demethylation effect on genomic DNA. DBP(n demethylate the promoter regions of the tumor suppressor genes PTEN and RARB. DBP(n promotes expression of the genes RARB, PTEN, CDKN2A, RUNX3, Apaf-1 and APC "silent" in the MCF-7 because of the hypermethylation of their promoter regions. Simultaneously with the demethylation of the DNA in the nucleus a significant increase in the methylation level of rRNA genes in the nucleolus was detected. Increased rDNA methylation correlated with a reduction of the rRNA amount in the cells by 20-30%. It is assumed that during DNA methyltransferase activity inhibition by the DBP(n in the nucleus, the enzyme is sequestered in the nucleolus and provides additional methylation of the rDNA that are not shielded by DBP(n.It is concluded that DBP (n are able to accumulate in the nucleus (excluding the nucleolus area and in the mitochondria of cancer cells, reducing mitochondrial potential. The DBP (n induce the demethylation of a cancer cell's genome, including the demethylation of the promoters of tumor suppressor genes. DBP (n significantly increase the methylation of ribosomal RNA genes in the nucleoli. Therefore the further study of these compounds is needed

Assay of Calcium Transients and Synapses in Rat Hippocampal Neurons by Kinetic Image Cytometry and High-Content Analysis: An In Vitro Model System for Postchemotherapy Cognitive Impairment.

Science.gov (United States)

McDonough, Patrick M; Prigozhina, Natalie L; Basa, Ranor C B; Price, Jeffrey H

2017-07-01

Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days. Kinetic Image Cytometry™ (KIC™) methods were developed to quantify spontaneously occurring intracellular calcium transients representing the activity of the neurons, and high-content analysis (HCA) methods were developed to quantify the expression, colocalization, and puncta formed by synaptic proteins (postsynaptic density protein-95 [PSD-95] and presynaptic protein Synapsin-1 [Syn-1]). As quantified by KIC, FSK increased the occurrence and synchronization of the calcium transients indicating stimulatory effects on RHN activity, whereas TAM had inhibitory effects. As quantified by HCA, FSK also increased PSD-95 puncta and PSD-95:Syn-1 colocalization, whereas ES increased the puncta of both PSD-95 and Syn-1 with little effect on colocalization. The estrogen receptor antagonist FUL also increased PSD-95 puncta. In contrast, TAM reduced Syn-1 and PSD-95:Syn-1 colocalization, consistent with its inhibitory effects on the calcium transients. Thus TAM reduced activity and synapse formation by the RHNs, which may relate to the ability of this agent to cause PCCI. The results illustrate that KIC and HCA can be used to quantify neurotoxic and neuroprotective effects of chemicals in RHNs to investigate mechanisms and potential therapeutics for PCCI.

Mining Significant Semantic Locations from GPS Data

DEFF Research Database (Denmark)

Cao, Xin; Cong, Gao; Jensen, Christian Søndergaard

2010-01-01

With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

Mining significant semantic locations from GPS data

DEFF Research Database (Denmark)

Cao, Xin; Cong, Gao; Jensen, Christian S.

2010-01-01

With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

CB1 receptor antagonism increases hippocampal acetylcholine release: site and mechanism of action.

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Degroot, Aldemar; Köfalvi, Attila; Wade, Mark R; Davis, Richard J; Rodrigues, Ricardo J; Rebola, Nelson; Cunha, Rodrigo A; Nomikos, George G

2006-10-01

Evidence indicates that blockade of cannabinoid receptors increases acetylcholine (ACh) release in brain cortical regions. Although it is assumed that this type of effect is mediated through CB1 receptor (CB1R) antagonism, several in vitro functional studies recently have suggested non-CB1R involvement. In addition, neither the precise neuroanatomical site nor the exact mechanisms underlying this effect are known. We thoroughly examined these issues using a combination of systemic and local administration of CB1R antagonists, different methods of in vivo microdialysis, CB1R knockout (KO) mice, tissue measurements of ACh, and immunochemistry. First, we showed that systemic injections of the CB1R antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR-141716A) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) dose-dependently increased hippocampal ACh efflux. Likewise, local hippocampal, but not septal, infusions of SR141716A or AM251 increased hippocampal ACh release. It is noteworthy that the stimulatory effects of systemically administered CB1R antagonists on hippocampal ACh release were completely abolished in CB1R KO mice. CB1R KO mice had similar basal but higher stress-enhanced hippocampal ACh levels compared with wild-type controls. It is interesting that dopamine D1 receptor antagonism counteracted the stimulatory effect of CB1R blockade on hippocampal ACh levels. Finally, immunohistochemical methods revealed that a high proportion of CB1R-positive nerve terminals were found in hippocampus and confirmed the colocalization of CB1 receptors with cholinergic and dopaminergic nerve terminals. In conclusion, hippocampal ACh release may specifically be controlled through CB1Rs located on both cholinergic and dopaminergic neuronal projections, and CB1R antagonism increases hippocampal ACh release, probably through both a direct

Impulsive-antisocial psychopathic traits linked to increased volume and functional connectivity within prefrontal cortex.

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Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S; Kiehl, Kent A; Koenigs, Michael

2017-07-01

Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Studies of brain structure and function in psychopathy have frequently identified abnormalities in the prefrontal cortex. However, findings have not yet converged to yield a clear relationship between specific subregions of prefrontal cortex and particular psychopathic traits. We performed a multimodal neuroimaging study of prefrontal cortex volume and functional connectivity in psychopathy, using a sample of adult male prison inmates (N = 124). We conducted volumetric analyses in prefrontal subregions, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. We found that overall psychopathy severity and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger prefrontal subregion volumes, particularly in the medial orbitofrontal cortex and dorsolateral prefrontal cortex. Furthermore, Factor 2 scores were also positively correlated with functional connectivity between several areas of the prefrontal cortex. The results were not attributable to age, race, IQ, substance use history, or brain volume. Collectively, these findings provide evidence for co-localized increases in prefrontal cortex volume and intra-prefrontal functional connectivity in relation to impulsive/antisocial psychopathic traits. © The Author (2017). Published by Oxford University Press.

Infections and mixed infections with the selected species of Borrelia burgdorferi sensu lato complex in Ixodes ricinus ticks collected in eastern Poland: a significant increase in the course of 5 years.

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Wójcik-Fatla, Angelina; Zając, Violetta; Sawczyn, Anna; Sroka, Jacek; Cisak, Ewa; Dutkiewicz, Jacek

2016-02-01

In the years 2008-2009 and 2013-2014, 1620 and 1500 questing Ixodes ricinus ticks, respectively, were examined on the territory of the Lublin province (eastern Poland). The presence of three pathogenic species causing Lyme disease was investigated: Borrelia burgdorferi sensu stricto, B. afzelii and B. garinii. The proportion of I. ricinus ticks infected with B. burgdorferi sensu lato showed a highly significant increase between 2008-2009 and 2013-2014, from 6.0 to 15.3%. A significant increase was noted with regard to all types of infections with individual species: single (4.7-7.8%), dual (1.2-6.6%), and triple (0.1-0.9%). When expressed as the percent of all infections, the frequency of mixed infections increased from 21.4 to 49.2%. Statistical analysis performed with two methods (by calculating of odds ratios and by Fisher's exact test) showed that the frequencies of mixed infections in most cases proved to be significantly greater than expected. The strongest associations were found between B. burgdorferi s. s. and B. afzelii, and between B. burgdorferi s. s. and B. garinii. They appeared to be highly significant (P eastern Poland, and dramatic enhancement of mixed infections with individual species, which may result in mixed infections of humans and exacerbation of the clinical course of Lyme disease cases on the studied area.

Significance testing in ridge regression for genetic data

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De Iorio Maria

2011-09-01

Full Text Available Abstract Background Technological developments have increased the feasibility of large scale genetic association studies. Densely typed genetic markers are obtained using SNP arrays, next-generation sequencing technologies and imputation. However, SNPs typed using these methods can be highly correlated due to linkage disequilibrium among them, and standard multiple regression techniques fail with these data sets due to their high dimensionality and correlation structure. There has been increasing interest in using penalised regression in the analysis of high dimensional data. Ridge regression is one such penalised regression technique which does not perform variable selection, instead estimating a regression coefficient for each predictor variable. It is therefore desirable to obtain an estimate of the significance of each ridge regression coefficient. Results We develop and evaluate a test of significance for ridge regression coefficients. Using simulation studies, we demonstrate that the performance of the test is comparable to that of a permutation test, with the advantage of a much-reduced computational cost. We introduce the p-value trace, a plot of the negative logarithm of the p-values of ridge regression coefficients with increasing shrinkage parameter, which enables the visualisation of the change in p-value of the regression coefficients with increasing penalisation. We apply the proposed method to a lung cancer case-control data set from EPIC, the European Prospective Investigation into Cancer and Nutrition. Conclusions The proposed test is a useful alternative to a permutation test for the estimation of the significance of ridge regression coefficients, at a much-reduced computational cost. The p-value trace is an informative graphical tool for evaluating the results of a test of significance of ridge regression coefficients as the shrinkage parameter increases, and the proposed test makes its production computationally feasible.

Clinical significance of increased gelatinolytic activity in the rectal mucosa during external beam radiation therapy of prostate cancer

International Nuclear Information System (INIS)

Hovdenak, Nils; Wang Junru; Sung, C.-C.; Kelly, Thomas; Fajardo, Luis F.; Hauer-Jensen, Martin

2002-01-01

Purpose: Rectal toxicity (proctitis) is a dose-limiting factor in pelvic radiation therapy. Mucosal atrophy, i.e., net extracellular matrix degradation, is a prominent feature of radiation proctitis, but the underlying mechanisms are not known. We prospectively examined changes in matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinase A and B) in the rectal mucosa during radiation therapy of prostate cancer, as well as the relationships of these changes with symptomatic, structural, and cellular evidence of radiation proctitis. Methods and Materials: Seventeen patients scheduled for external beam radiation therapy for prostate cancer were prospectively enrolled. Symptoms of gastrointestinal toxicity were recorded, and endoscopy with biopsy of the rectal mucosa was performed before radiation therapy, as well as 2 and 6 weeks into the treatment course. Radiation proctitis was assessed by endoscopic scoring, quantitative histology, and quantitative immunohistochemistry. MMP-2 and MMP-9 were localized immunohistochemically, and activities were determined by gelatin zymography. Results: Symptoms, endoscopic scores, histologic injury, and mucosal macrophages and neutrophils increased from baseline to 2 weeks. Symptoms increased further from 2 weeks to 6 weeks, whereas endoscopic and cellular evidence of proctitis did not. Compared to pretreatment values, there was increased total gelatinolytic activity of MMP-2 and MMP-9 at 2 weeks (p=0.02 and p=0.004, respectively) and 6 weeks (p=0.006 and p=0.001, respectively). Active MMP-2 was increased at both time points (p=0.0001 and p=0.002). Increased MMP-9 and MMP-2 at 6 weeks was associated with radiation-induced diarrhea (p=0.007 and p=0.02, respectively) and with mucosal neutrophil infiltration (rho=0.62). Conclusions: Pelvic radiation therapy causes increased MMP-2 and MMP-9 activity in the rectal mucosa. These changes correlate with radiation-induced diarrhea and granulocyte infiltration and may contribute to abnormal

Addition of sodium caseinate to skim milk increases nonsedimentable casein and causes significant changes in rennet-induced gelation, heat stability, and ethanol stability.

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Lin, Yingchen; Kelly, Alan L; O'Mahony, James A; Guinee, Timothy P

2017-02-01

The protein content of skim milk was increased from 3.3 to 4.1% (wt/wt) by the addition of a blend of skim milk powder and sodium caseinate (NaCas), in which the weight ratio of skim milk powder to NaCas was varied from 0.8:0.0 to 0.0:0.8. Addition of NaCas increased the levels of nonsedimentable casein (from ∼6 to 18% of total casein) and calcium (from ∼36 to 43% of total calcium) and reduced the turbidity of the fortified milk, to a degree depending on level of NaCas added. Rennet gelation was adversely affected by the addition of NaCas at 0.2% (wt/wt) and completely inhibited at NaCas ≥0.4% (wt/wt). Rennet-induced hydrolysis was not affected by added NaCas. The proportion of total casein that was nonsedimentable on centrifugation (3,000 × g, 1 h, 25°C) of the rennet-treated milk after incubation for 1 h at 31°C increased significantly on addition of NaCas at ≥0.4% (wt/wt). Heat stability in the pH range 6.7 to 7.2 and ethanol stability at pH 6.4 were enhanced by the addition of NaCas. It is suggested that the negative effect of NaCas on rennet gelation is due to the increase in nonsedimentable casein, which upon hydrolysis by chymosin forms into small nonsedimentable particles that physically come between, and impede the aggregation of, rennet-altered para-casein micelles, and thereby inhibit the development of a gel network. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Gadolinium-enhanced cardiac MR exams of human subjects are associated with significant increases in the DNA repair marker 53BP1, but not the damage marker γH2AX.

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Jennifer S McDonald

Full Text Available Magnetic resonance imaging is considered low risk, yet recent studies have raised a concern of potential damage to DNA in peripheral blood leukocytes. This prospective Institutional Review Board-approved study examined potential double-strand DNA damage by analyzing changes in the DNA damage and repair markers γH2AX and 53BP1 in patients who underwent a 1.5 T gadolinium-enhanced cardiac magnetic resonance (MR exam. Sixty patients were enrolled (median age 55 years, 39 males. Patients with history of malignancy or who were receiving chemotherapy, radiation therapy, or steroids were excluded. MR sequence data were recorded and blood samples obtained immediately before and after MR exposure. An automated immunofluorescence assay quantified γH2AX or 53BP1 foci number in isolated peripheral blood mononuclear cells. Changes in foci number were analyzed using the Wilcoxon signed-rank test. Clinical and MR procedural characteristics were compared between patients who had a >10% increase in γH2AX or 53BP1 foci numbers and patients who did not. The number of γH2AX foci did not significantly change following cardiac MR (median foci per cell pre-MR = 0.11, post-MR = 0.11, p = .90, but the number of 53BP1 foci significantly increased following MR (median foci per cell pre-MR = 0.46, post-MR = 0.54, p = .0140. Clinical and MR characteristics did not differ significantly between patients who had at least a 10% increase in foci per cell and those who did not. We conclude that MR exposure leads to a small (median 25% increase in 53BP1 foci, however the clinical relevance of this increase is unknown and may be attributable to normal variation instead of MR exposure.

Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain.

Directory of Open Access Journals (Sweden)

Kazuo Nakamoto

Full Text Available GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA. However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently increased at day 7, but not at days 1, 3 and 14, after CFA injection. GPR40 was co-localized with NeuN, a neuron marker, but not with glial fibrillary acidic protein (GFAP, an astrocyte marker. At day 1 after CFA injection, GFAP protein expression was markedly increased in the hypothalamus. These increases were significantly inhibited by the intracerebroventricular injection of flavopiridol (15 nmol, a cyclin-dependent kinase inhibitor, depending on the decreases in both the increment of GPR40 protein expression and the induction of mechanical allodynia and thermal hyperalgesia at day 7 after CFA injection. Furthermore, the level of DHA in the hypothalamus tissue was significantly increased in a flavopiridol reversible manner at day 1, but not at day 7, after CFA injection. The intracerebroventricular injection of DHA (50 µg and GW9508 (1.0 µg, a GPR40-selective agonist, significantly reduced mechanical allodynia and thermal hyperalgesia at day 7, but not at day 1, after CFA injection. These effects were inhibited by intracerebroventricular pretreatment with GW1100 (10 µg, a GPR40 antagonist. The protein expression of GPR40 was colocalized with that of β-endorphin and proopiomelanocortin, and a single intracerebroventricular injection of GW9508 (1.0 µg significantly increased the number of neurons double-stained for c-Fos and proopiomelanocortin in the arcuate nucleus of the hypothalamus. Our findings suggest that hypothalamic GPR40 activated by free long

Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain.

Science.gov (United States)

Nakamoto, Kazuo; Nishinaka, Takashi; Sato, Naoya; Mankura, Mitsumasa; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

2013-01-01

GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently increased at day 7, but not at days 1, 3 and 14, after CFA injection. GPR40 was co-localized with NeuN, a neuron marker, but not with glial fibrillary acidic protein (GFAP), an astrocyte marker. At day 1 after CFA injection, GFAP protein expression was markedly increased in the hypothalamus. These increases were significantly inhibited by the intracerebroventricular injection of flavopiridol (15 nmol), a cyclin-dependent kinase inhibitor, depending on the decreases in both the increment of GPR40 protein expression and the induction of mechanical allodynia and thermal hyperalgesia at day 7 after CFA injection. Furthermore, the level of DHA in the hypothalamus tissue was significantly increased in a flavopiridol reversible manner at day 1, but not at day 7, after CFA injection. The intracerebroventricular injection of DHA (50 µg) and GW9508 (1.0 µg), a GPR40-selective agonist, significantly reduced mechanical allodynia and thermal hyperalgesia at day 7, but not at day 1, after CFA injection. These effects were inhibited by intracerebroventricular pretreatment with GW1100 (10 µg), a GPR40 antagonist. The protein expression of GPR40 was colocalized with that of β-endorphin and proopiomelanocortin, and a single intracerebroventricular injection of GW9508 (1.0 µg) significantly increased the number of neurons double-stained for c-Fos and proopiomelanocortin in the arcuate nucleus of the hypothalamus. Our findings suggest that hypothalamic GPR40 activated by free long chain fatty

Glutamate Receptors GluR1 and GluR4 in the Hamster Superior Colliculus: Distribution and Co-localization with Calcium-Binding Proteins and GABA

International Nuclear Information System (INIS)

Choi, Jae-Sik; Lee, Jea-Young; Jeon, Chang-Jin

2009-01-01

We investigated the distributions of AMPA glutamate receptor subtypes GluR1 and GluR4 in the hamster superior colliculus (SC) with antibody immunocytochemistry and the effect of enucleation on these distributions. We compared these labelings to those of GluR2/3 in our previous report (Park et al., 2004, Neurosci Res., 49:139–155) and calcium-binding proteins calbindin D28K, calretinin, parvalbumin, and GABA. Anti-GluR1-immunoreactive (IR) cells were scattered throughout the SC. By contrast, anti-GluR4-IR cells formed distinct clusters within the lower lateral stratum griseum intermediale (SGI) and lateral stratum album intermediale (SAI). The GluR1- and GluR4-IR neurons varied in size and morphology. The average diameter of the GluR1-IR cells was 13.00 µm, while the GluR4-IR cells was 20.00 µm. The large majority of IR neurons were round or oval cells, but they also included stellate, vertical fusiform and horizontal cells. Monocular enucleation appeared to have no effect on the GluR1 and GluR4 immunoreactivity. Some GluR1-IR cells expressed calbindin D28K (9.50%), calretinin (6.59%), parvalbumin (2.53%), and GABA (20.54%). By contrast, no GluR4-IR cells expressed calcium-binding proteins or GABA. Although the function of the AMPA receptor subunits in SC is not yet clear, the distinct segregation of the GluR subunits, its differential colocalization with calcium-binding proteins and GABA, and differential responses to enucleation suggest the functional diversity of the receptor subunits in visuo-motor integration in the SC

pPKCδ activates SC35 splicing factor during H9c2 myoblastic differentiation.

Science.gov (United States)

Zara, Susi; Falconi, Mirella; Rapino, Monica; Zago, Michela; Orsini, Giovanna; Mazzotti, Giovanni; Cataldi, Amelia; Teti, Gabriella

2011-01-01

Although Protein Kinase C (PKC) isoforms' role in the neonatal and adult cardiac tissue development and ageing has been widely described "in vivo", the interaction of such enzymes with specific nuclear substrates needs to be investigated. The aim of our research has been the study of the expression, localization and interaction with the splicing factor SC35 of PKC isoforms (α, δ, ε, ζ) and their potential role in modulating the transcription machinery. H9c2 cells induced to myoblast differentiation in the presence of 1% Horse Serum (HS) have represented our experimental model. The expression of PKC isoforms, their distribution and interaction with SC35 have been evaluated by western blotting, co-immunoprecipitation and double gold immunolabeling for transmission and scanning electron microscopy. Our results show PKCδ as the most expressed isoform in differentiated cells. Surprisingly, the distribution of PKCδ and SC35 does not show any significant modification between 10%FBS and 1%HS treated samples and no co-localization is observed. Moreover the interaction between the phosphorylated form of PKCδ (pPKCδ) and SC35 increases, is distributed and co-localizes within the nucleus of differentiated H9c2. These data represent reasonable evidence of pPKCδ mediated SC35 splicing factor activation, suggesting its direct effect on transcription via interaction with the transcription machinery. Furthermore, this co-localization represents a crucial event resulting in downstream changes in transcription of components which determine the morphological modifications related to cardiomyoblast differentiated phenotype.

WE-H-207A-05: Spatial Co-Localization of F-18 NaF Vs. F-18 FDG Defined Disease Volumes

Energy Technology Data Exchange (ETDEWEB)

Ferjancic, P; Harmon, S; Jeraj, R [University of Wisconsin, Madison, WI (United States); Chen, S [1st Hospital of China Medical University, Shenyang, Liaoning (China); Simoncic, U [Jozef Stefan Institute, Ljubljana (Slovenia)

2016-06-15

Purpose: Both [F-18]NaF and [F-18]FDG show promise for quantitative PET/CT assessment in metastatic prostate cancer to bone. Broad agreement between the tracers has been shown but voxel-wise correspondence has not been explored in depth. This study evaluates the spatial co-localization of [F-18]NaF PET and [F-18]FDG PET in bone lesions. Methods: Seventy-three lesion contours were identified in six patients receiving dynamic NaF PET/CT and FDG PET/CT scans two hours apart using identical fields-of-view. Tracer uptake (SUV) reflecting 60 minutes post-injection was modeled from kinetic parameters. Lesions were segmented by a physician separately on NaF PET and FDG PET. PET images were rigidly aligned using skeletal references on CT images. Lesion size, degree of overlap, voxel-wise tracer uptake values (SUV), and CT density distributions were compared using Dice coefficient, Positive Predictive Value (PPV), and Spearman rank correlation tests. Results: Across all patients, 42 lesions were identified on NaF PET (median 1.4 cm{sup 3}, range <1–204 cm{sup 3}) compared to 31 using FDG PET (median 1.8 cm{sup 3}, range <1–244 cm{sup 3}). Spatial cooccurrence was found in 25 lesion pairs. Lesions on NaF PET had PPV of 0.91 and on FDG a PPV of 0.65. Overall, NaF-defined lesions were 47% (±24%) larger by volume with moderate overlap to FDG, resulting in mean Dice coefficient of 34% (±22%). In areas of overlap, voxel-wise correlation of NaF and FDG SUV was moderate (ρ=0.56). Expanding to regions of non-spatial overlap, voxels contained in FDG-only contours were almost exclusively low HU (median 118), compared to dense regions of NaF-only voxels (median 250). In sclerotic sub-volumes (HU > 300) NaF-defined contours encompassed 83% of total FDG volume. Conclusion: Moderate voxel-wise correlation of FDG and NaF PET/CT uptake was observed. Spatial discrepancies in FDG and NaF PET/CT imaging of boney metastases could be influenced by poor sensitivity of FDG PET/CT in

Cathepsin K expression is increased in oral lichen planus.

Science.gov (United States)

Siponen, Maria; Bitu, Carolina Cavalcante; Al-Samadi, Ahmed; Nieminen, Pentti; Salo, Tuula

2016-11-01

Oral lichen planus (OLP) is an idiopathic T-cell-mediated mucosal inflammatory disease. Cathepsin K (Cat K) is one of the lysosomal cysteine proteases. It is involved in many pathological conditions, including osteoporosis and cancer. The expression and role of Cat K in OLP are unknown. Twenty-five oral mucosal specimens diagnosed histopathologically as OLP and fourteen healthy controls (HC) were used to study the immunohistochemical (IHC) expression of Cat K. Colocalization of Cat K with CD1a, Melan-A, CD68, CD45, mast cell tryptase (MCT), and Toll-like receptors (TLRs) 4 and 9 were studied using double IHC and/or immunofluorescence (IF) staining. Expression of Cat K was also evaluated in OLP tissue samples before and after topical tacrolimus treatment. Cat K was expressed in a higher percentage of cells in the epithelial zone, and the staining intensity was stronger in the stroma in OLP compared to controls (P < 0.001). In OLP, Cat K was present mostly in melanocytes and macrophages and sporadically in basal keratinocytes, endothelial cells, and extracellularly. Cat K was found also in some fibroblasts in HC and OLP samples. Coexpression of Cat K and TLRs 4 and 9 was seen in some dendritic cells (presumably melanocytes) and macrophages. In OLP, tacrolimus treatment reduced the expression of Cat K in the epithelium but increased it in the stroma. These results suggest that Cat K is involved in the pathogenesis of OLP. Cat K possibly takes part in the modulation of matrix molecules and cellular receptors. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dephytinisation with Intrinsic Wheat Phytase and Iron Fortification Significantly Increase Iron Absorption from Fonio (Digitaria exilis) Meals in West African Women

Science.gov (United States)

Moretti, Diego; Schuth, Stephan; Egli, Ines; Zimmermann, Michael B.; Brouwer, Inge D.

2013-01-01

Low iron and high phytic acid content make fonio based meals a poor source of bioavailable iron. Phytic acid degradation in fonio porridge using whole grain cereals as phytase source and effect on iron bioavailability when added to iron fortified fonio meals were investigated. Grains, nuts and seeds collected in Mali markets were screened for phytic acid and phytase activity. We performed an iron absorption study in Beninese women (n = 16), using non-dephytinised fonio porridge (FFP) and dephytinised fonio porridge (FWFP; 75% fonio-25% wheat), each fortified with 57Fe or 58Fe labeled FeSO4. Iron absorption was quantified by measuring the erythrocyte incorporation of stable iron isotopes. Phytic acid varied from 0.39 (bambara nut) to 4.26 g/100 g DM (pumpkin seed), with oilseeds values higher than grains and nuts. Phytase activity ranged from 0.17±1.61 (fonio) to 2.9±1.3 phytase unit (PU) per g (whole wheat). Phytic acid was almost completely degraded in FWFP after 60 min of incubation (pH≈5.0, 50°C). Phytate∶iron molar ratios decreased from 23.7∶1 in FFP to 2.7∶1 in FWFP. Iron fortification further reduced phytate∶iron molar ratio to 1.9∶1 in FFP and 0.3∶1 in FWFP, respectively. Geometric mean (95% CI) iron absorption significantly increased from 2.6% (0.8–7.8) in FFP to 8.3% (3.8–17.9) in FWFP (Pphytase increased fractional iron absorption 3.2 times, suggesting it could be a possible strategy to decrease PA in cereal-based porridges. PMID:24124445

Cellular regulation of the dopamine transporter

DEFF Research Database (Denmark)

Eriksen, Jacob

2010-01-01

-membrane spanning protein Tac, thereby creating an extracellular antibody epitope. Upon expression in HEK293 cells this TacDAT fusion protein displayed functional properties similar to the wild type transporter. In an ELISA based internalization assay, TacDAT intracellular accumulation was increased by inhibitors...... of lysosomal degradation and moreover TacDAT colocalized with the late endosomal marker Rab7. In the DA cell line 1Rb3An27 TacDAT also co-localized with EGFP-Rab7 and not with the recycling endosomal marker EGFP-Rab11. To assess whether sorting to late endosomes/lysosomes was a property also inherent...... to natively expressed transporter, DAT was visualized directly in cultured DA neurons using the fluorescent cocaine analog JHC 1-64. These data showed pronounced colocalization upon constitutive internalization with Lysotracker, a late endosomal/lysosomal marker; however only little cololization was observed...

Development of Quantitative Framework for Event Significance Evaluation

International Nuclear Information System (INIS)

Lee, Durk Hun; Kim, Min Chull; Kim, Inn Seock

2010-01-01

There is an increasing trend in quantitative evaluation of the safety significance of operational events using Probabilistic Safety Assessment (PSA) technique. An integrated framework for evaluation of event significance has been developed by Korea Institute of Nuclear Safety (KINS), which consists of an assessment hierarchy and a number of matrices. The safety significance of various events, e.g., internal or external initiating events that occurred during at-power or shutdown conditions, can be quantitatively analyzed using this framework, and then, the events rated according to their significance. This paper briefly describes the basic concept of the integrated quantitative framework for evaluation of event significance, focusing on the assessment hierarchy

The fate of task-irrelevant visual motion: perceptual load versus feature-based attention.

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Taya, Shuichiro; Adams, Wendy J; Graf, Erich W; Lavie, Nilli

2009-11-18

We tested contrasting predictions derived from perceptual load theory and from recent feature-based selection accounts. Observers viewed moving, colored stimuli and performed low or high load tasks associated with one stimulus feature, either color or motion. The resultant motion aftereffect (MAE) was used to evaluate attentional allocation. We found that task-irrelevant visual features received less attention than co-localized task-relevant features of the same objects. Moreover, when color and motion features were co-localized yet perceived to belong to two distinct surfaces, feature-based selection was further increased at the expense of object-based co-selection. Load theory predicts that the MAE for task-irrelevant motion would be reduced with a higher load color task. However, this was not seen for co-localized features; perceptual load only modulated the MAE for task-irrelevant motion when this was spatially separated from the attended color location. Our results suggest that perceptual load effects are mediated by spatial selection and do not generalize to the feature domain. Feature-based selection operates to suppress processing of task-irrelevant, co-localized features, irrespective of perceptual load.

Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

Science.gov (United States)

Korhan, Peyda; Erdal, Esra; Kandemiş, Emine; Cokaklı, Murat; Nart, Deniz; Yılmaz, Funda; Can, Alp; Atabey, Neşe

2014-01-01

c-Met, the receptor for Hepatocyte Growth Factor (HGF), overexpressed and deregulated in Hepatocellular Carcinoma (HCC). Caveolin 1 (CAV1), a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

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Peyda Korhan

Full Text Available c-Met, the receptor for Hepatocyte Growth Factor (HGF, overexpressed and deregulated in Hepatocellular Carcinoma (HCC. Caveolin 1 (CAV1, a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

Short-Term High-Fat Diet Increases Leptin Activation of CART Neurons and Advances Puberty in Female Mice.

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Venancio, Jade Cabestre; Margatho, Lisandra Oliveira; Rorato, Rodrigo; Rosales, Roberta Ribeiro Costa; Debarba, Lucas Kniess; Coletti, Ricardo; Antunes-Rodrigues, Jose; Elias, Carol F; Elias, Lucila Leico K

2017-11-01

Leptin is a permissive factor for puberty initiation, participating as a metabolic cue in the activation of the kisspeptin (Kiss1)-gonadotropin-releasing hormone neuronal circuitry; however, it has no direct effect on Kiss1 neurons. Leptin acts on hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons, participating in the regulation of energy homeostasis. We investigated the influence of a short-term high-fat diet (HFD) on the effect of leptin on puberty timing. Kiss1-hrGFP female mice received a HFD or regular diet (RD) after weaning at postnatal day (PN)21 and were studied at PN28 and PN32. The HFD increased body weight and plasma leptin concentrations and decreased the age at vaginal opening (HFD, 32 ± 0.53 days; RD, 38 ± 0.67 days). Similar colocalization of neurokinin B and dynorphin in Kiss1-hrGFP neurons of the arcuate nucleus (ARC) was observed between the HFD and RD groups. The HFD increased CART expression in the ARC and Kiss1 messenger RNA expression in the anteroventral periventricular (AVPV)/anterior periventricular (Pe). The HFD also increased the number of ARC CART neurons expressing leptin-induced phosphorylated STAT3 (signal transducer and activator of transcription 3) at PN32. Close apposition of CART fibers to Kiss1-hrGFP neurons was observed in the ARC of both RD- and HFD-fed mice. In conclusion, these data reinforce the notion that a HFD increases kisspeptin expression in the AVPV/Pe and advances puberty initiation. Furthermore, we have demonstrated that the HFD-induced earlier puberty is associated with an increase in CART expression in the ARC. Therefore, these data indicate that CART neurons in the ARC can mediate the effect of leptin on Kiss1 neurons in early puberty induced by a HFD. Copyright © 2017 Endocrine Society.

Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication

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Helen C. Atkinson

2015-01-01

Full Text Available Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL and treated with modern COG protocols (n=80 to determine longitudinal changes in body mass index (BMI and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5% were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P<0.004 for females but remained relatively unchanged for males (9.8% to 13.7%, P=0.7. Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P=0.0005, disease risk (P<0.0001, age (P=0.0001, and BMI z-score (P<0.0001 at diagnosis and total dose of steroid during maintenance (P=0.01. Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.

Combining modularity, conservation, and interactions of proteins significantly increases precision and coverage of protein function prediction

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Sers Christine T

2010-12-01

Full Text Available Abstract Background While the number of newly sequenced genomes and genes is constantly increasing, elucidation of their function still is a laborious and time-consuming task. This has led to the development of a wide range of methods for predicting protein functions in silico. We report on a new method that predicts function based on a combination of information about protein interactions, orthology, and the conservation of protein networks in different species. Results We show that aggregation of these independent sources of evidence leads to a drastic increase in number and quality of predictions when compared to baselines and other methods reported in the literature. For instance, our method generates more than 12,000 novel protein functions for human with an estimated precision of ~76%, among which are 7,500 new functional annotations for 1,973 human proteins that previously had zero or only one function annotated. We also verified our predictions on a set of genes that play an important role in colorectal cancer (MLH1, PMS2, EPHB4 and could confirm more than 73% of them based on evidence in the literature. Conclusions The combination of different methods into a single, comprehensive prediction method infers thousands of protein functions for every species included in the analysis at varying, yet always high levels of precision and very good coverage.

Among Metabolic Factors, Significance of Fasting and Postprandial Increases in Acyl and Desacyl Ghrelin and the Acyl/Desacyl Ratio in Obstructive Sleep Apnea before and after Treatment.

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Chihara, Yuichi; Akamizu, Takashi; Azuma, Masanori; Murase, Kimihiko; Harada, Yuka; Tanizawa, Kiminobu; Handa, Tomohiro; Oga, Toru; Mishima, Michiaki; Chin, Kazuo

2015-08-15

There are reports suggesting that obstructive sleep apnea (OSA) may itself cause weight gain. However, recent reports showed increases in body mass index (BMI) following continuous positive airway pressure (CPAP) treatments. When considering weight changes, changes in humoral factors that have significant effects on appetite such as acyl (AG) and desacyl ghrelin (DAG), leptin, insulin, and glucose and their interactions, examples of which are AG/DAG and AG/insulin, are important. The aim of this study was to test the hypothesis that some appetite-related factors had a specific profile before and after CPAP treatment. Metabolic parameters were measured cross-sectionally while fasting and 30, 60, 90, and 120 min following breakfast in no or mild OSA (apnea-hypopnea index fasting and postprandial glucose, insulin, and leptin levels did not differ between no or mild OSA and moderate-to-severe OSA participants, AG and DAG, including AG/DAG and AG/insulin, under fasting and postprandial conditions were significantly increased in the moderate-to-severe OSA patients (p continuous changes in ghrelin secretion in OSA patients existed at least within 3 months of CPAP treatment. Methods to prevent OSA as well as treatment in its early stage may be recommended. © 2015 American Academy of Sleep Medicine.

TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke

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Buckwalter Marion S

2010-10-01

Full Text Available Abstract Background TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging. Methods We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia. Results TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes. Conclusions We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial

TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke.

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Doyle, Kristian P; Cekanaviciute, Egle; Mamer, Lauren E; Buckwalter, Marion S

2010-10-11

TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging. We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia. TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes. We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial scar formation and the immune response to stroke.

Empirical Green's function analysis: Taking the next step

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Hough, S.E.

1997-01-01

An extension of the empirical Green's function (EGF) method is presented that involves determination of source parameters using standard EGF deconvolution, followed by inversion for a common attenuation parameter for a set of colocated events. Recordings of three or more colocated events can thus be used to constrain a single path attenuation estimate. I apply this method to recordings from the 1995-1996 Ridgecrest, California, earthquake sequence; I analyze four clusters consisting of 13 total events with magnitudes between 2.6 and 4.9. I first obtain corner frequencies, which are used to infer Brune stress drop estimates. I obtain stress drop values of 0.3-53 MPa (with all but one between 0.3 and 11 MPa), with no resolved increase of stress drop with moment. With the corner frequencies constrained, the inferred attenuation parameters are very consistent; they imply an average shear wave quality factor of approximately 20-25 for alluvial sediments within the Indian Wells Valley. Although the resultant spectral fitting (using corner frequency and ??) is good, the residuals are consistent among the clusters analyzed. Their spectral shape is similar to the the theoretical one-dimensional response of a layered low-velocity structure in the valley (an absolute site response cannot be determined by this method, because of an ambiguity between absolute response and source spectral amplitudes). I show that even this subtle site response can significantly bias estimates of corner frequency and ??, if it is ignored in an inversion for only source and path effects. The multiple-EGF method presented in this paper is analogous to a joint inversion for source, path, and site effects; the use of colocated sets of earthquakes appears to offer significant advantages in improving resolution of all three estimates, especially if data are from a single site or sites with similar site response.

Significantly increased detection rate of drugs of abuse in urine following the introduction of new German driving licence re-granting guidelines.

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Agius, Ronald; Nadulski, Thomas; Kahl, Hans-Gerhard; Dufaux, Bertin

2012-02-10

In this paper we present the first assessment of the new German driving licence re-granting medical and psychological assessment (MPA) guidelines by comparing over 3500 urine samples tested under the old MPA cut-offs to over 5000 samples tested under the new MPA cut-offs. Since the enzyme multiplied immunoassay technique (EMIT) technology used previously was not sensitive enough to screen for drugs at such low concentrations, as suggested by the new MPA guidelines, enzyme-linked immunosorbent assay (ELISA) screening kits were used to screen for the drugs of abuse at the new MPA cut-offs. The above comparison revealed significantly increased detection rates of drug use or exposure during the rehabilitation period as follows: 1.61, 2.33, 3.33, and 7 times higher for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), morphine, benzoylecgonine and amphetamine respectively. The present MPA guidelines seem to be more effective to detect non-abstinence from drugs of abuse and hence to detecting drivers who do not yet fulfil the MPA requirements to regain their revoked driving licence. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The Oral Bioavailability of Trans-Resveratrol from a Grapevine-Shoot Extract in Healthy Humans is Significantly Increased by Micellar Solubilization.

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Calvo-Castro, Laura A; Schiborr, Christina; David, Franziska; Ehrt, Heidi; Voggel, Jenny; Sus, Nadine; Behnam, Dariush; Bosy-Westphal, Anja; Frank, Jan

2018-05-01

Grapevine-shoot extract Vineatrol30 contains abundant resveratrol monomers and oligomers with health-promoting potential. However, the oral bioavailability of these compounds in humans is low (˂1-2%). The aim of this study was to improve the oral bioavailability of resveratrol from vineatrol by micellar solubilization. Twelve healthy volunteers (six women, six men) randomly ingested a single dose of 500 mg vineatrol (30 mg trans-resveratrol, 75 mg trans-ε-viniferin) as native powder or liquid micelles. Plasma and urine were collected at baseline and over 24 h after intake. Resveratrol and viniferin were analyzed by HPLC. The area under the plasma concentration-time curve (AUC) and mean maximum plasma trans-resveratrol concentrations were 5.0-fold and 10.6-fold higher, respectively, after micellar supplementation relative to the native powder. However, no detectable amounts of trans-ε-viniferin were found in either plasma or urine. The transepithelial permeability of trans-resveratrol and trans-ε-viniferin across differentiated Caco-2 monolayers was consistent to the absorbed fractions in vivo. The oral bioavailability of trans-resveratrol from the grapevine-shoot extract Vineatrol30 was significantly increased using a liquid micellar formulation, without any treatment-related adverse effects, making it a suitable system for improved supplementation of trans-resveratrol. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Non-alcoholic steatohepatitis : Clinical significance and pathogenesis

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de Knegt, RJ

2001-01-01

Non-alcoholic steatohepatitis (NASH) is a form of liver disease resembling alcoholic liver disease in a patient who does not consume significant amounts of alcohol. Since its first description in 1980 it has been recognized with increasing frequency. The natural course is relatively benign, but

Short-term increases in transient receptor potential vanilloid-1 mediate stress-induced enhancement of neuronal excitation.

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Weitlauf, Carl; Ward, Nicholas J; Lambert, Wendi S; Sidorova, Tatiana N; Ho, Karen W; Sappington, Rebecca M; Calkins, David J

2014-11-12

Progression of neurodegeneration in disease and injury is influenced by the response of individual neurons to stressful stimuli and whether this response includes mechanisms to counter declining function. Transient receptor potential (TRP) cation channels transduce a variety of disease-relevant stimuli and can mediate diverse stress-dependent changes in physiology, both presynaptic and postsynaptic. Recently, we demonstrated that knock-out or pharmacological inhibition of the TRP vanilloid-1 (TRPV1) capsaicin-sensitive subunit accelerates degeneration of retinal ganglion cell neurons and their axons with elevated ocular pressure, the critical stressor in the most common optic neuropathy, glaucoma. Here we probed the mechanism of the influence of TRPV1 on ganglion cell survival in mouse models of glaucoma. We found that induced elevations of ocular pressure increased TRPV1 in ganglion cells and its colocalization at excitatory synapses to their dendrites, whereas chronic elevation progressively increased ganglion cell Trpv1 mRNA. Enhanced TRPV1 expression in ganglion cells was transient and supported a reversal of the effect of TRPV1 on ganglion cells from hyperpolarizing to depolarizing, which was also transient. Short-term enhancement of TRPV1-mediated activity led to a delayed increase in axonal spontaneous excitation that was absent in ganglion cells from Trpv1(-/-) retina. In isolated ganglion cells, pharmacologically activated TRPV1 mobilized to discrete nodes along ganglion cell dendrites that corresponded to sites of elevated Ca(2+). These results suggest that TRPV1 may promote retinal ganglion cell survival through transient enhancement of local excitation and axonal activity in response to ocular stress. Copyright © 2014 the authors 0270-6474/14/3415369-13$15.00/0.

Co-localization of a CD1d-binding glycolipid with a radiation-attenuated sporozoite vaccine in LN-resident DCs for a robust adjuvant effect

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Li, Xiangming; Kawamura, Akira; Andrews, Chasity D.; Miller, Jessica L.; Wu, Douglass; Tsao, Tiffany; Zhang, Min; Oren, Deena; Padte, Neal N.; Porcelli, Steven A.; Wong, Chi-Huey; Kappe, Stefan H. I.; Ho, David D.; Tsuji, Moriya

2015-01-01

A CD1d-binding glycolipid, α-Galactosylceramide (αGalCer), activates invariant natural killer T (iNKT) cells and acts as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying nearly 100-fold stronger CD1d binding affinity. In the present study, 7DW8-5 was found to exert a more potent adjuvant effect than αGalCer for a vaccine based on radiation-attenuated sporozoites (RAS) of a rodent malaria parasite, Plasmodium yoelii, also referred to as irradiated P. yoelii sporozoites (IrPySpz). 7DW8-5 had a superb adjuvant effect only when the glycolipid and IrPySpz were conjointly administered intramuscularly (i.m.). Therefore, we evaluated the impact of distinctly different biodistribution patterns of αGalCer and 7DW8-5 on their respective adjuvant activities. While both glycolipids induce a similar cytokine response in sera of mice injected intravenously, after i.m. injection, αGalCer induces a systemic cytokine response, whereas 7DW8-5 is locally trapped by CD1d expressed by dendritic cells (DCs) in draining lymph nodes (dLNs). Moreover, the i.m. co-administration of 7DW8-5 with IrPySpz results in the recruitment of DCs to dLNs and the activation and maturation of DCs. These events cause the potent adjuvant effect of 7DW8-5, resulting in the enhancement of the CD8+ T-cell response induced by IrPySpz, and, ultimately, improved protection against malaria. Our study is the first to show that the co-localization of a CD1d-binding iNKT-cell stimulatory glycolipid and a vaccine, like RAS, in dLN-resident DCs upon i.m. conjoin administration governs the potency of the adjuvant effect of the glycolipid. PMID:26254338

Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy.

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Li, Chao; Vu, Kent; Hazelgrove, Krystina; Kuemmerle, John F

2015-12-01

The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-β1. Erk5 and MEF2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression of α-smooth muscle actin, γ-smooth muscle actin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-β1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation. Copyright © 2015 the American Physiological Society.

Factoring local sequence composition in motif significance analysis.

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Ng, Patrick; Keich, Uri

2008-01-01

We recently introduced a biologically realistic and reliable significance analysis of the output of a popular class of motif finders. In this paper we further improve our significance analysis by incorporating local base composition information. Relying on realistic biological data simulation, as well as on FDR analysis applied to real data, we show that our method is significantly better than the increasingly popular practice of using the normal approximation to estimate the significance of a finder's output. Finally we turn to leveraging our reliable significance analysis to improve the actual motif finding task. Specifically, endowing a variant of the Gibbs Sampler with our improved significance analysis we demonstrate that de novo finders can perform better than has been perceived. Significantly, our new variant outperforms all the finders reviewed in a recently published comprehensive analysis of the Harbison genome-wide binding location data. Interestingly, many of these finders incorporate additional information such as nucleosome positioning and the significance of binding data.

Expression patterns of emmprin and monocarboxylate transporter-1 in ovarian epithelial tumors.

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Fukuoka, Miyoko; Hamasaki, Makoto; Koga, Kaori; Hayashi, Hiroyuki; Aoki, Mikiko; Kawarabayashi, Tatsuhiko; Miyamoto, Shingo; Nabeshima, Kazuki

2012-10-01

Emmprin is a transmembrane glycoprotein known as a matrix metalloproteinase inducer and is highly up-regulated in malignant cancer cells. The monocarboxylate transporters (MCTs) are responsible for H(+)-linked transport of monocarboxylates across the cell membrane. It was recently demonstrated that proper plasma membrane localization and activity of MCTs require the presence of emmprin as a chaperone and that MCT-1 also acts as chaperone for emmprin. The objectives of this study were to clarify emmprin and MCT-1 expression patterns in ovarian epithelial tumors and to elucidate the clinicopathological significance of co-localization of the two molecules. Immunohistochemical analysis of 205 epithelial tumors indicated that emmprin is always localized in cell membranes but its distribution differs according to tumor type: in lateral membranes in 89 % of adenomas, in lateral and basal membranes in 76 % of borderline tumors, and in membranes surrounding the entire cell in 98 % of carcinomas. Most carcinomas in situ also showed a lateral and basal expression pattern. In only 21 % of the carcinomas, the cells expressing membranous MCT-1 showed co-localized emmprin expression. Poor co-localization of the two molecules was more frequently found in serous carcinomas. However, the overall survival was not significantly different for the good and poor co-localization carcinoma groups. These findings indicate that the emmprin expression pattern might discriminate between invasive carcinomas and borderline tumors including carcinoma in situ. Moreover, there may be an as yet unidentified regulatory mechanism(s), for localization of MCT-1 and emmprin in cell membranes in vivo.

Development and functional significance of dorsal air bags in ...

African Journals Online (AJOL)

Histological examination of the air bags showed that they were integumentary structures composed of an outer epidermis and an inner dermis. The air bags were not connected to the respiratory system. The body temperature (Tb) of Monteiro's Hornbill nestlings increased significantly with increasing age. Comparisons of ...

Measurements of recent microchannel-plate photomultipliers with significantly increased lifetime

Energy Technology Data Exchange (ETDEWEB)

Uhlig, Fred; Eyrich, Wolfgang; Lehmann, Albert; Britting, Alexander [Universitaet Erlangen, Physikal. Institut IV (Germany); Collaboration: PANDA-Collaboration

2015-07-01

Microchannel-plate photomultipliers (MCP-PMTs) are the favored sensors for the DIRC detectors (Detection of Internally Reflected Cherenkov Light) of the PANDA experiment. They are usable in high magnetic fields of up to 2T and reach a time resolution of better than 50 ps (σ). The anticipated average luminosity of 2.10{sup 32} cm{sup -2} s{sup -1} in the detector requires a rate capability high enough to withstand a detected photon rate of about 200 kHz cm{sup -2} at the MCP-PMT surfaces. The major drawback until recently was the limited lifetime of MCP-PMTs, which appears to be solved for the latest generation of MCP-PMT prototype devices. The aging parameter is the quantum efficiency as a function of the integrated anode charge, which will be in the region of 5 C/cm{sup 2} for the Barrel- and the Disc-DIRC. We simultaneously measured the aging of several MCP-PMTs, which were treated with different methods to enhance the lifetime. Results of these measurements are presented.

Increased NMDA receptor inhibition at an increased Sevoflurane MAC

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Brosnan Robert J

2012-06-01

Full Text Available Abstract Background Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC. Methods Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 μL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL plus 0.4 mg/mL dizocilpine (MK-801 was administered intrathecally at 4 μL/min, and the post-dizocilpine sevoflurane MAC was measured. Results Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P  Conclusions Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability.

Colocalization of Mating-Induced Fos and D2-Like Dopamine Receptors in the Medial Preoptic Area: Influence of Sexual Experience.

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Nutsch, Victoria L; Will, Ryan G; Robison, Christopher L; Martz, Julia R; Tobiansky, Daniel J; Dominguez, Juan M

2016-01-01

Dopamine in the medial preoptic area (mPOA) stimulates sexual activity in males. This is evidenced by microdialysis and microinjection experiments revealing that dopamine receptor antagonists in the mPOA inhibit sexual activity, whereas agonists facilitate behavior. Microdialysis experiments similarly show a facilitative role for dopamine, as levels of dopamine in the mPOA increase with mating. While the majority of evidence suggests an important role for dopamine receptors in the mPOA in the regulation of male sexual behaviors, whether sexual activity or sexual experience influence dopamine receptor function in the mPOA has not been previously shown. Here we used immunohistochemical assays to determine whether varying levels of sexual activity or experience influence the number of cells containing Fos or D2 receptor immunoreactivity. Results show that sexual experience facilitated subsequent behavior, namely experience decreased latencies. Moreover, the number of cells with immunoreactivity for Fos or D2 correlated with levels of sexual experience and sexual activity. Sexual activity increased Fos immunoreactivity. Sexually experienced animals also had significantly more D2-positive cells. Sexually inexperienced animals copulating for the first time had a larger percentage of D2-positive cells containing Fos, when compared to sexually experienced animals. Finally, regardless of experience, animals that had sex prior to sacrifice had significantly more D2-positive cells that contained Fos, vs. animals that did not copulate. These findings are noteworthy because sexually experienced animals display increased sexual efficiency. The differences in activation of D2 and changes in receptor density may play a role in this efficiency and other behavioral changes across sexual experience.

Elicitor Mixtures Significantly Increase Bioactive Compounds, Antioxidant Activity, and Quality Parameters in Sweet Bell Pepper

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Lina Garcia-Mier

2015-01-01

Full Text Available Sweet bell peppers are greatly appreciated for their taste, color, pungency, and aroma. Additionally, they are good sources of bioactive compounds with antioxidant activity, which can be improved by the use of elicitors. Elicitors act as metabolite-inducing factors (MIF by mimic stress conditions. Since plants rarely experience a single stress condition one by one but are more likely to be exposed to simultaneous stresses, it is important to evaluate the effect of elicitors on plant secondary metabolism as mixtures. Jasmonic acid (JA, hydrogen peroxide (HP, and chitosan (CH were applied to fruits and plants of bell pepper as mixtures. Bioactive compounds, antioxidant activity, and quality parameters were evaluated. The assessed elicitor cocktail leads to an increase in the variables evaluated (P ≤ 0.05 when applied to mature fruits after harvest, whereas the lowest values were observed in the treatment applied to immature fruits. Therefore, the application of the elicitor cocktail to harvested mature fruits is recommended in order to improve bioactive compounds and the antioxidant activity of sweet bell peppers.

Localization of aPKC lambda/iota and its interacting protein, Lgl2, is significantly associated with lung adenocarcinoma progression.

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Imamura, Naoko; Horikoshi, Yosuke; Matsuzaki, Tomohiko; Toriumi, Kentaro; Kitatani, Kanae; Ogura, Go; Masuda, Ryota; Nakamura, Naoya; Takekoshi, Susumu; Iwazaki, Masayuki

2013-12-20

Atypical protein kinase C lambda/iota (aPKC λ/ι) is expressed in several human cancers; however, the correlation between aPKC λ/ι localization and cancer progression in human lung adenocarcinoma (LAC) remains to be clarified. We found that patients with a high level of aPKC λ/ι expression in LAC had significantly shorter overall survival than those with a low level of aPKC λ/ι expression. In addition, localization of aPKC λ/ι in the apical membrane or at the cell-cell contact was associated with both lymphatic invasion and metastasis. The intercellular adhesion molecule, E-cadherin, was decreased in LACs with highly expressed aPKC λ/ι at the invasion site of tumor cells. This result suggested that the expression levels of aPKC λ/ι and E-cadherin reflect the progression of LAC. On double-immunohistochemical analysis, aPKC λ/ι and Lgl2, a protein that interacts with aPKC λ/ι, were co-localized within LACs. Furthermore, we found that Lgl2 bound the aPKC λ/ι-Par6 complex in tumor tissue by immune-cosedimentation analysis. Apical membrane localization of Lgl2 was correlated with lymphatic invasion and lymph node metastasis. These results thus indicate that aPKC λ/ι expression is altered upon the progression of LAC. This is also the first evidence to show aPKC λ/ι overexpression in LAC and demonstrates that aPKC λ/ι localization at the apical membrane or cell-cell contact is associated with lymphatic invasion and metastasis of the tumor.

Clinical significance of Phosphatidyl Inositol Synthase overexpression in oral cancer

International Nuclear Information System (INIS)

Kaur, Jatinder; Sawhney, Meenakshi; DattaGupta, Siddartha; Shukla, Nootan K; Srivastava, Anurag; Ralhan, Ranju

2010-01-01

We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure. Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems. Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p = 0.000). Further, PI synthase expression was significantly associated with de-differentiation of OSCCs, (p = 0.005) and tobacco consumption (p = 0.03, OR = 9.0). Exposure of oral cell systems to smokeless tobacco (ST) in vitro confirmed increase in PI synthase, Phosphatidylinositol 3-kinase (PI3K) and cyclin D1 levels. Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco

A subpopulation of dopaminergic neurons co-expresses serotonin in ventral mesencephalic cultures but not after intrastriatal transplantation in a rat model of Parkinsons disease

DEFF Research Database (Denmark)

Di Santo, Stefano; Seiler, Stefanie; Ducray, Angélique

2017-01-01

Cell replacement therapy is a promising avenue into the investigation and treatment of Parkinson’s disease (PD) and in some cases significant long-term motor improvements have been demonstrated. The main source of donor tissue is the human fetal ventral mesencephalon (VM), which consists...... 30% of the dopaminergic neurons in the donor tissue co-expressed serotonin, no co-localization could be detected in grafts one month after intrastriatal transplantation into hemi-parkinsonian rats. In conclusion, a significant and susceptible sub-population of dopaminergic neurons in fetal VM tissues...... both fetal rat and human dissociated, organotypic and neurosphere VM cultures as well as an animal model of PD were investigated. In dissociated rat VM cultures approximately 30% of the TH positive neurons co-expressed serotonin, while no co-localization with GABA was observed. Interestingly, co...

Significance of Lead Residues in Mallard Tissues

Science.gov (United States)

Longcore, J.R.; Locke, L.N.; Bagley, George E.; Andrews, R.

1974-01-01

Tissues of adult, lead-dosed mallards that either died or were sacrificed were analyzed for lead. Lead levels in brains, tibiae, and breast muscle of ducks that died and in tibiae of ducks that were sacrificed increased significantly from dosage until death. Lead in the heart, lung, and blood from sacrificed ducks decreased significantly from dosage until death. Lead concentrations in tissues from ducks in the two groups were not significantly different except for the liver, kidney, and lung. Average lead levels in the livers and kidneys of ducks that died were significantly higher than those in ducks that were sacrificed. The mean concentration of lead in the lungs of the ducks sacrificed was significantly higher than the mean level in the lungs of ducks that died. Measurements of the lead concentrations in this study, when compared with lead levels reported in the literature for avian and non-avian species, showed that arbitrary diagnostic levels indicating lead poisoning could be set. In mallard ducks, lead levels exceeding 3 ppm in the brain, 6 to 20 ppm in the kidney or liver, or 10 ppm in clotted blood from the heart indicated acute exposure to lead.

Molecular markers validation to drought resistance in wheat meal (Triticum aestivum L. under greenhouse conditions

Directory of Open Access Journals (Sweden)

Gabriel Julio

2013-08-01

Full Text Available With the aim to study the genetic resistance to drought and validate molecular markers co-localized with genes/QTLs for this factor, 16 varieties were evaluated as well as advanced lines of wheat meal (Triticum aestivum in two stages of crop development. Physiological parameters were considered: amount of chlorophyll (clo, wilting or severity degree (SEV and recovery (reco, morphological parameters: foliage dry matter (FDM and root dry matter (RDM, the integrated resistance mechanisms: water use efficiency (WUE, other parameters: number of grains (Ngrain and grain weight (Wgrain, biochemical parameters: Catalaza (CAT, Ascorbate Peroxidase (APX and Guaiacol Peroxidase (POX and three microsatellite markers (Xwmc603, Xwmc596, Xwmc9. Results showed significant differences for MSR and Ngrain. It was observed that Anzaldo, ERR2V.L-20, EARII2V.L-5, EARIZV.L-11, ERR2V.L-11 and EE2V.L-19 were the most resistant to drough water stress. There was a highly significant negative correlation between the MSR and Ngrain. All other variables showed low and non-significant correlations. In biochemical analyzes, the Anzaldo variety showed an increased enzymatic activity compared to controls in all cases (CAT-APX and POX, being the most resistant to water stress by drought. Finally, it was found that SSR markers (Xwmc596 and Xwmc9 are co-located with the gene / QTL of drought resistance and can be used for marker-assisted selection.

Was there significant tax evasion after the 1999 50 cent per pack cigarette tax increase in California?

Science.gov (United States)

Emery, S; White, M; Gilpin, E; Pierce, J

2002-01-01

Objectives: Several states, including California, have implemented large cigarette excise tax increases, which may encourage smokers to purchase their cigarettes in other lower taxed states, or from other lower or non-taxed sources. Such tax evasion thwarts tobacco control objectives and may cost the state substantial tax revenues. Thus, this study investigates the extent of tax evasion in the 6–12 months after the implementation of California's $0.50/pack excise tax increase. Design and setting: Retrospective data analysis from the 1999 California Tobacco Surveys (CTS), a random digit dialled telephone survey of California households. Main outcome measures: Sources of cigarettes, average daily cigarette consumption, and reported price paid. Results: Very few (5.1 (0.7)% (±95% confidence limits)) of California smokers avoided the excise tax by usually purchasing cigarettes from non- or lower taxed sources, such as out-of-state outlets, military commissaries, or the internet. The vast majority of smokers purchased their cigarettes from the most convenient and expensive sources: convenience stores/gas (petrol) stations (45.0 (1.9)%), liquor/drug stores (16.4 (1.6)%), and supermarkets (8.8 (1.2)%). Conclusions: Despite the potential savings, tax evasion by individual smokers does not appear to pose a serious threat to California's excise tax revenues or its tobacco control objectives. PMID:12035006

GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow

DEFF Research Database (Denmark)

Guan, Xinfu; Karpen, Heidi E; Stephens, John

2006-01-01

. These actions are mediated by the G-protein-coupled receptor, GLP-2R. Cellular localization of the GLP-2R and the nature of its signaling network in the gut, however, are poorly defined. Thus, our aim was to establish cellular localization of GLP-2R and functional connection to vascular action of GLP-2......-dependently stimulated intestinal blood flow and coordinately upregulated the expression of intestinal eNOS mRNA, protein, and phosphorylation (eNOS-Ser1117). CONCLUSIONS: We conclude that the GLP-2-induced stimulation of blood flow is mediated by vasoactive neurotransmitters that are colocalized with GLP-2R in 2...

Super-resolution imaging of ESCRT-proteins at HIV-1 assembly sites.

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Jens Prescher

2015-02-01

Full Text Available The cellular endosomal sorting complex required for transport (ESCRT machinery is involved in membrane budding processes, such as multivesicular biogenesis and cytokinesis. In HIV-infected cells, HIV-1 hijacks the ESCRT machinery to drive HIV release. Early in the HIV-1 assembly process, the ESCRT-I protein Tsg101 and the ESCRT-related protein ALIX are recruited to the assembly site. Further downstream, components such as the ESCRT-III proteins CHMP4 and CHMP2 form transient membrane associated lattices, which are involved in virus-host membrane fission. Although various geometries of ESCRT-III assemblies could be observed, the actual membrane constriction and fission mechanism is not fully understood. Fission might be driven from inside the HIV-1 budding neck by narrowing the membranes from the outside by larger lattices surrounding the neck, or from within the bud. Here, we use super-resolution fluorescence microscopy to elucidate the size and structure of the ESCRT components Tsg101, ALIX, CHMP4B and CHMP2A during HIV-1 budding below the diffraction limit. To avoid the deleterious effects of using fusion proteins attached to ESCRT components, we performed measurements on the endogenous protein or, in the case of CHMP4B, constructs modified with the small HA tag. Due to the transient nature of the ESCRT interactions, the fraction of HIV-1 assembly sites with colocalizing ESCRT complexes was low (1.5%-3.4%. All colocalizing ESCRT clusters exhibited closed, circular structures with an average size (full-width at half-maximum between 45 and 60 nm or a diameter (determined using a Ripley's L-function analysis of roughly 60 to 100 nm. The size distributions for colocalizing clusters were narrower than for non-colocalizing clusters, and significantly smaller than the HIV-1 bud. Hence, our results support a membrane scission process driven by ESCRT protein assemblies inside a confined structure, such as the bud neck, rather than by large lattices

A single amino acid change (Y318F) in the L-arabitol dehydrogenase (LadA) from Aspergillus niger results in a significant increase in affinity for D-sorbitol

Science.gov (United States)

2009-01-01

Background L-arabitol dehydrogenase (LAD) and xylitol dehydrogenase (XDH) are involved in the degradation of L-arabinose and D-xylose, which are among the most abundant monosaccharides on earth. Previous data demonstrated that LAD and XDH not only differ in the activity on their biological substrate, but also that only XDH has significant activity on D-sorbitol and may therefore be more closely related to D-sorbitol dehydrogenases (SDH). In this study we aimed to identify residues involved in the difference in substrate specificity. Results Phylogenetic analysis demonstrated that LAD, XDH and SDH form 3 distinct groups of the family of dehydrogenases containing an Alcohol dehydrogenase GroES-like domain (pfam08240) and likely have evolved from a common ancestor. Modelling of LadA and XdhA of the saprobic fungus Aspergillus niger on human SDH identified two residues in LadA (M70 and Y318), that may explain the absence of activity on D-sorbitol. While introduction of the mutation M70F in LadA of A. niger resulted in a nearly complete enzyme inactivation, the Y318F resulted in increased activity for L-arabitol and xylitol. Moreover, the affinity for D-sorbitol was increased in this mutant. Conclusion These data demonstrates that Y318 of LadA contributes significantly to the substrate specificity difference between LAD and XDH/SDH. PMID:19674460

Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation

DEFF Research Database (Denmark)

Kim, S.G.; Rostrup, Egill; Larsson, H.B.

1999-01-01

signal changes were measured simultaneously using the flow-sensitive alternating inversion recovery (FAIR) technique. During hypercapnia established by an end-tidal CO2 increase of 1.46 kPa, CBF in the visual cortex increased by 47.3 +/- 17.3% (mean +/- SD; n = 9), and deltaR2* was -0.478 +/- 0.147 sec......The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging depends on at least partial uncoupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) changes. By measuring CBF and BOLD simultaneously, the relative change in CMRO2 can...

Quantifying the Contribution of Urban-Industrial Efficiency and Symbiosis to Deep Decarbonization: Impact of 637 Chinese Cities

Science.gov (United States)

Ramaswami, A.; Tong, K.; Fang, A.; Lal, R.; Nagpure, A.; Li, Y.; Yu, H.; Jiang, D.; Russell, A. G.; Shi, L.; Chertow, M.; Wang, Y.; Wang, S.

2016-12-01

Urban activities in China contribute significantly to global greenhouse gas (GHG) emissions and to local air pollution-related health risks. Co-location analysis can help inform the potential for energy- and material-exchanges across homes, businesses, infrastructure and industries co-located in cities. Such co-location dependent urban-industrial symbiosis strategies offer a new pathway toward urban energy efficiency and health that have not previously been quantified. Key examples includes the use of waste industrial heat in other co-located industries, and in residential-commercial district heating-cooling systems of cities. To quantify the impact of these strategies: (1) We develop a new data-set of 637 Chinese cities to assess the potential for efficiency and symbiosis across co-located homes, businesses, industries and the energy and construction sectors in the different cities. (2) A multi-scalar urban systems model quantifies trans-boundary CO2 impacts as well as local health benefits of these uniquely urban, co-location-dependent strategies. (3) CO2 impacts are aggregated across the 637 Chinese cities (home to 701 million people) to quantify national CO2 mitigation potential. (4) The local health benefits are modeled specific to each city and mapped geospatially to identify areas where co-benefits between GHG mitigation and health are maximized. Results: A first order conservative analysis of co-location dependent urban symbiosis indicates potential for reducing 6% of China's national total CO2 emissions in a relatively short time period, yielding a new pathway not previously considered in China's energy futures models. The magnitude of these reductions (6%) was similar in magnitude to sector specific industrial, power sector and buildings efficiency strategeies that together contributed 9% CO2 reduction aggregated across the nation. CO2 reductions mapped to the 637 cities ranged from 40,000 premature deaths (avoided) across all cities. These results

Intracellular Trafficking Modulation by Ginsenoside Rg3 Inhibits Brucella abortus Uptake and Intracellular Survival within RAW 264.7 Cells.

Science.gov (United States)

Huy, Tran Xuan Ngoc; Reyes, Alisha Wehdnesday Bernardo; Hop, Huynh Tan; Arayan, Lauren Togonon; Min, WonGi; Lee, Hu Jang; Rhee, Man Hee; Chang, Hong Hee; Kim, Suk

2017-03-28

Ginsenoside Rg3, a saponin extracted from ginseng, has various pharmacological and biological activities; however, its effects against Brucella infection are still unclear. Herein, the inhibitory effects of ginsenoside Rg3 against intracellular parasitic Brucella infection were evaluated through bacterial infection, adherence assays, and LAMP-1 colocalization, as well as immunoblotting and FACS for detecting MAPK signaling proteins and F-actin polymerization, respectively. The internalization, intracellular growth, and adherence of Brucella abortus in Rg3-treated RAW 264.7 cells were significantly decreased compared with the Rg3-untreated control. Furthermore, an apparent reduction of F-actin content and intensity of F-actin fluorescence in Rg3-treated cells was observed compared with B. abortus -infected cells without treatment by flow cytometry analysis and confocal microscopy, respectively. In addition, treating cells with Rg3 decreased the phosphorylation of MAPK signaling proteins such as ERK 1/2 and p38 compared with untreated cells. Moreover, the colocalization of B. abortus -containing phagosomes with LAMP-1 was markedly increased in Rg3-treated cells. These findings suggest that ginsenoside Rg3 inhibits B. abortus infection in mammalian cells and can be used as an alternative approach in the treatment of brucellosis.

Biological, ecological and agronomic significance of plant phenolic ...

African Journals Online (AJOL)

Our understanding of some phenolic compounds in the last few decades has greatly improved. However, their biological, ecological and agronomical significance in the rhizosphere of most symbiotic legumes is much less clear. Further understanding of these biomolecules will increase our knowledge of their contribution in ...

The energetic significance of cooking.

Science.gov (United States)

Carmody, Rachel N; Wrangham, Richard W

2009-10-01

While cooking has long been argued to improve the diet, the nature of the improvement has not been well defined. As a result, the evolutionary significance of cooking has variously been proposed as being substantial or relatively trivial. In this paper, we evaluate the hypothesis that an important and consistent effect of cooking food is a rise in its net energy value. The pathways by which cooking influences net energy value differ for starch, protein, and lipid, and we therefore consider plant and animal foods separately. Evidence of compromised physiological performance among individuals on raw diets supports the hypothesis that cooked diets tend to provide energy. Mechanisms contributing to energy being gained from cooking include increased digestibility of starch and protein, reduced costs of digestion for cooked versus raw meat, and reduced energetic costs of detoxification and defence against pathogens. If cooking consistently improves the energetic value of foods through such mechanisms, its evolutionary impact depends partly on the relative energetic benefits of non-thermal processing methods used prior to cooking. We suggest that if non-thermal processing methods such as pounding were used by Lower Palaeolithic Homo, they likely provided an important increase in energy gain over unprocessed raw diets. However, cooking has critical effects not easily achievable by non-thermal processing, including the relatively complete gelatinisation of starch, efficient denaturing of proteins, and killing of food borne pathogens. This means that however sophisticated the non-thermal processing methods were, cooking would have conferred incremental energetic benefits. While much remains to be discovered, we conclude that the adoption of cooking would have led to an important rise in energy availability. For this reason, we predict that cooking had substantial evolutionary significance.

Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

Science.gov (United States)

Xiao, Xing; Zhao, Xiao-Tao; Xu, Ling-Chi; Yue, Lu-Peng; Liu, Feng-Yu; Cai, Jie; Liao, Fei-Fei; Kong, Jin-Ge; Xing, Guo-Gang; Yi, Ming; Wan, You

2015-04-01

Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal injection of sodium stibogluconate aggravated CFA-induced inflammatory pain, whereas Shp-1 overexpression in DRG neurons alleviated it. These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

Statistical significance of cis-regulatory modules

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Smith Andrew D

2007-01-01

Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM and MODSTORM software.

Timescales for detecting a significant acceleration in sea level rise.

Science.gov (United States)

Haigh, Ivan D; Wahl, Thomas; Rohling, Eelco J; Price, René M; Pattiaratchi, Charitha B; Calafat, Francisco M; Dangendorf, Sönke

2014-04-14

There is observational evidence that global sea level is rising and there is concern that the rate of rise will increase, significantly threatening coastal communities. However, considerable debate remains as to whether the rate of sea level rise is currently increasing and, if so, by how much. Here we provide new insights into sea level accelerations by applying the main methods that have been used previously to search for accelerations in historical data, to identify the timings (with uncertainties) at which accelerations might first be recognized in a statistically significant manner (if not apparent already) in sea level records that we have artificially extended to 2100. We find that the most important approach to earliest possible detection of a significant sea level acceleration lies in improved understanding (and subsequent removal) of interannual to multidecadal variability in sea level records.

PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells

International Nuclear Information System (INIS)

Ghorai, Atanu; Sarma, Asitikantha; Chowdhury, Priyanka; Ghosh, Utpal

2016-01-01

Hadron therapy is an innovative technique where cancer cells are precisely killed leaving surrounding healthy cells least affected by high linear energy transfer (LET) radiation like carbon ion beam. Anti-metastatic effect of carbon ion exposure attracts investigators into the field of hadron biology, although details remain poor. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are well-known radiosensitizer and several PARP-1 inhibitors are in clinical trial. Our previous studies showed that PARP-1 depletion makes the cells more radiosensitive towards carbon ion than gamma. The purpose of the present study was to investigate combining effects of PARP-1 inhibition with carbon ion exposure to control metastatic properties in HeLa cells. Activities of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) were measured using the gelatin zymography after 85 MeV carbon ion exposure or gamma irradiation (0- 4 Gy) to compare metastatic potential between PARP-1 knock down (HsiI) and control cells (H-vector - HeLa transfected with vector without shRNA construct). Expression of MMP-2, MMP-9, tissue inhibitor of MMPs such as TIMP-1, TIMP-2 and TIMP-3 were checked by immunofluorescence and western blot. Cell death by trypan blue, apoptosis and autophagy induction were studied after carbon ion exposure in each cell-type. The data was analyzed using one way ANOVA and 2-tailed paired-samples T-test. PARP-1 silencing significantly reduced MMP-2 and MMP-9 activities and carbon ion exposure further diminished their activities to less than 3 % of control H-vector. On the contrary, gamma radiation enhanced both MMP-2 and MMP-9 activities in H-vector but not in HsiI cells. The expression of MMP-2 and MMP-9 in H-vector and HsiI showed different pattern after carbon ion exposure. All three TIMPs were increased in HsiI, whereas only TIMP-1 was up-regulated in H-vector after irradiation. Notably, the expressions of all TIMPs were significantly higher in HsiI than H-vector at 4 Gy. Apoptosis was

Thalidomide has a significant effect in patients with thalassemia intermedia.

Science.gov (United States)

Li, YunShuan; Ren, Quan; Zhou, Yali; Li, Pingping; Lin, Wanhua; Yin, Xiaolin

2018-01-01

To investigate the effect of thalidomide in patients with thalassemia intermedia. We observed the effect of thalidomide in seven patients with thalassemia intermedia requiring blood transfusion. Four of the patients were transfusion-independent, and three patients were transfusion-dependent. For the four transfusion-independent patients, hemoglobin concentration increased significantly (≥2 g/dl) in three and moderately (1-2 g/dl) in one. After 3 months of treatment, hemoglobin concentration increased 3.2 ± 1.2 g/dl compared to pretreatment. Among the three transfusion-dependent patients, transfusion was terminated after one month of treatment in one patient and decreased >50% in the other two patients, accompanied by an increase in the average hemoglobin concentration. Thalidomide had a significant effect in patients with thalassemia intermedia. Further studies of a larger scale and more rigorous design are warranted.

Identification of sequence motifs significantly associated with antisense activity

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Peek Andrew S

2007-06-01

Full Text Available Abstract Background Predicting the suppression activity of antisense oligonucleotide sequences is the main goal of the rational design of nucleic acids. To create an effective predictive model, it is important to know what properties of an oligonucleotide sequence associate significantly with antisense activity. Also, for the model to be efficient we must know what properties do not associate significantly and can be omitted from the model. This paper will discuss the results of a randomization procedure to find motifs that associate significantly with either high or low antisense suppression activity, analysis of their properties, as well as the results of support vector machine modelling using these significant motifs as features. Results We discovered 155 motifs that associate significantly with high antisense suppression activity and 202 motifs that associate significantly with low suppression activity. The motifs range in length from 2 to 5 bases, contain several motifs that have been previously discovered as associating highly with antisense activity, and have thermodynamic properties consistent with previous work associating thermodynamic properties of sequences with their antisense activity. Statistical analysis revealed no correlation between a motif's position within an antisense sequence and that sequences antisense activity. Also, many significant motifs existed as subwords of other significant motifs. Support vector regression experiments indicated that the feature set of significant motifs increased correlation compared to all possible motifs as well as several subsets of the significant motifs. Conclusion The thermodynamic properties of the significantly associated motifs support existing data correlating the thermodynamic properties of the antisense oligonucleotide with antisense efficiency, reinforcing our hypothesis that antisense suppression is strongly associated with probe/target thermodynamics, as there are no enzymatic

Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

Science.gov (United States)

Gómez-Reino, Juan J; Carmona, Loreto; Valverde, Vicente Rodríguez; Mola, Emilio Martín; Montero, Maria Dolores

2003-08-01

The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

FTY720-loaded poly(DL-lactide-co-glycolide) electrospun scaffold significantly increases microvessel density over 7 days in streptozotocin-induced diabetic C57b16/J mice: preliminary results.

Science.gov (United States)

Bowers, D T; Chhabra, P; Langman, L; Botchwey, E A; Brayman, K L

2011-11-01

Nanofiber scaffolds could improve islet transplant success by physically mimicking the shape of extracellular matrix and by acting as a drug-delivery vehicle. Scaffolds implanted in alternate transplant sites must be prevascularized or very quickly vascularized following transplantation to prevent hypoxia-induced islet necrosis. The local release of the S1P prodrug FTY720 induces diameter enlargement and increases in length density. The objective of this preliminary study was to evaluate length and diameter differences between diabetic and nondiabetic animals implanted with FTY720-containing electrospun scaffolds using intravital imaging of dorsal skinfold window chambers. Electrospun mats of randomly oriented fibers we created from polymer solutions of PLAGA (50:50 LA:GA) with and without FTY720 loaded at a ratio of 1:200 (FTY720:PLAGA by wt). The implanted fiber mats were 4 mm in diameter and ∼0.2 mm thick. Increases in length density and vessel diameter were assessed by automated analysis of images over 7 days in RAVE, a Matlab program. Image analysis of repeated measures of microvessel metrics demonstrated a significant increase in the length density from day 0 to day 7 in the moderately diabetic animals of this preliminary study (P < .05). Furthermore, significant differences in length density at day 0 and day 3 were found between recently STZ-induced moderately diabetic and nondiabetic animals in response to FTY720 local release (P < .05, Student t test). Driving the islet revascularization process using local release of factors, such as FTY720, from biodegradable polymers makes an attractive system for the improvement of islet transplant success. Preliminary study results suggest that a recently induced moderately diabetic state may potentiate the mechanism by which local release of FTY720 from polymer fibers increases length density of microvessels. Therefore, local release of S1P receptor-targeted drugs is under further investigation for improvement of

2D Presentation Techniques of Mind-maps for Blind Meeting Participants.

Science.gov (United States)

Pölzer, Stephan; Miesenberger, Klaus

2015-01-01

Mind-maps, used as ideation technique in co-located meetings (e.g. in brainstorming sessions), which meet with increased importance in business and education, show considerably accessibility challenges for blind meeting participants. Besides an overview of general aspects of accessibility issues in co-located meetings, this paper focuses on the design and development of alternative non-visual presentation techniques for mind-maps. The different aspects of serialized presentation techniques (e.g. treeview) for Braille and audio rendering and two dimensional presentation techniques (e.g. tactile two dimensional array matrix and edge-projection method [1]) are discussed based on the user feedback gathered in intermediate tests following a user centered design approach.

Prolonged continuous intravenous infusion of the dipeptide L-alanine- L-glutamine significantly increases plasma glutamine and alanine without elevating brain glutamate in patients with severe traumatic brain injury.

Science.gov (United States)

Nägeli, Mirjam; Fasshauer, Mario; Sommerfeld, Jutta; Fendel, Angela; Brandi, Giovanna; Stover, John F

2014-07-02

Low plasma glutamine levels are associated with worse clinical outcome. Intravenous glutamine infusion dose- dependently increases plasma glutamine levels, thereby correcting hypoglutaminemia. Glutamine may be transformed to glutamate which might limit its application at a higher dose in patients with severe traumatic brain injury (TBI). To date, the optimal glutamine dose required to normalize plasma glutamine levels without increasing plasma and cerebral glutamate has not yet been defined. Changes in plasma and cerebral glutamine, alanine, and glutamate as well as indirect signs of metabolic impairment reflected by increased intracranial pressure (ICP), lactate, lactate-to-pyruvate ratio, electroencephalogram (EEG) activity were determined before, during, and after continuous intravenous infusion of 0.75 g L-alanine-L-glutamine which was given either for 24 hours (group 1, n = 6) or 5 days (group 2, n = 6) in addition to regular enteral nutrition. Lab values including nitrogen balance, urea and ammonia were determined daily. Continuous L-alanine-L-glutamine infusion significantly increased plasma and cerebral glutamine as well as alanine levels, being mostly sustained during the 5 day infusion phase (plasma glutamine: from 295 ± 62 to 500 ± 145 μmol/ l; brain glutamine: from 183 ± 188 to 549 ± 120 μmol/ l; plasma alanine: from 327 ± 91 to 622 ± 182 μmol/ l; brain alanine: from 48 ± 55 to 89 ± 129 μmol/ l; p alanine-L-glutamine infusion (0.75 g/ kg/ d up to 5 days) increased plasma and brain glutamine and alanine levels. This was not associated with elevated glutamate or signs of potential glutamate-mediated cerebral injury. The increased nitrogen load should be considered in patients with renal and hepatic dysfunction. Clinicaltrials.gov NCT02130674. Registered 5 April 2014.

Computation of spatial significance of mountain objects extracted from multiscale digital elevation models

International Nuclear Information System (INIS)

Sathyamoorthy, Dinesh

2014-01-01

The derivation of spatial significance is an important aspect of geospatial analysis and hence, various methods have been proposed to compute the spatial significance of entities based on spatial distances with other entities within the cluster. This paper is aimed at studying the spatial significance of mountain objects extracted from multiscale digital elevation models (DEMs). At each scale, the value of spatial significance index SSI of a mountain object is the minimum number of morphological dilation iterations required to occupy all the other mountain objects in the terrain. The mountain object with the lowest value of SSI is the spatially most significant mountain object, indicating that it has the shortest distance to the other mountain objects. It is observed that as the area of the mountain objects reduce with increasing scale, the distances between the mountain objects increase, resulting in increasing values of SSI. The results obtained indicate that the strategic location of a mountain object at the centre of the terrain is more important than its size in determining its reach to other mountain objects and thus, its spatial significance

Prenatal exposure to chromium induces early reproductive senescence by increasing germ cell apoptosis and advancing germ cell cyst breakdown in the F1 offspring.

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Sivakumar, Kirthiram K; Stanley, Jone A; Arosh, Joe A; Pepling, Melissa E; Burghardt, Robert C; Banu, Sakhila K

2014-04-01

Hexavalent chromium (CrVI), one of the more toxic heavy metals, is widely used in more than 50 industries such as chrome plating, welding, wood processing and tanneries. As one of the world's leading producers of chromium compounds, the U.S. is facing growing challenges in protecting human health against multiple adverse effects of CrVI. CrVI is rapidly converted to CrIII intracellularly, and can induce apoptosis through different mechanisms. Our previous studies demonstrated postnatal exposure to CrVI results in a delay or arrest in follicle development and puberty. Pregnant rats were treated with 25 ppm potassium dichromate (CrVI) from gestational day (GD) 9.5 to 14.5 through drinking water, placentae were removed on GD 20, and total Cr was estimated in the placentae; ovaries were removed from the F1 offspring on postnatal day (PND)-1 and various analyses were performed. Our results show that gestational exposure to CrVI resulted in (i) increased Cr concentration in the placenta, (ii) increased germ cell apoptosis by up-regulating p53/p27-Bax-caspase-3 proteins and by increasing p53-SOD-2 co-localization; (iii) accelerated germ cell cyst (GCC) breakdown; (iv) advanced primordial follicle assembly and primary follicle transition and (v) down regulation of p-AKT, p-ERK and XIAP. As a result of the above events, CrVI induced early reproductive senescence and decrease in litter size in F1 female progeny. Published by Elsevier Inc.

Pro-inflammatory interleukin-18 increases Alzheimer’s disease-associated amyloid-β production in human neuron-like cells

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Sutinen Elina M

2012-08-01

Full Text Available Abstract Background Alzheimer’s disease (AD involves increased accumulation of amyloid-β (Aβ plaques and neurofibrillary tangles as well as neuronal loss in various regions of the neocortex. Neuroinflammation is also present, but its role in AD is not fully understood. We previously showed increased levels of pro-inflammatory cytokine interleukin-18 (IL-18 in different regions of AD brains, where it co-localized with Aβ-plaques, as well as the ability of IL-18 to increase expression of glycogen synthase kinase-3β (GSK-3β and cyclin dependent kinase 5, involved in hyperphosphorylation of tau-protein. Elevated IL-18 has been detected in several risk conditions for AD, including obesity, type-II diabetes, and cardiovascular diseases as well as in stress. Methods We differentiated SH-SY5Y neuroblastoma cells as neuron-like and exposed them to IL-18 for various times. We examined the protein levels of amyloid-β precursor protein (APP and its processing products, its cleaving enzymes, involved in amyloidogenic processing of APP, and markers of apoptosis. Results IL-18 increased protein levels of the β-site APP-cleaving enzyme BACE-1, the N-terminal fragment of presenilin-1 and slightly presenilin enhancer 2, both of which are members of the γ-secretase complex, as well as Fe65, which is a binding protein of the C-terminus of APP and one regulator for GSK-3β. IL-18 also increased APP expression and phosphorylation, which preceded increased BACE-1 levels. Further, IL-18 altered APP processing, increasing Aβ40 production in particular, which was inhibited by IL-18 binding protein. Increased levels of soluble APPβ were detected in culture medium after the IL-18 exposure. IL-18 also increased anti-apoptotic bcl-xL levels, which likely counteracted the minor increase of the pro-apoptotic caspase-3. Lactate dehydrogenase activity in culture medium was unaffected. Conclusions The IL-18 induction of BACE-1, APP processing, and Aβ is likely to be

Autophagy postpones apoptotic cell death in PRRSV infection through Bad-Beclin1 interaction.

Science.gov (United States)

Zhou, Ao; Li, Shuaifeng; Khan, Faheem Ahmed; Zhang, Shujun

2016-01-01

Autophagy and apoptosis play significant roles in PRRSV infection and replication. However, the interaction between these 2 processes in PRRSV replication is still far from been completely understood. In our studies, the exposure of MARC-145 cells to PRRSV confirmed the activation of autophagy and subsequent induction of apoptosis. The inhibition of autophagy by 3-methyladenine (3-MA) caused a significant increase in PRRSV-induced apoptosis, showing a potential connection between both mechanisms. Moreover, we observed an increase in Bad expression (a pro-apoptotic protein) and Beclin1 (an autophagy regulator) in virus-infected cells up to 36h. Co-immunoprecipitation assays showed the formation of Bad and Beclin1 complex in PRRSV infected cells. Accordingly, Bad co-localized with Beclin1 in MARC-145 infected cells. Knockdown of Beclin1 significantly decreased PRRSV replication and PRRSV-induced autophagy, while Bad silencing resulted in increased autophagy and enhanced viral replication. Furthermore, PRRSV infection phosphorylated Bad (Ser112) to promote cellular survival. These results demonstrate that autophagy can favor PRRSV replication by postponing apoptosis through the formation of a Bad-Beclin1 complex.

Nucleobindin co-localizes and associates with cyclooxygenase (COX-2 in human neutrophils.

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Patrick Leclerc

2008-05-01

Full Text Available The inducible cyclooxygenase isoform (COX-2 is associated with inflammation, tumorigenesis, as well as with physiological events. Despite efforts deployed in order to understand the biology of this multi-faceted enzyme, much remains to be understood. Nucleobindin (Nuc, a ubiquitous Ca(2+-binding protein, possesses a putative COX-binding domain. In this study, we investigated its expression and subcellular localization in human neutrophils, its affinity for COX-2 as well as its possible impact on PGE(2 biosynthesis. Complementary subcellular localization approaches including nitrogen cavitation coupled to Percoll fractionation, immunofluorescence, confocal and electron microscopy collectively placed Nuc, COX-2, and all of the main enzymes involved in prostanoid synthesis, in the Golgi apparatus and endoplasmic reticulum of human neutrophils. Immunoprecipitation experiments indicated a high affinity between Nuc and COX-2. Addition of human recombinant (hr Nuc to purified hrCOX-2 dose-dependently caused an increase in PGE(2 biosynthesis in response to arachidonic acid. Co-incubation of Nuc with COX-2-expressing neutrophil lysates also increased their capacity to produce PGE(2. Moreover, neutrophil transfection with hrNuc specifically enhanced PGE(2 biosynthesis. Together, these results identify a COX-2-associated protein which may have an impact in prostanoid biosynthesis.

The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae

DEFF Research Database (Denmark)

Hansson Petersen, Camilla A; Alikhani, Nyosha; Behbahani, Homira

2008-01-01

that extracellulary applied Abeta can be internalized by human neuroblastoma cells and can colocalize with mitochondrial markers. Together, these results provide further insight into the mitochondrial uptake of Abeta, a peptide considered to be of major significance in Alzheimer's disease....

Significance and radioimmunoassay of gastric inhibitory polypeptide

International Nuclear Information System (INIS)

Zheng Ping; Zeng Minde; Yuan Jimin

1995-01-01

We have established the GIP Radioimmunoassay which has high sensitivity and specificity by labelling with iodogen and purified with HPLC. Using this method, the plasma GIP level was measured in 64 cases of which there are 10 normal individuals, 25 cases of diabetes and 29 cases of liver cirrhosis . The results showed that the plasma GIP level was significantly increased in patients with liver cirrhosis and correlated to degree of glucose tolerance damage

Single-source dual-energy spectral multidetector CT of pancreatic adenocarcinoma: Optimization of energy level viewing significantly increases lesion contrast

International Nuclear Information System (INIS)

Patel, B.N.; Thomas, J.V.; Lockhart, M.E.; Berland, L.L.; Morgan, D.E.

2013-01-01

V was 31 ± 25 HU (p = 0.007). Conclusion: Significantly increased pancreatic lesion contrast was noted at lower viewing energies using spectral MDCT. Individual patient CNR-optimized energy level images have the potential to improve lesion conspicuity.

Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

Directory of Open Access Journals (Sweden)

Aihua Hu

Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

Epidermal growth factor-induced mobilization of a ganglioside-specific sialidase (NEU3) to membrane ruffles

International Nuclear Information System (INIS)

Yamaguchi, Kazunori; Hata, Keiko; Wada, Tadashi; Moriya, Setsuko; Miyagi, Taeko

2006-01-01

Human ganglioside-specific sialidase, NEU3, localized at cell membranes is thought to regulate various biological processes at cell surfaces. We here explored functional subcellular localization of the sialidase by immunofluorescence and found accumulation at leading edges of cell membranes in the presence of serum in culture. In response to EGF, the sialidase redistributed rapidly to ruffling cell membranes of squamous carcinoma A431 cells and co-localized with Rac-1. NEU3 overexpression enhanced Rac-1 activation and cell migration as compared with controls in HeLa cells as well as in A431 cells. Consistent with co-localization with Rac-1 by immunofluorescence, NEU3 was found to co-precipitate with activated Rac bound to GST-PAK-1 fusion protein. NEU3 silencing by siRNA, in contrast, resulted in inhibition of Rac-1 activation. These results indicate that NEU3 is able to mobilize to membrane ruffles in response to growth stimuli and activate the Rac-1 signaling by co-localization with Rac-1, leading to increased cell motility

Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3.

Science.gov (United States)

Lammers, Karen M; Lu, Ruliang; Brownley, Julie; Lu, Bao; Gerard, Craig; Thomas, Karen; Rallabhandi, Prasad; Shea-Donohue, Terez; Tamiz, Amir; Alkan, Sefik; Netzel-Arnett, Sarah; Antalis, Toni; Vogel, Stefanie N; Fasano, Alessio

2008-07-01

Celiac disease is an immune-mediated enteropathy triggered by gliadin, a component of the grain protein gluten. Gliadin induces an MyD88-dependent zonulin release that leads to increased intestinal permeability, a postulated early element in the pathogenesis of celiac disease. We aimed to establish the molecular basis of gliadin interaction with intestinal mucosa leading to intestinal barrier impairment. Alpha-gliadin affinity column was loaded with intestinal mucosal membrane lysates to identify the putative gliadin-binding moiety. In vitro experiments with chemokine receptor CXCR3 transfectants were performed to confirm binding of gliadin and/or 26 overlapping 20mer alpha-gliadin synthetic peptides to the receptor. CXCR3 protein and gene expression were studied in intestinal epithelial cell lines and human biopsy specimens. Gliadin-CXCR3 interaction was further analyzed by immunofluorescence microscopy, laser capture microscopy, real-time reverse-transcription polymerase chain reaction, and immunoprecipitation/Western blot analysis. Ex vivo experiments were performed using C57BL/6 wild-type and CXCR3(-/-) mouse small intestines to measure intestinal permeability and zonulin release. Affinity column and colocalization experiments showed that gliadin binds to CXCR3 and that at least 2 alpha-gliadin 20mer synthetic peptides are involved in this binding. CXCR3 is expressed in mouse and human intestinal epithelia and lamina propria. Mucosal CXCR3 expression was elevated in active celiac disease but returned to baseline levels following implementation of a gluten-free diet. Gliadin induced physical association between CXCR3 and MyD88 in enterocytes. Gliadin increased zonulin release and intestinal permeability in wild-type but not CXCR3(-/-) mouse small intestine. Gliadin binds to CXCR3 and leads to MyD88-dependent zonulin release and increased intestinal permeability.

Step-function increase of significance of waste form in RWM strategy

International Nuclear Information System (INIS)

Roy, R.

1979-01-01

Radioactive waste management on the technical side is composed of four subsystems: storage, radionuclide immobilization, isolation, and post-emplacement. Thus far, emphasis has been on the isolation subsystem, with the assumption that all the radionuclides placed in the geological formation would be released. Findings by a committee of the National Academy of Science on the types of solid forms for radioactive wastes are summarized. The most important research findings of the last two or three years are evaluated, findings which impinge on the role of the newly developed radionuclide immobilization subsystems. 24 refs

Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

Directory of Open Access Journals (Sweden)

Rivinius R

2016-02-01

group (P=0.0123. There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596, 2-year (P=0.8620, 5-year (P=0.2737, or overall follow-up mortality after HTX (P=0.1049. Moreover, Kaplan–Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786.Conclusion: Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with increased mortality after HTX. Keywords: amiodarone, atrial fibrillation, heart failure, heart transplantation, mortality

Understanding the Sampling Distribution and Its Use in Testing Statistical Significance.

Science.gov (United States)

Breunig, Nancy A.

Despite the increasing criticism of statistical significance testing by researchers, particularly in the publication of the 1994 American Psychological Association's style manual, statistical significance test results are still popular in journal articles. For this reason, it remains important to understand the logic of inferential statistics. A…

DNA and protein co-administration induces tolerogenic dendritic cells through DC-SIGN mediated negative signals.

Science.gov (United States)

Li, Jinyao; Geng, Shuang; Liu, Xiuping; Liu, Hu; Jin, Huali; Liu, Chang-Gong; Wang, Bin

2013-10-01

We previously demonstrated that DNA and protein co-administration induced differentiation of immature dendritic cells (iDCs) into CD11c(+)CD40(low)IL-10(+) regulatory DCs (DCregs) via the caveolin-1 (Cav-1) -mediated signal pathway. Here, we demonstrate that production of IL-10 and the low expression of CD40 play a critical role in the subsequent induction of regulatory T cells (Tregs) by the DCregs. We observed that DNA and protein were co-localized with DC-SIGN in caveolae and early lysosomes in the treated DCs, as indicated by co-localization with Cav-1 and EEA-1 compartment markers. DNA and protein also co-localized with LAMP-2. Gene-array analysis of gene expression showed that more than a thousand genes were significantly changed by the DC co-treatment with DNA + protein compared with controls. Notably, the level of DC-SIGN expression was dramatically upregulated in pOVA + OVA co-treated DCs. The expression levels of Rho and Rho GNEF, the down-stream molecules of DC-SIGN mediated signal pathway, were also greatly upregulated. Further, the level of TLR9, the traditional DNA receptor, was significantly downregulated. These results suggest that DC-SIGN as the potential receptor for DNA and protein might trigger the negative pathway to contribute the induction of DCreg combining with Cav-1 mediated negative signal pathway.

Colocalization of a CD1d-Binding Glycolipid with a Radiation-Attenuated Sporozoite Vaccine in Lymph Node-Resident Dendritic Cells for a Robust Adjuvant Effect.

Science.gov (United States)

Li, Xiangming; Kawamura, Akira; Andrews, Chasity D; Miller, Jessica L; Wu, Douglass; Tsao, Tiffany; Zhang, Min; Oren, Deena; Padte, Neal N; Porcelli, Steven A; Wong, Chi-Huey; Kappe, Stefan H I; Ho, David D; Tsuji, Moriya

2015-09-15

A CD1d-binding glycolipid, α-Galactosylceramide (αGalCer), activates invariant NK T cells and acts as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying nearly 100-fold stronger CD1d binding affinity. In the current study, 7DW8-5 was found to exert a more potent adjuvant effect than αGalCer for a vaccine based on radiation-attenuated sporozoites of a rodent malaria parasite, Plasmodium yoelii, also referred to as irradiated P. yoelii sporozoites (IrPySpz). 7DW8-5 had a superb adjuvant effect only when the glycolipid and IrPySpz were conjointly administered i.m. Therefore, we evaluated the effect of distinctly different biodistribution patterns of αGalCer and 7DW8-5 on their respective adjuvant activities. Although both glycolipids induce a similar cytokine response in sera of mice injected i.v., after i.m. injection, αGalCer induces a systemic cytokine response, whereas 7DW8-5 is locally trapped by CD1d expressed by dendritic cells (DCs) in draining lymph nodes (dLNs). Moreover, the i.m. coadministration of 7DW8-5 with IrPySpz results in the recruitment of DCs to dLNs and the activation and maturation of DCs. These events cause the potent adjuvant effect of 7DW8-5, resulting in the enhancement of the CD8(+) T cell response induced by IrPySpz and, ultimately, improved protection against malaria. Our study is the first to show that the colocalization of a CD1d-binding invariant NK T cell-stimulatory glycolipid and a vaccine, like radiation-attenuated sporozoites, in dLN-resident DCs upon i.m. conjoint administration governs the potency of the adjuvant effect of the glycolipid. Copyright © 2015 by The American Association of Immunologists, Inc.

Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

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Du, Yijun [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan (China); Pattnaik, Asit K. [School of Veterinary Medicine and Biomedical Sciences and the Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583-0900 (United States); Song, Cheng [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Yoo, Dongwan, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Li, Gang, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Institute of Animal Science and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing (China)

2012-03-01

The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 ({omega} - 2, where {omega} is the GPI moiety at E160), P159 ({omega} - 1), and M162 ({omega} + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide-anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

International Nuclear Information System (INIS)

Du, Yijun; Pattnaik, Asit K.; Song, Cheng; Yoo, Dongwan; Li, Gang

2012-01-01

The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 (ω − 2, where ω is the GPI moiety at E160), P159 (ω − 1), and M162 (ω + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide–anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

Clinical significance of determination of serum C-peptide levels

International Nuclear Information System (INIS)

Wang Guohong; Xu Ruiji; Zhang Zhongshu; Wang Xiaoji

2006-01-01

Objective: To study the clinical meanings of changes of serum C-peptide levels and insulin/C-peptide ratio. Methods: Serum insulin and C-peptide levels were determined with RIA in 171 patients with DM-2 of all ages (31-50, n= 50, 51-60, n=60, over 60, n=61) and 50 patients with renal insufficiency. The insulin/C-peptide ratio were calculated. Results: The serum C-peptide and insulin levels in patients with renal insufficiency were significantly higher than those in diabetics of all age groups and the insulin/C-peptide ratio were significantly lower than those in diabetics (P 0.05), but the serum C-peptide levels increased as the age of patients increased with decrease of insulin/C-peptide ratio (P<0.01). Conclusion: Abnormal changes of C-peptide levels and insulin/C-peptide ratio in diabetics (the age-factor corrected) might reflect renal dysfunction. (authors)

Pacific Northwest logistics patterns : the Port of Prince Rupert as a successful national getaway strategy.

Science.gov (United States)

2009-12-01

The Port of Prince Rupert is developing a significant marine container terminal (2 million TEUs by 2012). This port : will be the closest major port to Southeast Alaska, and co-located with the terminus, and only Canadian port of the : Alaska Marine ...

Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Ruy M [Los Alamos National Laboratory

2008-01-01

Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell prolifeation are key factors in AIDS pathogenesis.

Increased superior frontal gyrus activation during working memory processing in psychosis: Significant relation to cumulative antipsychotic medication and to negative symptoms.

Science.gov (United States)

Vogel, Tobias; Smieskova, Renata; Schmidt, André; Walter, Anna; Harrisberger, Fabienne; Eckert, Anne; Lang, Undine E; Riecher-Rössler, Anita; Graf, Marc; Borgwardt, Stefan

2016-08-01

Impairment in working memory (WM) is a core symptom in schizophrenia. However, little is known about how clinical features influence functional brain activity specific to WM processing during the development of first-episode psychosis (FEP) to schizophrenia (SZ). We compared functional WM-specific brain activity in FEP and SZ patients, including the effects of the duration of illness, psychopathological factors and antipsychotic medication. Cross-sectional study of male FEP (n=22) and SZ (n=20) patients performing an n-back task when undergoing functional magnetic resonance imaging (fMRI). Clinical features were collected by semi-structured interviews and medical records. The SZ group performed significantly worse than the FEP group in the 2-back condition. The SZ group also showed significantly higher activation in the left superior frontal gyrus in the 2-back versus 0-back condition (2-back>0-back). This frontal activation correlated positively with negative symptoms and with cumulative antipsychotic medication during the year before the fMRI examination. There were no significant correlations between activation and duration of illness. There was greater frontal neural activation in SZ than in FEP. This indicated differences in WM processing, and was significantly related to cumulative antipsychotic exposure and negative symptoms, but not to the duration of illness. Copyright © 2016 Elsevier B.V. All rights reserved.

Modifications resulting in significant increases in the beam usage time of a 60 keV electron beam welder

International Nuclear Information System (INIS)

Zielinski, R.E.; Harrison, J.L.

1976-01-01

Short beam usage times were encountered using a 60 keV electron beam welder. These short times were the direct result of a buildup of a reaction product (WO 2 . 90 ) that occurred on graphite washers which housed the tungsten emitter plate. While it was not possible to prevent the reaction product, its growth rate was sufficiently altered by changing graphite materials and minor design changes of the washers. With these modifications beam usage times increased from an original 40 min to approximately 675 min

Zinc release from Schaffer collaterals and its significance.

Science.gov (United States)

Takeda, Atsushi; Nakajima, Satoko; Fuke, Sayuri; Sakurada, Naomi; Minami, Akira; Oku, Naoto

2006-02-15

On the basis of the evidence that approximately 45% of Schaffer collateral boutons are zinc-positive, zinc release from Schaffer collaterals and its action were examined in hippocampal slices. When zinc release from Schaffer collaterals was examined using ZnAF-2, a membrane-impermeable zinc indicator, ZnAF-2 signal in the stratum radiatum of the CA1 was increased by tetanic stimuli at 100 Hz for 1s, suggesting that zinc is released from Schaffer collaterals in a calcium- and impulse-dependent manner. An in vivo microdialysis experiment indicated that the perfusion with 10 microM zinc significantly decreases extracellular glutamate concentration in the CA1. When tetanic stimuli at 100 Hz for 5s were delivered to the dentate granule cells, the increase in calcium signal in the stratum radiatum of the CA1, as well as in the stratum lucidum of the CA3, was attenuated by addition of 10 microM zinc, while enhanced by addition of 1mM CaEDTA, a membrane-impermeable zinc chelator. The increase in calcium signal in the CA1, in which Schaffer collateral synapses exist, during delivery of tetanic stimuli at 100 Hz for 1s to the Schaffer collateral-commissural pathway was also significantly enhanced by addition of 1mM CaEDTA. These results suggest that zinc released from Schaffer collaterals suppressively modulates presynaptic and postsynaptic calcium signaling in the CA1, followed by the suppression of glutamate release.

pancreatic steatosis: diagnosis and clinical significance

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Murat Daðdeviren

2017-03-01

Full Text Available Pancreatic steatosis (PS, with increased use of abdominal imaging in recent years generally appears as incidental. But it is a condition that is often overlooked. The reason for this is not yet fully demonstrated the clinical significance of PS while. However, in recent years, there are some studies conducted on the relationship with ps and other disease such as diabetes, metabolic syndrome, acute and chronic pancreatitis and pancreatic cancer. In this review, the etiology, diagnosis, treatment and clinical characteristics of ps were evaluated in the light of recent literature and current approaches. [J Contemp Med 2017; 7(1.000: 107-112

Single-source dual-energy spectral multidetector CT of pancreatic adenocarcinoma: optimization of energy level viewing significantly increases lesion contrast.

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Patel, B N; Thomas, J V; Lockhart, M E; Berland, L L; Morgan, D E

2013-02-01

.007). Significantly increased pancreatic lesion contrast was noted at lower viewing energies using spectral MDCT. Individual patient CNR-optimized energy level images have the potential to improve lesion conspicuity. Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

THE SIGNIFICANCE OF INTERCULTURAL COMPETENCE IN CROSS-CULTURAL COMMUNICATION

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Jadranka Zlomislić

2016-12-01

Full Text Available The aim of this study is to explore the influence of education and additional factors influencing students’ awareness of intercultural differences. For the purposes of this research assessment was carried out with regard to their role in promoting cultural awareness and facing cross-cultural challenges posed by unfamiliar cross-cultural contexts. Cultural education is presumed to be a key factor for achieving a significant increase of cultural sensitivity and cultural awareness in order to ensure successful cross-cultural communication and increase mobility of students/working professionals. For this study, it was assumed that the cultural awareness of students increases due to the courses they take and their overall study experience. A special questionnaire was developed for the purposes of this research, and the obtained results were statistically analyzed with the help of descriptive statistics, the non-parametric chi-square test, and the Mann-Whitney test. The research has shown that intercultural competence has a statistically significant positive effect on the readiness of students to participate in study and work programs abroad. Thus, it is mandatory that foreign language competence as well as intercultural competence be a priority of the curriculum if we are to increase the number of highly educated experts who will be capable to compete successfully as students or professionals in all fields and all cultural areas. If we recognize that globalization has made the world a global village, we all need the intercultural competence to successfully live in it.

Igf1r+/CD34+ immature ICC are putative adult progenitor cells, identified ultrastructurally as fibroblast-like ICC in Ws/Ws rat colon

DEFF Research Database (Denmark)

Wang, X Y; Albertí, E; White, E J

2009-01-01

by ICC in the wild-type rat colon, suggesting them to be immature ICC. In addition, a marked increase in immunoreactivity for insulin-like growth factor 1 receptor (Igf1r) occurred, co-localized with CD34 but not with c-Kit. A significantly higher number of Igf1r(+)/CD34(+) cells were found in Ws....../Ws compared to wild-type rat colons. These CD34(+)/Igf1r(+) cells in the Ws/Ws colon occupied the same space as FL-ICC. Hence we propose that a subset of immature ICC (FL-ICC) consists of adult progenitor cells. Immunohistochemistry revealed a reduction of neurons positive for neuronal nitric oxide synthase...

How significant is the ‘significant other’? Associations between significant others’ health behaviors and attitudes and young adults’ health outcomes

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Berge Jerica M

2012-04-01

Full Text Available Abstract Background Having a significant other has been shown to be protective against physical and psychological health conditions for adults. Less is known about the period of emerging young adulthood and associations between significant others’ weight and weight-related health behaviors (e.g. healthy dietary intake, the frequency of physical activity, weight status. This study examined the association between significant others’ health attitudes and behaviors regarding eating and physical activity and young adults’ weight status, dietary intake, and physical activity. Methods This study uses data from Project EAT-III, a population-based cohort study with emerging young adults from diverse ethnic and socioeconomic backgrounds (n = 1212. Logistic regression models examining cross-sectional associations, adjusted for sociodemographics and health behaviors five years earlier, were used to estimate predicted probabilities and calculate prevalence differences. Results Young adult women whose significant others had health promoting attitudes/behaviors were significantly less likely to be overweight/obese and were more likely to eat ≥ 5 fruits/vegetables per day and engage in ≥ 3.5 hours/week of physical activity, compared to women whose significant others did not have health promoting behaviors/attitudes. Young adult men whose significant other had health promoting behaviors/attitudes were more likely to engage in ≥ 3.5 hours/week of physical activity compared to men whose significant others did not have health promoting behaviors/attitudes. Conclusions Findings suggest the protective nature of the significant other with regard to weight-related health behaviors of young adults, particularly for young adult women. Obesity prevention efforts should consider the importance of including the significant other in intervention efforts with young adult women and potentially men.

Love is the triumph of the imagination: Daydreams about significant others are associated with increased happiness, love and connection.

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Poerio, Giulia L; Totterdell, Peter; Emerson, Lisa-Marie; Miles, Eleanor

2015-05-01

Social relationships and interactions contribute to daily emotional well-being. The emotional benefits that come from engaging with others are known to arise from real events, but do they also come from the imagination during daydreaming activity? Using experience sampling methodology with 101 participants, we obtained 371 reports of naturally occurring daydreams with social and non-social content and self-reported feelings before and after daydreaming. Social, but not non-social, daydreams were associated with increased happiness, love and connection and this effect was not solely attributable to the emotional content of the daydreams. These effects were only present when participants were lacking in these feelings before daydreaming and when the daydream involved imagining others with whom the daydreamer had a high quality relationship. Findings are consistent with the idea that social daydreams may function to regulate emotion: imagining close others may serve the current emotional needs of daydreamers by increasing positive feelings towards themselves and others. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Increasing diversity in radiologic technology.

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Carwile, Laura

2003-01-01

Diversity is increasingly important in the radiologic technology workplace. For significant changes to occur in work force diversity, educators must first recruit and retain students from a wide variety of backgrounds. This article examines personality, race and gender as factors affecting career choice and how educators can use these factors to increase diversity in their programs. An overview of the ASRT's efforts to improve diversity within the profession is presented, along with suggestions for developing effective recruitment and retention plans to increase diversity.

Manipulation of Ovarian Function Significantly Influenced Sarcopenia in Postreproductive-Age Mice

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Rhett L. Peterson

2016-01-01

Full Text Available Previously, transplantation of ovaries from young cycling mice into old postreproductive-age mice increased life span. We anticipated that the same factors that increased life span could also influence health span. Female CBA/J mice received new (60 d ovaries at 12 and 17 months of age and were evaluated at 16 and 25 months of age, respectively. There were no significant differences in body weight among any age or treatment group. The percentage of fat mass was significantly increased at 13 and 16 months of age but was reduced by ovarian transplantation in 16-month-old mice. The percentages of lean body mass and total body water were significantly reduced in 13-month-old control mice but were restored in 16- and 25-month-old recipient mice by ovarian transplantation to the levels found in six-month-old control mice. In summary, we have shown that skeletal muscle mass, which is negatively influenced by aging, can be positively influenced or restored by reestablishment of active ovarian function in aged female mice. These findings provide strong incentive for further investigation of the positive influence of young ovaries on restoration of health in postreproductive females.

Deletion of T-type calcium channels Cav3.1 or Cav3.2 attenuates endothelial dysfunction in aging mice

DEFF Research Database (Denmark)

Thuesen, Anne D; Andersen, Kenneth; Lyngsø, Kristina S

2018-01-01

Impairment of endothelial function with aging is accompanied by reduced nitric oxide (NO) production. T-type Cav3.1 channels augment nitric oxide and co-localize with eNOS. Therefore, the hypothesis was that T-type channels contribute to the endothelial dysfunction of aging. Endothelial function...... was determined in mesenteric arteries (perfusion) and aortae (isometric contraction) of young and old wild-type (WT), Cav3.1, and Cav3.2 knockout mice. NO production was measured by fluorescence imaging in mesenteric arteries. With age, endothelium-dependent subsequent dilatation (following depolarization...... significantly reduced in mesenteric arteries of old compared to young WT mice. In Cav3.1(-/-) and Cav3.2(-/-) preparations, NO levels increased significantly with age. Relaxations to acetylcholine were significantly smaller in the aortae of old compared to young WT mice, while such responses were comparable...

Australasian disasters of national significance: an epidemiological analysis, 1900-2012.

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Bradt, David A; Bartley, Bruce; Hibble, Belinda A; Varshney, Kavita

2015-04-01

A regional epidemiological analysis of Australasian disasters in the 20th century to present was undertaken to examine trends in disaster epidemiology; to characterise the impacts on civil society through disaster policy, practice and legislation; and to consider future potential limitations in national disaster resilience. A surveillance definition of disaster was developed conforming to the Centre for Research on the Epidemiology of Disasters (CRED) criteria (≥10 deaths, ≥100 affected, or declaration of state emergency or appeal for international assistance). The authors then applied economic and legislative inclusion criteria to identify additional disasters of national significance. The surveillance definition yielded 165 disasters in the period, from which 65 emerged as disasters of national significance. There were 38 natural disasters, 22 technological disasters, three offshore terrorist attacks and two domestic mass shootings. Geographic analysis revealed that states with major population centres experienced the vast majority of disasters of national significance. Timeline analysis revealed an increasing incidence of disasters since the 1980s, which peaked in the period 2005-2009. Recent seasonal bushfires and floods have incurred the highest death toll and economic losses in Australasian history. Reactive hazard-specific legislation emerged after all terrorist acts and after most disasters of national significance. Timeline analysis reveals an increasing incidence in natural disasters over the past 15 years, with the most lethal and costly disasters occurring in the past 3 years. Vulnerability to disaster in Australasia appears to be increasing. Reactive legislation is a recurrent feature of Australasian disaster response that suggests legislative shortsightedness and a need for comprehensive all-hazards model legislation in the future. © 2015 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

The significance of eosinophilia during external irradiation for uterine cervix cancer

International Nuclear Information System (INIS)

Kikuchi, Yuzo; Washizuka, Norio; Kishiyama, Kazutaka; Yamada, Ryuichi; Hasegawa, Tenmatsu

1980-01-01

To study the mechanism of eosinophilia, correlation between immunological skin test including DNCB, PHA and PPD test, the grade of diarrhea were evaluated 32 cases of uterine cancer which received external irradiation. Also the comparison of eosinophilia and diarrhea among the three fraction group and each score group of skin test were done. The maximum value of absolute eosinophils and multiple increase in eosinophils increased more significantly in 4750 rads/20f/5 weeks group than in other group, but did'nt correlate among each score group of skin test. Also eosinophilia did'nt correlate significantly to skin test and the grade of diarrhea. (author)

Co-location of space geodetic techniques carried out at the Geodetic Observatory Wettzell using a closure in time and a multi-technique reference target

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Kodet, J.; Schreiber, K. U.; Eckl, J.; Plötz, C.; Mähler, S.; Schüler, T.; Klügel, T.; Riepl, S.

2018-01-01

The quality of the links between the different space geodetic techniques (VLBI, SLR, GNSS and DORIS) is still one of the major limiting factors for the realization of a unique global terrestrial reference frame that is accurate enough to allow the monitoring of the Earth system, i.e., of processes like sea level change, postglacial rebound and silent earthquakes. According to the specifications of the global geodetic observing system of the International Association of Geodesy, such a reference frame should be accurate to 1 mm over decades, with rates of change stable at the level of 0.1 mm/year. The deficiencies arise from inaccurate or incomplete local ties at many fundamental sites as well as from systematic instrumental biases in the individual space geodetic techniques. Frequently repeated surveys, the continuous monitoring of antenna heights and the geometrical mount stability (Lösler et al. in J Geod 90:467-486, 2016. https://doi.org/10.1007/s00190-016-0887-8) have not provided evidence for insufficient antenna stability. Therefore, we have investigated variations in the respective system delays caused by electronic circuits, which is not adequately captured by the calibration process, either because of subtle differences in the circuitry between geodetic measurement and calibration, high temporal variability or because of lacking resolving bandwidth. The measured system delay variations in the electric chain of both VLBI- and SLR systems reach the order of 100 ps, which is equivalent to 3 cm of path length. Most of this variability is usually removed by the calibrations but by far not all. This paper focuses on the development of new technologies and procedures for co-located geodetic instrumentation in order to identify and remove systematic measurement biases within and between the individual measurement techniques. A closed-loop optical time and frequency distribution system and a common inter-technique reference target provide the possibility to remove

Significant increase in cultivation of Gardnerella vaginalis, Alloscardovia omnicolens, Actinotignum schaalii, and Actinomyces spp. in urine samples with total laboratory automation.

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Klein, Sabrina; Nurjadi, Dennis; Horner, Susanne; Heeg, Klaus; Zimmermann, Stefan; Burckhardt, Irene

2018-04-13

While total laboratory automation (TLA) is well established in laboratory medicine, only a few microbiological laboratories are using TLA systems. Especially in terms of speed and accuracy, working with TLA is expected to be superior to conventional microbiology. We compared in total 35,564 microbiological urine cultures with and without incubation and processing with BD Kiestra TLA for a 6-month period each retrospectively. Sixteen thousand three hundred thirty-eight urine samples were analyzed in the pre-TLA period and 19,226 with TLA. Sixty-two percent (n = 10,101/16338) of the cultures processed without TLA and 68% (n = 13,102/19226) of the cultures processed with TLA showed growth. There were significantly more samples with two or more species per sample and with low numbers of colony forming units (CFU) after incubation with TLA. Regarding the type of bacteria, there were comparable amounts of Enterobacteriaceae in the samples, slightly less non-fermenting Gram-negative bacteria, but significantly more Gram-positive cocci, and Gram-positive rods. Especially Alloscardivia omnicolens, Gardnerella vaginalis, Actinomyces spp., and Actinotignum schaalii were significantly more abundant in the samples incubated and processed with TLA. The time to report was significantly lower in the TLA processed samples by 1.5 h. We provide the first report in Europe of a large number of urine samples processed with TLA. TLA showed enhanced growth of non-classical and rarely cultured bacteria from urine samples. Our findings suggest that previously underestimated bacteria may be relevant pathogens for urinary tract infections. Further studies are needed to confirm our findings.

Significance of heel pad confinement for the shock absorption at heel strike.

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Jørgensen, U; Ekstrand, J

1988-12-01

Shock absorption (SA) is a simple way to reduce the body load and can be used in the prevention and treatment of injuries. The heel pad is the most important shock absorber in the shoe heel complex. The purpose of this study was to investigate whether the SA at heel strike can be increased by heel support in people and shoes with high or low SA. The impact forces at heel strike were measured on an AMTI (R) force platform. Fourteen legs were tested in seven persons (nine with normal and five with low heel pad SA) in gait analysis and in human drop tests. The tests were performed barefooted, and in a soccer and a running shoe (selected by shoe drop test), with and without the distal 2 cm of the heel counter. The heel pad confinement produced by the heel counter (the heel counter effect) increased the SA in both shoe types significantly in both impact situations. The mean increase in SA was 8.8% (range 5.8%-15.5%). The heel counter effect was in all situations significantly higher in persons with low heel pad shock absorbency (LHPSA) than in those with normal heel pads. The barefoot impact peak force per kg body weight was significantly higher (6% mean) on the side with LHPSA. The running shoe provided the significantly greatest SA compared with the soccer shoe. It is concluded that the shock absorbency at heel strike can be increased significantly by heel support, with highest effect in persons with LHPSA, both in shoes with high and low SA.(ABSTRACT TRUNCATED AT 250 WORDS)

The intermediate filament protein vimentin binds specifically to a recombinant integrin α2/β1 cytoplasmic tail complex and co-localizes with native α2/β1 in endothelial cell focal adhesions

International Nuclear Information System (INIS)

Kreis, Stephanie; Schoenfeld, Hans-Joachim; Melchior, Chantal; Steiner, Beat; Kieffer, Nelly

2005-01-01

Integrin receptors are crucial players in cell adhesion and migration. Identification and characterization of cellular proteins that interact with their short α and β cytoplasmic tails will help to elucidate the molecular mechanisms by which integrins mediate bi-directional signaling across the plasma membrane. Integrin α2β1 is a major collagen receptor but to date, only few proteins have been shown to interact with the α2 cytoplasmic tail or with the α2β1 complex. In order to identify novel binding partners of a α2β1cytoplasmic domain complex, we have generated recombinant GST-fusion proteins, incorporating the leucine zipper heterodimerization cassettes of Jun and Fos. To ascertain proper functionality of the recombinant proteins, interaction with natural binding partners was tested. GST-α2 and GST-Jun α2 bound His-tagged calreticulin while GST-β1 and GST-Fos β1 proteins bound talin. In screening assays for novel binding partners, the immobilized GST-Jun α2/GST-Fos β1 heterodimeric complex, but not the single subunits, interacted specifically with endothelial cell-derived vimentin. Vimentin, an abundant intermediate filament protein, has previously been shown to co-localize with αvβ3-positive focal contacts. Here, we provide evidence that this interaction also occurs with α2β1-enriched focal adhesions and we further show that this association is lost after prolonged adhesion of endothelial cells to collagen

Surface water change as a significant contributor to global evapotranspiration change

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Zhan, S.; Song, C.

2017-12-01

Water comprises a critical component of global/regional hydrological and biogeochemical cycles and is essential to all organisms including humans. In the past several decades, climate change has intensified the hydrological cycle, with significant implications for ecosystem services and feedback to regional and global climate. Evapotranspiration (ET) as a linking mechanism between land surface and atmosphere is central to the water cycle and an excellent indicator of the intensity of water cycle. Knowledge of the temporal changes of ET is crucial for accurately estimating global or regional water budgets and better understanding climate and hydrological interactions. While studies have examined changes in global ET, they were conducted using a constant land and surface water (SW) area. However, as many studies have found that global SW is very dynamic and their surface areas have generally been increasing since the 1980s. The conversion from land to water and vice versa significantly changes the local ET since water bodies evaporate at a rate that can be much higher than that of the land. Here, we quantify the global changes in ET caused by such land-water conversion using remotely-sensed SW area and various ET and potential ET products. New SW and lost SW between circa-1985 and circa-2015 were derived from remote sensing and were used to modify the local ET estimates. We found an increase in ET in all continents as consistent with the net increase in SW area. The increasing SW area lead to a global increase in ET by 30.38 ± 5.28 km3/yr. This is a significant contribution when compared to the 92.95 km3/yr/yr increase in ET between 1982-1997 and 103.43 km3/yr/yr decrease between 1998-2008 by Jung et al., (2010) assuming a constant SW. The results enhance our understanding of the water fluxes between the land and atmosphere and supplement land water budget estimates. We conclude that changes in SW lead to a significant change in global ET that cannot be neglected in

Coassembly of big conductance Ca2+-activated K+ channels and L-type voltage-gated Ca2+ channels in rat brain

DEFF Research Database (Denmark)

Grunnet, Morten; Kaufmann, Walter A

2004-01-01

Based on electrophysiological studies, Ca(2+)-activated K(+) channels and voltage-gated Ca(2+) channels appear to be located in close proximity in neurons. Such colocalization would ensure selective and rapid activation of K(+) channels by local increases in the cytosolic calcium concentration...

Functional significance of cardiac reinnervation in heart transplant recipients.

Science.gov (United States)

Schwaiblmair, M; von Scheidt, W; Uberfuhr, P; Ziegler, S; Schwaiger, M; Reichart, B; Vogelmeier, C

1999-09-01

There is accumulating evidence of structural sympathetic reinnervation after human cardiac transplantation. However, the functional significance of reinnervation in terms of exercise capacity has not been established as yet; we therefore investigated the influence of reinnervation on cardiopulmonary exercise testing. After orthotopic heart transplantation 35 patients (mean age, 49.1 +/- 8.4 years) underwent positron emission tomography with scintigraphically measured uptake of C11-hydroxyephedrine (HED), lung function testing, and cardiopulmonary exercise testing. Two groups were defined based on scintigraphic findings, indicating a denervated group (n = 15) with a HED uptake of 5.45%/min and a reinnervated group (n = 20) with a HED uptake of 10.59%/min. The two study groups did not show significant differences with regard to anthropometric data, number of rejection episodes, preoperative hemodynamics, and postoperative lung function data. The reinnervated group had a significant longer time interval from transplantation (1625 +/- 1069 versus 800 +/- 1316 days, p exercise (137 +/- 15 versus 120 +/- 20 beats/min, p = .012), peak oxygen uptake (21.0 +/- 4 versus 16.1 +/- 5 mL/min/kg, p = .006), peak oxygen pulse (12.4 +/- 2.9 versus 10.2 +/- 2.7 mL/min/beat, p = .031), and anaerobic threshold (11.2 +/- 1.8 versus 9.5 +/- 2.1 mL/min, p = .046) were significantly increased in comparison to denervated transplant recipients. Additionally, a decreased functional dead space ventilation (0.24 +/- 0.05 versus 0.30 +/- 0.05, p = .004) was observed in the reinnervated group. Our study results support the hypothesis that partial sympathetic reinnervation after cardiac transplantation is of functional significance. Sympathetic reinnervation enables an increased peak oxygen uptake. This is most probably due to partial restoration of the chronotropic and inotropic competence of the heart as well as an improved oxygen delivery to the exercising muscles and a reduced ventilation

Health Promotion and Healthier Products Increase Vending Purchases: A Randomized Factorial Trial.

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Hua, Sophia V; Kimmel, Lisa; Van Emmenes, Michael; Taherian, Rafi; Remer, Geraldine; Millman, Adam; Ickovics, Jeannette R

2017-07-01

The current food environment has a high prevalence of nutrient-sparse foods and beverages, most starkly seen in vending machine offerings. There are currently few studies that explore different interventions that might lead to healthier vending machine purchases. To examine how healthier product availability, price reductions, and/or promotional signs affect sales and revenue of snack and beverage vending machines. A 2×2×2 factorial randomized controlled trial was conducted. Students, staff, and employees on a university campus. All co-located snack and beverage vending machines (n=56, 28 snack and 28 beverage) were randomized into one of eight conditions: availability of healthier products and/or 25% price reduction for healthier items and/or promotional signs on machines. Aggregate sales and revenue data for the 5-month study period (February to June 2015) were compared with data from the same months 1 year prior. Analyses were conducted July 2015. The change in units sold and revenue between February through June 2014 and 2015. Linear regression models (main effects and interaction effects) and t test analyses were performed. The interaction between healthier product guidelines and promotional signs in snack vending machines documented increased revenue (Prevenue change. Price reductions alone had no effect, nor were there any effects for the three-way interaction of the factors. Examining top-selling products for all vending machines combined, pre- to postintervention, we found an overall shift to healthier purchasing. When healthier vending snacks are available, promotional signs are also important to ensure consumers purchase those items in greater amounts. Mitigating potential loss in profits is essential for sustainability of a healthier food environment. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Isoflurane increases cardiorespiratory coordination in rats

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Kabir, Muammar M.; Beig, Mirza I.; Nalivaiko, Eugene; Abbott, Derek; Baumert, Mathias

2008-12-01

Anesthetics such as isoflurane adversely affect heart rate. In this study we analysed the interaction between heart rhythm and respiration at different concentrations of isoflurane and ventilation rates. In two rats, the electrocardiogram (ECG) and respiratory signals were recorded under the influence of isoflurane. For the assessment of cardiorespiratory coordination, we analysed the phase locking between heart rate, computed from the R-R intervals of body surface ECG, and respiratory rate, computed from impedance changes, using Hilbert transform. The changes in heart rate, percentage of synchronization and duration of synchronized epochs at different isoflurane concentrations and ventilation rates were assessed using linear regression model. From this study it appears that the amount of phase locking between cardiac and respiratory rates increases with the increase in concentration of isoflurane. Heart rate and duration of synchronized epochs increased significantly with the increase in the level of isoflurane concentration while respiratory rate was not significantly affected. Cardiorespiratory coordination also showed a considerable increase at the ventilation rates of 50- 55 cpm in both the rats, suggesting that the phase-locking between the cardiac and respiratory oscillators can be increased by breathing at a particular respiratory frequency.

Complex Inflammation mRNA-Related Response in ALS Is Region Dependent

Directory of Open Access Journals (Sweden)

Sara Berjaoui

2015-01-01

Full Text Available Inflammatory changes are analyzed in the anterior spinal cord and frontal cortex area 8 in typical spinal-predominant ALS cases. Increased numbers of astrocytes and activated microglia are found in the anterior horn of the spinal cord and pyramidal tracts. Significant increased expression of TLR7, CTSS, and CTSC mRNA and a trend to increased expression of IL10RA, TGFB1, and TGFB2 are found in the anterior lumbar spinal cord in ALS cases compared to control cases, whereas C1QTNF7 and TNFRSF1A mRNA expression levels are significantly decreased. IL6 is significantly upregulated and IL1B shows a nonsignificant increased expression in frontal cortex area 8 in ALS cases. IL-6 immunoreactivity is found in scattered monocyte-derived macrophages/microglia and TNF-α in a few cells of unknown origin in ALS cases. Increased expression and abnormal distribution of IL-1β occurred in motor neurons of the lumbar spinal cord in ALS. Strong IL-10 immunoreactivity colocalizes with TDP-43-positive inclusions in motor neurons in ALS cases. The present observations show a complex participation of cytokines and mediators of the inflammatory response in ALS consistent with increased proinflammatory cytokines and sequestration of anti-inflammatory IL-10 in affected neurons.

Human Digital Meissner Corpuscles Display Immunoreactivity for the Multifunctional Ion Channels Trpc6 and Trpv4.

Science.gov (United States)

Alonso-González, Paula; Cabo, Roberto; San José, Isabel; Gago, Angel; Suazo, Iván C; García-Suárez, Olivia; Cobo, Juan; Vega, José A

2017-06-01

Ion channels are at the basis of the sensory processes including mechanosensing. Some members of the transient receptor potential (TRP) ion channel superfamily have been proposed as mechanosensors, but their putative role in mechanotransduction is controversial. Among them there are TRP canonical 6 (TRPC6) and TRP vanilloid 4 (TRPV4) ion channels, which are known to cooperate in mechanical hyperalgesia. Here, we investigated the occurrence, distribution, and possible colocalization of TRPC6 and TRPV4 in human digital Meissner sensory corpuscles using immunohistochemistry and double immunofluorescence (associate with markers for specific corpuscular constituents). TRPC6 immunoreactivity was restricted to the axon of Meissner corpuscles, whereas TRPV4 was detected in the axon but also in the lamellar cells. Moreover, axonal colocalization of TRPV4 and TRPC6 was found in the digital Meissner corpuscles. Present results demonstrate for the first time the occurrence and colocalization of two ion channels candidates to mechanosensors in human cutaneous mechanoreceptors. The functional significance of these ion channels in that place remains to be clarified, but should be related to different properties of mechanosensitivity. Anat Rec, 300:1022-1031, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Occult pneumothoraces in Chinese patients with significant blunt chest trauma: radiological classification and proposed clinical significance.

Science.gov (United States)

Lee, Ryan K L; Graham, Colin A; Yeung, Janice H H; Ahuja, Anil T; Rainer, Timothy H

2012-12-01

An occult pneumothorax (OP) is a pneumothorax not seen on a supine chest X-ray (CXR) but detected on abdominal or thoracic computed tomography (CT) scanning. With the increasing use of CT in the management of significantly injured trauma patients, more OPs are being detected. The aim of this study was to classify OPs diagnosed on thoracic CT (TCT) and correlate them with their clinical significance. Retrospective analysis of prospectively collected trauma registry data. Total 36 (N=36) consecutive significantly injured trauma patients admitted through the emergency department (ED) who sustained blunt chest trauma and underwent TCT between 1 January 2007 and 31 December 2008 were included. OP was defined as the identification (by a consultant radiologist) of a pneumothorax on TCT that had not been detected on supine CXR. OPs were classified by laterality (unilateral/bilateral) and location (apical, basal, non apical/basal). The size of pneumothoraces, severity of injury [including number of associated thoracic injuries and injury severity score (ISS)], length of hospital stay and mortality were compared between groups. The need for tube thoracostomy and clinical outcome were also analysed. Patients with bilateral OPs (N=8) had significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 23, p=0.02) and longer hospital stay (median: 20 days vs. 11 days, p=0.01) than those with a unilateral OP (N=28). Basal OPs (N=7) were significantly larger than apical (N=10) and non-apical/basal Ops (N=11). Basal OPs were associated with significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 17 days, p=0.02) than apical Ops, which had higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 15 days, p=0.02) than non-apical/basal OPs. Non-apical/basal OPs were associated with more related injuries (median: 2

Affibody scaffolds improve sesquiterpene production in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Tippmann, Stefan; Anfelt, Josefine; David, Florian

2017-01-01

Enzyme fusions have been widely used as a tool in metabolic engineering to increase pathway efficiency by reducing substrate loss and accumulation of toxic intermediates. Alternatively, enzymes can be co-localized through attachment to a synthetic scaffold via non-covalent interactions. Here we d...

Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

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Jaroslaw Suchanski

Full Text Available In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first

Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

Science.gov (United States)

Suchanski, Jaroslaw; Tejchman, Anna; Zacharski, Maciej; Piotrowska, Aleksandra; Grzegrzolka, Jedrzej; Chodaczek, Grzegorz; Nowinska, Katarzyna; Rys, Janusz; Dziegiel, Piotr; Kieda, Claudine; Ugorski, Maciej

2017-01-01

In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such

Significant association between parathyroid hormone and uric acid level in men

Directory of Open Access Journals (Sweden)

Chin KY

2015-08-01

Full Text Available Kok-Yong Chin,1 Soelaiman Ima Nirwana,1 Wan Zurinah Wan Ngah21Department of Pharmacology, 2Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MalaysiaBackground: Previous reports of patients undergoing parathyroidectomy and of patients receiving teriparatide as antiosteoporotic treatment have suggested a plausible relationship between parathyroid hormone (PTH and uric acid. However, similar data at population level were lacking. The current study aimed to determine the relationship between PTH and uric acid in a group of apparently healthy Malaysian men.Methods: A cross-sectional study was conducted among 380 Malay and Chinese men aged 20 years and above, residing in the Klang Valley, Malaysia. Their body anthropometry was measured, and their fasting blood samples were collected for biochemical analysis. The relationship between PTH and uric acid was analyzed using regression analysis.Results: Increased serum PTH level was significantly associated with increased serum uric acid level (β=0.165; P=0.001. Increased PTH level was also significantly associated with the condition of hyperuricemia in the study population (odds ratio [OR], 1.045; 95% confidence interval [CI], 1.017–1.075; P=0.002. All analyses were adjusted for age, body mass index, vitamin D, total calcium, inorganic phosphate, blood urea nitrogen and creatinine levels.Conclusion: There is a significant positive relationship between PTH level and uric acid level in Malaysian men. This relationship and its clinical significance should be further investigated in a larger longitudinal study. Keywords: hyperuricemia, Asian, cross-sectional study, uric acid, urate

Bayesian approaches for detecting significant deterioration

International Nuclear Information System (INIS)

Roed, Willy; Aven, Terje

2009-01-01

Risk indicators can provide useful input to risk management processes and are given increased attention in the Norwegian petroleum industry. Examples include indicators expressing the proportion of test failures of safety and barrier systems. Such indicators give valuable information about the performance of the systems and provide a basis for trend evaluations. Early warning of a possible deterioration is essential due to the importance of the systems in focus, but what should be the basis for the warning criterion? This paper presents and discusses several Bayesian approaches for the establishment of a warning criterion to disclose significant deterioration. The Norwegian petroleum industry is the starting point for this paper, but the study is relevant for other application areas as well

Eosinophilic pleural effusion: incidence, etiology and prognostic significance.

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Ferreiro, Lucía; San José, Esther; González-Barcala, Francisco Javier; Alvarez-Dobaño, José Manuel; Golpe, Antonio; Gude, Francisco; Anchorena, Christian; Pereyra, Marco F; Zamarrón, Carlos; Valdés, Luis

2011-10-01

Eosinophilic pleural effusion (EPE) has been associated with less risk for malignancy with a potential causal relationship with the presence of air and/or blood in the pleural space. However, these theories have fallen by the wayside in the light of recent publications. To determine the incidence and etiology of EPE and to observe whether the eosinophils in the pleural liquid (PL) increase in successive thoracocenteses. We analyzed 730 PL samples from 605 patients hospitalized between January 2004 and December 2010. We identified 55 samples with EPE from 50 patients (8.3%). The most frequent etiologies of EPE were: unknown (36%) and neoplasm (30%). There were no significant differences in the incidence of neoplasms between the non-eosinophilic pleural effusions (non-EPE) (25.9%) and the EPE (30%) (p=0.533). One hundred patients (16.5%) underwent a second thoracocentesis. Out of the 9 who had EPE in the first, 6 maintained EPE in the second. Out of the 91 with non-EPE in the first thoracocentesis, 8 (8.8%) had EPE in the repeat thoracocentesis. The percentage of eosinophils did not increase in the successive thoracocenteses (p=0.427). In the EPE, a significant correlation was found between the number of hematites and eosinophils in the PL (r=0.563; p=0.000). An EPE cannot be considered an indicator of benignancy, therefore it should be studied as any other pleural effusion. The number of eosinophils does not seem to increase with the of repetition of thoracocentesis and, lastly, the presence of blood in the PL could explain the existence of EPE. Copyright © 2011 SEPAR. Published by Elsevier Espana. All rights reserved.

'Knowledge for better health' revisited - the increasing significance of health research systems: a review by departing Editors-in-Chief.

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Hanney, Stephen R; González-Block, Miguel A

2017-10-02

How can nations organise research investments to obtain the best bundle of knowledge and the maximum level of improved health, spread as equitably as possible? This question was the central focus of a major initiative from WHO led by Prof Tikki Pang, which resulted in a range of developments, including the publication of a conceptual framework for national health research systems - Knowledge for better health - in 2003, and in the founding of the journal Health Research Policy and Systems (HARPS). As Editors-in-Chief of the journal since 2006, we mark our retirement by tracking both the progress of the journal and the development of national health research systems. HARPS has maintained its focus on a range of central themes that are key components of a national health research system in any country. These include building capacity to conduct and use health research, identifying appropriate priorities, securing funds and allocating them accountably, producing scientifically valid research outputs, promoting the use of research in polices and practice in order to improve health, and monitoring and evaluating the health research system. Some of the themes covered in HARPS are now receiving increased attention and, for example, with the assessment of research impact and development of knowledge translation platforms, the journal has covered their progress throughout that expansion of interest. In addition, there is increasing recognition of new imperatives, including the importance of promoting gender equality in health research if benefits are to be maximised. In this Editorial, we outline some of the diverse and developing perspectives considered within each theme, as well as considering how they are held together by the growing desire to build effective health research systems in all countries.From 2003 until mid-June 2017, HARPS published 590 articles on the above and related themes, with authors being located in 76 countries. We present quantitative data tracing

Analysis of Co-Located MODIS and CALIPSO Observations Near Clouds

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Varnai, Tamas; Marshak, Alexander

2011-01-01

closer than 5 km to clouds implies that pronounced near-cloud changes in aerosol properties have significant implications for overall clear-sky characteristics, including the radiative impact of aerosols.

The Significance of Barriers to Entry in the Construction Industry

Directory of Open Access Journals (Sweden)

Gerard de Valence

2012-11-01

Full Text Available This research looks at the significance of barriers that firms considering entry into the construction industry might face. Drawing on the microeconomic characteristics of imperfectly competitive and oligopolistic markets the analysis finds that there are a dozen barriers to entry that affect the industry, but their significance depends on the product type. The discussion covers the question of product homogeneity in construction and evidence for the existence of barriers to entry in concentration levels. Barriers to entry specific to construction are then identified, which leads to an analysis of how they operate and their significance (high, medium or low in different market types, thus increasing our understanding of construction industry dynamics.

Electronic prompts significantly increase response rates to postal questionnaires: a randomized trial within a randomized trial and meta-analysis.

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Clark, Laura; Ronaldson, Sarah; Dyson, Lisa; Hewitt, Catherine; Torgerson, David; Adamson, Joy

2015-12-01

To assess the effectiveness of sending electronic prompts to randomized controlled trial participants to return study questionnaires. A "trial within a trial" embedded within a study determining the effectiveness of chronic obstructive pulmonary disease (DOC) screening on smoking cessation. Those participants taking part in DOC who provided a mobile phone number and/or an electronic mail address were randomized to either receive an electronic prompt or no electronic prompt to return a study questionnaire. The results were combined with two previous studies in a meta-analysis. A total of 437 participants were randomized: 226 to the electronic prompt group and 211 to the control group. A total of 285 (65.2%) participants returned the follow-up questionnaire: 157 (69.5%) in the electronic prompt group and 128 (60.7%) in the control group [difference 8.8%; 95% confidence interval (CI): -0.11%, 17.7%; P = 0.05]. The mean time to response was 23 days in the electronic prompt group and 33 days in the control group (hazard ratio = 1.27; 95% CI: 1.105, 1.47). The meta-analysis of all three studies showed an increase in response rate of 7.1% (95% CI: 0.8%, 13.3%). The use of electronic prompts increased response rates and reduces the time to response. Copyright © 2015 Elsevier Inc. All rights reserved.

Detecting Novelty and Significance

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Ferrari, Vera; Bradley, Margaret M.; Codispoti, Maurizio; Lang, Peter J.

2013-01-01

Studies of cognition often use an “oddball” paradigm to study effects of stimulus novelty and significance on information processing. However, an oddball tends to be perceptually more novel than the standard, repeated stimulus as well as more relevant to the ongoing task, making it difficult to disentangle effects due to perceptual novelty and stimulus significance. In the current study, effects of perceptual novelty and significance on ERPs were assessed in a passive viewing context by presenting repeated and novel pictures (natural scenes) that either signaled significant information regarding the current context or not. A fronto-central N2 component was primarily affected by perceptual novelty, whereas a centro-parietal P3 component was modulated by both stimulus significance and novelty. The data support an interpretation that the N2 reflects perceptual fluency and is attenuated when a current stimulus matches an active memory representation and that the amplitude of the P3 reflects stimulus meaning and significance. PMID:19400680

ProSAAS-derived peptides are differentially processed and sorted in mouse brain and AtT-20 cells.

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Jonathan H Wardman

Full Text Available ProSAAS is the precursor for some of the most abundant peptides found in mouse brain and other tissues, including peptides named SAAS, PEN, and LEN. Both SAAS and LEN are found in big and little forms due to differential processing. Initial processing of proSAAS is mediated by furin (and/or furin-like enzymes and carboxypeptidase D, while the smaller forms are generated by secretory granule prohormone convertases and carboxypeptidase E. In mouse hypothalamus, PEN and big LEN colocalize with neuropeptide Y. In the present study, little LEN and SAAS were detected in mouse hypothalamus but not in cell bodies of neuropeptide Y-expressing neurons. PEN and big LEN show substantial colocalization in hypothalamus, but big LEN and little LEN do not. An antiserum to SAAS that detects both big and little forms of this peptide did not show substantial colocalization with PEN or big LEN. To further study this, the AtT-20 cells mouse pituitary corticotrophic cell line was transfected with rat proSAAS and the distribution of peptides examined. As found in mouse hypothalamus, only some of the proSAAS-derived peptides colocalized with each other in AtT-20 cells. The two sites within proSAAS that are known to be efficiently cleaved by furin were altered by site-directed mutagenesis to convert the P4 Arg into Lys; this change converts the sequences from furin consensus sites into prohormone convertase consensus sites. Upon expression of the mutated form of proSAAS in AtT-20 cells, there was significantly more colocalization of proSAAS-derived peptides PEN and SAAS. Taken together, these results indicate that proSAAS is initially cleaved in the Golgi or trans-Golgi network by furin and/or furin-like enzymes and the resulting fragments are sorted into distinct vesicles and further processed by additional enzymes into the mature peptides.

Social Interactions and Games

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Uz, Cigdem; Cagiltay, Kursat

2015-01-01

Digital games have become popular due to great technological improvements in recent years. They have been increasingly transformed from co-located experiences into multi-played, socially oriented platforms (Herodotou, 2009). Multi-User Online Games provide the opportunity to create a social environment for friendships and strengthen the…

Clinical significance of quantitative analysis of facial nerve enhancement on MRI in Bell's palsy.

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Song, Mee Hyun; Kim, Jinna; Jeon, Ju Hyun; Cho, Chang Il; Yoo, Eun Hye; Lee, Won-Sang; Lee, Ho-Ki

2008-11-01

Quantitative analysis of the facial nerve on the lesion side as well as the normal side, which allowed for more accurate measurement of facial nerve enhancement in patients with facial palsy, showed statistically significant correlation with the initial severity of facial nerve inflammation, although little prognostic significance was shown. This study investigated the clinical significance of quantitative measurement of facial nerve enhancement in patients with Bell's palsy by analyzing the enhancement pattern and correlating MRI findings with initial severity of facial palsy and clinical outcome. Facial nerve enhancement was measured quantitatively by using the region of interest on pre- and postcontrast T1-weighted images in 44 patients diagnosed with Bell's palsy. The signal intensity increase on the lesion side was first compared with that of the contralateral side and then correlated with the initial degree of facial palsy and prognosis. The lesion side showed significantly higher signal intensity increase compared with the normal side in all of the segments except for the mastoid segment. Signal intensity increase at the internal auditory canal and labyrinthine segments showed correlation with the initial degree of facial palsy but no significant difference was found between different prognostic groups.

Sensitivity and specificity of in situ proximity ligation for protein interaction analysis in a model of steatohepatitis with Mallory-Denk bodies.

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Bernhard Zatloukal

Full Text Available The in situ proximity ligation assay (isPLA is an increasingly used technology for in situ detection of protein interactions, post-translational modifications, and spatial relationships of antigens in cells and tissues, in general. In order to test its performance we compared isPLA with immunofluorescence microscopy by analyzing protein interactions in cytoplasmic protein aggregates, so-called Mallory Denk bodies (MDBs. These structures represent protein inclusions in hepatocytes typically found in human steatohepatitis and they can be generated in mice by feeding of 3,5-diethoxy-carbonyl-1,4-dihydrocollidine (DDC. We investigated the colocalization of all three key MDB components, namely keratin 8 (K8, keratin 18 (K18, and p62 (sequestosome 1 by isPLA and immunofluorescence microscopy. Sensitivity and specificity of isPLA was assessed by using Krt8-/- and Krt18-/- mice as biological controls, along with a series of technical controls. isPLA signal visualization is a robust technology with excellent sensitivity and specificity. The biological relevance of signals generated critically depends on the performance of antibodies used, which requires careful testing of antibodies like in immunofluorescence microscopy. There is a clear advantage of isPLA in visualizing protein co-localization, particularly when antigens are present at markedly different concentrations. Furthermore, isPLA is superior to confocal microscopy with respect to spatial resolution of colocalizing antigens. Disadvantages compared to immunofluorescence are increased costs and longer duration of the laboratory protocol.

Bleed-through correction for rendering and correlation analysis in multi-colour localization microscopy

International Nuclear Information System (INIS)

Kim, Dahan; Curthoys, Nikki M; Parent, Matthew T; Hess, Samuel T

2013-01-01

Multi-colour localization microscopy has enabled sub-diffraction studies of colocalization between multiple biological species and quantification of their correlation at length scales previously inaccessible with conventional fluorescence microscopy. However, bleed-through, or misidentification of probe species, creates false colocalization and artificially increases certain types of correlation between two imaged species, affecting the reliability of information provided by colocalization and quantified correlation. Despite the potential risk of these artefacts of bleed-through, neither the effect of bleed-through on correlation nor methods for its correction in correlation analyses have been systematically studied at typical rates of bleed-through reported to affect multi-colour imaging. Here, we present a reliable method of bleed-through correction applicable to image rendering and correlation analysis of multi-colour localization microscopy. Application of our bleed-through correction shows that our method accurately corrects the artificial increase in both types of correlation studied (Pearson coefficient and pair correlation), at all rates of bleed-through tested, in all types of correlation examined. In particular, anti-correlation could not be quantified without our bleed-through correction, even at rates of bleed-through as low as 2%. While it is demonstrated with dichroic-based multi-colour FPALM here, our presented method of bleed-through correction can be applied to all types of localization microscopy (PALM, STORM, dSTORM, GSDIM, etc), including both simultaneous and sequential multi-colour modalities, provided the rate of bleed-through can be reliably determined. (special issue article)

The prognostic significance of angina pectoris experienced during the first month following acute myocardial infarction

DEFF Research Database (Denmark)

Jespersen, C M

1997-01-01

BACKGROUND: Angina pectoris accompanied by transient ST-segment changes during the in-hospital phase of acute myocardial infarction (AMI) is a well established marker of subsequent cardiac death and reinfarction. HYPOTHESIS: This study was undertaken to record the prognostic significance of angina...... on study treatment 1 month after discharge. Of these patients, 311 (39%) reported chest pain during the first month following discharge. RESULTS: Patients with angina pectoris had a significantly increased risk of reinfarction [hazard 1.71; 95%-confidence limit (CL): 1.09, 2.69] and increased mortality...... risk which, however, only reached borderline statistical significance (hazard 1.52; 95%-CL: 0.96, 2.40). When patients were subdivided according to both angina pectoris and heart failure, those with one or both of these risk markers had significantly increased mortality (p 0.03) and reinfarction (p 0...

The stage-classified matrix models project a significant increase in biomass carbon stocks in China's forests between 2005 and 2050.

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Hu, Huifeng; Wang, Shaopeng; Guo, Zhaodi; Xu, Bing; Fang, Jingyun

2015-06-25

China's forests are characterized by young age, low carbon (C) density and a large plantation area, implying a high potential for increasing C sinks in the future. Using data of provincial forest area and biomass C density from China's forest inventories between 1994 and 2008 and the planned forest coverage of the country by 2050, we developed a stage-classified matrix model to predict biomass C stocks of China's forests from 2005 to 2050. The results showed that total forest biomass C stock would increase from 6.43 Pg C (1 Pg = 10(15) g) in 2005 to 9.97 Pg C (95% confidence interval: 8.98 ~ 11.07 Pg C) in 2050, with an overall net C gain of 78.8 Tg C yr(-1) (56.7 ~ 103.3 Tg C yr(-1); 1 Tg = 10(12) g). Our findings suggest that China's forests will be a large and persistent biomass C sink through 2050.

Assessing Clinical Significance: Does it Matter which Method we Use?

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Atkins, David C.; Bedics, Jamie D.; Mcglinchey, Joseph B.; Beauchaine, Theodore P.

2005-01-01

Measures of clinical significance are frequently used to evaluate client change during therapy. Several alternatives to the original method devised by N. S. Jacobson, W. C. Follette, & D. Revenstorf (1984) have been proposed, each purporting to increase accuracy. However, researchers have had little systematic guidance in choosing among…

Antibiotic resistance increases with local temperature

Science.gov (United States)

MacFadden, Derek R.; McGough, Sarah F.; Fisman, David; Santillana, Mauricio; Brownstein, John S.

2018-06-01

Bacteria that cause infections in humans can develop or acquire resistance to antibiotics commonly used against them1,2. Antimicrobial resistance (in bacteria and other microbes) causes significant morbidity worldwide, and some estimates indicate the attributable mortality could reach up to 10 million by 20502-4. Antibiotic resistance in bacteria is believed to develop largely under the selective pressure of antibiotic use; however, other factors may contribute to population level increases in antibiotic resistance1,2. We explored the role of climate (temperature) and additional factors on the distribution of antibiotic resistance across the United States, and here we show that increasing local temperature as well as population density are associated with increasing antibiotic resistance (percent resistant) in common pathogens. We found that an increase in temperature of 10 °C across regions was associated with an increases in antibiotic resistance of 4.2%, 2.2%, and 2.7% for the common pathogens Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The associations between temperature and antibiotic resistance in this ecological study are consistent across most classes of antibiotics and pathogens and may be strengthening over time. These findings suggest that current forecasts of the burden of antibiotic resistance could be significant underestimates in the face of a growing population and climate change4.

Significance of insulin for glucose metabolism in skeletal muscle during contractions

DEFF Research Database (Denmark)

Hespel, P; Vergauwen, Lieven; Vandenberghe, K

1996-01-01

is essentially effected via increased blood flow, significantly contributes to stimulate glucose uptake. Again, however, increased glucose delivery appears to be a more potent stimulus of muscle glucose uptake as the circulating insulin level is increased. Furthermore, contractions and elevated flow prove...... is effected primarily via mechanisms exerted within the muscle cell related to the contractile activity per se. Yet contractions become a more potent stimulus of muscle glucose uptake as the plasma insulin level is increased. In addition, enhanced glucose delivery to muscle, which during exercise...... to be additive stimuli of muscle glucose uptake at any plasma insulin level. In conclusion, the extent to which muscle glucose uptake is stimulated during exercise depends on various factors, including 1) the intensity of the contractile activity, 2) the magnitude of the exercise-associated increase in muscle...

Role and significance of total phenols during rooting of Protea ...

African Journals Online (AJOL)

The high total phenol content was associated with significantly higher rooting percentage and increased the number of roots formed. Blanching reduced the time needed for the cuttings to root sufficiently to be transplanted to the field by 30 days. Analyses of different parts of cuttings throughout the entire rooting period ...

Detection and significance of serum inflammatory factors and oxidative stress indicators in diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

Wei Gao; Jing Wang; Chao Zhang; Ping Qin

2017-01-01

Objective:To determine the serum inflammatory cytokines and oxidative stress parameters of diabetic retinopathy (DR) patients to explore their possible role in the DR.Methods: 116 cases of type 2 diabetic patients were selected from June 2015 to June 2016 in our hospital as research subjects, divided into diabetic Diabetes without retinopathy (NDR group,n = 63) and diabetic with retinopathy patients (DR group,n = 53). And 60 cases of healthy check-ups of the same period in our hospital medical center were selected as normal control group (NC). The VEGF, IL-6, TNF-α , MDA and SOD levels of three groups of patients were detected. Results:The IL-6 levels of NC group, NDR group and DR group were increased gradually, and the difference was statistically significant (P<0.05). The TNF-α levels of NC group, NDR group and DR group were increased gradually, and the difference was statistically significant (P<0.05). The VEGF levels of NC group, NDR group and DR group were increased gradually, and the difference was statistically significant (P<0.05). The malondialdehyde (MDA) levels of NC group, NDR group and DR group increased gradually, and the difference was statistically significant (P<0.05). The superoxide dismutase (SOD) levels of NC group, NDR group and DR group were decreased gradually, and the difference was statistically significant (P<0.05). Conclusions: DR patients express high levels of IL-6, TNF-α and VEGF, and there exists significant oxidative stress in DR, which shows that the inflammation occurrence and oxidative stress state play an important role in the development of DR.

Minimizing Co-location Potential of Moving Entities

NARCIS (Netherlands)

Evans, Will; Kirkpatrick, David; Löffler, Maarten; Staals, Frank

2016-01-01

We study the problem of maintaining knowledge of the locations of $n$ entities that are moving, each with some, possibly different, upper bound on their speed. We assume a setting where we can query the current location of any one entity, but this query takes a unit of time, during which we cannot

Group colocation behavior in technological social networks.

Directory of Open Access Journals (Sweden)

Chloë Brown

Full Text Available We analyze two large datasets from technological networks with location and social data: user location records from an online location-based social networking service, and anonymized telecommunications data from a European cellphone operator, in order to investigate the differences between individual and group behavior with respect to physical location. We discover agreements between the two datasets: firstly, that individuals are more likely to meet with one friend at a place they have not visited before, but tend to meet at familiar locations when with a larger group. We also find that groups of individuals are more likely to meet at places that their other friends have visited, and that the type of a place strongly affects the propensity for groups to meet there. These differences between group and solo mobility has potential technological applications, for example, in venue recommendation in location-based social networks.

Meeting increased demand.

Science.gov (United States)

Blair, Andrew

2004-07-01

New Zealand is a little country with a little economy but with a population that's rapidly aging. New Zealand's population is only 4.3 million people. It's GDP is only $US58.6 billion (2002). New Zealand's expenditure on health as a percentage of GDP is not out of line with that of other countries. As a nation we have been increasing expenditure on health over recent years. In 1990 we spent 7% of GDP on health. In 1995 that increased to 7.65% and is now 8.3%. However, in per capita terms our expenditure on health does not compare so well with like countries. The size of New Zealand's economy is restricting what our country spends on health. Health is already the second highest demand on the New Zealand tax dollar. The tolerance of New Zealanders would be challenged if a Government attempted to increase taxes further to meet the growing demands for expenditure on health, but at the same time the population's expectations are increasing. This is the challenging situation we face today. What lies ahead? Like all industrialized countries New Zealand is facing an aging population. The population below age 40 is decreasing, but it is increasing significantly over that age. 16% of the population is currently aged over 60. By 2051 this proportion will almost double to just over 31%. Coupled with the aging population is increased awareness and expectations, as access to options for treatment and technology becomes readily accessible to the population through such media as the internet. The extent of the impact of the aging population can be clearly represented by focusing on one specialty such as orthopaedics. The New Zealand Orthopaecic Association undertook a study in July 2003 which concluded (among other things) that as a result of the projected aging of the population, over the next 50 years: Musculo-skeletal operations will increase by over 30%. The number of hip replacements will nearly double. The incidence of osteoporosis will increase by a massive 201%. The number

Increased intracranial volume in Parkinson's disease

DEFF Research Database (Denmark)

Krabbe, Katja; Karlsborg, Merete; Hansen, Andreas

2005-01-01

segmentation and outlining of regions in order to identify regional volume changes that might be useful in the diagnosis of the two diseases. RESULTS: Patients with PD had significantly larger intracranial volumes (ICVs) and significantly smaller putaminal and sustantia nigra volumes than controls. MSA...... patients had significantly smaller substantia nigra and caudate volumes than controls but normal intracranial volume. In both patient groups there was a further trend towards smaller amygdala volumes. DISCUSSION: Increased ICV in PD patients is a new finding that may be explained by genetic factors...

Barnacle geese achieve significant energetic savings by changing posture.

Science.gov (United States)

Tickle, Peter G; Nudds, Robert L; Codd, Jonathan R

2012-01-01

Here we report the resting metabolic rate in barnacle geese (Branta leucopsis) and provide evidence for the significant energetic effect of posture. Under laboratory conditions flow-through respirometry together with synchronous recording of behaviour enabled a calculation of how metabolic rate varies with posture. Our principal finding is that standing bipedally incurs a 25% increase in metabolic rate compared to birds sitting on the ground. In addition to the expected decrease in energy consumption of hindlimb postural muscles when sitting, we hypothesise that a change in breathing mechanics represents one potential mechanism for at least part of the observed difference in energetic cost. Due to the significant effect of posture, future studies of resting metabolic rates need to take into account and/or report differences in posture.

Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries.

Directory of Open Access Journals (Sweden)

Joana Beatriz Sousa

Full Text Available Nitric oxide (NO seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells and Confocal Microscopy. Results indicated that: 1 in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2 in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3 confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation.

FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures

DEFF Research Database (Denmark)

Wong, Kah Keng; Gascoyne, Duncan M; Soilleux, Elizabeth J

2016-01-01

frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which...

One arm exercise induces significant interarm diastolic blood pressure difference.

Science.gov (United States)

Hong, Dezhi; Wang, Jiwei; Su, Hai; Xu, Jingsong; Liu, Yanna; Peng, Qiang; Wang, Lijuan

2011-06-01

This study is designed to investigate the inducing effect of one arm exercise on interarm difference (IAD) in the blood pressure (BP). Fifty healthy young participants were included in the study. Three-minute exercises of the right arm elbow flexion and extension were performed. The bilateral brachial BP was simultaneously measured with two automatic BP measurement devices before (basic) and immediately 0, 5, 10, 15, 20, and 30 min after exercise. The absolute difference in the systolic BP (SBP) and diastolic BP (DBP) between the left and right BP of at least 10 mmHg was recognized as sIAD and dIAD. The baseline data of the SBP and DBP in left and right arms revealed no significant difference (SBP: 110 ± 10 vs. 111 ± 11 mmHg; DBP: 66 ± 8 vs. 66 ± 9 mmHg, both not significant). The prevalence of dIAD was 2% at the baseline. However, this prevalence increased to 80% at 0 min, as right arm exercise induced the right DBP decrease and left DBP increase, and then the prevalence decreased gradually within a 30-min recovery period. The prevalence of sIAD was zero at the baseline and the maximal prevalence was 8% during the 20-min postexercise period. One arm exercise can lead to a significant IAD in DBP. Any arm exercise should be avoided before BP measurement.

Effects of increasing age, dosage, and duration of PTH treatment on BMD increase--a meta-analysis

DEFF Research Database (Denmark)

Schwarz, Peter; Jorgensen, Niklas Rye; Mosekilde, Leif

2012-01-01

were included. By metaregression analysis, we found that the increase in spine BMD (Z-score) after PTH treatment was blunted by increasing age (R (2) = 0.27; 2p = 0.01, slope -0.023 Z-scores per year, 11 studies). By increasing PTH dosage (μg/d), spine BMD increased significantly (2p = 0.......002) with a slope of +0.011 Z-scores/μg/d of teriparatide. Furthermore, the duration of treatment was positively correlated to spine BMD (P ......We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present...

Regulation of myosin IIA and filamentous actin during insulin-stimulated glucose uptake in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Stall, Richard; Ramos, Joseph; Kent Fulcher, F.; Patel, Yashomati M.

2014-01-01

Insulin stimulated glucose uptake requires the colocalization of myosin IIA (MyoIIA) and the insulin-responsive glucose transporter 4 (GLUT4) at the plasma membrane for proper GLUT4 fusion. MyoIIA facilitates filamentous actin (F-actin) reorganization in various cell types. In adipocytes F-actin reorganization is required for insulin-stimulated glucose uptake. What is not known is whether MyoIIA interacts with F-actin to regulate insulin-induced GLUT4 fusion at the plasma membrane. To elucidate the relationship between MyoIIA and F-actin, we examined the colocalization of MyoIIA and F-actin at the plasma membrane upon insulin stimulation as well as the regulation of this interaction. Our findings demonstrated that MyoIIA and F-actin colocalized at the site of GLUT4 fusion with the plasma membrane upon insulin stimulation. Furthermore, inhibition of MyoII with blebbistatin impaired F-actin localization at the plasma membrane. Next we examined the regulatory role of calcium in MyoIIA-F-actin colocalization. Reduced calcium or calmodulin levels decreased colocalization of MyoIIA and F-actin at the plasma membrane. While calcium alone can translocate MyoIIA it did not stimulate F-actin accumulation at the plasma membrane. Taken together, we established that while MyoIIA activity is required for F-actin localization at the plasma membrane, it alone is insufficient to localize F-actin to the plasma membrane. - Highlights: • Insulin induces colocalization of MyoIIA and F-actin at the cortex in adipocytes. • MyoIIA is necessary but not sufficient to localize F-actin at the cell cortex. • MyoIIA-F-actin colocalization is regulated by calcium and calmodulin

Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency?

DEFF Research Database (Denmark)

Klefter, Oliver; Feldt-Rasmussen, Ulla

2009-01-01

to a muscle modulating effect, and if treatment with GH would primarily increase muscle mass and strength with a secondary increase in BMD/BMC, thus supporting the present physiological concept that mass and strength of bones are mainly determined by dynamic loads from the skeletal muscles. METHOD: We...... performed a systematic literature analysis, including 51 clinical trials published between 1996 and 2008, which had studied the development in muscle mass, muscle strength, BMD, and/or BMC in GH-treated adult GHD patients. RESULTS: GH therapy had an anabolic effect on skeletal muscle. The largest increase...... in muscle mass occurred during the first 12 months of therapy. Most trials measuring BMD/BMC reported significant increases from baseline values. The significant increases in BMD/BMC occurred after 12-18 months of treatment, i.e. usually later than the increases in muscle parameters. Only seven trials...

Using vignettes to assess contributions to the work of addressing child mental health problems in primary care.

Science.gov (United States)

Wissow, Lawrence S; Zafar, Waleed; Fothergill, Kate; Ruble, Anne; Slade, Eric

2016-01-22

To further efforts to integrate mental health and primary care, this study develops a novel approach to quantifying the amount and sources of work involved in shifting care for common mental health problems to pediatric primary care providers. Email/web-based survey of a convenience sample (n = 58) of Maryland pediatricians (77% female, 58% at their site 10 or more years; 44% in private practice, 52 % urban, 48 % practicing with a co-located mental health provider). Participants were asked to review 11 vignettes, which described primary care management of child/youth mental health problems, and rate them on an integer-based ordinal scale for the overall amount of work involved compared to a 12th reference vignette describing an uncomplicated case of ADHD. Respondents were also asked to indicate factors (time, effort, stress) accounting for their ratings. Vignettes presented combinations of three diagnoses (ADHD, anxiety, and depression) and three factors (medical co-morbidity, psychiatric co-morbidity, and difficult families) reported to complicate mental health care. The reference case was pre-assigned a work value of 2. Estimates of the relationship of diagnosis and complicating factors with workload were obtained using linear regression, with random effects at the respondent level. The 58 pediatricians gave 593 vignette responses. Depression was associated with a 1.09 unit (about 50%) increase in work (95% CL .94, 1.25), while anxiety did not differ significantly from the reference case of uncomplicated ADHD (p = .28). Although all three complicating factors increased work ratings compared with the reference case, family complexity and psychiatric co-morbidity did so the most (.87 and 1.07 units, respectively, P work were physician time, physician mental effort, and stress; those least strongly associated were staff time, physician physical effort, and malpractice risk. Pediatricians working with co-located mental health providers gave higher work

The significance of postangiographic CT for differentiation of hepatic masses

International Nuclear Information System (INIS)

Lee, Jae Kyo; Chang, Jae Chun; Chang, You Song

1994-01-01

To identify the long term hemodynamics of various hepatic masses and to determine any differential findings by using postangiograpic CT performed with increased amount of contrast media and time than conventional contrast CT. 50 confirmed masses consisted of 22 hepatocellular carcinoma, 10 cholangiocarcinoma, 9 metastasis, and 9 cavernous hemangioma were included. The changes of the density of internal viable tumor portion relative to surrounding normal liver parenchyma in postangiograhic CT from that in conventional CT were classified as 3 patients; no specific changes, increase, or decrease. In 22 cases of hepatocellular carcinoma, six cases showed no relative density change, four cases increase, and twelve cases decrease. In ten cases of cholangiocacinoma, one case showed no change, nine cases increase. In nine cases of metastasis, four cases showed no change, five cases increase. In nine cases of hemangioma, all cases showed increase. In postangiographic CT which emphasize the significance of postequilibrium and delayed phase, other hemodynamic changes undetected in angiography could more easily be comprehended. Considering the differing amount of consumed contrast media and time duration, and with reference of other imaging modalities, differential diagnosis of hepatic masses based on long term hemodynamics could easily be made

Gains from resistance: contesting a new digital technology in a service sector workplace

DEFF Research Database (Denmark)

Shulzhenko, Elena; Holmgren, Jens

2017-01-01

Increasing expectations of efficiency enabled by new digital technology have led to renewed interest in spaces remaining for employee resistance to management power. The study contributes to this debate by analysing resistance to a new technology introduced in the home-nursing sector in Denmark....... Nurses succeeded in halting a technological change that allowed them to report data related to their visits online from inside patients’ homes and reduced their co-located working time. Work location became a central area of contestation between nurses and management. The study offers a nuanced analysis...... of power relations during the technological change. It shows that the capacity of IT management – a management actor uninhibited by a care ethos - to influence nursing workplaces rose along with the increasing significance of expertise in digital technologies in performing care work. Nurses’ alliances...

Significance of a diagnosis of atypical squamous cells of undetermined significance for Papanicolaou smears in perimenopausal and postmenopausal women.

Science.gov (United States)

Keating, J T; Wang, H H

2001-04-25

The current study was conducted to determine the significance of a diagnosis of atypical squamous cells of undetermined significance (ASCUS) in perimenopausal and postmenopausal women. The reports for all Papanicolaou (Pap) smears viewed in the study institution's cytology laboratory over a 6-month period were reviewed. Women were divided into premenopausal (age ages 46-54 years), and postmenopausal (age > or = 55 years) categories. Slide review and 2-year follow-up were obtained for selected cases diagnosed as ASCUS. ASCUS cases among the perimenopausal women were compared with an age-matched control group. The total number of abnormal Pap smears in the premenopausal, perimenopausal, and postmenopausal categories were 770 (6.8%), 104 (4.3%), and 67 (2.9%), with 482, 83, and 41 diagnoses of ASCUS, respectively. The ratio of ASCUS to squamous intraepithelial lesions (SIL) was 2.2 overall and 1.9, 7.5, and 4.1, respectively, for each group (P ASCUS cases appeared to have a higher percentage of nuclear-cytoplasmic ratio increase and nuclear membrane irregularities compared with the other categories (P = 0.03 and P = 0.02, respectively) and the perimenopausal group was found to have more ASCUS in metaplastic cells (P = 0.03). In perimenopausal women, slides diagnosed as ASCUS demonstrated more air-drying artifact than the control group (P = 0.004) but had less obvious atrophy (P = 0.01). Despite a decreased abnormality rate with increasing age, the results of the current study show that the perimenopausal and postmenopausal groups appear to have elevated ASCUS-to-SIL ratios. ASCUS appears to have a particularly low positive predictive value for SIL in perimenopausal women, and therefore most likely is overcalled in this age group. This may be attributable in part to air-drying artifact and subtle atrophic changes.

Pseudomonas aeruginosa vesicles associate with and are internalized by human lung epithelial cells

Directory of Open Access Journals (Sweden)

Kuehn Meta J

2009-02-01

Full Text Available Abstract Background Pseudomonas aeruginosa is the major pathogen associated with chronic and ultimately fatal lung infections in patients with cystic fibrosis (CF. To investigate how P. aeruginosa-derived vesicles may contribute to lung disease, we explored their ability to associate with human lung cells. Results Purified vesicles associated with lung cells and were internalized in a time- and dose-dependent manner. Vesicles from a CF isolate exhibited a 3- to 4-fold greater association with lung cells than vesicles from the lab strain PAO1. Vesicle internalization was temperature-dependent and was inhibited by hypertonic sucrose and cyclodextrins. Surface-bound vesicles rarely colocalized with clathrin. Internalized vesicles colocalized with the endoplasmic reticulum (ER marker, TRAPα, as well as with ER-localized pools of cholera toxin and transferrin. CF isolates of P. aeruginosa abundantly secrete PaAP (PA2939, an aminopeptidase that associates with the surface of vesicles. Vesicles from a PaAP knockout strain exhibited a 40% decrease in cell association. Likewise, vesicles from PAO1 overexpressing PaAP displayed a significant increase in cell association. Conclusion These data reveal that PaAP promotes the association of vesicles with lung cells. Taken together, these results suggest that P. aeruginosa vesicles can interact with and be internalized by lung epithelial cells and contribute to the inflammatory response during infection.

Creating a Middle Grades Environment that Significantly Improves Student Achievement

Science.gov (United States)

L'Esperance, Mark E.; Lenker, Ethan; Bullock, Ann; Lockamy, Becky; Mason, Cathy

2013-01-01

This article offers an overview of the framework that Sampson County Public Schools (North Carolina) used to critically reflect on the current state of their middle grades schools. The article also highlights the changes that resulted from the district-wide analysis and the ways in which these changes led to a significant increase in the academic…

Barnacle Geese Achieve Significant Energetic Savings by Changing Posture

OpenAIRE

Tickle, Peter G.; Nudds, Robert L.; Codd, Jonathan R.

2012-01-01

Here we report the resting metabolic rate in barnacle geese (Branta leucopsis) and provide evidence for the significant energetic effect of posture. Under laboratory conditions flow-through respirometry together with synchronous recording of behaviour enabled a calculation of how metabolic rate varies with posture. Our principal finding is that standing bipedally incurs a 25% increase in metabolic rate compared to birds sitting on the ground. In addition to the expected decrease in energy con...