Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle

Science.gov (United States)

Sakhnini, Lama

2003-05-01

In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.

Human-accelerated weathering increases salinization, major ions, and alkalinization in fresh water across land use

Science.gov (United States)

Human land use increases transport of dissolved inorganic carbon and major ions in watersheds due to the combination of easily weathered materials in watersheds and anthropogenic inputs. Here, we show that dissolved inorganic carbon (DIC), alkalinity, and major ions are significa...

Expressive Writing: Enhancing the Emotional Intelligence of Human Services Majors

Science.gov (United States)

Castillo, Yuleinys; Fischer, Jerome M.

2017-01-01

The skills and tasks in the human services field are highly connected to emotional intelligence abilities. The purpose of the study was to investigate the effect of an expressive writing program involving human service students in an undergraduate rehabilitation services course. The program was developed to enhance their emotional intelligence.…

Inferring high-confidence human protein-protein interactions

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Yu Xueping

2012-05-01

Full Text Available Abstract Background As numerous experimental factors drive the acquisition, identification, and interpretation of protein-protein interactions (PPIs, aggregated assemblies of human PPI data invariably contain experiment-dependent noise. Ascertaining the reliability of PPIs collected from these diverse studies and scoring them to infer high-confidence networks is a non-trivial task. Moreover, a large number of PPIs share the same number of reported occurrences, making it impossible to distinguish the reliability of these PPIs and rank-order them. For example, for the data analyzed here, we found that the majority (>83% of currently available human PPIs have been reported only once. Results In this work, we proposed an unsupervised statistical approach to score a set of diverse, experimentally identified PPIs from nine primary databases to create subsets of high-confidence human PPI networks. We evaluated this ranking method by comparing it with other methods and assessing their ability to retrieve protein associations from a number of diverse and independent reference sets. These reference sets contain known biological data that are either directly or indirectly linked to interactions between proteins. We quantified the average effect of using ranked protein interaction data to retrieve this information and showed that, when compared to randomly ranked interaction data sets, the proposed method created a larger enrichment (~134% than either ranking based on the hypergeometric test (~109% or occurrence ranking (~46%. Conclusions From our evaluations, it was clear that ranked interactions were always of value because higher-ranked PPIs had a higher likelihood of retrieving high-confidence experimental data. Reducing the noise inherent in aggregated experimental PPIs via our ranking scheme further increased the accuracy and enrichment of PPIs derived from a number of biologically relevant data sets. These results suggest that using our high

Major national human biomonitoring programs in chemical exposure assessment

Directory of Open Access Journals (Sweden)

Judy Choi

2015-07-01

Full Text Available Human biomonitoring (HBM programs have been established in several countries around the world in order to monitor the levels of chemical exposures in the general population and qualify health risk assessment of national and international interest. Study design, population, sample collection, and chemical analysis must be considered when comparing and interpreting the results. In this review, the objectives and brief descriptions of the major national HBM programs in North America, Europe, and Asia are provided. Similarities and differences observed from a comparative analysis among these programs, including the stratification of data according to age, sex, socioeconomic background, etc. as well as the identification of chemical exposure associated with food intake, are discussed. Overall, although there are some discrepancies in the study designs among the reviewed national HBM programs, results from the programs can provide useful information such as chemical levels found within the general population of a country that can be compared. Furthermore, the results can be used by regulatory authorities or the government to enforce legislations in order to reduce the exposure of chemicals into the human body.

Human Rights/Human Needs.

Science.gov (United States)

Canning, Cynthia

1978-01-01

The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia

DEFF Research Database (Denmark)

Lundby, Carsten; Pilegaard, Henriette; van Hall, Gerrit

2003-01-01

Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming...

Comparative genomics of the major agents of human and animal Sporotrichosis: Sporothrix schenckii and Sporothrix brasiliensis

NARCIS (Netherlands)

Teixeira, M.M.; de Almeida, L.G.P.; Kubitschek-Barreira, P.; Alves, F.L.; Kioshima, E.S.; Abadio, A.K.R.; Fernandes, L.; Derengowski, L.S.; Ferreira, K.S.; Souza, R.C.; Ruiz, J.C.; de Andrade, N.C.; Paes, H.C.; Nicola, A.M.; Albuquerque, P.; Gerber, A.L.; Martins, V.P.; Peconick, L.D.F.; Neto, A.V.; Chaucanez, C.B.; Silva, P.A.; cunha, O.L.; de Oliveira, F.F.M.; dos Santos, T.C.; Barros, A.L.N.; Soares, M.A.; de Oliveira, L.M.; Marini, M.M.; Villalobos-Duno, H.; Cunha, M.M.L.; de Hoog, S.; da Silveira, J.F.; Henrissat, B.; Niño-Vega, G.A.; Cisalpino, P.S.; Mora-Montes, H.M.; Almeida, S.R.; Stajich, J.E.; Lopes-Bezerra, L.M.; Vasconcelos, A.T.R.; Felipe, M.S.S.

2014-01-01

Background: The fungal genus Sporothrix includes at least four human pathogenic species. One of these species, S. brasiliensis, is the causal agent of a major ongoing zoonotic outbreak of sporotrichosis in Brazil. Elsewhere, sapronoses are caused by S. schenckii and S. globosa. The major aims on

Low vascularization of the nephrogenic zone of the fetal kidney suggests a major role for hypoxia in human nephrogenesis.

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Gerosa, C; Fanni, D; Faa, A; Van Eyken, P; Ravarino, A; Fanos, V; Faa, G

2017-09-01

CD31 reactivity is generally utilized as a marker of endothelial cells. CD31 immunoreactivity in the developing human kidney revealed that fetal glomerular capillary endothelial cells change their immunohistochemical phenotype during maturation. The aim of this study was to analyze CD31 reactivity in the fetal human kidney in the different stages of intrauterine development: We observed different distribution of CD31-reactive vascular progenitors in the different areas of the developing kidney. In particular, the nephrogenic zone and the renal capsule were characterized by a scarcity of CD31-reactive cells at all gestational ages. These data suggest the hypothesis that nephrogenesis does not need high oxygen levels and confirms a major role of hypoxia in nephrogenesis.

Leishmania major Infection Activates NF-κB and Interferon Regulatory Factors 1 and 8 in Human Dendritic Cells▿

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Jayakumar, Asha; Donovan, Michael J.; Tripathi, Vinita; Ramalho-Ortigao, Marcelo; McDowell, Mary Ann

2008-01-01

The salient feature of dendritic cells (DC) is the initiation of appropriate adaptive immune responses by discriminating between pathogens. Using a prototypic model of intracellular infection, we previously showed that Leishmania major parasites prime human DC for efficient interleukin-12 (IL-12) secretion. L. major infection is associated with self-limiting cutaneous disease and powerful immunity. In stark contrast, the causative agent of visceral leishmaniasis, Leishmania donovani, does not prime human DC for IL-12 production. Here, we report that DC priming by L. major infection results in the early activation of NF-κB transcription factors and the up-regulation and nuclear translocation of interferon regulatory factor 1 (IRF-1) and IRF-8. The inhibition of NF-κB activation by the pretreatment of DC with caffeic acid phenethyl ester blocks L. major-induced IRF-1 and IRF-8 activation and IL-12 expression. We further demonstrate that IRF-1 and IRF-8 obtained from L. major-infected human DC specifically bind to their consensus binding sites on the IL-12p35 promoter, indicating that L. major infection either directly stimulates a signaling cascade or induces an autocrine pathway that activates IRF-1 and IRF-8, ultimately resulting in IL-12 transcription. PMID:18316378

Statistical evaluation of major human errors during the development of new technological systems

International Nuclear Information System (INIS)

Campbell, G; Ott, K.O.

1979-01-01

Statistical procedures are presented to evaluate major human errors during the development of a new system, errors that have led or can lead to accidents or major failures. The first procedure aims at estimating the average residual occurrence rate for s or major failures after several have occurred. The procedure is solely based on the historical record. Certain idealizations are introduced that allow the application of a sound statistical evaluation procedure. These idealizations are practically realized to a sufficient degree such that the proposed estimation procedure yields meaningful results, even for situations with a sparse data base, represented by very few accidents. Under the assumption that the possible human-error-related failure times have exponential distributions, the statistical technique of isotonic regression is proposed to estimate the failure rates due to human design error at the failure times of the system. The last value in the sequence of estimates gives the residual accident chance. In addition, theactual situation is tested against the hypothesis that the failure rate of the system remains constant over time. This test determines the chance for a decreasing failure rate being incidental, rather than an indication of an actual learning process. Both techniques can be applied not merely to a single system but to an entire series of similar systems that a technology would generate, enabling the assessment of technological improvement. For the purpose of illustration, the nuclear decay of isotopes was chosen as an example, since the assumptions of the model are rigorously satisfied in this case. This application shows satisfactory agreement of the estimated and actual failure rates (which are exactly known in this example), although the estimation was deliberately based on a sparse historical record

Qualitative and quantitative analysis of N-acetyllactosamine and lacto-N-biose, the two major building blocks of human milk oligosaccharides in human milk samples by high-performance liquid chromatography-tandem mass spectrometry using a porous graphitic carbon column.

Science.gov (United States)

Balogh, Réka; Jankovics, Péter; Béni, Szabolcs

2015-11-27

This study presents a validated, porous graphitic carbon stationary phase-based LC-MS/MS method for the identification and quantification of lacto-N-biose (LNB) and N-acetyllactosamine (LacNAc). These compounds are the major building blocks of human milk oligosaccharides, however the presence of their unbound form in human milk has not been examined so far. The separation of these highly related structures in their alditol form was accomplished by a gradient LC method and multiple reaction monitoring (MRM) analysis after appropriate sample preparation including size-exclusion chromatography and solid-phase extraction. Baseline separation of the components provides the selectivity for the method. Validation was performed according to the European Medicines Agency (EMA) Guidelines and the method was found to be precise and accurate. Using our developed and validated method we were able to identify and quantify both saccharides in human milk for the first time. Based on our results the LacNAc concentration is in the range of 6.7-31μg/mL while LNB concentration decreased from 26μg/mL below the detection limit during the first week of lactation. The presence of LNB and LacNAc in human milk also implies new biological functions which can lead us closer to the understanding of the various functions of this complex biofluid. Copyright © 2015 Elsevier B.V. All rights reserved.

Evolution of Gender Differences in Post-Secondary Human Capital Investments: College Majors. Working Paper #03-11

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Gemici, Ahu; Wiswall, Matthew

2011-01-01

Over the past 40 years, the level of human capital investments has changed substantially for men and women. Changes in the intensive margin of college major selection have been also been substantial, as the number of graduates in humanities, social science, and teaching has declined, and the number in science, engineering, and business has…

The academic and nonacademic characteristics of science and nonscience majors in Yemeni high schools

Science.gov (United States)

Anaam, Mahyoub Ali

The purposes of this study were: (a) to identify the variables associated with selection of majors; (b) to determine the differences between science and nonscience majors in general, and high and low achievers in particular, with respect to attitudes toward science, integrated science process skills, and logical thinking abilities; and (c) to determine if a significant relationship exists between students' majors and their personality types and learning styles. Data were gathered from 188 twelfth grade male and female high school students in Yemen, who enrolled in science (45 males and 47 females) and art and literature (47 males and 49 females) tracks. Data were collected by the following instruments: Past math and science achievement (data source taken from school records), Kolb's Learning Styles Inventory (1985), Integrated Science Process Skills Test, Myers-Briggs Type Indicator, Attitude Toward Science in School Assessment, Group Assessment of Logical Thinking, Yemeni High School Students Questionnaire. The Logistic Regression Model and the Linear Discriminant Analysis identified several variables that are associated with selection of majors. Moreover, some of the characteristics of science and nonscience majors that were revealed by these models include the following: Science majors seem to have higher degrees of curiosity in science, high interest in science at high school level, high tendency to believe that their majors will help them to find a potential job in the future, and have had higher achievement in science subjects, and have rated their math teachers higher than did nonscience majors. In contrast, nonscience majors seem to have higher degrees of curiosity in nonscience subjects, higher interest in science at elementary school, higher anxiety during science lessons than did science majors. In addition, General Linear Models allow that science majors generally demonstrate more positive attitudes towards science than do nonscience majors and they

The major surface glycoprotein (gp63) from Leishmania major and Leishmania donovani cleaves CD4 molecules on human T cells

DEFF Research Database (Denmark)

Hey, A S; Theander, T G; Hviid, L

1994-01-01

The effect of Leishmania major and L. donovani surface protease gp63 on surface markers on human T cells was studied using fluorescence-activated flow cytometry. Purified gp63 (63,000 m.w. glycoprotein) at concentrations above 10 micrograms/ml completely inhibited binding of six different anti-CD4......-expression of CD4, reaching 50% of the initial level after 72 h of incubation in medium. Preincubation of cells with live promastigotes showed an inhibitory effect on CD4 comparable to that seen with purified gp63. The binding of Abs directed against other surface markers present on human T-cells--CD2, CD3, CD5......, CD8, CD11A, CD25, CD45RO, CD45RA, CD58, TCR-alpha, TCR-gamma, and HLA DQ--was not inhibited by gp63. These data suggest that gp63, both in its purified form and in the form anchored to the parasite membrane, cleaves CD4 on human T cells. The cleavage of CD4 by the protease might play a role...

High-throughput telomere length quantification by FISH and its application to human population studies.

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Canela, Andrés; Vera, Elsa; Klatt, Peter; Blasco, María A

2007-03-27

A major limitation of studies of the relevance of telomere length to cancer and age-related diseases in human populations and to the development of telomere-based therapies has been the lack of suitable high-throughput (HT) assays to measure telomere length. We have developed an automated HT quantitative telomere FISH platform, HT quantitative FISH (Q-FISH), which allows the quantification of telomere length as well as percentage of short telomeres in large human sample sets. We show here that this technique provides the accuracy and sensitivity to uncover associations between telomere length and human disease.

Diffusion tensor tractography of the mammillothalamic tract in the human brain using a high spatial resolution DTI technique.

Science.gov (United States)

Kamali, Arash; Zhang, Caroline C; Riascos, Roy F; Tandon, Nitin; Bonafante-Mejia, Eliana E; Patel, Rajan; Lincoln, John A; Rabiei, Pejman; Ocasio, Laura; Younes, Kyan; Hasan, Khader M

2018-03-27

The mammillary bodies as part of the hypothalamic nuclei are in the central limbic circuitry of the human brain. The mammillary bodies are shown to be directly or indirectly connected to the amygdala, hippocampus, and thalami as the major gray matter structures of the human limbic system. Although it is not primarily considered as part of the human limbic system, the thalamus is shown to be involved in many limbic functions of the human brain. The major direct connection of the thalami with the hypothalamic nuclei is known to be through the mammillothalamic tract. Given the crucial role of the mammillothalamic tracts in memory functions, diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of this pathway noninvasively. This study aimed to investigate the utility of high spatial resolution diffusion tensor tractography for mapping the trajectory of the mammillothalamic tract in the human brain. Fifteen healthy adults were studied after obtaining written informed consent. We used high spatial resolution diffusion tensor imaging data at 3.0 T. We delineated, for the first time, the detailed trajectory of the mammillothalamic tract of the human brain using deterministic diffusion tensor tractography.

Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major.

Science.gov (United States)

Lombraña, Rodrigo; Álvarez, Alba; Fernández-Justel, José Miguel; Almeida, Ricardo; Poza-Carrión, César; Gomes, Fábia; Calzada, Arturo; Requena, José María; Gómez, María

2016-08-09

Faithful inheritance of eukaryotic genomes requires the orchestrated activation of multiple DNA replication origins (ORIs). Although origin firing is mechanistically conserved, how origins are specified and selected for activation varies across different model systems. Here, we provide a complete analysis of the nucleosomal landscape and replication program of the human parasite Leishmania major, building on a better evolutionary understanding of replication organization in Eukarya. We found that active transcription is a driving force for the nucleosomal organization of the L. major genome and that both the spatial and the temporal program of DNA replication can be explained as associated to RNA polymerase kinetics. This simple scenario likely provides flexibility and robustness to deal with the environmental changes that impose alterations in the genetic programs during parasitic life cycle stages. Our findings also suggest that coupling replication initiation to transcription elongation could be an ancient solution used by eukaryotic cells for origin maintenance. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major

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Rodrigo Lombraña

2016-08-01

Full Text Available Faithful inheritance of eukaryotic genomes requires the orchestrated activation of multiple DNA replication origins (ORIs. Although origin firing is mechanistically conserved, how origins are specified and selected for activation varies across different model systems. Here, we provide a complete analysis of the nucleosomal landscape and replication program of the human parasite Leishmania major, building on a better evolutionary understanding of replication organization in Eukarya. We found that active transcription is a driving force for the nucleosomal organization of the L. major genome and that both the spatial and the temporal program of DNA replication can be explained as associated to RNA polymerase kinetics. This simple scenario likely provides flexibility and robustness to deal with the environmental changes that impose alterations in the genetic programs during parasitic life cycle stages. Our findings also suggest that coupling replication initiation to transcription elongation could be an ancient solution used by eukaryotic cells for origin maintenance.

mtDNA variation predicts population size in humans and reveals a major Southern Asian chapter in human prehistory.

Science.gov (United States)

Atkinson, Quentin D; Gray, Russell D; Drummond, Alexei J

2008-02-01

The relative timing and size of regional human population growth following our expansion from Africa remain unknown. Human mitochondrial DNA (mtDNA) diversity carries a legacy of our population history. Given a set of sequences, we can use coalescent theory to estimate past population size through time and draw inferences about human population history. However, recent work has challenged the validity of using mtDNA diversity to infer species population sizes. Here we use Bayesian coalescent inference methods, together with a global data set of 357 human mtDNA coding-region sequences, to infer human population sizes through time across 8 major geographic regions. Our estimates of relative population sizes show remarkable concordance with the contemporary regional distribution of humans across Africa, Eurasia, and the Americas, indicating that mtDNA diversity is a good predictor of population size in humans. Plots of population size through time show slow growth in sub-Saharan Africa beginning 143-193 kya, followed by a rapid expansion into Eurasia after the emergence of the first non-African mtDNA lineages 50-70 kya. Outside Africa, the earliest and fastest growth is inferred in Southern Asia approximately 52 kya, followed by a succession of growth phases in Northern and Central Asia (approximately 49 kya), Australia (approximately 48 kya), Europe (approximately 42 kya), the Middle East and North Africa (approximately 40 kya), New Guinea (approximately 39 kya), the Americas (approximately 18 kya), and a second expansion in Europe (approximately 10-15 kya). Comparisons of relative regional population sizes through time suggest that between approximately 45 and 20 kya most of humanity lived in Southern Asia. These findings not only support the use of mtDNA data for estimating human population size but also provide a unique picture of human prehistory and demonstrate the importance of Southern Asia to our recent evolutionary past.

Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections

Energy Technology Data Exchange (ETDEWEB)

Li, Fang (UMM)

2008-09-23

It is believed that a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), was passed from palm civets to humans and caused the epidemic of SARS in 2002 to 2003. The major species barriers between humans and civets for SARS-CoV infections are the specific interactions between a defined receptor-binding domain (RBD) on a viral spike protein and its host receptor, angiotensin-converting enzyme 2 (ACE2). In this study a chimeric ACE2 bearing the critical N-terminal helix from civet and the remaining peptidase domain from human was constructed, and it was shown that this construct has the same receptor activity as civet ACE2. In addition, crystal structures of the chimeric ACE2 complexed with RBDs from various human and civet SARS-CoV strains were determined. These structures, combined with a previously determined structure of human ACE2 complexed with the RBD from a human SARS-CoV strain, have revealed a structural basis for understanding the major species barriers between humans and civets for SARS-CoV infections. They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479 and 487. These results enhance our understanding of host adaptations and cross-species infections of SARS-CoV and other emerging animal viruses.

The Major Histocompatibility Complex and Perfumers' Descriptions of Human Body Odors

Directory of Open Access Journals (Sweden)

Claus Wedekind

2007-04-01

Full Text Available The MHC (major histocompatibility complex is a group of genes that play a crucial role in immune recognition and in tolerance of tissue grafting. The MHC has also been found to influence body odors, body odor preferences, and mate choice in mice and humans. Here we test whether verbal descriptions of human body odors can be linked to the MHC. We asked 45 male students to live as odor neutral as possible for two consecutive days and to wear a T-shirt during the nights. The odors of these T-shirts were then described by five evaluators: two professional perfumers and three laymen. One of the perfumers was able to describe the T-shirt odors in such a way that some of the allelic specificity of the MHC was significantly revealed (after Bonferroni correction for multiple testing. This shows that, although difficult, some people are able to describe MHC-correlated body odor components.

Developing and Evaluating Medical Humanities Problem-Based Learning Classes Facilitated by the Teaching Assistants Majored in the Liberal Arts

Science.gov (United States)

Tseng, Fen-Yu; Shieh, Jeng-Yi; Kao, Tze-Wah; Wu, Chau-Chung; Chu, Tzong-Shinn; Chen, Yen-Yuan

2016-01-01

Abstract Although medical humanities courses taught by teachers from nonmedical backgrounds are not unusual now, few studies have compared the outcome of medical humanities courses facilitated by physicians to that by teaching assistants majored in the liberal arts. The objectives of this study were to (1) analyze the satisfaction of medical students with medical humanities problem-based learning (PBL) classes facilitated by nonmedical teaching assistants (TAF) majored in the liberal arts, and those facilitated by the attending physicians (APF) and (2) examine the satisfaction of medical students with clinical medicine-related and clinical medicine-unrelated medical humanities PBL classes. A total of 123 medical students, randomly assigned to 16 groups, participated in this study. There were 16 classes in the course: 8 of them were TAF classes; and the others were APF classes. Each week, each group rotated from 1 subject of the 16 subjects of PBL to another subject. All of the 16 groups went through all the 16 subjects in the 2013 spring semester. We examined the medical students’ satisfaction with each class, based on a rating score collected after each class was completed, using a scale from 0 (the lowest satisfaction) to 100 (the highest satisfaction). We also conducted multivariate linear regression analysis to examine the association between the independent variables and the students’ satisfaction. Medical students were more satisfied with the TAF (91.35 ± 7.75) medical humanities PBL classes than APF (90.40 ± 8.42) medical humanities PBL classes (P = 0.01). Moreover, medical students were more satisfied with the clinical medicine-unrelated topics (92.00 ± 7.10) than the clinical medicine-related topics (90.36 ± 7.99) in the medical humanities PBL course (P = 0.01). This medical humanities PBL course, including nonmedical subjects and topics, and nonmedical teaching assistants from the liberal arts as class facilitators, was

High density of Leishmania major and rarity of other mammals' Leishmania in zoonotic cutaneous leishmaniasis foci, Iran.

Science.gov (United States)

Bordbar, Ali; Parvizi, Parviz

2014-03-01

Only Leishmania major is well known as a causative agent of zoonotic cutaneous leishmaniasis (ZCL) in Iran. Our objective was to find Leishmania parasites circulating in reservoir hosts, sand flies and human simultaneously. Sand flies, rodents and prepared smears of humans were sampled. DNA of Leishmania parasites was extracted, and two fragments of ITS-rDNA gene amplified by PCR. RFLP and sequencing were employed to identify Leishmania parasites. Leishmania major and L. turanica were identified unequivocally by targeting and sequencing ITS-rDNA from humans, rodents and sand flies. The new Leishmania species close to gerbilli (GenBank Accession Nos. EF413076; EF413087) was discovered only in sand flies. Based on parasite detection of ITS-rDNA in main and potential reservoir hosts and vectors and humans, we conclude that at least two Leishmania species are common in the Turkmen Sahra ZCL focus. Phylogenetic analysis proved that the new Leishmania is closely related to Leishmania mammal parasites (Leishmania major, Leishmania turanica, Leishmania gerbilli). Its role as a principal agent of ZCL is unknown because it was found only in sand flies. Our findings shed new light on the transmission cycles of several Leishmania parasites in sand flies, reservoir hosts and humans. © 2014 John Wiley & Sons Ltd.

Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane.

Science.gov (United States)

Groffen, A J; Ruegg, M A; Dijkman, H; van de Velden, T J; Buskens, C A; van den Born, J; Assmann, K J; Monnens, L A; Veerkamp, J H; van den Heuvel, L P

1998-01-01

Agrin is a heparan sulfate proteoglycan (HSPG) that is highly concentrated in the synaptic basal lamina at the neuromuscular junction (NMJ). Agrin-like immunoreactivity is also detected outside the NMJ. Here we show that agrin is a major HSPG component of the human glomerular basement membrane (GBM). This is in addition to perlecan, a previously characterized HSPG of basement membranes. Antibodies against agrin and against an unidentified GBM HSPG produced a strong staining of the GBM and the NMJ, different from that observed with anti-perlecan antibodies. In addition, anti-agrin antisera recognized purified GBM HSPG and competed with an anti-GBM HSPG monoclonal antibody in ELISA. Furthermore, both antibodies recognized a molecule that migrated in SDS-PAGE as a smear and had a molecular mass of approximately 200-210 kD after deglycosylation. In immunoelectron microscopy, agrin showed a linear distribution along the GBM and was present throughout the width of the GBM. This was again different from perlecan, which was exclusively present on the endothelial side of the GBM and was distributed in a nonlinear manner. Quantitative ELISA showed that, compared with perlecan, the agrin-like GBM HSPG showed a sixfold higher molarity in crude glomerular extract. These results show that agrin is a major component of the GBM, indicating that it may play a role in renal ultrafiltration and cell matrix interaction. (J Histochem Cytochem 46:19-27, 1998)

Communication Capacity Research in the Majority World: Supporting the human right to communication specialist services.

Science.gov (United States)

Hopf, Suzanne C

2018-02-01

Receipt of accessible and appropriate specialist services and resources by all people with communication and/or swallowing disability is a human right; however, it is a right rarely achieved in either Minority or Majority World contexts. This paper considers communication specialists' efforts to provide sustainable services for people with communication difficulties living in Majority World countries. The commentary draws on human rights literature, particularly Article 19 of the Universal Declaration of Human Rights and the Communication Capacity Research program that includes: (1) gathering knowledge from policy and literature; (2) gathering knowledge from the community; (3) understanding speech, language and literacy use and proficiency; and (4) developing culturally and linguistically appropriate resources and assessments. To inform the development of resources and assessments that could be used by speech-language pathologists as well as other communication specialists in Fiji, the Communication Capacity Research program involved collection and analysis of data from multiple sources including 144 community members, 75 school students and their families, and 25 teachers. The Communication Capacity Research program may be applicable for achieving the development of evidence-based, culturally and linguistically sustainable SLP services in similar contexts.

Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.

Science.gov (United States)

van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O

1992-01-01

Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes. Images PMID:1360671

Credentialism and Career Aspirations: How Urban Chinese Youth Chose High School and College Majors

Science.gov (United States)

Kim, Sung Won; Brown, Kari-Elle; Fong, Vanessa L.

2016-01-01

This article explores how graduates of a junior high school in Dalian City, Liaoning Province, China, chose their high school and college major subject of study and the extent to which their majors fit with their work trajectories. We found that most interviewees considered the likelihood of a major and degree leading to better job opportunities…

Combining Human and Machine Learning to Map Cropland in the 21st Century's Major Agricultural Frontier

Science.gov (United States)

Estes, L. D.; Debats, S. R.; Caylor, K. K.; Evans, T. P.; Gower, D.; McRitchie, D.; Searchinger, T.; Thompson, D. R.; Wood, E. F.; Zeng, L.

2016-12-01

In the coming decades, large areas of new cropland will be created to meet the world's rapidly growing food demands. Much of this new cropland will be in sub-Saharan Africa, where food needs will increase most and the area of remaining potential farmland is greatest. If we are to understand the impacts of global change, it is critical to accurately identify Africa's existing croplands and how they are changing. Yet the continent's smallholder-dominated agricultural systems are unusually challenging for remote sensing analyses, making accurate area estimates difficult to obtain, let alone important details related to field size and geometry. Fortunately, the rapidly growing archives of moderate to high-resolution satellite imagery hosted on open servers now offer an unprecedented opportunity to improve landcover maps. We present a system that integrates two critical components needed to capitalize on this opportunity: 1) human image interpretation and 2) machine learning (ML). Human judgment is needed to accurately delineate training sites within noisy imagery and a highly variable cover type, while ML provides the ability to scale and to interpret large feature spaces that defy human comprehension. Because large amounts of training data are needed (a major impediment for analysts), we use a crowdsourcing platform that connects amazon.com's Mechanical Turk service to satellite imagery hosted on open image servers. Workers map visible fields at pre-assigned sites, and are paid according to their mapping accuracy. Initial tests show overall high map accuracy and mapping rates >1800 km2/hour. The ML classifier uses random forests and randomized quasi-exhaustive feature selection, and is highly effective in classifying diverse agricultural types in southern Africa (AUC > 0.9). We connect the ML and crowdsourcing components to make an interactive learning framework. The ML algorithm performs an initial classification using a first batch of crowd-sourced maps, using

Metabolite characterization of a novel sedative drug, remimazolam in human plasma and urine using ultra high-performance liquid chromatography coupled with synapt high-definition mass spectrometry.

Science.gov (United States)

Zhou, Ying; Hu, Pei; Jiang, Ji

2017-04-15

Remimazolam is a new chemical entity belonging to the benzodiazepine class of sedative drugs, which shows faster-acting onset and recovery than currently available short-acting sedatives. In the present study, ultra high performance liquid chromatography with synapt high-definition mass spectrometry method combined with MassLynx software was established to characterize metabolites of remimazolam in human plasma and urine. In total, 5 human metabolites were detected, including 3 phase I and 2 phase II metabolites. There was no novel human metabolite detected compared to that in rat. Hydrolysis, glucuronidation and oxidation were the major metabolic reactions. To our knowledge, this is the first report of the human metabolic profile of remimazolam. Copyright © 2017 Elsevier B.V. All rights reserved.

TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1

OpenAIRE

Allam, Atef; Majji, Sai; Peachman, Kristina; Jagodzinski, Linda; Kim, Jiae; Ratto-Kim, Silvia; Wijayalath, Wathsala; Merbah, Melanie; Kim, Jerome H.; Michael, Nelson L.; Alving, Carl R.; Casares, Sofia; Rao, Mangala

2015-01-01

CD4+ T follicular helper cells (TFH) in germinal centers are required for maturation of B-cells. While the role of TFH-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of TFH (CXCR5+PD-1++) and precursor-TFH (CXCR5+PD-1+) cells. The majority of TFH-cells expressed CCR...

A mathematical high bar-human body model for analysing and interpreting mechanical-energetic processes on the high bar.

Science.gov (United States)

Arampatzis, A; Brüggemann, G P

1998-12-01

The aims of this study were: 1. To study the transfer of energy between the high bar and the gymnast. 2. To develop criteria from the utilisation of high bar elasticity and the utilisation of muscle capacity to assess the effectiveness of a movement solution. 3. To study the influence of varying segment movement upon release parameters. For these purposes a model of the human body attached to the high bar (high bar-human body model) was developed. The human body was modelled using a 15-segment body system. The joint-beam element method (superelement) was employed for modelling the high bar. A superelement consists of four rigid segments connected by joints (two Cardan joints and one rotational-translational joint) and springs (seven rotation springs and one tension-compression spring). The high bar was modelled using three superelements. The input data required for the high bar human body model were collected with video-kinematographic (50 Hz) and dynamometric (500 Hz) techniques. Masses and moments of inertia of the 15 segments were calculated using the data from the Zatsiorsky et al. (1984) model. There are two major phases characteristic of the giant swing prior to dismounts from the high bar. In the first phase the gymnast attempts to supply energy to the high bar-humanbody system through muscle activity and to store this energy in the high bar. The difference between the energy transferred to the high bar and the reduction in the total energy of the body could be adopted as a criterion for the utilisation of high bar elasticity. The energy previously transferred into the high bar is returned to the body during the second phase. An advantageous increase in total body energy at the end of the exercise could only be obtained through muscle energy supply. An index characterising the utilisation of muscle capacity was developed out of the difference between the increase in total body energy and the energy returned from the high bar. A delayed and initially slow but

TYPES OF LANGUAGE LEARNING STRATEGIES USED BY TERTIARY ENGLISH MAJORS

OpenAIRE

TAN KHYE CHUIN; SARJIT KAUR

2015-01-01

This study investigated the types of language learning strategies used by 73 English majors from the School of Humanities in Universiti Sains Malaysia. Using questionnaires adopted from Oxford’s (1990) Strategy Inventory of Language Learning (SILL) and focus group interviews, the study also examined the English major students’ perceptions of using language learning strategies while learning English. The results revealed that the English majors were generally high users of all six types of lan...

5' diversity of human hepatic PXR (NR1I2) transcripts and identification of the major transcription initiation site.

Science.gov (United States)

Kurose, Kouichi; Koyano, Satoru; Ikeda, Shinobu; Tohkin, Masahiro; Hasegawa, Ryuichi; Sawada, Jun-Ichi

2005-05-01

The human pregnane X receptor (PXR) is a crucial regulator of the genes encoding several major cytochrome P450 enzymes and transporters, such as CYP3A4 and MDR1, but its own transcriptional regulation remains unclear. To elucidate the transcriptional mechanisms of human PXR gene, we first endeavored to identify the transcription initiation site of human PXR using 5'-RACE. Five types of 5'-variable transcripts (a, b, c, d, and e) with common exon 2 sequence were found, and comparison of these sequences with the genomic sequence suggested that their 5' diversity is derived from initiation by alternative promoters and alternative splicing. None of the exons found in our study contain any new in-frame coding regions. Newly identified introns IVS-a and IVS-b were found to have CT-AC splice sites that do not follow the GT-AG rule of conventional donor and acceptor splice sites. Of the five types of 5' variable transcripts identified, RT-PCR showed that type-a was the major transcript type. Four transcription initiation sites (A-D) for type-a transcript were identified by 5'-RACE using GeneRacer RACE Ready cDNA (human liver) constructed by the oligo-capping method. Putative TATA boxes were located approximately 30 bp upstream from the transcriptional start sites of the major transcript (C) and the longest minor transcript (A) expressed in the human liver. These results indicate that the initiation of transcription of human PXR is more complex than previously reported.

Human-Robot Interaction in High Vulnerability Domains

Science.gov (United States)

Gore, Brian F.

2016-01-01

Future NASA missions will require successful integration of the human with highly complex systems. Highly complex systems are likely to involve humans, automation, and some level of robotic assistance. The complex environments will require successful integration of the human with automation, with robots, and with human-automation-robot teams to accomplish mission critical goals. Many challenges exist for the human performing in these types of operational environments with these kinds of systems. Systems must be designed to optimally integrate various levels of inputs and outputs based on the roles and responsibilities of the human, the automation, and the robots; from direct manual control, shared human-robotic control, or no active human control (i.e. human supervisory control). It is assumed that the human will remain involved at some level. Technologies that vary based on contextual demands and on operator characteristics (workload, situation awareness) will be needed when the human integrates into these systems. Predictive models that estimate the impact of the technologies on the system performance and the on the human operator are also needed to meet the challenges associated with such future complex human-automation-robot systems in extreme environments.

Identification of copy number variants defining genomic differences among major human groups.

Directory of Open Access Journals (Sweden)

Lluís Armengol

Full Text Available BACKGROUND: Understanding the genetic contribution to phenotype variation of human groups is necessary to elucidate differences in disease predisposition and response to pharmaceutical treatments in different human populations. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the genome-wide profile of structural variation on pooled samples from the three populations studied in the HapMap project by comparative genome hybridization (CGH in different array platforms. We have identified and experimentally validated 33 genomic loci that show significant copy number differences from one population to the other. Interestingly, we found an enrichment of genes related to environment adaptation (immune response, lipid metabolism and extracellular space within these regions and the study of expression data revealed that more than half of the copy number variants (CNVs translate into gene-expression differences among populations, suggesting that they could have functional consequences. In addition, the identification of single nucleotide polymorphisms (SNPs that are in linkage disequilibrium with the copy number alleles allowed us to detect evidences of population differentiation and recent selection at the nucleotide variation level. CONCLUSIONS: Overall, our results provide a comprehensive view of relevant copy number changes that might play a role in phenotypic differences among major human populations, and generate a list of interesting candidates for future studies.

Humans with chimpanzee-like major histocompatibility complex-specificities control HIV-1 infection

DEFF Research Database (Denmark)

Hoof, Ilka; Kesmir, Can; Lund, Ole

2008-01-01

and the progression rate to AIDS. Chimpanzees control HIV-1 viral replication and develop a chronic infection without progressing to AIDS. A similar course of disease is observed in human long-term non-progressors. Objective: To investigate if long-term non-progressors and chimpanzees have functional similarities...... in their MHC class I repertoire. Methods: We compared the specificity of groups of human MHC molecules associated with different levels of viremia in HIV-1 infected individuals with those of chimpanzee. Results and conclusion: We demonstrate that human MHC with control of HIV-1 viral load share binding motifs...... with chimpanzee MHC. Moreover, we find that chimpanzee and human MHC associated with low viral load are predicted to elicit broader Gag-specific immune responses than human MHC associated with high viral load, thus supporting earlier findings that Gag-specific immune responses are essential for HIV-1 control....

Comparative genomics of the major fungal agents of human and animal Sporotrichosis: Sporothrix schenckii and Sporothrix brasiliensis.

Science.gov (United States)

Teixeira, Marcus M; de Almeida, Luiz G P; Kubitschek-Barreira, Paula; Alves, Fernanda L; Kioshima, Erika S; Abadio, Ana K R; Fernandes, Larissa; Derengowski, Lorena S; Ferreira, Karen S; Souza, Rangel C; Ruiz, Jeronimo C; de Andrade, Nathalia C; Paes, Hugo C; Nicola, André M; Albuquerque, Patrícia; Gerber, Alexandra L; Martins, Vicente P; Peconick, Luisa D F; Neto, Alan Viggiano; Chaucanez, Claudia B; Silva, Patrícia A; Cunha, Oberdan L; de Oliveira, Fabiana F M; dos Santos, Tayná C; Barros, Amanda L N; Soares, Marco A; de Oliveira, Luciana M; Marini, Marjorie M; Villalobos-Duno, Héctor; Cunha, Marcel M L; de Hoog, Sybren; da Silveira, José F; Henrissat, Bernard; Niño-Vega, Gustavo A; Cisalpino, Patrícia S; Mora-Montes, Héctor M; Almeida, Sandro R; Stajich, Jason E; Lopes-Bezerra, Leila M; Vasconcelos, Ana T R; Felipe, Maria S S

2014-10-29

The fungal genus Sporothrix includes at least four human pathogenic species. One of these species, S. brasiliensis, is the causal agent of a major ongoing zoonotic outbreak of sporotrichosis in Brazil. Elsewhere, sapronoses are caused by S. schenckii and S. globosa. The major aims on this comparative genomic study are: 1) to explore the presence of virulence factors in S. schenckii and S. brasiliensis; 2) to compare S. brasiliensis, which is cat-transmitted and infects both humans and cats with S. schenckii, mainly a human pathogen; 3) to compare these two species to other human pathogens (Onygenales) with similar thermo-dimorphic behavior and to other plant-associated Sordariomycetes. The genomes of S. schenckii and S. brasiliensis were pyrosequenced to 17x and 20x coverage comprising a total of 32.3 Mb and 33.2 Mb, respectively. Pair-wise genome alignments revealed that the two species are highly syntenic showing 97.5% average sequence identity. Phylogenomic analysis reveals that both species diverged about 3.8-4.9 MYA suggesting a recent event of speciation. Transposable elements comprise respectively 0.34% and 0.62% of the S. schenckii and S. brasiliensis genomes and expansions of Gypsy-like elements was observed reflecting the accumulation of repetitive elements in the S. brasiliensis genome. Mitochondrial genomic comparisons showed the presence of group-I intron encoding homing endonucleases (HE's) exclusively in S. brasiliensis. Analysis of protein family expansions and contractions in the Sporothrix lineage revealed expansion of LysM domain-containing proteins, small GTPases, PKS type1 and leucin-rich proteins. In contrast, a lack of polysaccharide lyase genes that are associated with decay of plants was observed when compared to other Sordariomycetes and dimorphic fungal pathogens, suggesting evolutionary adaptations from a plant pathogenic or saprobic to an animal pathogenic life style. Comparative genomic data suggest a unique ecological shift in the

Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors.

Science.gov (United States)

Sabri, F; Tresoldi, E; Di Stefano, M; Polo, S; Monaco, M C; Verani, A; Fiore, J R; Lusso, P; Major, E; Chiodi, F; Scarlatti, G

1999-11-25

Human immunodeficiency virus type 1 (HIV-1) infection of the brain is associated with neurological manifestations both in adults and in children. The primary target for HIV-1 infection in the brain is the microglia, but astrocytes can also be infected. We tested 26 primary HIV-1 isolates for their capacity to infect human fetal astrocytes in culture. Eight of these isolates, independent of their biological phenotype and chemokine receptor usage, were able to infect astrocytes. Although no sustained viral replication could be demonstrated, the virus was recovered by coculture with receptive cells such as macrophages or on stimulation with interleukin-1beta. To gain knowledge into the molecular events that regulate attachment and penetration of HIV-1 in astrocytes, we investigated the expression of several chemokine receptors. Fluorocytometry and calcium-mobilization assay did not provide evidence of expression of any of the major HIV-1 coreceptors, including CXCR4, CCR5, CCR3, and CCR2b, as well as the CD4 molecule on the cell surface of human fetal astrocytes. However, mRNA transcripts for CXCR4, CCR5, Bonzo/STRL33/TYMSTR, and APJ were detected by RT-PCR. Furthermore, infection of astrocytes by HIV-1 isolates with different chemokine receptor usage was not inhibited by the chemokines SDF-1beta, RANTES, MIP-1beta, or MCP-1 or by antibodies directed against the third variable region or the CD4 binding site of gp120. These data show that astrocytes can be infected by primary HIV-1 isolates via a mechanism independent of CD4 or major chemokine receptors. Furthermore, astrocytes are potential carriers of latent HIV-1 and on activation may be implicated in spreading the infection to other neighbouring cells, such as microglia or macrophages. Copyright 1999 Academic Press.

The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major

DEFF Research Database (Denmark)

Kemp, M; Handman, E; Kemp, K

1998-01-01

The promastigote surface antigen-2 (PSA-2) is a Leishmania parasite antigen, which can induce Th1-mediated protection against murine leishmaniasis when used as a vaccine. To evaluate PSA-2 as a human vaccine candidate the specific T-cell response to PSA-2 was characterised in individuals immune...... to cutaneous leishmaniasis. Peripheral blood mononuclear cells from Sudanese individuals with a past history of self-healing cutaneous leishmaniasis proliferated vigorously in response to PSA-2 isolated from Leishmania major, whereas the antigen did not activate cells from presumably unexposed Danes....... Peripheral blood mononuclear cells from individuals with previous L. major infection had varying proliferative responses to PSA-2 derived from L. donovani promastigotes. Peripheral blood mononuclear cells activated by PSA-2 from L. major produced high amounts of interferon-gamma and tumour necrosis factor...

Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.

Science.gov (United States)

Priyandoko, Didik; Ishii, Tetsuro; Kaul, Sunil C; Wadhwa, Renu

2011-05-04

The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera) leaf extract on methoxyacetic acid (MAA) induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.

Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.

Directory of Open Access Journals (Sweden)

Didik Priyandoko

Full Text Available The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera leaf extract on methoxyacetic acid (MAA induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.

Molecular cloning of human protein 4.2: A major component of the erythrocyte membrane

International Nuclear Information System (INIS)

Sung, L.A.; Chien, Shu; Lambert, K.; Chang, Longsheng; Bliss, S.A.; Bouhassira, E.E.; Nagel, R.L.; Schwartz, R.S.; Rybicki, A.C.

1990-01-01

Protein 4.2 (P4.2) comprises ∼5% of the protein mass of human erythrocyte (RBC) membranes. Anemia occurs in patients with RBCs deficient in P4.2, suggesting a role for this protein in maintaining RBC stability and integrity. The authors now report the molecular cloning and characterization of human RBC P4.2 cDNAs. By immunoscreening a human reticulocyte cDNA library and by using the polymerase chain reaction, two cDNA sequences of 2.4 and 2.5 kilobases (kb) were obtained. These cDNAs differ only by a 90-base-air insert in the longer isoform located three codons downstream from the putative initiation site. The 2.4- and 2.5-kb cDNAs predict proteins of ∼77 and ∼80 kDa, respectively, and the authenticity was confirmed by sequence identity with 46 amino acids of three cyanogen bromide-cleaved peptides of P4.2. Northern blot analysis detected a major 2.4-kb RNA species in reticulocytes. Isolation of two P4.2 cDNAs implies existence of specific regulation of P4.2 expression in human RBCs. Human RBC P4.2 has significant homology with human factor XIII subunit a and guinea pig liver transglutaminase. Sequence alignment of P4.2 with these two transglutaminases, however, revealed that P4.2 lacks the critical cysteine residue required for the enzymatic crosslinking of substrates

Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans.

Science.gov (United States)

Moyes, Catherine L; Vontas, John; Martins, Ademir J; Ng, Lee Ching; Koou, Sin Ying; Dusfour, Isabelle; Raghavendra, Kamaraju; Pinto, João; Corbel, Vincent; David, Jean-Philippe; Weetman, David

2017-07-01

Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans

Science.gov (United States)

Vontas, John; Martins, Ademir J.; Ng, Lee Ching; Koou, Sin Ying; Dusfour, Isabelle; Raghavendra, Kamaraju; Pinto, João; Corbel, Vincent; David, Jean-Philippe; Weetman, David

2017-01-01

Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance. PMID:28727779

Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans.

Directory of Open Access Journals (Sweden)

Catherine L Moyes

2017-07-01

Full Text Available Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus, making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids. Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls.

Science.gov (United States)

Möller, Ines; Wintermeyer, Annette; Bender, Katja; Jübner, Martin; Thomas, Andreas; Krug, Oliver; Schänzer, Wilhelm; Thevis, Mario

2011-09-01

Referred to as 'spice', several new drugs, advertised as herbal blends, have appeared on the market in the last few years, in which the synthetic cannabinoids JWH-018 and a C(8) homologue of CP 47,497 were identified as major active ingredients. Due to their reported cannabis-like effects, many European countries have banned these substances. The World Anti-Doping Agency has also explicitly prohibited synthetic cannabinoids in elite sport in-competition. Since urine specimens have been the preferred doping control samples, the elucidation of the metabolic pathways of these substances is of particular importance to implement them in sports drug testing programmes. In a recent report, an in vitro phase-I metabolism study of JWH-018 was presented yielding mainly hydroxylated and N-dealkylated metabolites. Due to these findings, a urine sample of a healthy man declaring to have smoked a 'spice' product was screened for potential phase-I and -II metabolites by high-resolution/high-accuracy mass spectrometry in the present report. The majority of the phase-I metabolites observed in earlier in vitro studies of JWH-018 were detected in this urine specimen and furthermore most of their respective monoglucuronides. As no intact JWH-018 was detectable, the monohydroxylated metabolite being the most abundant one was chosen as a target analyte for sports drug testing purposes; a detection method was subsequently developed and validated in accordance to conventional screening protocols based on enzymatic hydrolysis, liquid-liquid extraction, and liquid chromatography/electrospray tandem mass spectrometry analysis. The method was applied to approximately 7500 urine doping control samples yielding two JWH-018 findings and demonstrated its capability for a sensitive and selective identification of JWH-018 and its metabolites in human urine. Copyright © 2010 John Wiley & Sons, Ltd.

Determination of pyrazinamide in human by high performance liquid chromatography.

Directory of Open Access Journals (Sweden)

Revankar S

1994-01-01

Full Text Available A facile and sensitive high performance liquid chromatographic (HPLC technique has been developed for the determination pyrazinamide (PZA in human plasma. Nicotinamide(NIA is used as internal standard(IS. Plasma is deproteinized with 0.7 M perchloric acid; clear supernatant is neutralized with 1M NaOH and injected onto HPLC. The separation of pyrazinamide and the internal standard is carried out on a Supelco LC-18 (DB column with a basic mobile phase. Pyrazinoic acid, the major metabolite, other anti-tuberculous drugs and endogenous components do not interfere with measurement of pyrazinamide. The limit of detection of pyrazinamide with this method is 0.2 mg/0.2 ml plasma (CV 8.2%.

Contribution of the major and minor subunits to fimbria-mediated adherence of Haemophilus influenzae to human epithelial cells and erythrocytes

NARCIS (Netherlands)

van Ham, S. M.; van Alphen, L.; Mooi, F. R.; van Putten, J. P.

1995-01-01

Fimbriae are colonization factors of the human pathogen Haemophilus influenzae in that they mediate bacterial adherence to human eukaryotic cells. The contribution of the major (HifA) and putative minor (HifD and HifE) subunits of H. influenzae fimbriae to fimbria-specific adherence was studied by

[Distribution diversity of integrins and calcium channels on major human and mouse host cells of Leptospira species].

Science.gov (United States)

Li, Cheng-xue; Zhao, Xin; Qian, Jing; Yan, Jie

2012-07-01

To determine the distribution of integrins and calcium channels on major human and mouse host cells of Leptospira species. The expression of β1, β2 and β3 integrins was detected with immunofluorescence assay on the surface of human monocyte line THP-1, mouse mononuclear-macrophage-like cell line J774A.1, human vascular endothelial cell line HUVEC, mouse vascular endothelial cell EOMA, human hepatocyte line L-02, mouse hepatocyte line Hepa1-6, human renal tubular epithelial cell line HEK-293, mouse glomerular membrane epithelial cell line SV40-MES13, mouse collagen blast line NIH/3T3, human and mouse platelets. The distribution of voltage gate control calcium channels Cav3.1, Cav3.2, Cav3.3 and Cav2.3, and receptor gate calcium channels P(2)X(1), P(2)2X(2), P(2)X(3), P(2)X(4), P(2)X(5), P(2)X(6) and P(2)X(7) were determined with Western blot assay. β1 integrin proteins were positively expressed on the membrane surface of J774A.1, THP-1, HUVEC, EOMA, L-02, Hepa1-6 and HEK-239 cells as well as human and mouse platelets. β2 integrin proteins were expressed on the membrane surface of J774A.1, THP-1, HUVEC, EOMA, and NIH/3T3 cells. β3 integrin proteins were expressed on the membrane surface of J774A.1, THP-1, HUVEC, EOMA, Hepa1-6, HEK-239 and NIH/3T3 cells as well as human and mouse platelets. P(2)X(1) receptor gate calcium channel was expressed on the membrane surface of human and mouse platelets, while P(2)X(5) receptor gate calcium channel was expressed on the membrane surface of J774A.1, THP-1, L-02, Hepa1-6, HEK-239 and HUVEC cells. However, the other calcium channels were not detected on the tested cell lines or platelets. There is a large distribution diversity of integrins and calcium channel proteins on the major human and mouse host cells of Leptospira species, which may be associated with the differences of leptospira-induced injury in different host cells.

Expression and subcellular localization of ORC1 in Leishmania major

International Nuclear Information System (INIS)

Kumar, Diwakar; Mukherji, Agnideep; Saha, Swati

2008-01-01

The mechanism of DNA replication is highly conserved in eukaryotes, with the process being preceded by the ordered assembly of pre-replication complexes (pre-RCs). Pre-RC formation is triggered by the association of the origin replication complex (ORC) with chromatin. Leishmania major appears to have only one ORC ortholog, ORC1. ORC1 in other eukaryotes is the largest of the ORC subunits and is believed to play a significant role in modulating replication initiation. Here we report for the first time, the cloning of ORC1 from L. major, and the analysis of its expression in L. major promastigotes. In human cells ORC1 levels have been found to be upregulated in G1 and subsequently degraded, thus playing a role in controlling replication initiation. We examine the subcellular localization of L. major ORC1 in relation to the different stages of the cell cycle. Our results show that, unlike what is widely believed to be the case with ORC1 in human cells, ORC1 in L. major is nuclear at all stages of the cell cycle

Human factors: A major issue in plant aging

International Nuclear Information System (INIS)

Widrig, R.D.

1985-01-01

Humans play a significant role in the effects of aging on safe and reliable operation of nuclear power plants. These human issues may be more important than the issues of materials and component degradation with age. Human actions can accelerate or decelerate physical aging of a plant. And an aging plant can have a significant negative impact on staff quality and performance. The purpose of this paper is to provide some insights into the nature of these human factors issues and their relationship to plant aging. An early awareness of these issues facilitates timely action to at least mitigate these problems before they become insurmountable

Reduction in human Lyme neuroborreliosis associated with a major epidemic among roe deer

DEFF Research Database (Denmark)

Andersen, Nanna Skaarup; Skarphédinsson, Sigurdur; Knudtzen, Fredrikke C

2018-01-01

Lyme neuroborreliosis is the most severe clinical manifestation of Lyme borreliosis. In most of Denmark, and also Europe, the overall prevalence of Lyme borreliosis seems to be stabilising. This is not the case on the island of Funen, Denmark, where the number of human Lyme neuroborreliosis cases...... has markedly declined throughout the last decade. We propose the reason for the decline is a major epidemic among roe deer, killing almost half of their population, resulting in a reduction in the tick population which make it less likely to get a tick bite and therefore to contract Lyme...

Donor-recipient human leukocyte antigen matching practices in vascularized composite tissue allotransplantation: a survey of major transplantation centers.

Science.gov (United States)

Ashvetiya, Tamara; Mundinger, Gerhard S; Kukuruga, Debra; Bojovic, Branko; Christy, Michael R; Dorafshar, Amir H; Rodriguez, Eduardo D

2014-07-01

Vascularized composite tissue allotransplant recipients are often highly sensitized to human leukocyte antigens because of multiple prior blood transfusions and other reconstructive operations. The use of peripheral blood obtained from dead donors for crossmatching may be insufficient because of life support measures taken for the donor before donation. No study has been published investigating human leukocyte antigen matching practices in this field. A survey addressing human leukocyte antigen crossmatching methods was generated and sent to 22 vascularized composite tissue allotransplantation centers with active protocols worldwide. Results were compiled by center and compared using two-tailed t tests. Twenty of 22 centers (91 percent) responded to the survey. Peripheral blood was the most commonly reported donor sample for vascularized composite tissue allotransplant crossmatching [78 percent of centers (n=14)], with only 22 percent (n=4) using lymph nodes. However, 56 percent of the 18 centers (n=10) that had performed vascularized composite tissue allotransplantation reported that they harvested lymph nodes for crossmatching. Of responding individuals, 62.5 percent (10 of 16 individuals) felt that lymph nodes were the best donor sample for crossmatching. A slight majority of vascularized composite tissue allotransplant centers that have performed clinical transplants have used lymph nodes for human leukocyte antigen matching, and centers appear to be divided on the utility of lymph node harvest. The use of lymph nodes may offer a number of potential benefits. This study highlights the need for institutional review board-approved crossmatching protocols specific to vascularized composite tissue allotransplantation, and the need for global databases for sharing of vascularized composite tissue allotransplantation experiences.

Dynamics of major histocompatibility complex class I association with the human peptide-loading complex.

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Panter, Michaela S; Jain, Ankur; Leonhardt, Ralf M; Ha, Taekjip; Cresswell, Peter

2012-09-07

Although the human peptide-loading complex (PLC) is required for optimal major histocompatibility complex class I (MHC I) antigen presentation, its composition is still incompletely understood. The ratio of the transporter associated with antigen processing (TAP) and MHC I to tapasin, which is responsible for MHC I recruitment and peptide binding optimization, is particularly critical for modeling of the PLC. Here, we characterized the stoichiometry of the human PLC using both biophysical and biochemical approaches. By means of single-molecule pulldown (SiMPull), we determined a TAP/tapasin ratio of 1:2, consistent with previous studies of insect-cell microsomes, rat-human chimeric cells, and HeLa cells expressing truncated TAP subunits. We also report that the tapasin/MHC I ratio varies, with the PLC population comprising both 2:1 and 2:2 complexes, based on mutational and co-precipitation studies. The MHC I-saturated PLC may be particularly prevalent among peptide-selective alleles, such as HLA-C4. Additionally, MHC I association with the PLC increases when its peptide supply is reduced by inhibiting the proteasome or by blocking TAP-mediated peptide transport using viral inhibitors. Taken together, our results indicate that the composition of the human PLC varies under normal conditions and dynamically adapts to alterations in peptide supply that may arise during viral infection. These findings improve our understanding of the quality control of MHC I peptide loading and may aid the structural and functional modeling of the human PLC.

Human space flight and future major space astrophysics missions: servicing and assembly

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Thronson, Harley; Peterson, Bradley M.; Greenhouse, Matthew; MacEwen, Howard; Mukherjee, Rudranarayan; Polidan, Ronald; Reed, Benjamin; Siegler, Nicholas; Smith, Hsiao

2017-09-01

Some concepts for candidate future "flagship" space observatories approach the payload limits of the largest launch vehicles planned for the next few decades, specifically in the available volume in the vehicle fairing. This indicates that an alternative to autonomous self-deployment similar to that of the James Webb Space Telescope will eventually be required. Moreover, even before this size limit is reached, there will be significant motivation to service, repair, and upgrade in-space missions of all sizes, whether to extend the life of expensive facilities or to replace outworn or obsolete onboard systems as was demonstrated so effectively by the Hubble Space Telescope program. In parallel with these challenges to future major space astronomy missions, the capabilities of in-space robotic systems and the goals for human space flight in the 2020s and 2030s offer opportunities for achieving the most exciting science goals of the early 21st Century. In this paper, we summarize the history of concepts for human operations beyond the immediate vicinity of the Earth, the importance of very large apertures for scientific discovery, and current capabilities and future developments in robot- and astronaut-enabled servicing and assembly.

Differential Impact of LPG-and PG-Deficient Leishmania major Mutants on the Immune Response of Human Dendritic Cells.

Directory of Open Access Journals (Sweden)

Michelle A Favila

2015-12-01

Full Text Available Leishmania major infection induces robust interleukin-12 (IL12 production in human dendritic cells (hDC, ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of Leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG and other phosphoglycan-containing molecules (PGs, making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS responsible for IL12 induction.Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating L. major Friedlin V1 mutants defective in LPG alone, (FV1 lpg1-, or generally deficient for all PGs, (FV1 lpg2-. Infection with metacyclic, infective stage, L. major or purified LPG induced high levels of IL12B subunit gene transcripts in hDCs, which was abrogated with FV1 lpg1- infections. In contrast, hDC infections with FV1 lpg2- displayed increased IL12B expression, suggesting other PG-related/LPG2 dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 lpg1-, FV1 lpg2- infections revealed that FV1 lpg1- mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB and Interferon Regulatory Factor (IRF mediated transcription.These data suggest that L. major LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring Leishmania surface glycoconjugates that result in modulation of host cellular IL12.

Human enamel structure studied by high resolution electron microscopy

International Nuclear Information System (INIS)

Wen, S.L.

1989-01-01

Human enamel structural features are characterized by high resolution electron microscopy. The human enamel consists of polycrystals with a structure similar to Ca10(PO4)6(OH)2. This article describes the structural features of human enamel crystal at atomic and nanometer level. Besides the structural description, a great number of high resolution images are included. Research into the carious process in human enamel is very important for human beings. This article firstly describes the initiation of caries in enamel crystal at atomic and unit-cell level and secondly describes the further steps of caries with structural and chemical demineralization. The demineralization in fact, is the origin of caries in human enamel. The remineralization of carious areas in human enamel has drawn more and more attention as its potential application is realized. This process has been revealed by high resolution electron microscopy in detail in this article. On the other hand, the radiation effects on the structure of human enamel are also characterized by high resolution electron microscopy. In order to reveal this phenomenon clearly, a great number of electron micrographs have been shown, and a physical mechanism is proposed. 26 references

Quantitative determination of regorafenib and its two major metabolites in human plasma with high-performance liquid chromatography and ultraviolet detection.

Science.gov (United States)

Fujita, Kazuma; Miura, Masatomo; Shibata, Hiroyuki

2016-10-01

A simple, highly sensitive and specific high-performance liquid chromatography (HPLC) method was developed for the simultaneous quantitation of regorafenib, N-oxidemetabolite (M-2) and the desmethyl N-oxide metabolite (M-5) in human plasma. Regorafenib, M-2, M-5 and the internal standard sorafenib were separated using a mobile phase of 0.5% KH2 PO4 (pH 3.5)-acetonitrile (30:70, v/v), on a Capcell PAK MG II column at a flow rate of 0.5 mL/min and measurement at UV 260 nm. The lower limits of quantification for regorafenib, M-2 and M-5 were 10 ng/mL for each analyte. A procedure using solid-phase extraction required only a small amount of plasma (100 μL) for one analysis while providing high extraction recovery (>81% for all compounds) and good selectivity. Coefficients of variation for intra- and inter-day assays were HPLC assay is suitable for clinical pharmacokinetic studies of regorafenib. The present HPLC method is currently in use for our observational studies of patients under treatment. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Managing major chemical accidents in China: Towards effective risk information

NARCIS (Netherlands)

He, G.; Zhang, L.; Lu, Y.; Mol, A.P.J.

2011-01-01

Chemical industries, from their very inception, have been controversial due to the high risks they impose on safety of human beings and the environment. Recent decades have witnessed increasing impacts of the accelerating expansion of chemical industries and chemical accidents have become a major

Gains of ubiquitylation sites in highly conserved proteins in the human lineage

Directory of Open Access Journals (Sweden)

Kim Dong Seon

2012-11-01

Full Text Available Abstract Background Post-translational modification of lysine residues of specific proteins by ubiquitin modulates the degradation, localization, and activity of these target proteins. Here, we identified gains of ubiquitylation sites in highly conserved regions of human proteins that occurred during human evolution. Results We analyzed human ubiquitylation site data and multiple alignments of orthologous mammalian proteins including those from humans, primates, other placental mammals, opossum, and platypus. In our analysis, we identified 281 ubiquitylation sites in 252 proteins that first appeared along the human lineage during primate evolution: one protein had four novel sites; four proteins had three sites each; 18 proteins had two sites each; and the remaining 229 proteins had one site each. PML, which is involved in neurodevelopment and neurodegeneration, acquired three sites, two of which have been reported to be involved in the degradation of PML. Thirteen human proteins, including ERCC2 (also known as XPD and NBR1, gained human-specific ubiquitylated lysines after the human-chimpanzee divergence. ERCC2 has a Lys/Gln polymorphism, the derived (major allele of which confers enhanced DNA repair capacity and reduced cancer risk compared with the ancestral (minor allele. NBR1 and eight other proteins that are involved in the human autophagy protein interaction network gained a novel ubiquitylation site. Conclusions The gain of novel ubiquitylation sites could be involved in the evolution of protein degradation and other regulatory networks. Although gains of ubiquitylation sites do not necessarily equate to adaptive evolution, they are useful candidates for molecular functional analyses to identify novel advantageous genetic modifications and innovative phenotypes acquired during human evolution.

Developing and Evaluating Medical Humanities Problem-Based Learning Classes Facilitated by the Teaching Assistants Majored in the Liberal Arts: A Longitudinal Crossover Study.

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Tseng, Fen-Yu; Shieh, Jeng-Yi; Kao, Tze-Wah; Wu, Chau-Chung; Chu, Tzong-Shinn; Chen, Yen-Yuan

2016-02-01

Although medical humanities courses taught by teachers from nonmedical backgrounds are not unusual now, few studies have compared the outcome of medical humanities courses facilitated by physicians to that by teaching assistants majored in the liberal arts. The objectives of this study were to (1) analyze the satisfaction of medical students with medical humanities problem-based learning (PBL) classes facilitated by nonmedical teaching assistants (TAF) majored in the liberal arts, and those facilitated by the attending physicians (APF) and (2) examine the satisfaction of medical students with clinical medicine-related and clinical medicine-unrelated medical humanities PBL classes.A total of 123 medical students, randomly assigned to 16 groups, participated in this study. There were 16 classes in the course: 8 of them were TAF classes; and the others were APF classes. Each week, each group rotated from 1 subject of the 16 subjects of PBL to another subject. All of the 16 groups went through all the 16 subjects in the 2013 spring semester. We examined the medical students' satisfaction with each class, based on a rating score collected after each class was completed, using a scale from 0 (the lowest satisfaction) to 100 (the highest satisfaction). We also conducted multivariate linear regression analysis to examine the association between the independent variables and the students' satisfaction.Medical students were more satisfied with the TAF (91.35 ± 7.75) medical humanities PBL classes than APF (90.40 ± 8.42) medical humanities PBL classes (P = 0.01). Moreover, medical students were more satisfied with the clinical medicine-unrelated topics (92.00 ± 7.10) than the clinical medicine-related topics (90.36 ± 7.99) in the medical humanities PBL course (P = 0.01).This medical humanities PBL course, including nonmedical subjects and topics, and nonmedical teaching assistants from the liberal arts as class facilitators, was satisfactory. This

High-Throughput LC-MS/MS Method for Direct Quantification of Glucuronidated, Sulfated and Free Enterolactone in Human Plasma

DEFF Research Database (Denmark)

Nørskov, Natalja; Kyrø, Cecilie; Olsen, Anja

2016-01-01

Sulfation and glucuronidation constitute a major pathway in humans and may play an important role in biological activity of metabolites including the enterolignan, enterolactone. Because the aromatic structure of enterolactone has similarities to steroid metabolites, it was hypothesized that ente......Sulfation and glucuronidation constitute a major pathway in humans and may play an important role in biological activity of metabolites including the enterolignan, enterolactone. Because the aromatic structure of enterolactone has similarities to steroid metabolites, it was hypothesized......−MS/MS and a fluoroimmunoassay; however, most of these methods measure the total concentration of enterolactone, without any specification of its conjugation pattern. Here for the first time we present a high-throughput LC−MS/MS method to quantify enterolactone in its intact form as glucuronide, sulfate, and free enterolactone....... The method has shown good accuracy and precision at low concentration and very high sensitivity, with LLOQ for enterolactone sulfate at 16 pM, enterolactone glucuronide at 26 pM, and free enterolactone at 86 pM. The short run time of 2.6 min combined with simple sample clean up and high sensitivity make...

Characterization of the human RAB38 and RAB7 genes: exclusion of new major pathological loci for Japanese OCA.

Science.gov (United States)

Suzuki, Tamio; Miyamura, Yoshinori; Inagaki, Katsuhiko; Tomita, Yasushi

2003-08-01

Oculocutaneous albinisms (OCAs) are due to various gene mutations that cause a disruption of melanogenesis in the melanocyte. Four different genes associated with human OCA have been reported, however, not all of OCA patients can be classified according to these four genes. We have sought to find a new major locus for Japanese OCA. Recently two genes, RAB38 and RAB7, were reported to play an important role in melanogenesis in the melanocyte, suggesting that these two genes could be good candidates for new OCA loci. To determine the structures of the human RAB38 and RAB7 genes, and examine if the two genes are new major loci for Japanese OCA. We screened mutations in these genes of 25 Japanese OCA patients who lacked mutations in the OCA1 and OCA2 genes with SSCP/heteroduplexes method. We determined the both genes, and their genomic organizations to design the primers for SSCP/heteroduplexes method. And then we screened mutations, but no mutation was detected. Neither of the genes is a new major locus for Japanese OCA.

HUMAN RELATIONS LABORATORY TRAINING STUDENT NOTEBOOK.

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Springport High School, MI.

THE MAJOR OBJECTIVE OF THIS NOTEBOOK IS TO HELP THOSE STUDENTS INTERESTED IN TAKING PART IN THE SPRINGPORT HIGH SCHOOL HUMAN RELATIONS TRAINING LABORATORIES TO BETTER UNDERSTAND THEMSELVES, SOCIETY, AND HUMAN EMOTIONS SO THAT THEY MAY DEVELOP SOCIALLY AND EMOTIONALLY. THE SUBJECT MATTER OF THE NOTEBOOK IS DIVIDED INTO FOUR MAJOR AREAS--(1)…

TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1

Science.gov (United States)

Allam, Atef; Majji, Sai; Peachman, Kristina; Jagodzinski, Linda; Kim, Jiae; Ratto-Kim, Silvia; Wijayalath, Wathsala; Merbah, Melanie; Kim, Jerome H.; Michael, Nelson L.; Alving, Carl R.; Casares, Sofia; Rao, Mangala

2015-01-01

CD4+ T follicular helper cells (TFH) in germinal centers are required for maturation of B-cells. While the role of TFH-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of TFH (CXCR5+PD-1++) and precursor-TFH (CXCR5+PD-1+) cells. The majority of TFH-cells expressed CCR5 and CXCR3 and are the most permissive to HIV-1 infection. A single low-dose intravaginal HIV-1 challenge of humanized DRAG mice results in 100% infectivity with accumulation of TFH-cells mainly in the Peyer’s patches and FRT. The novel finding of TFH-cells in the FRT may contribute to the high susceptibility of DRAG mice to HIV-1 infection. This mouse model thus provides new opportunities to study TFH-cells and to evaluate HIV-1 vaccines. PMID:26034905

Major projects for the use of high power linacs

International Nuclear Information System (INIS)

Prome, M.

1996-01-01

A review of the major projects for high power linacs is given. The field covers the projects aiming at the transmutation of nuclear waste or the production of tritium, as well as the production of neutrons for hybrid reactors or basic research with neutron sources. The technologies which arc common to all the projects are discussed. Comments are made on the technical difficulties encountered by all the projects, and the special problems of the pulsed linacs are mentioned. Elements for a comparison of normal conducting linacs versus superconducting ones are given. Finally the technical developments being made in various laboratories are reviewed. (author)

Inactivation of high-risk human papillomaviruses by Holder pasteurization: implications for donor human milk banking.

Science.gov (United States)

Donalisio, Manuela; Cagno, Valeria; Vallino, Marta; Moro, Guido E; Arslanoglu, Sertac; Tonetto, Paola; Bertino, Enrico; Lembo, David

2014-01-01

Several studies have recently reported the detection of oncogenic human papillomaviruses (HPV) in human milk of a minority of lactating mothers. These findings raised safety concerns in the context of human donor milk banking given the potential risk of HPV transmission to recipient infants. The aim of this study was to investigate whether the Holder pasteurization, a procedure currently in use in human donor milk banks for milk pasteurization, completely inactivates high-risk and low-risk HPV. HPV pseudoviruses (PsV) were generated, spiked into cell culture medium or donor human milk and subjected to thermal inactivation. HPV PsV infectivity and morphological integrity was analyzed by cell-based assay and by electron microscopy, respectively. The Holder pasteurization completely inactivated the infectivity of high-risk (types 16 and 18) and low-risk (type 6) HPV both in cell culture medium and in human milk causing PsV particle disassembly. The results presented here indicate that the Holder pasteurization is an efficient procedure to inactivate high-risk and low-risk HPV thus preventing the potential risk of their transmission through human donor milk.

Anatomy and histology of rodent and human major salivary glands: -overview of the Japan salivary gland society-sponsored workshop-.

Science.gov (United States)

Amano, Osamu; Mizobe, Kenichi; Bando, Yasuhiko; Sakiyama, Koji

2012-10-31

MAJOR SALIVARY GLANDS OF BOTH HUMANS AND RODENTS CONSIST OF THREE PAIRS OF MACROSCOPIC GLANDS: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638-1686), Thomas Wharton (1614-1673), and Caspar Bartholin (1655-1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands.The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands.

Codon and amino acid usage in two major human pathogens of genus Bartonella--optimization between replicational-transcriptional selection, translational control and cost minimization.

Science.gov (United States)

Das, Sabyasachi; Paul, Sandip; Chatterjee, Sanjib; Dutta, Chitra

2005-01-01

Intra-genomic variation in synonymous codon and amino acid usage in two human pathogens Bartonella henselae and B. quintana has been carried out through multivariate analysis. Asymmetric mutational bias, coupled with replicational-transcriptional selection, has been identified as the prime selection force behind synonymous codon selection--a characteristic of the genus Bartonella, not exhibited by any other alpha-proteobacterial genome. Distinct codon usage patterns and low synonymous divergence values between orthologous sequences of highly expressed genes from the two Bartonella species indicate that there exists a residual intra-strand synonymous codon bias in the highly expressed genes, possibly operating at the level of translation. In the case of amino acid usage, the mean hydropathy level and aromaticity are the major sources of variation, both having nearly equal impact, while strand-specific mutational pressure and gene expressivity strongly influence the inter-strand variations. In both species under study, the highly expressed gene products tend not to contain heavy and/or aromatic residues, following the cost-minimization hypothesis in spite of their intracellular lifestyle. The codon and amino acid usage in these two human pathogens are, therefore, consequences of a complex balance between replicational-transcriptional selection, translational control, protein hydropathy and cost minimization.

Variations in riboflavin binding by human plasma: identification of immunoglobulins as the major proteins responsible

International Nuclear Information System (INIS)

Innis, W.S.; McCormick, D.B.; Merrill, A.H. Jr.

1985-01-01

Riboflavin binding by plasma proteins from healthy human subjects was examined by equilibrium dialysis using a physiological concentration of [2-14C]riboflavin (0.04 microM). Binding ranged from 0.080 to 0.917 pmole of riboflavin/mg of protein (with a mean +/- SD of 0.274 +/- 0.206), which corresponded to 4.14 to 49.4 pmole/ml of plasma (15.5 +/- 11.0) (N = 34). Males and females yielded similar results. Upon fractionation of plasma by gel filtration, the major riboflavin-binding components eluted with albumin and gamma-globulins. Albumin was purified and found to bind riboflavin only very weakly (Kd = 3.8 to 10.4 mM), although FMN and photochemical degradation products (e.g., lumiflavine and lumichrome) were more tightly bound. Binding in the gamma-globulin fraction was attributed to IgG and IGA because the binding protein(s) and immunoglobulins copurified using various methods were removed by treatment of plasma with protein A-agarose, and were coincident upon immunoelectrophoresis followed by autoradiography to detect [2-14C]riboflavin. Differences among the plasma samples correlated with the binding recovered with the immunoglobulins. Binding was not directly related to the total IgG or IgA levels of subjects. Hence, it appears that the binding is due to a subfraction of these proteins. These findings suggest that riboflavin-binding immunoglobulins are a major cause of variations in riboflavin binding in human circulation, and may therefore affect the utilization of this micronutrient

Human Embryonic Stem Cell-Derived Neurons Are Highly Permissive for Varicella-Zoster Virus Lytic Infection.

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Sadaoka, Tomohiko; Schwartz, Cindi L; Rajbhandari, Labchan; Venkatesan, Arun; Cohen, Jeffrey I

2018-01-01

Varicella-zoster virus (VZV) is highly cell associated when grown in culture and has a much higher (4,000- to 20,000-fold increased) particle-to-PFU ratio in vitro than herpes simplex virus (HSV). In contrast, VZV is highly infectious in vivo by airborne transmission. Neurons are major targets for VZV in vivo ; in neurons, the virus can establish latency and reactivate to produce infectious virus. Using neurons derived from human embryonic stem cells (hESC) and cell-free wild-type (WT) VZV, we demonstrated that neurons are nearly 100 times more permissive for WT VZV infection than very-early-passage human embryonic lung cells or MRC-5 diploid human fibroblasts, the cells used for vaccine production or virus isolation. The peak titers achieved after infection were ∼10-fold higher in human neurons than in MRC-5 cells, and the viral genome copy number-to-PFU ratio for VZV in human neurons was 500, compared with 50,000 for MRC-5 cells. Thus, VZV may not necessarily have a higher particle-to-PFU ratio than other herpesviruses; instead, the cells previously used to propagate virus in vitro may have been suboptimal. Furthermore, based on electron microscopy, neurons infected with VZV produced fewer defective or incomplete viral particles than MRC-5 cells. Our data suggest that neurons derived from hESC may have advantages compared to other cells for studies of VZV pathogenesis, for obtaining stocks of virus with high titers, and for isolating VZV from clinical specimens. IMPORTANCE Varicella-zoster virus (VZV) causes chickenpox and shingles. Cell-free VZV has been difficult to obtain, both for in vitro studies and for vaccine production. While numerous cells lines have been tested for their ability to produce high titers of VZV, the number of total virus particles relative to the number of viral particles that can form plaques in culture has been reported to be extremely high relative to that in other viruses. We show that VZV grows to much higher titers in human

Reduction in human Lyme neuroborreliosis associated with a major epidemic among roe deer.

Science.gov (United States)

Andersen, Nanna Skaarup; Skarphédinsson, Sigurdur; Knudtzen, Fredrikke C; Olesen, Carsten Riis; Jensen, Thøger Gorm; Jensen, Per Moestrup

2018-02-01

Lyme neuroborreliosis is the most severe clinical manifestation of Lyme borreliosis. In most of Denmark, and also Europe, the overall prevalence of Lyme borreliosis seems to be stabilising. This is not the case on the island of Funen, Denmark, where the number of human Lyme neuroborreliosis cases has markedly declined throughout the last decade. We propose the reason for the decline is a major epidemic among roe deer, killing almost half of their population, resulting in a reduction in the tick population which make it less likely to get a tick bite and therefore to contract Lyme neuroborreliosis. This is the first time such a relationship is described as a naturally occurring phenomenon in Europe. Copyright © 2017 Elsevier GmbH. All rights reserved.

Human Milk Composition and Preservation: Evaluation of High-pressure Processing as a Nonthermal Pasteurization Technology.

Science.gov (United States)

Sousa, Sílvia G; Delgadillo, Ivonne; Saraiva, Jorge A

2016-01-01

Human milk is seen not only as a food, but as a functional and dynamic biologic system. It provides nutrients, bioactive components, and immune factors, promoting adequate and healthy growth of newborn infants. When mothers cannot supply their children, donated breast milk is the nutrition recommended by the World Health Organization, as it is a better alternative than infant formula. However, because of the manner in which donor milk is handled in human milk banks (HMB) many of the properties ascribed to mother's own milk are diminished or destroyed. The major process responsible for these losses is Holder pasteurization. High-pressure processing (HPP) is a novel nonthermal pasteurization technology that is being increasingly applied in food industries worldwide, primarily as an alternative to thermal treatment. This is due to its capacity to inactivate microorganisms while preserving both nutritional and bioactive components of foods. This review describes human milk composition and preservation, and critically discusses HMB importance and practices, highlighting HPP as a potential nonthermal pasteurization technology for human milk preservation. HPP technology is described and the few currently existing studies of its effects in human milk are presented.

HUMAN COMFORT AND THE MICROCLIMATIC DRIVERS ...

African Journals Online (AJOL)

Osondu

mean heat stress (poor human comfort), followed by high density residential areas. A major attribute ... Key words: Heat stress, human comfort, microclimate, land use, urban, vegetation. Introduction ... defined by the meteorological Glossary as the physical state of .... which is the focus of the study is characterized by. Human ...

The fraction dose absorbed, in humans, and high jejunal human permeability relationship.

Science.gov (United States)

Dahan, Arik; Lennernäs, Hans; Amidon, Gordon L

2012-06-04

The drug intestinal permeability (P(eff)) measure has been widely used as one of the main factors governing both the rate and/or extent of drug absorption (F(abs)) in humans following oral administration. In this communication we emphasize the complexity behind and the care that must be taken with this in vivo P(eff) measurement. Intestinal permeability, considering the whole of the human intestine, is more complex than generally recognized, and this can lead to misjudgment regarding F(abs) and P(eff) in various settings, e.g. drug discovery, formulation design, drug development and regulation. Setting the adequate standard for the low/high permeability class boundary, the different experimental methods for the permeability measurement, and segmental-dependent permeability throughout the human intestine due to different mechanisms are some of the main points that are discussed. Overall, the use of jejunal P(eff) as a surrogate for extent of absorption is sound and scientifically justified; a compound with high jejunal P(eff) will have high F(abs), eliminating the risk for misclassification as a BCS class I drug. Much more care should be taken, however, when jejunal P(eff) does not support a high-permeability classification; a thorough examination may reveal high-permeability after all, attributable to e.g. segmental-dependent permeability due to degree of ionization or transporter expression. In this situation, the use of multiple permeability experimental methods, including the use of metabolism, which except for luminal degradation requires absorption, is prudent and encouraged.

Podocalyxin as a major pluripotent marker and novel keratan sulfate proteoglycan in human embryonic and induced pluripotent stem cells.

Science.gov (United States)

Toyoda, Hidenao; Nagai, Yuko; Kojima, Aya; Kinoshita-Toyoda, Akiko

2017-04-01

Podocalyxin (PC) was first identified as a heavily sialylated transmembrane protein of glomerular podocytes. Recent studies suggest that PC is a remarkable glycoconjugate that acts as a universal glyco-carrier. The glycoforms of PC are responsible for multiple functions in normal tissue, human cancer cells, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). PC is employed as a major pluripotent marker of hESCs and hiPSCs. Among the general antibodies for human PC, TRA-1-60 and TRA-1-81 recognize the keratan sulfate (KS)-related structures. Therefore, It is worthwhile to summarize the outstanding chemical characteristic of PC, including the KS-related structures. Here, we review the glycoforms of PC and discuss the potential of PC as a novel KS proteoglycan in undifferentiated hESCs and hiPSCs.

RNA of Enterococcus faecalis Strain EC-12 Is a Major Component Inducing Interleukin-12 Production from Human Monocytic Cells.

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Ryoichiro Nishibayashi

Full Text Available Interleukin-12 (IL-12 is an important cytokine for the immunomodulatory effects of lactic acid bacteria (LAB. Using murine immune cells, we previously reported that the RNA of Enterococcus faecalis EC-12, a LAB strain exerting probiotic-like beneficial effects, is the major IL-12-inducing immunogenic component. However, it was recently revealed that bacterial RNA can be a ligand for Toll-like receptor (TLR 13, which is only expressed in mice. Because TLR13 is not expressed in humans, the immuno-stimulatory and -modulatory effects of LAB RNA in human cells should be augmented excluding TLR13 contribution. In experiment 1 of this study, the role of LAB RNA in IL-12 induction in human immune cells was studied using three LAB strains, E.faecalis EC-12, Lactobacillus gasseri JCM5344, and Bifidobacterium breve JCM1192. RNase A treatment of heat-killed LAB significantly decreased the IL-12 production of human peripheral blood mononuclear cells on stimulation, while RNase III treatment revealed virtually no effects. Further, IL-12 production against heat-killed E. faecalis EC-12 was abolished by depleting monocytes. These results demonstrated that single stranded RNA (ssRNA of LAB is a strong inducer of IL-12 production from human monocytes. In experiment 2, major receptor for ssRNA of E. faecalis EC-12 was identified using THP-1 cells, a human monocytic cell line. The type of RNA molecules of E. faecalis EC-12 responsible for IL-12 induction was also identified. IL-12 production induced by the total RNA of E. faecalis EC-12 was significantly reduced by the treatment of siRNA for TLR8 but not for TLR7. Furthermore, both 23S and 16S rRNA, but not mRNA, of E. faecalis EC-12 markedly induced IL-12 production from THP-1 cells. These results suggested that the recognition of ssRNA of E. faecalis EC-12 was mediated by TLR8 and that rRNA was the RNA molecule that exhibited IL-12-inducing ability in human cells.

The International Human Epigenome Consortium

DEFF Research Database (Denmark)

Stunnenberg, Hendrik G; Hirst, Martin

2016-01-01

The International Human Epigenome Consortium (IHEC) coordinates the generation of a catalog of high-resolution reference epigenomes of major primary human cell types. The studies now presented (see the Cell Press IHEC web portal at http://www.cell.com/consortium/IHEC) highlight the coordinated ac...

Public Spending On Human Capital In Major Industrialized Countries = Endüstrileşmenin En Yüksek Olduğu Ülkelerde Beşeri Sermayeye Yönelik Kamu Harcamalari

Directory of Open Access Journals (Sweden)

Meriç Subaşı ERTEKİN

2005-06-01

Full Text Available Human capital is important for firms and nations in the knowledge based economy that needs skills. Thus, investment in education is a public policy to support human capital formation and offset the magnitude of capital looses. Policies and reforms designed to foster early learning which are determined as a high quality of education, early intervention and job training programs and promote skill formation. The public sector plays an important role in the funding of all education in major industrialized countries. Public spending on primary, secondary, post-secondary and tertiary educational institutions is higher than private spending.

CpG methylation differences between neurons and glia are highly conserved from mouse to human.

Science.gov (United States)

Kessler, Noah J; Van Baak, Timothy E; Baker, Maria S; Laritsky, Eleonora; Coarfa, Cristian; Waterland, Robert A

2016-01-15

Understanding epigenetic differences that distinguish neurons and glia is of fundamental importance to the nascent field of neuroepigenetics. A recent study used genome-wide bisulfite sequencing to survey differences in DNA methylation between these two cell types, in both humans and mice. That study minimized the importance of cell type-specific differences in CpG methylation, claiming these are restricted to localized genomic regions, and instead emphasized that widespread and highly conserved differences in non-CpG methylation distinguish neurons and glia. We reanalyzed the data from that study and came to markedly different conclusions. In particular, we found widespread cell type-specific differences in CpG methylation, with a genome-wide tendency for neuronal CpG-hypermethylation punctuated by regions of glia-specific hypermethylation. Alarmingly, our analysis indicated that the majority of genes identified by the primary study as exhibiting cell type-specific CpG methylation differences were misclassified. To verify the accuracy of our analysis, we isolated neuronal and glial DNA from mouse cortex and performed quantitative bisulfite pyrosequencing at nine loci. The pyrosequencing results corroborated our analysis, without exception. Most interestingly, we found that gene-associated neuron vs. glia CpG methylation differences are highly conserved across human and mouse, and are very likely to be functional. In addition to underscoring the importance of independent verification to confirm the conclusions of genome-wide epigenetic analyses, our data indicate that CpG methylation plays a major role in neuroepigenetics, and that the mouse is likely an excellent model in which to study the role of DNA methylation in human neurodevelopment and disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of caffeine on the expression of a major X-ray induced protein in human tumor cells

Energy Technology Data Exchange (ETDEWEB)

Hughes, E.N.; Boothman, D.A. (Univ. of Pennsylvania School of Medicine, Philadelphia (USA))

1991-03-01

We have examined the effect of caffeine on the concomitant processes of the repair of potentially lethal damage (PLD) and the synthesis of X-ray-induced proteins in the human malignant melanoma cell line, Ul-Mel. Caffeine administered at a dose of 5mM after X radiation not only inhibited PLD repair but also markedly reduced the level of XIP269, a major X-ray-induced protein whose expression has been shown to correlate with the capacity to repair PLD. The expression of the vast majority of other cellular proteins, including seven other X-ray-induced proteins, remained unchanged following caffeine treatment. A possible role for XIP269 in cell cycle delay following DNA damage by X irradiation is discussed.

CRISPR-Cas9-Mediated Silencing of CD44 in Human Highly Metastatic Osteosarcoma Cells

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Tang Liu

2018-04-01

Full Text Available Background/Aims: Metastasis is the major cause of death in patients with osteosarcoma. There is an urgent need to identify molecular markers that promote metastasis. Cluster of differentiation 44 is a receptor for hyaluronic acid (HA and HA-binding has been proven to participate in various biological tumor activities, including tumor progression and metastasis. Methods: We performed a meta-analysis to investigate the relationship between CD44 expression, survival, and metastasis in patients with osteosarcoma. We then utilized the CRISPR-Cas9 system to specifically silence CD44 in highly metastatic human osteosarcoma cells (MNNG/HOS and 143B and further determined the functional effects of CD44 knockout in these cells. Results: The meta-analysis demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis in patients with osteosarcoma. The expression of CD44 in highly metastatic human osteosarcoma cell lines was efficiently blocked by CRISPR-Cas9. When CD44 was silenced, the proliferation and spheroid formation of these osteosarcoma cells was inhibited under 3-D culture conditions. Furthermore, the migratory and invasive functions were also impaired in these highly metastatic osteosarcoma cells. Conclusion: These results suggest that developing new strategies to target CD44 in osteosarcoma may prevent metastasis and improve the clinical outcome of osteosarcoma patients.

Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia

International Nuclear Information System (INIS)

Lundby, Carsten; Pilegaard, Henriette; Hall, Gerrit van; Sander, Mikael; Calbet, Jose; Loft, Steffen; Moeller, Peter

2003-01-01

Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming tissue. Muscle biopsies from seven healthy humans were obtained at sea level and after 2 and 8 weeks of hypoxia at 4100 m.a.s.l. We found increased levels of strand breaks and endonuclease III-sensitive sites after 2 weeks of hypoxia, whereas oxidative DNA damage detected by formamidopyrimidine DNA glycosylase (FPG) protein was unaltered. The expression of 8-oxoguanine DNA glycosylase 1 (OGG1), determined by quantitative RT-PCR of mRNA levels did not significantly change during high-altitude hypoxia, although the data could not exclude a minor upregulation. The expression of heme oxygenase-1 (HO-1) was unaltered by prolonged hypoxia, in accordance with the notion that HO-1 is an acute stress response protein. In conclusion, our data indicate high-altitude hypoxia may serve as a good model for oxidative stress and that antioxidant genes are not upregulated in muscle tissue by prolonged hypoxia despite increased generation of oxidative DNA damage

Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

NARCIS (Netherlands)

D.R. Gasper (Des)

2007-01-01

markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

Human Rights, Human Needs, Human Development, Human Security : Relationships between four international 'human' discourses

NARCIS (Netherlands)

D.R. Gasper (Des)

2007-01-01

textabstractHuman rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each

High-throughput fractionation of human plasma for fast enrichment of low- and high-abundance proteins.

Science.gov (United States)

Breen, Lucas; Cao, Lulu; Eom, Kirsten; Srajer Gajdosik, Martina; Camara, Lila; Giacometti, Jasminka; Dupuy, Damian E; Josic, Djuro

2012-05-01

Fast, cost-effective and reproducible isolation of IgM from plasma is invaluable to the study of IgM and subsequent understanding of the human immune system. Additionally, vast amounts of information regarding human physiology and disease can be derived from analysis of the low abundance proteome of the plasma. In this study, methods were optimized for both the high-throughput isolation of IgM from human plasma, and the high-throughput isolation and fractionation of low abundance plasma proteins. To optimize the chromatographic isolation of IgM from human plasma, many variables were examined including chromatography resin, mobile phases, and order of chromatographic separations. Purification of IgM was achieved most successfully through isolation of immunoglobulin from human plasma using Protein A chromatography with a specific resin followed by subsequent fractionation using QA strong anion exchange chromatography. Through these optimization experiments, an additional method was established to prepare plasma for analysis of low abundance proteins. This method involved chromatographic depletion of high-abundance plasma proteins and reduction of plasma proteome complexity through further chromatographic fractionation. Purification of IgM was achieved with high purity as confirmed by SDS-PAGE and IgM-specific immunoblot. Isolation and fractionation of low abundance protein was also performed successfully, as confirmed by SDS-PAGE and mass spectrometry analysis followed by label-free quantitative spectral analysis. The level of purity of the isolated IgM allows for further IgM-specific analysis of plasma samples. The developed fractionation scheme can be used for high throughput screening of human plasma in order to identify low and high abundance proteins as potential prognostic and diagnostic disease biomarkers.

Human factors programs for high-level radioactive waste handling systems

International Nuclear Information System (INIS)

Pond, D.J.

1992-04-01

Human Factors is the discipline concerned with the acquisition of knowledge about human capabilities and limitations, and the application of such knowledge to the design of systems. This paper discusses the range of human factors issues relevant to high-level radioactive waste (HLRW) management systems and, based on examples from other organizations, presents mechanisms through which to assure application of such expertise in the safe, efficient, and effective management and disposal of high-level waste. Additionally, specific attention is directed toward consideration of who might be classified as a human factors specialist, why human factors expertise is critical to the success of the HLRW management system, and determining when human factors specialists should become involved in the design and development process

Human factors programs for high-level radioactive waste handling systems

International Nuclear Information System (INIS)

Pond, D.J.

1992-01-01

Human Factors is the discipline concerned with the acquisition of knowledge about human capabilities and limitations, and the application of such knowledge to the design of systems. This paper discusses the range of human factors issues relevant to high-level radioactive waste (HLRW) management systems and, based on examples form other organizations, presents mechanisms through which to assure application of such expertise in the safe, efficient, and effective management and disposal of high-level waste. Additionally, specific attention is directed toward consideration of who might be classified as a human factors specialist, why human factors expertise is critical to the success of the HLRW management system, and determining when human factors specialists should become involved in the design and development process

Identification of human cytochrome P450 and UGT enzymes involved in the metabolism of ferulic acid, a major bioactive component in traditional Chinese medicines.

Science.gov (United States)

Zhuang, Xiao-Mei; Chen, Lin; Tan, Yan; Yang, Hai-Ying; Lu, Chuang; Gao, Yue; Li, Hua

2017-09-01

Ferulic acid (FA) is an active component of herbal medicines. One of the best documented activities of FA is its antioxidant property. Moreover, FA exerts antiallergic, anti-inflammatory, and hepatoprotective effects. However, the metabolic pathways of FA in humans remain unclear. To identify whether human CYP or UGT enzymes are involved in the metabolism of FA, reaction phenotyping of FA was conducted using major CYP-selective chemical inhibitors together with individual CYP and UGT Supersomes. The CYP- and/or UGT-mediated metabolism kinetics were examined simultaneously or individually. Relative activity factor and total normalized rate approaches were used to assess the relative contributions of each major human CYPs towards the FA metabolism. Incubations of FA with human liver microsomes (HLM) displayed NADPH- and UDPGA-dependent metabolism with multiple CYP and UGT isoforms involved. CYPs and UGTs contributed equally to the metabolism of FA in HLM. Although CYP1A2 and CYP3A4 appeared to be the major contributors in the CYP-mediated clearance, their contributions to the overall clearance are still minor (medicines because multiple phase I and phase II enzymes are involved in its metabolism. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Frequency variations of discrete cranial traits in major human populations. III. Hyperostotic variations.

Science.gov (United States)

Hanihara, T; Ishida, H

2001-09-01

Seven discrete cranial traits usually categorised as hyperostotic characters, the medial palatine canal, hypoglossal canal bridging, precondylar tubercle, condylus tertius, jugular foramen bridging, auditory exostosis, and mylohyoid bridging were investigated in 81 major human population samples from around the world. Significant asymmetric occurrences of the bilateral traits were detected in the medial palatine canal and jugular foramen bridging in several samples. Significant intertrait associations were found between some pairs of the traits, but not consistently across the large geographical samples. The auditory exostosis showed a predominant occurrence in males. With the exception of the auditory exostosis and mylohyoid bridging in a few samples, significant sex differences were slight. The frequency distributions of the traits (except for the auditory exostosis) showed some interregional clinality and intraregional discontinuity, suggesting that genetic drift could have contributed to the observed pattern of variation.

HIV-related knowledge and perceptions by academic major: Implications for university interventions

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Matthew Lee Smith

2014-03-01

Full Text Available Most universities offer human sexuality courses, although they are not required for graduation. While students in health-related majors may receive sexuality education in formal settings, majority of college students never receive formal sexual health or HIV/AIDS-related education, which may lead to elevated engagement in high-risk sexual behaviors. This study examines perceived knowledge about HIV/AIDS, perceived risk, and perceived consequences among college students by two distinct classifications of academic majors. Data were collected from 510 college students. Binary and multinomial logistic regressions were performed to compare HIV-related covariates by academic major category. Limited differences were observed by Science, Technology, Engineering, and Mathematics (STEM categorization. Relative to health and kinesiology (HK majors, those who self-reported being completely knowledgeable about HIV were less likely to be physical sciences, math, engineering, business (PMEB [OR=0.41, P=0.047] or education, humanities, and social sciences (EHS majors [OR=0.25, P=0.004]. PMEB majors were less likely to report behavioral factors as a risk for contracting HIV [OR=0.86, P=0.004] and perceived acquiring HIV would be more detrimental to their quality of life [OR=2.14, P=0.012], but less detrimental to their mental wellbeing [OR=0.58, P=0.042]. Findings can inform college-wide campaigns and interventions to raise HIV/AIDS awareness and improve college health.

HUMANITIES IN A JUNIOR HIGH SCHOOL.

Science.gov (United States)

KNIGHT, BONNIE M.

A HUMANITIES COURSE HAS BEEN DEVELOPED FOR ACADEMICALLY ABLE SEVENTH-GRADE STUDENTS IN BRANCIFORTE JUNIOR HIGH SCHOOL IN SANTA CRUZ, CALIFORNIA. IN A TWO-PERIOD DAILY TIME BLOCK, STUDENTS LEARN ENGLISH, LITERATURE, AND LATIN, AND INVESTIGATE TOPICS IN ARCHEOLOGY, CULTURAL ANTHROPOLOGY, LINGUISTICS, PSYCHOLOGY, PHILOSOPHY, GREEK LITERATURE AND…

Leishmania major infection in a dog with cutaneous manifestations.

Science.gov (United States)

Baneth, Gad; Nachum-Biala, Yaarit; Shabat Simon, Maytal; Brenner, Ori; Gaier, Sarit; Rojas, Alicia; Yasur-Landau, Daniel

2016-05-10

Leishmania major is a main cause of cutaneous leishmaniasis in humans in an area that stretches from India through Central Asia, the Middle East, to North and West Africa. In Israel, it is a common infection of humans with rodents as the reservoir hosts and Phlebotomus papatasi as its sand fly vector. A 6 months old spayed female mixed breed dog was referred to the Hebrew University Veterinary Teaching Hospital with a large ulcerative dermal lesion on the muzzle, and lesions in the foot pads and left hind leg. Histopathology of a skin biopsy found chronic lymphohistiocytic dermatitis with the presence of Leishmania spp. amastigotes in the muzzle. Physical examination indicated that the dog was overall in a good clinical condition and the main findings were the skin lesions and enlarged prescapular lymph nodes. Complete blood count and serum biochemistry profile were within reference ranges. Serology by ELISA was positive for Leishmania spp. and PCR of the prescapular lymph node was positive by an ITS1 region PCR-high resolution melt analysis. However, the melt curve and subsequent DNA sequencing indicated that infection was caused by L. major and not L. infantum, which is the main causative agent of canine leishmaniosis in the Mediterranean region. DNA was extracted from the paraffin embedded muzzle biopsy and PCR with sequencing also indicated L. major. The dog's young age and the absence of hyperglobulinemia and anemia were not typical of L. infantum infection. The dog was treated with allopurinol and the skin lesions improved and later disappeared when the dog was re-evaluated. This is the first molecularly-confirmed case of L. major infection in a dog. Two previous reports of L. major in dogs originated from Saudi-Arabia and Egypt in 1985 and 1987 were confirmed by enzymatic biochemical techniques. Serology for L. infantum was positive probably due to the well documented serological cross-reactivity between Leishmania spp. Although dogs and wild carnivores are

Human factors: a major issue in plant aging

International Nuclear Information System (INIS)

Widrig, R.D.

1985-07-01

Human factors issues will be of great significance in the safe and reliable operation of aging nuclear power plants, and they may be more important than materials/component-type issues. Human actions can accelerate or decelerate te physical aging process. And an aging plant can have significant negative implications on staff performance and actions. Some examples include difficulties in attracting and retaining good managers, financial decisions based on a short and uncertain remaining plant life, difficulties in replacing retiring staff, increased maintenance complexity, and increased burden on training. These problems can be dealt with more effectively by early recognition and a well conceived mitigation effort

Can profiles of poly- and Perfluoroalkyl substances (PFASs) in human serum provide information on major exposure sources?

Science.gov (United States)

Hu, Xindi C; Dassuncao, Clifton; Zhang, Xianming; Grandjean, Philippe; Weihe, Pál; Webster, Glenys M; Nielsen, Flemming; Sunderland, Elsie M

2018-02-01

exposure sources in two North American populations, suggesting generalizability of results from the Faroese population. We conclude that PFAS homologue profiles in serum provide valuable information on major exposure sources. It is essential to compare samples collected at similar time periods and to correct for demographic groups that are highly affected by differences in physiological processes (e.g., pregnancy). Information on PFAS homologue profiles is crucial for attributing adverse health effects to the proper mixtures or individual PFASs.

Estimated Human and Economic Burden of Four Major Adult Vaccine-Preventable Diseases in the United States, 2013

OpenAIRE

McLaughlin, John M.; McGinnis, Justin J.; Tan, Litjen; Mercatante, Annette; Fortuna, Joseph

2015-01-01

Low uptake of routinely recommended adult immunizations is a public health concern. Using data from the peer-reviewed literature, government disease-surveillance programs, and the US Census, we developed a customizable model to estimate human and economic burden caused by four major adult vaccine-preventable diseases (VPD) in 2013 in the United States, and for each US state individually. To estimate the number of cases for each adult VPD for a given population, we multiplied age-specific inci...

A genetic electrophoretic variant of high-sulfur hair proteins for forensic hair comparisons. I. Characterization of variant high-sulfur proteins of human hair.

Science.gov (United States)

Miyake, B

1989-02-01

In a survey of the proteins from human hair, a genetic electrophoretic variant has been observed in the high-sulfur protein region. S-carboxymethylated proteins were examined by 15% polyacrylamide gel electrophoresis at pH 8.9. Out of 150 unrelated samples of Japanese head hairs analyzed, 107 showed 6 major high-sulfur protein bands (normal) and the remaining 43 samples showed an additional high-sulfur protein band (variant). Of 21 Caucasian samples analyzed only one variant sample was found. Characterization of the proteins by two-dimensional electrophoresis evidenced a variant protein spot which showed an apparent molecular weight of 30 k Da. Isoelectric points of the high-sulfur proteins ranged from 3.25-3.55 and that of variant protein band from 3.3-3.4. Family studies of 21 matings resulting in 49 children indicated that this variant was inherited in an autosomal fashion.

The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Louis, Simon N.S., E-mail: simonnsl@unimelb.edu.au; Chow, Laurie T.C.; Varghayee, Naghmeh; Rezmann, Linda A.; Frauman, Albert G.; Louis, William J. [Clinical Pharmacology and Therapeutics Unit, Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3084, Victoria (Australia)

2011-10-11

Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT{sub 2}-) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT{sub 2}-receptor, through an interaction with its putative signaling partner MTUS1/ATIP (AT{sub 2}-receptor interacting protein), inhibits the mitogenic effects of EGF in prostate cancer cell lines representing both early and late stage disease. This is the first report on the expression of ATIP in normal and malignant human prostatic biopsies. The expression of ATIP and its major isoforms, ATIP1 and ATIP3, in normal prostatic cells and three prostate cancer cell lines was examined using QPCR and immunohistochemistry. Human biopsies containing benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and well, moderately and poorly differentiated prostate cancer were also examined. Overall, ATIP1 and ATIP3 mRNA expression was increased in malignant compared to normal tissues and cell lines. ATIP immunostaining was low or absent in both the basal and columnar epithelial cell layers surrounding BPH acini; however, it was observed in high concentration in neoplastic epithelial cells of HGPIN and was clearly evident in cytoplasms of malignant cells in all prostate cancer grades. ATIP immunostaining was also identified in the cytoplasms of LNCaP and PC3 prostate cancer cells. As the AT{sub 2}-receptor/ATIP inhibitory signaling pathway exists in malignant cells in all grades of prostate cancer, enhancement of this pathway may be a therapeutic target even after the development of androgen-independence.

The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer

International Nuclear Information System (INIS)

Louis, Simon N.S.; Chow, Laurie T.C.; Varghayee, Naghmeh; Rezmann, Linda A.; Frauman, Albert G.; Louis, William J.

2011-01-01

Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT 2 -) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT 2 -receptor, through an interaction with its putative signaling partner MTUS1/ATIP (AT 2 -receptor interacting protein), inhibits the mitogenic effects of EGF in prostate cancer cell lines representing both early and late stage disease. This is the first report on the expression of ATIP in normal and malignant human prostatic biopsies. The expression of ATIP and its major isoforms, ATIP1 and ATIP3, in normal prostatic cells and three prostate cancer cell lines was examined using QPCR and immunohistochemistry. Human biopsies containing benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and well, moderately and poorly differentiated prostate cancer were also examined. Overall, ATIP1 and ATIP3 mRNA expression was increased in malignant compared to normal tissues and cell lines. ATIP immunostaining was low or absent in both the basal and columnar epithelial cell layers surrounding BPH acini; however, it was observed in high concentration in neoplastic epithelial cells of HGPIN and was clearly evident in cytoplasms of malignant cells in all prostate cancer grades. ATIP immunostaining was also identified in the cytoplasms of LNCaP and PC3 prostate cancer cells. As the AT 2 -receptor/ATIP inhibitory signaling pathway exists in malignant cells in all grades of prostate cancer, enhancement of this pathway may be a therapeutic target even after the development of androgen-independence

Simultaneous assessments of occurrence, ecological, human health, and organoleptic hazards for 77 VOCs in typical drinking water sources from 5 major river basins, China

International Nuclear Information System (INIS)

Chen, Xichao; Luo, Qian; Wang, Donghong; Gao, Jijun; Wei, Zi; Wang, Zijian; Zhou, Huaidong; Mazumder, Asit

2015-01-01

Owing to the growing public awareness on the safety and aesthetics in water sources, more attention has been given to the adverse effects of volatile organic compounds (VOCs) on aquatic organisms and human beings. In this study, 77 target VOCs (including 54 common VOCs, 13 carbonyl compounds, and 10 taste and odor compounds) were detected in typical drinking water sources from 5 major river basins (the Yangtze, the Huaihe, the Yellow, the Haihe and the Liaohe River basins) and their occurrences were characterized. The ecological, human health, and olfactory assessments were performed to assess the major hazards in source water. The investigation showed that there existed potential ecological risks (1.30 × 10 ≤ RQ_t_o_t_a_ls ≤ 8.99 × 10) but little human health risks (6.84 × 10"−"7 ≤ RQ_t_o_t_a_ls ≤ 4.24 × 10"−"4) by VOCs, while that odor problems occurred extensively. The priority contaminants in drinking water sources of China were also listed based on the present assessment criteria. - Highlights: • VOCs with various polarities were screened in typical water sources of China. • Ecological, human health and olfactory assessments were simultaneously performed. • The risk assessments were used to identify the major hazards by VOCs. • The detected VOCs posed potential ecological risks but little human health risks. • Odor problems occurred extensively in source water of China. - Detected VOCs with various polarities caused odor problems and posed potential ecological risks but little human health risks in drinking water sources in China.

Identification of neurotensin-related peptides in human thymic epithelial cell membranes and relationship with major histocompatibility complex class I molecules.

Science.gov (United States)

Vanneste, Y; Thome, A N; Vandersmissen, E; Charlet, C; Franchimont, D; Martens, H; Lhiaubet, A M; Schimpff, R M; Rostène, W; Geenen, V

1997-06-01

This study shows the expression at the cell surface of human thymic epithelial cells (TEC) of a neurotensin (NT)-like immunoreactivity. NT radio-immunoassay (RIA) revealed that cultured human TEC contain +/-5 ng immunoreactive (ir) NT/10(6) cells, of which 5% is associated with plasma cell membranes. HPLC analysis of NT-ir present in human TEC showed a major peak of NT-ir corresponding to NT1-13. NT-ir was not detected in the supernatant of human TEC cultures. Using an affinity column prepared with a anti-MHC class I monoclonal antibody, NT-ir-related peptides were retained on the column and eluted together with MHC class I-related proteins. According to the elution time on HPLC of these peptides, they correspond to intact NT1-13, as well as to smaller fragments of NT1-13.

Major groove binding track residues of the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase enhance cDNA synthesis at high temperatures.

Science.gov (United States)

Matamoros, Tania; Barrioluengo, Verónica; Abia, David; Menéndez-Arias, Luis

2013-12-23

At high temperatures, RNA denaturation can improve the efficiency and specificity of reverse transcription. Refined structures and molecular models of HIV-1 reverse transcriptases (RTs) from phylogenetically distant clades (i.e., group M subtype B and group O) revealed a major interaction between the template-primer and the Arg³⁵⁸-Gly³⁵⁹-Ala³⁶⁰ triad in the large subunit of HIV-1M/B RT. However, fewer contacts were predicted for the equivalent Lys³⁵⁸-Ala³⁵⁹-Ser³⁶⁰ triad of HIV-1O RT and the nucleic acid. An engineered HIV-1O K358R/A359G/S360A RT showed increased cDNA synthesis efficiency above 68 °C, as determined by qualitative and quantitative reverse transcription polymerase chain reactions. In comparison with wild-type HIV-1O RT, the mutant enzyme showed higher thermal stability but retained wild-type RNase H activity. Mutations that increased the accuracy of HIV-1M/B RTs were tested in combination with the K358R/A359G/S360A triple mutation. Some of them (e.g., F61A, K65R, K65R/V75I, and V148I) had a negative effect on reverse transcription efficiency above 65 °C. RTs with improved DNA binding affinities also showed higher cDNA synthesis efficiencies at elevated temperatures. Two of the most thermostable RTs (i.e., mutants T69SSG/K358R/A359G/S360A and K358R/A359G/S360A/E478Q) showed moderately increased fidelity in forward mutation assays. Our results demonstrate that the triad of Arg³⁵⁸, Gly³⁵⁹, and Ala³⁶⁰ in the major groove binding track of HIV-1 RT is a major target for RT stabilization, and most relevant for improving reverse transcription efficiency at high temperatures.

High Risk Human Papilloma Virus Genotypes in Kurdistan Region in Patients with Vaginal Discharge.

Science.gov (United States)

Hussein, Nawfal R; Balatay, Amer A; Assafi, Mahde S; AlMufty, Tamara Abdulezel

2016-01-01

The human papilloma virus (HPV) is considered as the major risk factor for the development of cervical cancer. This virus is of different genotypes and generally can be classified into high and low risk types. To determine the rate of high risk HPV genotypes in women with vaginal discharge and lower abdominal pain in Kurdistan region, Iraq. Cervical swabs were taken from 104 women. DNA was extracted and the polymerase chain reaction (PCR) technique was used to determine the presence of high risk genotypes. It was found that 13/104 (12.5%) of the samples were positive for high risk HPV genotypes. Amongst those who were positive, 4/13 (30.7%) were typed as genotype 16 and 7/13 (53.8%) showed mixed genotyping. On the other hand, genotypes 53 and 56 were found in only one sample each. High risk HPV genotypes are not uncommon and further community based study is needed to determine the prevalence of HPV and its genotypes and plan for prevention of infection.

Meat consumption is a major risk factor for hepatitis E virus infection

NARCIS (Netherlands)

Slot, Ed; Zaaijer, Hans L.; Molier, Michel; van den Hurk, Katja; Prinsze, Femmeke; Hogema, Boris M.

2017-01-01

The incidence of autochthonous hepatitis E virus genotype 3 (HEV gt3) infections in Western Europe is high. Although pigs are a major reservoir of the virus, the exact sources and transmission route(s) of HEV gt3 to humans remain unclear. To determine the role of meat consumption at a population

High Prevalence of Escherichia coli-Producing CTX-M-15 Extended-Spectrum Beta-Lactamases in Poultry and Human Clinical Isolates in Romania.

Science.gov (United States)

Maciuca, Iuliana E; Williams, Nicola J; Tuchilus, Cristina; Dorneanu, Olivia; Guguianu, Eleonora; Carp-Carare, Catalin; Rimbu, Cristina; Timofte, Dorina

2015-12-01

Use of antibiotics in food animals may contribute to development and spread of resistant organisms, particularly so in some countries. The aim of this study was two-fold; first, to establish the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in chicken production in a region within Romania. Second, to study the relatedness of ESBL-producing E. coli isolates recovered from broilers, abattoir workers where the chickens were slaughtered and from the human clinical specimens from two regional hospitals. The results indicated a very high (69%) rate of carriage of ESBL and AmpC-producing E. coli in chickens with 36% CTX-M producers. Sequencing showed that chickens in Romania have the highest worldwide prevalence (53%) of blaCTX-M-15 reported in poultry E. coli isolates. The majority (53%) of the extended-spectrum cephalosporin-resistant E. coli carried plasmid-mediated blaampC genes, mostly blaCMY-2 type, one of the highest prevalences reported in Europe. The predominant CTX-M type found in the human clinical E. coli isolates was blaCTX-M-15 and most isolates coharbored blaOXA-1, blaTEM, and aac(6')-ib-cr. The majority (60%) of the human clinical isolates belonged to the pandemic virulent clone B2-ST131. The clonal relationship between broiler and the human CTX-M-producing E. coli isolates was assessed by macrorestriction pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST), which indicated strain diversity with no common STs found between human and poultry isolates. Moreover, IncI1 was the most prevalent replicon found in broiler ESBL-producing E. coli isolates and also in transconjugants, indicating that plasmids and not clonal spread may play a role in the transfer of blaCTX-M genes. This study identifies a high prevalence of ESBL-producing E. coli from broiler chickens in Romania with a high occurrence incidence of blaCTX-M-15, which reflects the main ESBL type found in human E. coli infections in this

Methodology for and the determination of the major constituents and metabolites of the Amazonian botanical medicine ayahuasca in human urine.

Science.gov (United States)

McIlhenny, Ethan H; Riba, Jordi; Barbanoj, Manel J; Strassman, Rick; Barker, Steven A

2011-09-01

Ayahuasca, also known as caapi or yage among various South American groups, holds a highly esteemed and millennia-old position in these cultures' medical and religious pharmacopeia. There is now an increasing interest in the potential for modern medical applications of ayahuasca, as well as concerns regarding its increasing potential for abuse. Toxicological and clinical research to address these issues will require information regarding its metabolism and clearance. Thus, a rapid, sensitive and specific method for characterization and quantitation of the major constituents and of the metabolites of ayahuasca in urine is needed. The present research provides a protocol for conducting such analyses. The characteristics of the method, conducted by sample dilution and using HPLC-electrospray ionization (ESI)-selected reaction monitoring (SRM)-tandem mass spectrometry, are presented. The application of the analytical protocol to urine samples collected from three individuals that were administered ayahuasca has also been demonstrated. The data show that the major metabolite of the hallucinogenic component of ayahuasca, N,N-dimethyltryptamine (DMT), is the corresponding N-oxide, the first time this metabolite has been described in in vivo studies in humans. Further, very little DMT was detected in urine, despite the inhibition of monoamine oxidase afforded by the presence of the harmala alkaloids in ayahuasca. The major harmala alkaloid excreted was tetrahydroharmine. Other excretion products and metabolites were also identified and quantified. The method described would be suitable for use in further toxicological and clinical research on ayahuasca. Copyright © 2010 John Wiley & Sons, Ltd.

Investigation of prostaglandin levels in human milk after high performance liquid chromatography purification

International Nuclear Information System (INIS)

Wu-Wang, C.Y.; Neu, J.

1986-01-01

This study was conducted to investigate five prostaglandins (PGs), i.e. PGE 2 , PGF/sub 2α/, 13-14-dihydro-15-keto-PGF/sub 2α/ (DHKF/sub 2α/), thromboxane B 2 (TXB 2 ) and 6-keto-PGF/sub 1α/), measured by (RIA) after C 18 Sep-Pak extraction and reverse phase high performance liquid chromatography (HPLC). Two trials were performed. In each trial, 3-5 mature human milk samples were pooled, acidified and extracted for PGs. The separation of PGs by HPLC was achieved by using an isocratic solvent system of acetonitrile/water (pH 3.0) (32/68, V/V). The PG levels from the two trials were determined and averaged after monitoring the recoveries. The results indicate that PGE 2 and DHKF/sub 2α/ are the two major PGs found in extracted human milk. However, after HPLC purification, no predominant PG is found and the levels of all the five PGs are much lower compared to the extracted sample. Since the immunoreactive material was also detected in HPLC fractions not within the PG peak, low levels of PG found in human milk after HPLC is likely due to the purification step removing the bulk of nonspecific immunoreactive substances present in the sample

Human Rights, Human Needs, Human Development, Human Security

OpenAIRE

Gasper, Des

2009-01-01

Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

HUMAN CAPITAL: Major Human Capital Challenges at SEC and Key Trade Agencies

National Research Council Canada - National Science Library

Hillman, Richard

2002-01-01

.... The leadership provided by this subcommittee and the Senate Committee on Governmental Affairs has been especially important in focusing attention on the federal government s human capital challenges.

Student and high-school characteristics related to completing a science, technology, engineering or mathematics (STEM) major in college

Science.gov (United States)

LeBeau, Brandon; Harwell, Michael; Monson, Debra; Dupuis, Danielle; Medhanie, Amanuel; Post, Thomas R.

2012-04-01

Background: The importance of increasing the number of US college students completing degrees in science, technology, engineering or mathematics (STEM) has prompted calls for research to provide a better understanding of factors related to student participation in these majors, including the impact of a student's high-school mathematics curriculum. Purpose: This study examines the relationship between various student and high-school characteristics and completion of a STEM major in college. Of specific interest is the influence of a student's high-school mathematics curriculum on the completion of a STEM major in college. Sample: The sample consisted of approximately 3500 students from 229 high schools. Students were predominantly Caucasian (80%), with slightly more males than females (52% vs 48%). Design and method: A quasi-experimental design with archival data was used for students who enrolled in, and graduated from, a post-secondary institution in the upper Midwest. To be included in the sample, students needed to have completed at least three years of high-school mathematics. A generalized linear mixed model was used with students nested within high schools. The data were cross-sectional. Results: High-school predictors were not found to have a significant impact on the completion of a STEM major. Significant student-level predictors included ACT mathematics score, gender and high-school mathematics GPA. Conclusions: The results provide evidence that on average students are equally prepared for the rigorous mathematics coursework regardless of the high-school mathematics curriculum they completed.

Big Five personality group differences across academic majors

DEFF Research Database (Denmark)

Vedel, Anna

2016-01-01

During the past decades, a number of studies have explored personality group differences in the Big Five personality traits among students in different academic majors. To date, though, this research has not been reviewed systematically. This was the aim of the present review. A systematic...... literature search identified twelve eligible studies yielding an aggregated sample size of 13,389. Eleven studies reported significant group differences in one or multiple Big Five personality traits. Consistent findings across studies were that students of arts/humanities and psychology scored high...... on Conscientiousness. Effect sizes were calculated to estimate the magnitude of the personality group differences. These effect sizes were consistent across studies comparing similar pairs of academic majors. For all Big Five personality traits medium effect sizes were found frequently, and for Openness even large...

HUMAN CAPITAL: Major Human Capital Challenges at SEC and Key Trade Agencies

National Research Council Canada - National Science Library

Hillman, Richard

2002-01-01

We appreciate the opportunity to appear here today to discuss the human capital challenges facing the agencies that play key roles in monitoring publicly traded companies and enforcing our nation's trade laws...

PECULIARITIES OF AN INDIVIDUAL APPROACH TO HIGH SCHOOL STUDENTS MAJORING IN TECHNOLOGY

Directory of Open Access Journals (Sweden)

Andriy Uruskyi

2016-05-01

Full Text Available The features of the methodology of the implementation of an individual approach to high school students majoring in technology are analysed. The main stages of the implementation have been defined as the analysis of the individual student characteristics; grouping 10–11 grade students; usage of the modern informational and communicational techniques and a set of facilities of differentiated studying. The examples of the differentiated tasks for different phases of the high school training such as providing training material by teachers; academic progress monitoring; self-studying materials; fulfilling tasks of practical (laboratory and practical works; goods manufacturing; carrying out creative projects have been provided.

A high-quality human reference panel reveals the complexity and distribution of genomic structural variants

NARCIS (Netherlands)

Hehir-Kwa, J.Y.; Marschall, T.; Kloosterman, W.P.; Francioli, L.C.; Baaijens, J.A.; Dijkstra, L.J.; Abdellaoui, A.; Koval, V.; Thung, D.T.; Wardenaar, R.; Renkens, I.; Coe, B.P.; Deelen, P.; de Ligt, J.; Lameijer, E.W.; Dijk, F.; Hormozdiari, F.; Uitterlinden, A.G.; van Duijn, C.M.; Eichler, E.E.; Bakker, P.I.W.; Swertz, M.A.; Wijmenga, C.; van Ommen, G.J.B; Slagboom, P.E.; Boomsma, D.I.; Schönhuth, A.; Ye, K.; Guryev, V.

2016-01-01

Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority of studies provide neither a global view of the full spectrum of these variants nor integrate them into reference panels of genetic

[SWOT Analysis of the National Survey on Current Status of Major Human Parasitic Diseases in China].

Science.gov (United States)

ZHU, Hui-hui; ZHOU, Chang-hai; CHEN, Ying-dan; ZANG, Wei; XIAO, Ning; ZHOU, Xiao-nong

2015-10-01

The National Survey on Current Status of Major Human Parasitic Diseases in China has been carried out since 2014 under the organization of the National Health and Family Planning Commission of the People's Republic of China. The National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (NIPD, China CDC) provided technical support and was responsible for quality control in this survey. This study used SWOT method to analyze the strengths, weaknesses, opportunities and threats that were encountered by he NIPD, China CDC during the completion of the survey. Accordingly, working strategies were proposed to facilitate the future field work.

Foodstuff analyses show that seafood and water are major perfluoroalkyl acids (PFAAs) sources to humans in Korea

Energy Technology Data Exchange (ETDEWEB)

Heo, Jin-Ju; Lee, Ji-Woo [Department of Civil and Environmental Engineering, Pusan National University, Busan, 609-735 (Korea, Republic of); Kim, Seung-Kyu [Department of Marine Science, College of Natural Sciences, Incheon National University, Incheon, 406-772 (Korea, Republic of); Oh, Jeong-Eun, E-mail: jeoh@pusan.ac.kr [Department of Civil and Environmental Engineering, Pusan National University, Busan, 609-735 (Korea, Republic of)

2014-08-30

Graphical abstract: - Highlights: • 16 PFAAs in 397 samples of 66 food types and 34 tap water samples were analyzed. • Dietary exposure to PFAAs was estimated by using the PFAAs measured concentrations. • The major contributors of PFAAs dietary exposure were confirmed. - Abstract: We measured concentrations of PFAAs in 397 foods, of 66 types, in Korea, and determined the daily human dietary PFAAs intake and the contribution of each foodstuff to that intake. The PFAAs concentration in the 66 different food types ranged from below the detection limit to 48.3 ng/g. Perfluorooctane sulfonate (PFOS) and long-chain perfluorocarboxylic acids (PFCAs) were the dominant PFAAs in fish, shellfish, and processed foods, while perfluorooctanoic acid (PFOA) and short-chain PFCAs dominated dairy foodstuffs and beverages. The Korean adult dietary intake ranges, estimated for a range of scenarios, were 0.60–3.03 and 0.17–1.68 ng kg{sup −1} bw d{sup −1} for PFOS and PFOA, respectively, which were lower than the total daily intake limits suggested by European Food Safety Authority (PFOS: 150 ng kg{sup −1} bw d{sup −1}; PFOA: 1500 ng kg{sup −1} bw d{sup −1}). The major contributors to PFAAs dietary exposure varied with subject age and PFAAs. For example, fish was a major contributor of PFOS but dairy foods were major contributors of PFOA. However, tap water was a major contributor to PFOA intake when it was the main source of drinking water (rather than bottled water)

Foodstuff analyses show that seafood and water are major perfluoroalkyl acids (PFAAs) sources to humans in Korea

International Nuclear Information System (INIS)

Heo, Jin-Ju; Lee, Ji-Woo; Kim, Seung-Kyu; Oh, Jeong-Eun

2014-01-01

Graphical abstract: - Highlights: • 16 PFAAs in 397 samples of 66 food types and 34 tap water samples were analyzed. • Dietary exposure to PFAAs was estimated by using the PFAAs measured concentrations. • The major contributors of PFAAs dietary exposure were confirmed. - Abstract: We measured concentrations of PFAAs in 397 foods, of 66 types, in Korea, and determined the daily human dietary PFAAs intake and the contribution of each foodstuff to that intake. The PFAAs concentration in the 66 different food types ranged from below the detection limit to 48.3 ng/g. Perfluorooctane sulfonate (PFOS) and long-chain perfluorocarboxylic acids (PFCAs) were the dominant PFAAs in fish, shellfish, and processed foods, while perfluorooctanoic acid (PFOA) and short-chain PFCAs dominated dairy foodstuffs and beverages. The Korean adult dietary intake ranges, estimated for a range of scenarios, were 0.60–3.03 and 0.17–1.68 ng kg −1 bw d −1 for PFOS and PFOA, respectively, which were lower than the total daily intake limits suggested by European Food Safety Authority (PFOS: 150 ng kg −1 bw d −1 ; PFOA: 1500 ng kg −1 bw d −1 ). The major contributors to PFAAs dietary exposure varied with subject age and PFAAs. For example, fish was a major contributor of PFOS but dairy foods were major contributors of PFOA. However, tap water was a major contributor to PFOA intake when it was the main source of drinking water (rather than bottled water)

Pleistocene Mitochondrial Genomes Suggest a Single Major Dispersal of Non-Africans and a Late Glacial Population Turnover in Europe

NARCIS (Netherlands)

Posth, Cosimo; Renaud, Gabriel; Mittnik, Alissa; Drucker, Dorothée G; Rougier, Hélène; Cupillard, Christophe; Valentin, Frédérique; Thevenet, Corinne; Furtwängler, Anja; Wißing, Christoph; Francken, Michael; Malina, Maria; Bolus, Michael; Lari, Martina; Gigli, Elena; Capecchi, Giulia; Crevecoeur, Isabelle; Beauval, Cédric; Flas, Damien; Germonpré, Mietje; van der Plicht, Johannes; Cottiaux, Richard; Gély, Bernard; Ronchitelli, Annamaria; Wehrberger, Kurt; Grigourescu, Dan; Svoboda, Jiří; Semal, Patrick; Caramelli, David; Bocherens, Hervé; Harvati, Katerina; Conard, Nicholas J; Haak, Wolfgang; Powell, Adam; Krause, Johannes

2016-01-01

How modern humans dispersed into Eurasia and Australasia, including the number of separate expansions and their timings, is highly debated [1, 2]. Two categories of models are proposed for the dispersal of non-Africans: (1) single dispersal, i.e., a single major diffusion of modern humans across

Identifying areas of high risk of human exposure to coccidioidomycosis in Texas using serology data from dogs.

Science.gov (United States)

Gautam, R; Srinath, I; Clavijo, A; Szonyi, B; Bani-Yaghoub, M; Park, S; Ivanek, R

2013-03-01

Coccidioidomycosis or Valley Fever (VF) is an emerging soil-borne fungal zoonosis affecting humans and animals. Most non-human cases of VF are found in dogs, which we hypothesize may serve as sentinels for estimating the human exposure risk. The objective of this study is to use the spatial and temporal distribution and clusters of dogs seropositive for VF to define the geographic area in Texas where VF is endemic, and thus presents a higher risk of exposure to humans. The included specimens were seropositive dogs tested at a major diagnostic laboratory between 1999 and 2009. Data were aggregated by zip code and smoothed by empirical Bayesian estimation to develop an isopleth map of VF seropositive rates using kriging. Clusters of seropositive dogs were identified using the spatial scan test. Both the isopleth map and the scan test identified an area with a high rate of VF-seropositive dogs in the western and southwestern parts of Texas (relative risk = 31). This location overlapped an area that was previously identified as a potential endemic region based on human surveys. Together, these data suggest that dogs may serve as sentinels for estimating the risk of human exposure to VF. © 2012 Blackwell Verlag GmbH.

Major histocompatibility complex-unrestricted cytolytic activity of human T cells: analysis of precursor frequency and effector phenotype

International Nuclear Information System (INIS)

Patel, S.S.; Thiele, D.L.; Lipsky, P.E.

1987-01-01

The frequency and phenotype of human T cells that mediate major histocompatibility complex (MHC)-unrestricted cytolysis were analyzed. T cell clones were generated by culturing adherent cell-depleted peripheral blood mononuclear cells at a density of 0.3 cell/well with phytohemagglutinin, recombinant interleukin 2 (rIL-2), and irradiated autologous peripheral blood mononuclear cells and/or Epstein-Barr virus-transformed lymphoblastoid cell lines. All of the 198 clones generated by this method were T cells (CD2 + , CD3 + , CD4 + or CD2 + , CD3 + , CD8 + ) that possessed potent lytic activity against K562, an erythroleukemia line sensitive to lysis by human natural killer cells, and Cur, a renal carcinoma cell line resistant to human natural killer activity. Cytolysis, measured by 51 Cr release, was MHC-unrestricted, since the clones were able to lyse MHC class I or class II negative targets, as well as MHC class I and class II negative targets. Although the clones produced tissue necrosis factor/lymphotoxin-like molecules, lysis of Cur of K562 was not mediated by a soluble factor secreted by the clones. These data indicate that the capacity for MHC-unrestricted tumoricidal activity and expression of NKH1 and CD11b, but not CD 16, are properties common to all or nearly all human peripheral blood-derived T cell clones regardless of CD4 or CD8 phenotype

Highly Pathogenic Avian Influenza A(H5N1) Viruses at the Animal-Human Interface in Vietnam, 2003-2010.

Science.gov (United States)

Creanga, Adrian; Hang, Nguyen Le Khanh; Cuong, Vuong Duc; Nguyen, Ha T; Phuong, Hoang Vu Mai; Thanh, Le Thi; Thach, Nguyen Co; Hien, Pham Thi; Tung, Nguyen; Jang, Yunho; Balish, Amanda; Dang, Nguyen Hoang; Duong, Mai Thuy; Huong, Ngo Thu; Hoa, Do Ngoc; Tho, Nguyen Dang; Klimov, Alexander; Kapella, Bryan K; Gubareva, Larisa; Kile, James C; Hien, Nguyen Tran; Mai, Le Quynh; Davis, C Todd

2017-09-15

Mutation and reassortment of highly pathogenic avian influenza A(H5N1) viruses at the animal-human interface remain a major concern for emergence of viruses with pandemic potential. To understand the relationship of H5N1 viruses circulating in poultry and those isolated from humans, comprehensive phylogenetic and molecular analyses of viruses collected from both hosts in Vietnam between 2003 and 2010 were performed. We examined the temporal and spatial distribution of human cases relative to H5N1 poultry outbreaks and characterized the genetic lineages and amino acid substitutions in each gene segment identified in humans relative to closely related viruses from avian hosts. Six hemagglutinin clades and 8 genotypes were identified in humans, all of which were initially identified in poultry. Several amino acid mutations throughout the genomes of viruses isolated from humans were identified, indicating the potential for poultry viruses infecting humans to rapidly acquire molecular markers associated with mammalian adaptation and antiviral resistance. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Human major histocompatibility complex contains a minimum of 19 genes between the complement cluster and HLA-B

International Nuclear Information System (INIS)

Spies, T.; Bresnahan, M.; Strominger, J.L.

1989-01-01

A 600-kilobase (kb) DNA segment from the human major histocompatibility complex (MHC) class III region was isolated by extension of a previous 435-kb chromosome walk. The contiguous series of cloned overlapping cosmids contains the entire 555-kb interval between C2 in the complement gene cluster and HLA-B. This region is known to encode the tumor necrosis factors (TNFs) α and β, B144, and the major heat shock protein HSP70. Moreover, a cluster of genes, BAT1-BAT5 (HLA-B-associated transcripts) have been localized in the vicinity of the genes for TNFα and TNFβ. An additional four genes were identified by isolation of corresponding cDNA clones with cosmid DNA probes. These genes for BAT6-BAT9 were mapped near the gene for C2 within a 120-kb region that includes a HSP70 gene pair. These results, together with complementary data from a similar recent study, indicated the presence of a minimum of 19 genes within the C2-HLA-B interval of the MHC class III region. Although the functional properties of most of these genes are yet unknown, they may be involved in some aspects of immunity. This idea is supported by the genetic mapping of the hematopoietic histocompatibility locus-1 (Hh-1) in recombinant mice between TNFα and H-2S, which is homologous to the complement gene cluster in humans

Apamin does not inhibit human cardiac Na+ current, L-type Ca2+ current or other major K+ currents.

Directory of Open Access Journals (Sweden)

Chih-Chieh Yu

Full Text Available Apamin is commonly used as a small-conductance Ca2+-activated K+ (SK current inhibitor. However, the specificity of apamin in cardiac tissues remains unclear.To test the hypothesis that apamin does not inhibit any major cardiac ion currents.We studied human embryonic kidney (HEK 293 cells that expressed human voltage-gated Na+, K+ and Ca2+ currents and isolated rabbit ventricular myocytes. Whole-cell patch clamp techniques were used to determine ionic current densities before and after apamin administration.Ca2+ currents (CACNA1c+CACNB2b were not affected by apamin (500 nM (data are presented as median [25th percentile;75th percentile] (from -16 [-20;-10] to -17 [-19;-13] pA/pF, P = NS, but were reduced by nifedipine to -1.6 [-3.2;-1.3] pA/pF (p = 0.008. Na+ currents (SCN5A were not affected by apamin (from -261 [-282;-145] to -268 [-379;-132] pA/pF, P = NS, but were reduced by flecainide to -57 [-70;-47] pA/pF (p = 0.018. None of the major K+ currents (IKs, IKr, IK1 and Ito were inhibited by 500 nM of apamin (KCNQ1+KCNE1, from 28 [20]; [37] to 23 [18]; [32] pA/pF; KCNH2+KCNE2, from 28 [24]; [30] to 27 [24]; [29] pA/pF; KCNJ2, from -46 [-48;-40] to -46 [-51;-35] pA/pF; KCND3, from 608 [505;748] to 606 [454;684]. Apamin did not inhibit the INa or ICaL in isolated rabbit ventricular myocytes (INa, from -67 [-75;-59] to -68 [-71;-59] pA/pF; ICaL, from -16 [-17;-14] to -14 [-15;-13] pA/pF, P = NS for both.Apamin does not inhibit human cardiac Na+ currents, L-type Ca2+ currents or other major K+ currents. These findings indicate that apamin is a specific SK current inhibitor in hearts as well as in other organs.

High-sensitive LC-MS/MS method for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma: application to microdose clinical trials of mirodenafil.

Science.gov (United States)

Cho, Doo-Yeoun; Bae, Soo Hyeon; Shon, Ji-Hong; Bae, Soo Kyung

2013-03-01

A high-sensitivity LC/MS/MS method was developed and validated for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma. Mirodenafil, SK-3541, and udenafil as an internal standard were extracted from plasma samples with methyl tert-butyl ether. Chromatographic separation was performed on a Luna phenyl-hexyl column (100 × 2.0 mm) with an isocratic mobile phase consisting of 5 mM ammonium formate and ACN (23:77, v/v) at a flow rate of 0.35 mL/min. Detection and quantification were performed using a mass spectrometer in selected reaction monitoring mode with positive ESI at m/z 532.3 → 296.1 for mirodenafil, m/z 488.1 → 296.1 for SK-3541, and m/z 517.3 → 283.2 for udenafil. The calibration curves were linear over a concentration range of 2-500 pg/mL using 0.5 mL plasma for the microdose of mirodenafil (100 μg). Analytical method validation of the clinical dose (100 mg), with a calibration curve range of 2-500 ng/mL using 0.025-mL plasma, was also conducted. The other LC-MS/MS conditions were similar to those used for the microdosing. Each method was applied successfully to pharmacokinetic studies after a microdose or clinical dose of mirodenafil to six healthy Korean male volunteers. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human reliability in high dose rate afterloading radiotherapy based on FMECA

International Nuclear Information System (INIS)

Deng Jun; Fan Yaohua; Yue Baorong; Wei Kedao; Ren Fuli

2012-01-01

Objective: To put forward reasonable and feasible recommendations against the procedure with relative high risk during the high dose rate (HDR) afterloading radiotherapy, so as to enhance its clinical application safety, through studying the human reliability in the process of carrying out the HDR afterloading radiotherapy. Methods: Basic data were collected by on-site investigation and process analysis as well as expert evaluation. Failure mode, effect and criticality analysis (FMECA) employed to study the human reliability in the execution of HDR afterloading radiotherapy. Results: The FMECA model of human reliability for HDR afterloading radiotherapy was established, through which 25 procedures with relative high risk index were found,accounting for 14.1% of total 177 procedures. Conclusions: FMECA method in human reliability study for HDR afterloading radiotherapy is feasible. The countermeasures are put forward to reduce the human error, so as to provide important basis for enhancing clinical application safety of HDR afterloading radiotherapy. (authors)

Functional physiology of the human terminal antrum defined by high-resolution electrical mapping and computational modeling.

Science.gov (United States)

Berry, Rachel; Miyagawa, Taimei; Paskaranandavadivel, Niranchan; Du, Peng; Angeli, Timothy R; Trew, Mark L; Windsor, John A; Imai, Yohsuke; O'Grady, Gregory; Cheng, Leo K

2016-11-01

High-resolution (HR) mapping has been used to study gastric slow-wave activation; however, the specific characteristics of antral electrophysiology remain poorly defined. This study applied HR mapping and computational modeling to define functional human antral physiology. HR mapping was performed in 10 subjects using flexible electrode arrays (128-192 electrodes; 16-24 cm 2 ) arranged from the pylorus to mid-corpus. Anatomical registration was by photographs and anatomical landmarks. Slow-wave parameters were computed, and resultant data were incorporated into a computational fluid dynamics (CFD) model of gastric flow to calculate impact on gastric mixing. In all subjects, extracellular mapping demonstrated normal aboral slow-wave propagation and a region of increased amplitude and velocity in the prepyloric antrum. On average, the high-velocity region commenced 28 mm proximal to the pylorus, and activation ceased 6 mm from the pylorus. Within this region, velocity increased 0.2 mm/s per mm of tissue, from the mean 3.3 ± 0.1 mm/s to 7.5 ± 0.6 mm/s (P human terminal antral contraction is controlled by a short region of rapid high-amplitude slow-wave activity. Distal antral wave acceleration plays a major role in antral flow and mixing, increasing particle strain and trituration. Copyright © 2016 the American Physiological Society.

An α-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major.

Directory of Open Access Journals (Sweden)

Eva Iniguez

2017-10-01

Full Text Available Protozoan parasites from the genus Leishmania cause broad clinical manifestations known as leishmaniases, which affect millions of people worldwide. Cutaneous leishmaniasis (CL, caused by L. major, is one the most common forms of the disease in the Old World. There is no preventive or therapeutic human vaccine available for L. major CL, and existing drug treatments are expensive, have toxic side effects, and resistant parasite strains have been reported. Hence, further therapeutic interventions against the disease are necessary. Terminal, non-reducing, and linear α-galactopyranosyl (α-Gal epitopes are abundantly found on the plasma membrane glycolipids of L. major known as glycoinositolphospholipids. The absence of these α-Gal epitopes in human cells makes these glycans highly immunogenic and thus potential targets for vaccine development against CL.Here, we evaluated three neoglycoproteins (NGPs, containing synthetic α-Gal epitopes covalently attached to bovine serum albumin (BSA, as vaccine candidates against L. major, using α1,3-galactosyltransferase-knockout (α1,3GalT-KO mice. These transgenic mice, similarly to humans, do not express nonreducing, linear α-Gal epitopes in their cells and are, therefore, capable of producing high levels of anti-α-Gal antibodies. We observed that Galα(1,6Galβ-BSA (NGP5B, but not Galα(1,4Galβ-BSA (NGP12B or Galα(1,3Galα-BSA (NGP17B, was able to significantly reduce the size of footpad lesions by 96% in comparison to control groups. Furthermore, we observed a robust humoral and cellular immune response with production of high levels of protective lytic anti-α-Gal antibodies and induction of Th1 cytokines.We propose that NGP5B is an attractive candidate for the study of potential synthetic α-Gal-neoglycoprotein-based vaccines against L. major infection.

Evaluation of concentrations of major and trace elements in human lung using INAA and PIXE

International Nuclear Information System (INIS)

Altaf, W.J.; Spyrou, N.M.

1997-01-01

The elemental concentrations of Br, Ca, Ce, Cl, Co, Cr, Cs, F, Fe, Hf, K, Mg, Mn, Na, O, Rb, Sb, Sc, Se, V and Zn in 15 human lung autopsy samples, taken from subjects aged more than fifty years old, were determined by instrumental neutron activation analysis (INAA) using reactor neutrons in conjunction with a high resolution detection system. Two modes of irradiation and counting were applied; namely cyclic neutron activation analysis (CNAA) and conventional neutron activation analysis. Proton induced X-ray emission (PIXE) analysis, using a proton beam emerging from a 2 MV Van de Graaff accelerator, was additionally employed and Ge, Ni, P and Ti were also identified in the lung tissue. Detection of the X-ray spectra was performed using a high resolution Si(Li) semiconductor. The relevance of these results, including a comparison between the concentrations of elements measured in a pig's lung using CNAA and those found in the human lung is discussed. (author)

A high-throughput inhibition screening of major human cytochrome P450 enzymes using an in vitro cocktail and liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Qin, Chong-Zhen; Ren, Xian; Tan, Zhi-Rong; Chen, Yao; Yin, Ji-Ye; Yu, Jing; Qu, Jian; Zhou, Hong-Hao; Liu, Zhao-Qian

2014-02-01

A sensitive and high-throughput inhibition screening liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of five probe metabolites (7-hydroxycoumarin, CYP2A6; 4-hydroxytolbutamide, CYP2C9; 4'-hydroxymephenytoin, CYP2C19; α-hydroxymetoprolol, CYP2D6; and 1-hydroxymidazolam, CYP3A4) for in vitro cytochrome P450 activity determination in human liver microsome and recombinant. All the metabolites and the internal standard, tramadol, were separated on a Waters 2695 series liquid chromatograph with a Phenomenex Luna C18 column (150 × 2.0 mm, 5 µm). Quality control samples and a positive control CYP inhibitor were included in the method. The IC50 values determined for typical CYP inhibitors were reproducible and in agreement with the literature. The method was selective and showed good accuracy (99.13-103.37%), and inter-day (RSD high-quality and -throughput cocktail provides suitable information in drug discovery and screening for new drug entities. Copyright © 2013 John Wiley & Sons, Ltd.

Inhibitory Effects of Trapping Agents of Sulfur Drug Reactive Intermediates against Major Human Cytochrome P450 Isoforms

Directory of Open Access Journals (Sweden)

Jasleen K. Sodhi

2017-07-01

Full Text Available In some cases, the formation of reactive species from the metabolism of xenobiotics has been linked to toxicity and therefore it is imperative to detect potential bioactivation for candidate drugs during drug discovery. Reactive species can covalently bind to trapping agents in in vitro incubations of compound with human liver microsomes (HLM fortified with β-nicotinamide adenine dinucleotide phosphate (NADPH, resulting in a stable conjugate of trapping agent and reactive species, thereby facilitating analytical detection and providing evidence of short-lived reactive metabolites. Since reactive metabolites are typically generated by cytochrome P450 (CYP oxidation, it is important to ensure high concentrations of trapping agents are not inhibiting the activities of CYP isoforms. Here we assessed the inhibitory properties of fourteen trapping agents against the major human CYP isoforms (CYP1A2, 2C9, 2C19, 2D6 and 3A. Based on our findings, eleven trapping agents displayed inhibition, three of which had IC50 values less than 1 mM (2-mercaptoethanol, N-methylmaleimide and N-ethylmaleimide (NEM. Three trapping agents (dimedone, N-acetyl-lysine and arsenite did not inhibit CYP isoforms at concentrations tested. To illustrate effects of CYP inhibition by trapping agents on reactive intermediate trapping, an example drug (ticlopidine and trapping agent (NEM were chosen for further studies. For the same amount of ticlopidine (1 μM, increasing concentrations of the trapping agent NEM (0.007–40 mM resulted in a bell-shaped response curve of NEM-trapped ticlopidine S-oxide (TSO-NEM, due to CYP inhibition by NEM. Thus, trapping studies should be designed to include several concentrations of trapping agent to ensure optimal trapping of reactive metabolites.

High pressure inactivation of human norovirus-like particles: evidence that the capsid of human norovirus is highly pressure resistant

Science.gov (United States)

High pressure processing (HPP) is a promising non-thermal technology to inactivate foodborne viruses. However, the effectiveness of HPP on inactivating human norovirus (HuNoV), the leading cause of acute gastroenteritis, is unknown because it cannot be propagated in cell culture. Therefore, developi...

Human genetics and genomics a decade after the release of the draft sequence of the human genome

Science.gov (United States)

2011-01-01

Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade. PMID:22155605

Major Development Communication Paradigms and Practices ...

African Journals Online (AJOL)

info

major paradigms of development and communication practices on graphic ... mobilize, educate and persuade target audience to support human development ... facilitates the understanding of the themes, issues and facts of a campaign.

Condition-dependent clutch desertion in Great Tit (Parus major) females subjected to human disturbance

OpenAIRE

2011-01-01

Abstract Nest desertion behaviour in relation to body condition and timing of breeding was studied in Great Tit (Parus major) females during two breeding seasons. Desertion, most likely unintentionally provoked by catching females during the incubation period, occurred at a very high rate with 41.2 and 25.6% of deserted first clutches in the two study years. The association between desertion probability, body condition (index calculated as residuals from the regression of body mass...

Managing major chemical accidents in China: Towards effective risk information

International Nuclear Information System (INIS)

He Guizhen; Zhang Lei; Lu Yonglong; Mol, Arthur P.J.

2011-01-01

Chemical industries, from their very inception, have been controversial due to the high risks they impose on safety of human beings and the environment. Recent decades have witnessed increasing impacts of the accelerating expansion of chemical industries and chemical accidents have become a major contributor to environmental and health risks in China. This calls for the establishment of an effective chemical risk management system, which requires reliable, accurate and comprehensive data in the first place. However, the current chemical accident-related data system is highly fragmented and incomplete, as different responsible authorities adopt different data collection standards and procedures for different purposes. In building a more comprehensive, integrated and effective information system, this article: (i) reviews and assesses the existing data sources and data management, (ii) analyzes data on 976 recorded major hazardous chemical accidents in China over the last 40 years, and (iii) identifies the improvements required for developing integrated risk management in China.

Monitoring of heavy metal levels in the major rivers and in residents' blood in Zhenjiang City, China, and assessment of heavy metal elimination via urine and sweat in humans.

Science.gov (United States)

Sheng, Jianguo; Qiu, Wenhui; Xu, Bentuo; Xu, Hui; Tang, Chong

2016-06-01

The coastal areas of China face great challenges, owing to heavy metal contamination caused by rapid industrialization and urbanization. To our knowledge, this study is the first report of the levels of heavy metals in the major rivers of Zhenjiang, one of the most important cities of the Yangtze River Delta in China. In addition, we measured heavy metal levels in the blood of 76 residents of Zhenjiang. The results suggest that the presence of heavy metals in the blood may threaten human health and the distribution appeared to correspond to most highly populated areas and/or areas with high traffic. We also found that the concentration of heavy metals in human blood showed an accumulation effect with increase in age. Moreover, the levels of most heavy metals were lower in participants who regularly exercised than in those who did not. We studied heavy metal levels in the urine and sweat of another 17 volunteers to monitor the elimination of bioaccumulated heavy metal. Heavy metals were found in the urine and sweat of all the 17 participants and were more concentrated in sweat. Induced micturition and sweating appear to be potential methods for the elimination of heavy metals from the human body.

Involvement of the major histocompatibility complex region in the genetic regulation of circulating CD8 T-cell numbers in humans.

Science.gov (United States)

Cruz, E; Vieira, J; Gonçalves, R; Alves, H; Almeida, S; Rodrigues, P; Lacerda, R; Porto, G

2004-07-01

Variability in T-lymphocyte numbers is partially explained by a genetic regulation. From studies in animal models, it is known that the Major Histocompatibility Complex (MHC) is involved in this regulation. In humans, this has not been shown yet. The objective of the present study was to test the hypothesis that genes in the MHC region influence the regulation of T-lymphocyte numbers. Two approaches were used. Association studies between T-cell counts (CD4(+) and CD8(+)) or total lymphocyte counts and HLA class I alleles (A and B) or mutations in the HFE (C282Y and H63D), the hemochromatosis gene, in an unrelated population (n = 264). A second approach was a sibpair correlation analysis of the same T-cell counts in relation to HLA-HFE haplotypes in subjects belonging to 48 hemochromatosis families (n = 456 sibpairs). In the normal population, results showed a strong statistically significant association of the HLA-A*01 with high numbers of CD8(+) T cells and a less powerful association with the HLA-A*24 with low numbers of CD8(+) T cells. Sibpair correlations revealed the most significant correlation for CD8(+) T-cell numbers for sibpairs with HLA-HFE-identical haplotypes. This was not observed for CD4(+) T cells. These results show that the MHC region is involved in the genetic regulation of CD8(+) T-cell numbers in humans. Identification of genes responsible for this control may have important biological and clinical implications.

Anti-apoptotic BFL-1 is the major effector in activation-induced human mast cell survival.

Directory of Open Access Journals (Sweden)

Maria Ekoff

Full Text Available Mast cells are best known for their role in allergic reactions, where aggregation of FcεRI leads to the release of mast cell mediators causing allergic symptoms. The activation also induces a survival program in the cells, i.e., activation-induced mast cell survival. The aim of the present study was to investigate how the activation-induced survival is mediated. Cord blood-derived mast cells and the mast cell line LAD-2 were activated through FcεRI crosslinking, with or without addition of chemicals that inhibit the activity or expression of selected Bcl-2 family members (ABT-737; roscovitine. Cell viability was assessed using staining and flow cytometry. The expression and function of Bcl-2 family members BFL-1 and MCL-1 were investigated using real-time quantitative PCR and siRNA treatment. The mast cell expression of Bfl-1 was investigated in skin biopsies. FcεRI crosslinking promotes activation-induced survival of human mast cells and this is associated with an upregulation of the anti-apoptotic Bcl-2 family member Bfl-1. ABT-737 alone or in combination with roscovitine decreases viability of human mast cells although activation-induced survival is sustained, indicating a minor role for Bcl-X(L, Bcl-2, Bcl-w and Mcl-1. Reducing BFL-1 but not MCL-1 levels by siRNA inhibited activation-induced mast cell survival. We also demonstrate that mast cell expression of Bfl-1 is elevated in birch-pollen-provocated skin and in lesions of atopic dermatitis and psoriasis patients. Taken together, our results highlight Bfl-1 as a major effector in activation-induced human mast cell survival.

Simultaneous assessments of occurrence, ecological, human health, and organoleptic hazards for 77 VOCs in typical drinking water sources from 5 major river basins, China.

Science.gov (United States)

Chen, Xichao; Luo, Qian; Wang, Donghong; Gao, Jijun; Wei, Zi; Wang, Zijian; Zhou, Huaidong; Mazumder, Asit

2015-11-01

Owing to the growing public awareness on the safety and aesthetics in water sources, more attention has been given to the adverse effects of volatile organic compounds (VOCs) on aquatic organisms and human beings. In this study, 77 target VOCs (including 54 common VOCs, 13 carbonyl compounds, and 10 taste and odor compounds) were detected in typical drinking water sources from 5 major river basins (the Yangtze, the Huaihe, the Yellow, the Haihe and the Liaohe River basins) and their occurrences were characterized. The ecological, human health, and olfactory assessments were performed to assess the major hazards in source water. The investigation showed that there existed potential ecological risks (1.30 × 10 ≤ RQtotals ≤ 8.99 × 10) but little human health risks (6.84 × 10(-7) ≤ RQtotals ≤ 4.24 × 10(-4)) by VOCs, while that odor problems occurred extensively. The priority contaminants in drinking water sources of China were also listed based on the present assessment criteria. Copyright © 2015 Elsevier Ltd. All rights reserved.

Major threats of pollution and climate change to global coastal ecosystems and enhanced management for sustainability

NARCIS (Netherlands)

Lu, Y.; Yuan, J.; Lu, X.; Su, Chao; Zhang, Y.; Wang, C.; Cao, X.; Li, Q.; Su, Jilan; Ittekkot, Venugopalan; Garbutt, Richard Angus; Bush, S.R.; Fletcher, Stephen; Wagey, Tonny; Kachur, Anatolii; Sweijd, Neville

2018-01-01

Coastal zone is of great importance in the provision of various valuable ecosystem services. However, it is also sensitive and vulnerable to environmental changes due to high human populations and interactions between the land and ocean. Major threats of pollution from over enrichment of nutrients,

Visuoauditory mappings between high luminance and high pitch are shared by chimpanzees (Pan troglodytes) and humans

Science.gov (United States)

Ludwig, Vera U.; Adachi, Ikuma; Matsuzawa, Tetsuro

2011-01-01

Humans share implicit preferences for certain cross-sensory combinations; for example, they consistently associate higher-pitched sounds with lighter colors, smaller size, and spikier shapes. In the condition of synesthesia, people may experience such cross-modal correspondences to a perceptual degree (e.g., literally seeing sounds). So far, no study has addressed the question whether nonhuman animals share cross-modal correspondences as well. To establish the evolutionary origins of cross-modal mappings, we tested whether chimpanzees (Pan troglodytes) also associate higher pitch with higher luminance. Thirty-three humans and six chimpanzees were required to classify black and white squares according to their color while hearing irrelevant background sounds that were either high-pitched or low-pitched. Both species performed better when the background sound was congruent (high-pitched for white, low-pitched for black) than when it was incongruent (low-pitched for white, high-pitched for black). An inherent tendency to pair high pitch with high luminance hence evolved before the human lineage split from that of chimpanzees. Rather than being a culturally learned or a linguistic phenomenon, this mapping constitutes a basic feature of the primate sensory system. PMID:22143791

Personality Traits' Effects on Self-Efficacy and Outcome Expectations for High School Major Choice

Science.gov (United States)

Brown, Dikla; Cinamon, Rachel Gali

2016-01-01

The current study focuses on the contribution of the Big Five personality traits to the development of self-efficacy and outcome expectations regarding selection of a high school major among 368 Israeli adolescents (Mage = 16.07, SD = 0.41). Structural equation analyses showed that higher levels of conscientiousness and extraversion and lower…

Viable adenovirus vaccine prototypes: High-level production of a papillomavirus capsid antigen from the major late transcriptional unit

OpenAIRE

Berg, Michael; DiFatta, Julie; Hoiczyk, Egbert; Schlegel, Richard; Ketner, Gary

2005-01-01

Safe, effective, orally delivered, live adenovirus vaccines have been in use for three decades. Recombinant derivatives of the live adenovirus vaccines may prove an economical alternative to current vaccines for a variety of diseases. To explore that possibility, we constructed a series of recombinants that express the major capsid protein (L1) of canine oral papillomavirus (COPV), a model for mucosal human papillomavirus (HPV) infection. Vaccination with virus-like particles (VLPs) composed ...

A single point in protein trafficking by Plasmodium falciparum determines the expression of major antigens on the surface of infected erythrocytes targeted by human antibodies.

Science.gov (United States)

Chan, Jo-Anne; Howell, Katherine B; Langer, Christine; Maier, Alexander G; Hasang, Wina; Rogerson, Stephen J; Petter, Michaela; Chesson, Joanne; Stanisic, Danielle I; Duffy, Michael F; Cooke, Brian M; Siba, Peter M; Mueller, Ivo; Bull, Peter C; Marsh, Kevin; Fowkes, Freya J I; Beeson, James G

2016-11-01

Antibodies to blood-stage antigens of Plasmodium falciparum play a pivotal role in human immunity to malaria. During parasite development, multiple proteins are trafficked from the intracellular parasite to the surface of P. falciparum-infected erythrocytes (IEs). However, the relative importance of different proteins as targets of acquired antibodies, and key pathways involved in trafficking major antigens remain to be clearly defined. We quantified antibodies to surface antigens among children, adults, and pregnant women from different malaria-exposed regions. We quantified the importance of antigens as antibody targets using genetically engineered P. falciparum with modified surface antigen expression. Genetic deletion of the trafficking protein skeleton-binding protein-1 (SBP1), which is involved in trafficking the surface antigen PfEMP1, led to a dramatic reduction in antibody recognition of IEs and the ability of human antibodies to promote opsonic phagocytosis of IEs, a key mechanism of parasite clearance. The great majority of antibody epitopes on the IE surface were SBP1-dependent. This was demonstrated using parasite isolates with different genetic or phenotypic backgrounds, and among antibodies from children, adults, and pregnant women in different populations. Comparisons of antibody reactivity to parasite isolates with SBP1 deletion or inhibited PfEMP1 expression suggest that PfEMP1 is the dominant target of acquired human antibodies, and that other P. falciparum IE surface proteins are minor targets. These results establish SBP1 as part of a critical pathway for the trafficking of major surface antigens targeted by human immunity, and have key implications for vaccine development, and quantifying immunity in populations.

Overexpression of the human major vault protein in gangliogliomas.

NARCIS (Netherlands)

Aronica, E; Gorter, J.A.; Vliet, van EA; Spliet, WG; Veelen, van CW; Rijen, van PC; Leenstra, S.; Ramkema, MD; Scheffer, G.L.; Scheper, R.J.; Sisodiya, SM; Troost, D.

2003-01-01

PURPOSE: Recent evidence has been obtained that the major vault protein (MVP) may play a role in multidrug resistance (MDR). We investigated the expression and cellular localization of MVP in gangliogliomas (GGs), which are increasingly recognized causes of chronic pharmacoresistant epilepsy.

Overexpression of the human major vault protein in gangliogliomas

NARCIS (Netherlands)

Aronica, Eleonora; Gorter, Jan A.; van Vliet, Erwin A.; Spliet, Wim G. M.; van Veelen, Cees W. M.; van Rijen, Peter C.; Leenstra, Sieger; Ramkema, Marja D.; Scheffer, George L.; Scheper, Rik J.; Sisodiya, Sanjay M.; Troost, Dirk

2003-01-01

Purpose: Recent evidence has been obtained that the major vault protein (MVP) may play a role in multidrug resistance (MDR). We investigated the expression and cellular localization of MVP in gangliogliomas (GGs), which are increasingly recognized causes of chronic pharmacoresistant epilepsy.

Work-related threats and violence in human service sectors

DEFF Research Database (Denmark)

Andersen, Lars Peter Sønderbo; Hogh, Annie; Biering, Karin

2018-01-01

BACKGROUND: Threats and violence at work are major concerns for employees in many human service sectors. The prevention of work-related violence is a major challenge for employees and management. OBJECTIVE: The purpose of this study was to identify prospective associations between psycho-social w......BACKGROUND: Threats and violence at work are major concerns for employees in many human service sectors. The prevention of work-related violence is a major challenge for employees and management. OBJECTIVE: The purpose of this study was to identify prospective associations between psycho...... rewards at work, low role clarity, many role conflicts, many work-family conflicts and low organizational justice had statistically significant associations with high levels of work-related threats. Furthermore, high emotional demands, low predictability, low role clarity, many role conflicts, many work......-family conflicts, low supervisor quality and low support from nearest supervisor had statistically significant associations with high levels of work-related violence. Finally, across the four sectors both similar and different associations between psycho-social work environment and work-related violence...

Livestock-Associated Methicillin Resistant and Methicillin Susceptible Staphylococcus aureus Sequence Type (CC)1 in European Farmed Animals: High Genetic Relatedness of Isolates from Italian Cattle Herds and Humans

DEFF Research Database (Denmark)

Alba, Patricia; Feltrin, Fabiola; Cordaro, Gessica

2015-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) Sequence Type (ST)1, Clonal Complex( CC) 1, SCCmec V is one of the major Livestock-Associated (LA-) lineages in pig farming industry in Italy and is associated with pigs in other European countries. Recently, it has been increasingly detected...... in Italian dairy cattle herds. The aim of this study was to analyse the differences between ST1 MRSA and methicillin-susceptible S. aureus (MSSA) from cattle and pig herds in Italy and Europe and human isolates. Sixty-tree animal isolates from different holdings and 20 human isolates were characterized...... by pulsed-field gel electrophoresis (PFGE), spa-typing, SCCmec typing, and by micro-array analysis for several virulence, antimicrobial resistance, and strain/host-specific marker genes. Three major PFGE clusters were detected. The bovine isolates shared a high (>= 90% to 100%) similarity with human...

Personality, academic majors and performance

DEFF Research Database (Denmark)

Vedel, Anna; Thomsen, Dorthe Kirkegaard; Larsen, Lars

2015-01-01

Personality–performance research typically uses samples of psychology students without questioning their representativeness. The present article reports two studies challenging this practice. Study 1: group differences in the Big Five personality traits were explored between students (N = 1067......) in different academic majors (medicine, psychology, law, economics, political science, science, and arts/humanities), who were tested immediately after university enrolment. Study 2: six and a half years later the students’ academic records were obtained, and predictive validity of the Big Five personality...... traits and their subordinate facets was examined in the various academic majors in relation to Grade Point Average (GPA). Significant group differences in all Big Five personality traits were found between students in different academic majors. Also, variability in predictive validity of the Big Five...

YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene.

Science.gov (United States)

Stein, Ulrike; Bergmann, Stephan; Scheffer, George L; Scheper, Rik J; Royer, Hans-Dieter; Schlag, Peter M; Walther, Wolfgang

2005-05-19

Vaults have been suggested to play a direct role in multidrug resistance (MDR) to anticancer drugs. The human major vault protein (MVP) also known as lung resistance-related protein (LRP) represents the predominant component of vaults that may be involved in the defense against xenobiotics. Here, we demonstrate that besides MDR-related cytostatics, also the non-MDR-related drug 5-fluorouracil (5-FU) was able to induce MVP mRNA and protein expression. Treatment with 5-FU amplified the binding activity and interaction of the transcription factor Y-box binding protein-1 (YB-1) with the Y-box of the human MVP gene promoter in a time-dependent manner. 5-FU also induced reporter expressions driven by a panel of newly generated MVP promoter deletion mutants. Interestingly, stably YB-1 overexpressing cell clones showed enhanced binding of YB-1 to the Y-box motif, associated with enhanced basal as well as 5-FU-inducible MVP promoter-driven reporter expressions. Moreover, transduction of YB-1 cDNA led to increased expression of endogenous MVP protein. Under physiological conditions, we observed a strong coexpression of MVP and YB-1 in human colon carcinoma specimen. In summary, our data demonstrate a direct involvement of YB-1 in controlling basal and 5-FU-induced MVP promoter activity. Therefore, YB-1 is directly linked to MVP-mediated drug resistance.

Engineering chimeric human and mouse major histocompatibility complex (MHC) class I tetramers for the production of T-cell receptor (TCR) mimic antibodies

Science.gov (United States)

Bentley, Carol; Yates, Jenna; Salimi, Maryam; Greig, Jenny; Wiblin, Sarah; Hassanali, Tasneem; Banham, Alison H.

2017-01-01

Therapeutic monoclonal antibodies targeting cell surface or secreted antigens are among the most effective classes of novel immunotherapies. However, the majority of human proteins and established cancer biomarkers are intracellular. Peptides derived from these intracellular proteins are presented on the cell surface by major histocompatibility complex class I (MHC-I) and can be targeted by a novel class of T-cell receptor mimic (TCRm) antibodies that recognise similar epitopes to T-cell receptors. Humoural immune responses to MHC-I tetramers rarely generate TCRm antibodies and many antibodies recognise the α3 domain of MHC-I and β2 microglobulin (β2m) that are not directly involved in presenting the target peptide. Here we describe the production of functional chimeric human-murine HLA-A2-H2Dd tetramers and modifications that increase their bacterial expression and refolding efficiency. These chimeric tetramers were successfully used to generate TCRm antibodies against two epitopes derived from wild type tumour suppressor p53 (RMPEAAPPV and GLAPPQHLIRV) that have been used in vaccination studies. Immunisation with chimeric tetramers yielded no antibodies recognising the human α3 domain and β2m and generated TCRm antibodies capable of specifically recognising the target peptide/MHC-I complex in fully human tetramers and on the cell surface of peptide pulsed T2 cells. Chimeric tetramers represent novel immunogens for TCRm antibody production and may also improve the yield of tetramers for groups using these reagents to monitor CD8 T-cell immune responses in HLA-A2 transgenic mouse models of immunotherapy. PMID:28448627

Assessment of inhibitory effects on major human cytochrome P450 enzymes by spasmolytics used in the treatment of overactive bladder syndrome.

Science.gov (United States)

Dahlinger, Dominik; Aslan, Sevinc; Pietsch, Markus; Frechen, Sebastian; Fuhr, Uwe

2017-07-01

The objective of this study was to examine the inhibitory potential of darifenacin, fesoterodine, oxybutynin, propiverine, solifenacin, tolterodine and trospium chloride on the seven major human cytochrome P450 enzymes (CYP) by using a standardized and validated seven-in-one cytochrome P450 cocktail inhibition assay. An in vitro cocktail of seven highly selective probe substrates was incubated with human liver microsomes and varying concentrations of the seven test compounds. The major metabolites of the probe substrates were simultaneously analysed using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Enzyme kinetics were estimated by determining IC 50 and K i values via nonlinear regression. Obtained K i values were used for predictions of potential clinical impact of the inhibition using a static mechanistic prediction model. In this study, 49 IC 50 experiments were conducted. In six cases, IC 50 values lower than the calculated threshold for drug-drug interactions (DDIs) in the gut wall were observed. In these cases, no increase in inhibition was determined after a 30 min preincubation. Considering a typical dosing regimen and applying the obtained K i values of 0.72 µM (darifenacin, 15 mg daily) and 7.2 µM [propiverine, 30 mg daily, immediate release (IR)] for the inhibition of CYP2D6 yielded a predicted 1.9-fold and 1.4-fold increase in the area under the curve (AUC) of debrisoquine (CYP2D6 substrate), respectively. Due to the inhibition of the particular intestinal CYP3A4, the obtained K i values of 14 µM of propiverine (30 mg daily, IR) resulted in a predicted doubling of the AUC for midazolam (CYP3A4 substrate). In vitro / in vivo extrapolation based on pharmacokinetic data and the conducted screening experiments yielded similar effects of darifenacin on CYP2D6 and propiverine on CYP3A4 as obtained in separately conducted in vivo DDI studies. As a novel finding, propiverine was identified to potentially inhibit CYP2D6 at

Two putative subunits of a peptide pump encoded in the human major histocompatability complex class 2 region

International Nuclear Information System (INIS)

Bahram, S.; Arnold, D.; Bresnahan, M.; Strominger, J.L.; Spies, T.

1991-01-01

The class 2 region of the human major histocompatibility complex (MHC) may encode several genes controlling the processing of endogenous antigen and the presentation of peptide epitopes by MHC class 1 molecules to cytotoxic T lymphocytes. A previously described peptide supply factor (PSF1) is a member of the multidrug-resistance family of transporters and may pump cytosolic peptides into the membrane-bound compartment where class 1 molecules assemble. A second transporter gene, PSF2, was identified 10 kilobases (kb) from PSF1, near the class 2 DOB gene. The complete sequences of PSF1 and PSF2 were determined from cDNA clones. The translation products are closely related in sequence and predicted secondary structure. Both contain a highly conserved ATP-binding fold and share 25% homology in a hydrophobic domain with a tentative number of eight membrane-spanning segments. Based on the principle dimeric organization of these two domains in other transporters, PSF1 and PSF2 may function as complementary subunits, independently as homodimers, or both. Taken together with previous genetic evidence, the coregulation of PSF1 and PSF2 by γ interferon and the to-some-degree coordinate transcription of these genes suggest a common role in peptide-loading of class 1 molecules, although a distinct function of PSF2 cannot be ruled out

Slaughterhouse pigs are a major reservoir of Streptococcus suis serotype 2 capable of causing human infection in southern Vietnam.

Directory of Open Access Journals (Sweden)

Thi Hoa Ngo

2011-03-01

Full Text Available Streptococcus suis is a pathogen of major economic significance to the swine industry and is increasingly recognized as an emerging zoonotic agent in Asia. In Vietnam, S. suis is the leading cause of bacterial meningitis in adult humans. Zoonotic transmission is most frequently associated with serotype 2 strains and occupational exposure to pigs or consumption of infected pork. To gain insight into the role of pigs for human consumption as a reservoir for zoonotic infection in southern Vietnam, we determined the prevalence and diversity of S. suis carriage in healthy slaughterhouse pigs. Nasopharyngeal tonsils were sampled from pigs at slaughterhouses serving six provinces in southern Vietnam and Ho Chi Minh City area from September 2006 to November 2007. Samples were screened by bacterial culture. Isolates of S. suis were serotyped and characterized by multi locus sequence typing (MLST and pulse field gel electrophoresis (PFGE. Antibiotic susceptibility profiles and associated genetic resistance determinants, and the presence of putative virulence factors were determined. 41% (222/542 of pigs carried S. suis of one or multiple serotypes. 8% (45/542 carried S. suis serotype 2 which was the most common serotype found (45/317 strains, 14%. 80% of serotype 2 strains belonged to the MLST clonal complex 1,which was previously associated with meningitis cases in Vietnam and outbreaks of severe disease in China in 1998 and 2005. These strains clustered with representative strains isolated from patients with meningitis in PFGE analysis, and showed similar antimicrobial resistance and virulence factor profiles. Slaughterhouse pigs are a major reservoir of S. suis serotype 2 capable of causing human infection in southern Vietnam. Strict hygiene at processing facilities, and health education programs addressing food safety and proper handling of pork should be encouraged.

High pressure inactivation of human norovirus virus-like particles: evidence that the capsid of human norovirus is highly pressure resistant

Science.gov (United States)

Human norovirus (NoV) is the leading cause of non-bacterial acute gastroenteritis epidemics worldwide. High pressure processing (HPP) has been considered a promising non-thermal processing technology to inactivate food- and water-borne viral pathogens. Due to the lack of an effective cell culture fo...

Progress on major genes for high fecundity in ewes

Directory of Open Access Journals (Sweden)

Qiuyue LIU,Zhangyuan PAN,Xiangyu WANG,Wenping HU,Ran DI,Yaxing YAO,Mingxing CHU

2014-12-01

Full Text Available The existence of major genes affecting fecundity in sheep flocks throughout the world has been demonstrated. Three major genes whose mutations can increase ovulation rate have been discovered, and all related to the transforming growth factor β (TGF-β superfamily. The mutant FecB of bone morphogenetic protein receptor 1B (BMPR1B has an additive effect on ovulation rate. Six mutations (FecXI, FecXH, FecXG, FecXB, FecXL, FecXR of bone morphogenetic protein 15 (BMP15 related with fertility have been identified that share the same mechanism. All the mutants can increase ovulation rate in heterozygotes and cause complete sterility in homozygotes. Homozygous ewes with two new mutations (FecXGr, FecXO of BMP15 had increased ovulation rate without causing sterility. There are five mutations in growth differentiation factor 9 (GDF9 associated with sheep prolificacy where FecGE and FecGF have additive an effect on ovulation rate and litter size. The newly identified β-1,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2 gene of FecL is proposed as a new mechanism of ovulation rate regulation in sheep. Woodlands is an X-linked maternally imprinted gene which increases ovulation rate. In addition, several putative major genes need to be verified. This review is focused on the identification of the mutations and mechanisms whereby the major genes affecting ovulation rate.

High Performers in Marketing and Advertising Majors: Do Their Perceptions of Business Programs Differ from Their Peers?

Science.gov (United States)

Walsh, Ann D.; Woosley, Sherry A.

2013-01-01

This study examined the perceptions of high performing undergraduate students in marketing and advertising majors. Specifically, it examined the relationships among three levels of student performance and student satisfaction with their business programs and learning outcomes. High performing students were more satisfied with their programs and…

Molecular identification and population dynamics of the major ...

African Journals Online (AJOL)

Adult female mosquito vectors were collected from three villages in a typical rain forest area of Nigeria where no information exists on the major malaria vectors associated with human malaria. Sampling was carried out between January 2004 and January 2005 using pyrethrum and Human landing catch (HLC) techniques.

MGH-USC Human Connectome Project datasets with ultra-high b-value diffusion MRI.

Science.gov (United States)

Fan, Qiuyun; Witzel, Thomas; Nummenmaa, Aapo; Van Dijk, Koene R A; Van Horn, John D; Drews, Michelle K; Somerville, Leah H; Sheridan, Margaret A; Santillana, Rosario M; Snyder, Jenna; Hedden, Trey; Shaw, Emily E; Hollinshead, Marisa O; Renvall, Ville; Zanzonico, Roberta; Keil, Boris; Cauley, Stephen; Polimeni, Jonathan R; Tisdall, Dylan; Buckner, Randy L; Wedeen, Van J; Wald, Lawrence L; Toga, Arthur W; Rosen, Bruce R

2016-01-01

The MGH-USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing a magnetic field gradient of up to 300 mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH-USC Adult Diffusion Dataset (N=35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU-Minn Connectome Database (ConnectomeDB). Another purpose of sharing the data is to facilitate methodological studies of diffusion MRI (dMRI) analyses utilizing high diffusion contrast, which perhaps is not easily feasible with standard MR gradient system. In addition, acquisition of the MGH-Harvard-USC Lifespan Dataset is currently underway to include 120 healthy participants ranging from 8 to 90 years old, which will also be shared through LONI IDA and ConnectomeDB. Here we describe the efforts of the MGH-USC HCP consortium in acquiring and sharing the ultra-high b-value diffusion MRI data and provide a report on data preprocessing and access. We conclude with a demonstration of the example data, along with results of standard diffusion analyses, including q-ball Orientation Distribution Function (ODF) reconstruction and tractography. Copyright © 2015 Elsevier Inc. All rights reserved.

High-speed adaptive optics line scan confocal retinal imaging for human eye.

Science.gov (United States)

Lu, Jing; Gu, Boyu; Wang, Xiaolin; Zhang, Yuhua

2017-01-01

Continuous and rapid eye movement causes significant intraframe distortion in adaptive optics high resolution retinal imaging. To minimize this artifact, we developed a high speed adaptive optics line scan confocal retinal imaging system. A high speed line camera was employed to acquire retinal image and custom adaptive optics was developed to compensate the wave aberration of the human eye's optics. The spatial resolution and signal to noise ratio were assessed in model eye and in living human eye. The improvement of imaging fidelity was estimated by reduction of intra-frame distortion of retinal images acquired in the living human eyes with frame rates at 30 frames/second (FPS), 100 FPS, and 200 FPS. The device produced retinal image with cellular level resolution at 200 FPS with a digitization of 512×512 pixels/frame in the living human eye. Cone photoreceptors in the central fovea and rod photoreceptors near the fovea were resolved in three human subjects in normal chorioretinal health. Compared with retinal images acquired at 30 FPS, the intra-frame distortion in images taken at 200 FPS was reduced by 50.9% to 79.7%. We demonstrated the feasibility of acquiring high resolution retinal images in the living human eye at a speed that minimizes retinal motion artifact. This device may facilitate research involving subjects with nystagmus or unsteady fixation due to central vision loss.

The simultaneous identification of metoprolol and its major acidic and basic metabolites in human urine by gas chromatography-mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Li, Feng; Cooper, S.F. [Universite du Quebec, Pointe-Claire (Canada)

1996-12-31

A novel gas chromatography-mass spectrometric (GC-MS) method was developed to confirm and identify metoprolol and its metabolites by double derivatization with S-(-)menthyl chloroformate [(-)-MCF] and N-methyl(trimethylsilyl-trifluoroacetamide) (MSTFA). This is the first report, which describes the simultaneous identification of metoprolol, its one major acidc and other basic metabolites in human urine based on solid-phase extraction with C{sub 18} reversed-phase cartridges. 12 refs., 4 figs.

High-speed AFM of human chromosomes in liquid

Energy Technology Data Exchange (ETDEWEB)

Picco, L M; Dunton, P G; Ulcinas, A; Engledew, D J; Miles, M J [H H Wills Physics Laboratory and IRC in Nanotechnology, University of Bristol, Tyndall Avenue, Bristol BS8 1TL (United Kingdom); Hoshi, O; Ushiki, T [Division of Microscopic Anatomy and Bio-Imaging, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-Dori 1, Niigata, 951-8150 (Japan)], E-mail: m.j.miles@bristol.ac.uk

2008-09-24

Further developments of the previously reported high-speed contact-mode AFM are described. The technique is applied to the imaging of human chromosomes at video rate both in air and in water. These are the largest structures to have been imaged with high-speed AFM and the first imaging in liquid to be reported. A possible mechanism that allows such high-speed contact-mode imaging without significant damage to the sample is discussed in the context of the velocity dependence of the measured lateral force on the AFM tip.

Identification of ALK as the Major Familial Neuroblastoma Predisposition Gene

Science.gov (United States)

Mossë, Yalë P; Laudenslager, Marci; Longo, Luca; Cole, Kristina A; Wood, Andrew; Attiyeh, Edward F; Laquaglia, Michael J; Sennett, Rachel; Lynch, Jill E; Perri, Patrizia; Laureys, Geneviève; Speleman, Frank; Hakonarson, Hakon; Torkamani, Ali; Schork, Nicholas J; Brodeur, Garrett M; Tonini, Gian Paolo; Rappaport, Eric; Devoto, Marcella; Maris, John M

2009-01-01

SUMMARY Survival rates for the childhood cancer neuroblastoma have not substantively improved despite dramatic escalation in chemotherapy intensity. Like most human cancers, this embryonal malignancy can be inherited, but the genetic etiology of familial and sporadically occurring neuroblastoma was largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase gene (ALK) explain the majority of hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at the short arm of chromosome 2 (maximum nonparametric LOD=4.23 at rs1344063) using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate missense mutations in the tyrosine kinase domain of ALK (G1128A, R1192P and R1275Q) that segregated with the disease in eight separate families. Examination of 491 sporadically occurring human neuroblastoma samples showed that the ALK locus was gained in 22.8%, and highly amplified in an additional 3.3%, and that these aberrations were highly associated with death from disease (P=0.0003). Resequencing of 194 high-risk neuroblastoma samples showed somatically acquired mutations within the tyrosine kinase domain in 12.4%. Nine of the ten mutations map to critical regions of the kinase domain and were predicted to be oncogenic drivers with high probability. Mutations resulted in constitutive phosphorylation consistent with activation, and targeted knockdown of ALK mRNA resulted in profound growth inhibition of 4 of 4 cell lines harboring mutant or amplified ALK, as well as 2 of 6 wild type for ALK. Our results demonstrate that heritable mutations of ALK are the major cause of familial neuroblastoma, and that germline or acquired activation of this cell surface kinase is a tractable therapeutic target for this lethal pediatric malignancy. PMID:18724359

Rapid detection and identification of four major Schistosoma species by high-resolution melt (HRM) analysis.

Science.gov (United States)

Li, Juan; Zhao, Guang-Hui; Lin, RuiQing; Blair, David; Sugiyama, Hiromu; Zhu, Xing-Quan

2015-11-01

Schistosomiasis, caused by blood flukes belonging to several species of the genus Schistosoma, is a serious and widespread parasitic disease. Accurate and rapid differentiation of these etiological agents of animal and human schistosomiasis to species level can be difficult. We report a real-time PCR assay coupled with a high-resolution melt (HRM) assay targeting a portion of the nuclear 18S rDNA to detect, identify, and distinguish between four major blood fluke species (Schistosoma japonicum, Schistosoma mansoni, Schistosoma haematobium, and Schistosoma mekongi). Using this system, the Schistosoma spp. was accurately identified and could also be distinguished from all other trematode species with which they were compared. As little as 10(-5) ng genomic DNA from a Schistosoma sp. could be detected. This process is inexpensive, easy, and can be completed within 3 h. Examination of 21 representative Schistosoma samples from 15 geographical localities in seven endemic countries validated the value of the HRM detection assay and proved its reliability. The melting curves were characterized by peaks of 83.65 °C for S. japonicum and S. mekongi, 85.65 °C for S. mansoni, and 85.85 °C for S. haematobium. The present study developed a real-time PCR coupled with HRM analysis assay for detection and differential identification of S. mansoni, S. haematobium, S. japonicum, and S. mekongi. This method is rapid, sensitive, and inexpensive. It has important implications for epidemiological studies of Schistosoma.

Data Sets from Major NCI Initiaves

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The NCI Data Catalog includes links to data collections produced by major NCI initiatives and other widely used data sets, including animal models, human tumor cell lines, epidemiology data sets, genomics data sets from TCGA, TARGET, COSMIC, GSK, NCI60.

Human reliability

International Nuclear Information System (INIS)

Embrey, D.E.

1987-01-01

Concepts and techniques of human reliability have been developed and are used mostly in probabilistic risk assessment. For this, the major application of human reliability assessment has been to identify the human errors which have a significant effect on the overall safety of the system and to quantify the probability of their occurrence. Some of the major issues within human reliability studies are reviewed and it is shown how these are applied to the assessment of human failures in systems. This is done under the following headings; models of human performance used in human reliability assessment, the nature of human error, classification of errors in man-machine systems, practical aspects, human reliability modelling in complex situations, quantification and examination of human reliability, judgement based approaches, holistic techniques and decision analytic approaches. (UK)

Vocational Preference Inventory High Point Codes Versus Expressed Choices as Predictors of College Major and Career Entry

Science.gov (United States)

Gade, Eldon M.; Soliah, David

1975-01-01

For 151 male graduates of the University of North Dakota, expressed choices measured by preferences made as high school seniors on the ACT Student Profile Section were significantly more accurate predictors of graduating college major and of career entry occupation than were their Vocational Preference Inventory high point codes. (Author)

Major hazards onshore and offshore

International Nuclear Information System (INIS)

1992-01-01

This symposium continues the tradition of bringing together papers on a topic of current interest and importance in terms of process safety - in this case, Major Hazards Onshore and Offshore. Lord Cullen in his report on the Piper Alpha disaster has, in effect, suggested that the experience gained in the control of major hazards onshore during the 1980s should be applied to improve safety offshore during the 1990s. This major three-day symposium reviews what has been learned so far with regard to major hazards and considers its present and future applications both onshore and offshore. The topics covered in the programme are wide ranging and deal with all aspects of legislation, the application of regulations, techniques for evaluating hazards and prescribing safety measures in design, construction and operation, the importance of the human factors, and recent technical developments in protective measures, relief venting and predicting the consequences of fires and explosions. (author)

A high density of human communication-associated genes in chromosome 7q31-q36: differential expression in human and non-human primate cortices.

Science.gov (United States)

Schneider, E; Jensen, L R; Farcas, R; Kondova, I; Bontrop, R E; Navarro, B; Fuchs, E; Kuss, A W; Haaf, T

2012-01-01

The human brain is distinguished by its remarkable size, high energy consumption, and cognitive abilities compared to all other mammals and non-human primates. However, little is known about what has accelerated brain evolution in the human lineage. One possible explanation is that the appearance of advanced communication skills and language has been a driving force of human brain development. The phenotypic adaptations in brain structure and function which occurred on the way to modern humans may be associated with specific molecular signatures in today's human genome and/or transcriptome. Genes that have been linked to language, reading, and/or autism spectrum disorders are prime candidates when searching for genes for human-specific communication abilities. The database and genome-wide expression analyses we present here revealed a clustering of such communication-associated genes (COAG) on human chromosomes X and 7, in particular chromosome 7q31-q36. Compared to the rest of the genome, we found a high number of COAG to be differentially expressed in the cortices of humans and non-human primates (chimpanzee, baboon, and/or marmoset). The role of X-linked genes for the development of human-specific cognitive abilities is well known. We now propose that chromosome 7q31-q36 also represents a hot spot for the evolution of human-specific communication abilities. Selective pressure on the T cell receptor beta locus on chromosome 7q34, which plays a pivotal role in the immune system, could have led to rapid dissemination of positive gene variants in hitchhiking COAG. Copyright © 2012 S. Karger AG, Basel.

Effective population sizes of a major vector of human diseases, Aedes aegypti.

Science.gov (United States)

Saarman, Norah P; Gloria-Soria, Andrea; Anderson, Eric C; Evans, Benjamin R; Pless, Evlyn; Cosme, Luciano V; Gonzalez-Acosta, Cassandra; Kamgang, Basile; Wesson, Dawn M; Powell, Jeffrey R

2017-12-01

The effective population size ( N e ) is a fundamental parameter in population genetics that determines the relative strength of selection and random genetic drift, the effect of migration, levels of inbreeding, and linkage disequilibrium. In many cases where it has been estimated in animals, N e is on the order of 10%-20% of the census size. In this study, we use 12 microsatellite markers and 14,888 single nucleotide polymorphisms (SNPs) to empirically estimate N e in Aedes aegypti , the major vector of yellow fever, dengue, chikungunya, and Zika viruses. We used the method of temporal sampling to estimate N e on a global dataset made up of 46 samples of Ae. aegypti that included multiple time points from 17 widely distributed geographic localities. Our N e estimates for Ae. aegypti fell within a broad range (~25-3,000) and averaged between 400 and 600 across all localities and time points sampled. Adult census size (N c ) estimates for this species range between one and five thousand, so the N e / N c ratio is about the same as for most animals. These N e values are lower than estimates available for other insects and have important implications for the design of genetic control strategies to reduce the impact of this species of mosquito on human health.

Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging

Directory of Open Access Journals (Sweden)

Lilach Soreq

2017-01-01

Full Text Available Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases.

Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

Science.gov (United States)

Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

2017-01-10

Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Strategic issues for the oil majors - 1992

Energy Technology Data Exchange (ETDEWEB)

Oppenheimer, P M [Oxford Univ. (United Kingdom)

1992-01-01

Strategic issues facing major oil producers in the 1990s are very diffuse - in contrast with both the 1970s (when strategy meant the response to high oil prices) and the 1980s (when it meant anticipating and exploiting a drop in prices). Mainly upstream issues include the future of price management by OPEC or a successor, the speed of development of new markets for natural gas in power generation and the role of Russia in world energy markets. Other issues include the impact of environmental regulations and taxes on the product mix and on marketing. Human-resource management will continue to face the task of reconciling career opportunities with static or declining manpower requirements; and corporate cash mountains may periodically recur. (Author).

Strategic issues for the oil majors - 1992

International Nuclear Information System (INIS)

Oppenheimer, P.M.

1992-01-01

Strategic issues facing major oil producers in the 1990s are very diffuse - in contrast with both the 1970s (when strategy meant the response to high oil prices) and the 1980s (when it meant anticipating and exploiting a drop in prices). Mainly upstream issues include the future of price management by OPEC or a successor, the speed of development of new markets for natural gas in power generation and the role of Russia in world energy markets. Other issues include the impact of environmental regulations and taxes on the product mix and on marketing. Human-resource management will continue to face the task of reconciling career opportunities with static or declining manpower requirements; and corporate cash mountains may periodically recur. (Author)

Global risk of radioactive fallout after major nuclear reactor accidents

International Nuclear Information System (INIS)

Lelieveld, J.; Kunkel, D.; Lawrence, M.G.

2012-01-01

Major reactor accidents of nuclear power plants are rare, yet the consequences are catastrophic. But what is meant by ''rare''? And what can be learned from the Chernobyl and Fukushima incidents? Here we assess the cumulative, global risk of exposure to radioactivity due to atmospheric dispersion of gases and particles following severe nuclear accidents (the most severe ones on the International Nuclear Event Scale, INES 7), using particulate "1"3"7Cs and gaseous "1"3"1I as proxies for the fallout. Our results indicate that previously the occurrence of INES 7 major accidents and the risks of radioactive contamination have been underestimated. Using a global model of the atmosphere we compute that on average, in the event of a major reactor accident of any nuclear power plant worldwide, more than 90% of emitted "1"3"7Cs would be transported beyond 50 km and about 50% beyond 1000 km distance before being deposited. This corroborates that such accidents have large-scale and trans-boundary impacts. Although the emission strengths and atmospheric removal processes of "1"3"7Cs and "1"3"1I are quite different, the radioactive contamination patterns over land and the human exposure due to deposition are computed to be similar. High human exposure risks occur around reactors in densely populated regions, notably in West Europe and South Asia, where a major reactor accident can subject around 30 million people to radioactive contamination. The recent decision by Germany to phase out its nuclear reactors will reduce the national risk, though a large risk will still remain from the reactors in neighbouring countries.

Cellular homeoproteins, SATB1 and CDP, bind to the unique region between the human cytomegalovirus UL127 and major immediate-early genes

International Nuclear Information System (INIS)

Lee Jialing; Klase, Zachary; Gao Xiaoqi; Caldwell, Jeremy S.; Stinski, Mark F.; Kashanchi, Fatah; Chao, S.-H.

2007-01-01

An AT-rich region of the human cytomegalovirus (CMV) genome between the UL127 open reading frame and the major immediate-early (MIE) enhancer is referred to as the unique region (UR). It has been shown that the UR represses activation of transcription from the UL127 promoter and functions as a boundary between the divergent UL127 and MIE genes during human CMV infection [Angulo, A., Kerry, D., Huang, H., Borst, E.M., Razinsky, A., Wu, J., Hobom, U., Messerle, M., Ghazal, P., 2000. Identification of a boundary domain adjacent to the potent human cytomegalovirus enhancer that represses transcription of the divergent UL127 promoter. J. Virol. 74 (6), 2826-2839; Lundquist, C.A., Meier, J.L., Stinski, M.F., 1999. A strong negative transcriptional regulatory region between the human cytomegalovirus UL127 gene and the major immediate-early enhancer. J. Virol. 73 (11), 9039-9052]. A putative forkhead box-like (FOX-like) site, AAATCAATATT, was identified in the UR and found to play a key role in repression of the UL127 promoter in recombinant virus-infected cells [Lashmit, P.E., Lundquist, C.A., Meier, J.L., Stinski, M.F., 2004. Cellular repressor inhibits human cytomegalovirus transcription from the UL127 promoter. J. Virol. 78 (10), 5113-5123]. However, the cellular factors which associate with the UR and FOX-like region remain to be determined. We reported previously that pancreatic-duodenal homeobox factor-1 (PDX1) bound to a 45-bp element located within the UR [Chao, S.H., Harada, J.N., Hyndman, F., Gao, X., Nelson, C.G., Chanda, S.K., Caldwell, J.S., 2004. PDX1, a Cellular Homeoprotein, Binds to and Regulates the Activity of Human Cytomegalovirus Immediate Early Promoter. J. Biol. Chem. 279 (16), 16111-16120]. Here we demonstrate that two additional cellular homeoproteins, special AT-rich sequence binding protein 1 (SATB1) and CCAAT displacement protein (CDP), bind to the human CMV UR in vitro and in vivo. Furthermore, CDP is identified as a FOX-like binding protein

The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

Directory of Open Access Journals (Sweden)

Michael Nevels

2009-11-01

Full Text Available The major immediate-early (IE gene of human cytomegalovirus (CMV is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses.

Using an Ablation Gradient Model to Characterize Annual Glacial Melt Contribution to Major Rivers in High Asia

Science.gov (United States)

Brodzik, M. J.; Armstrong, R. L.; Khalsa, S. J. S.; Painter, T. H.; Racoviteanu, A.; Rittger, K.

2014-12-01

Ice melt from mountain glaciers can represent a significant contribution to freshwater hydrological budgets, along with seasonal snow melt, rainfall and groundwater. In the rivers of High Asia, understanding the proportion of glacier ice melt is critical for water resource management of irrigation and planning for hydropower generation and human consumption. Current climate conditions are producing heterogeneous glacier responses across the Hindu Kush-Karakoram-Himalayan ranges. However, it is not yet clear how contrasting glacier patterns affect regional water resources. For example, in the Upper Indus basin, estimates of glacial contribution to runoff are often not distinguished from seasonal snow contribution, and vary widely, from as little as 15% to as much as 55%. While many studies are based on reasonable concepts, most are based on assumptions uninformed by actual snow or ice cover measurements. While straightforward temperature index models have been used to estimate glacier runoff in some Himalayan basins, application of these models in larger Himalayan basins is limited by difficulties in estimating key model parameters, particularly air temperature. Estimating glacial area from the MODIS Permanent Snow and Ice Extent (MODICE) product for the years 2000-2013, with recently released Shuttle Radar Topography Mission (SRTMGL3) elevation data, we use a simple ablation gradient approach to calculate an upper limit on the contribution of clean glacier ice melt to streamflow data. We present model results for the five major rivers with glaciated headwaters in High Asia: the Bramaputra, Ganges, Indus, Amu Darya and Syr Darya. Using GRDC historical discharge records, we characterize the annual contribution from glacier ice melt. We use MODICE interannual trends in each basin to estimate glacier ice melt uncertainties. Our results are being used in the USAID project, Contribution to High Asia Runoff from Ice and Snow (CHARIS), to inform regional-scale planning for

Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder.

Science.gov (United States)

Tripp, Adam; Oh, Hyunjung; Guilloux, Jean-Philippe; Martinowich, Keri; Lewis, David A; Sibille, Etienne

2012-11-01

The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known. Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdnf(KIV)] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results. Based on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and CORT) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex. These parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis

Revisit the Candidacy of Brain Cell Types as the Cell(s of Origin for Human High-Grade Glioma

Directory of Open Access Journals (Sweden)

Fangjie Shao

2018-02-01

Full Text Available High-grade glioma, particularly, glioblastoma, is the most aggressive cancer of the central nervous system (CNS in adults. Due to its heterogeneous nature, glioblastoma almost inevitably relapses after surgical resection and radio-/chemotherapy, and is thus highly lethal and associated with a dismal prognosis. Identifying the cell of origin has been considered an important aspect in understanding tumor heterogeneity, thereby holding great promise in designing novel therapeutic strategies for glioblastoma. Taking advantage of genetic lineage-tracing techniques, performed mainly on genetically engineered mouse models (GEMMs, multiple cell types in the CNS have been suggested as potential cells of origin for glioblastoma, among which adult neural stem cells (NSCs and oligodendrocyte precursor cells (OPCs are the major candidates. However, it remains highly debated whether these cell types are equally capable of transforming in patients, given that in the human brain, some cell types divide so slowly, therefore may never have a chance to transform. With the recent advances in studying adult NSCs and OPCs, particularly from the perspective of comparative biology, we now realize that notable differences exist among mammalian species. These differences have critical impacts on shaping our understanding of the cell of origin of glioma in humans. In this perspective, we update the current progress in this field and clarify some misconceptions with inputs from important findings about the biology of adult NSCs and OPCs. We propose to re-evaluate the cellular origin candidacy of these cells, with an emphasis on comparative studies between animal models and humans.

The Science and Issues of Human DNA Polymoprhisms: A Training Workshop for High School Biology Teachers

Energy Technology Data Exchange (ETDEWEB)

David. A Micklos

2006-10-30

This project achieved its goal of implementing a nationwide training program to introduce high school biology teachers to the key uses and societal implications of human DNA polymorphisms. The 2.5-day workshop introduced high school biology faculty to a laboratory-based unit on human DNA polymorphisms – which provides a uniquely personal perspective on the science and Ethical, Legal and Social Implications (ELSI) of the Human Genome Project. As proposed, 12 workshops were conducted at venues across the United States. The workshops were attended by 256 high school faculty, exceeding proposed attendance of 240 by 7%. Each workshop mixed theoretical, laboratory, and computer work with practical and ethical implications. Program participants learned simplified lab techniques for amplifying three types of chromosomal polymorphisms: an Alu insertion (PV92), a VNTR (pMCT118/D1S80), and single nucleotide polymorphisms (SNPs) in the mitochondrial control region. These polymorphisms illustrate the use of DNA variations in disease diagnosis, forensic biology, and identity testing - and provide a starting point for discussing the uses and potential abuses of genetic technology. Participants also learned how to use their Alu and mitochondrial data as an entrée to human population genetics and evolution. Our work to simplify lab techniques for amplifying human DNA polymorphisms in educational settings culminated with the release in 1998 of three Advanced Technology (AT) PCR kits by Carolina Biological Supply Company, the nation’s oldest educational science supplier. The kits use a simple 30-minute method to isolate template DNA from hair sheaths or buccal cells and streamlined PCR chemistry based on Pharmacia Ready-To-Go Beads, which incorporate Taq polymerase, deoxynucleotide triphosphates, and buffer in a freeze-dried pellet. These kits have greatly simplified teacher implementation of human PCR labs, and their use is growing at a rapid pace. Sales of human polymorphism

The Science and Issues of Human DNA Polymorphisms: A Training Workshop for High School Biology Teachers

Energy Technology Data Exchange (ETDEWEB)

Micklos, David A.

2006-10-30

This project achieved its goal of implementing a nationwide training program to introduce high school biology teachers to the key uses and societal implications of human DNA polymorphisms. The 2.5-day workshop introduced high school biology faculty to a laboratory-based unit on human DNA polymorphisms â which provides a uniquely personal perspective on the science and Ethical, Legal and Social Implications (ELSI) of the Human Genome Project. As proposed, 12 workshops were conducted at venues across the United States. The workshops were attended by 256 high school faculty, exceeding proposed attendance of 240 by 7%. Each workshop mixed theoretical, laboratory, and computer work with practical and ethical implications. Program participants learned simplified lab techniques for amplifying three types of chromosomal polymorphisms: an Alu insertion (PV92), a VNTR (pMCT118/D1S80), and single nucleotide polymorphisms (SNPs) in the mitochondrial control region. These polymorphisms illustrate the use of DNA variations in disease diagnosis, forensic biology, and identity testing - and provide a starting point for discussing the uses and potential abuses of genetic technology. Participants also learned how to use their Alu and mitochondrial data as an entrée to human population genetics and evolution. Our work to simplify lab techniques for amplifying human DNA polymorphisms in educational settings culminated with the release in 1998 of three Advanced Technology (AT) PCR kits by Carolina Biological Supply Company, the nationâÂÂs oldest educational science supplier. The kits use a simple 30-minute method to isolate template DNA from hair sheaths or buccal cells and streamlined PCR chemistry based on Pharmacia Ready-To-Go Beads, which incorporate Taq polymerase, deoxynucleotide triphosphates, and buffer in a freeze-dried pellet. These kits have greatly simplified teacher implementation of human PCR labs, and their use is growing at a rapid pace. Sales of human

Space Radiation and Risks to Human Health

Science.gov (United States)

Huff, Janice L.; Patel, Zarana S.; Simonsen, Lisa C.

2014-01-01

The radiation environment in space poses significant challenges to human health and is a major concern for long duration manned space missions. Outside the Earth's protective magnetosphere, astronauts are exposed to higher levels of galactic cosmic rays, whose physical characteristics are distinct from terrestrial sources of radiation such as x-rays and gamma-rays. Galactic cosmic rays consist of high energy and high mass nuclei as well as high energy protons; they impart unique biological damage as they traverse through tissue with impacts on human health that are largely unknown. The major health issues of concern are the risks of radiation carcinogenesis, acute and late decrements to the central nervous system, degenerative tissue effects such as cardiovascular disease, as well as possible acute radiation syndromes due to an unshielded exposure to a large solar particle event. The NASA Human Research Program's Space Radiation Program Element is focused on characterization and mitigation of these space radiation health risks along with understanding these risks in context of the other biological stressors found in the space environment. In this overview, we will provide a description of these health risks and the Element's research strategies to understand and mitigate these risks.

High Throughput Heuristics for Prioritizing Human Exposure to ...

Science.gov (United States)

The risk posed to human health by any of the thousands of untested anthropogenic chemicals in our environment is a function of both the potential hazard presented by the chemical, and the possibility of being exposed. Without the capacity to make quantitative, albeit uncertain, forecasts of exposure, the putative risk of adverse health effect from a chemical cannot be evaluated. We used Bayesian methodology to infer ranges of exposure intakes that are consistent with biomarkers of chemical exposures identified in urine samples from the U.S. population by the National Health and Nutrition Examination Survey (NHANES). We perform linear regression on inferred exposure for demographic subsets of NHANES demarked by age, gender, and weight using high throughput chemical descriptors gleaned from databases and chemical structure-based calculators. We find that five of these descriptors are capable of explaining roughly 50% of the variability across chemicals for all the demographic groups examined, including children aged 6-11. For the thousands of chemicals with no other source of information, this approach allows rapid and efficient prediction of average exposure intake of environmental chemicals. The methods described by this manuscript provide a highly improved methodology for HTS of human exposure to environmental chemicals. The manuscript includes a ranking of 7785 environmental chemicals with respect to potential human exposure, including most of the Tox21 in vit

Effect of high sugar intake on glucose transporter and weight regulating hormones in mice and humans.

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Yvonne Ritze

Full Text Available OBJECTIVE: Sugar consumption has increased dramatically over the last decades in Western societies. Especially the intake of sugar-sweetened beverages seems to be a major risk for the development of obesity. Thus, we compared liquid versus solid high-sugar diets with regard to dietary intake, intestinal uptake and metabolic parameters in mice and partly in humans. METHODS: Five iso-caloric diets, enriched with liquid (in water 30% vol/vol or solid (in diet 65% g/g fructose or sucrose or a control diet were fed for eight weeks to C57bl/6 mice. Sugar, liquid and caloric intake, small intestinal sugar transporters (GLUT2/5 and weight regulating hormone mRNA expression, as well as hepatic fat accumulation were measured. In obese versus lean humans that underwent either bariatric surgery or small bowel resection, we analyzed small intestinal GLUT2, GLUT5, and cholecystokinin expression. RESULTS: In mice, the liquid high-sucrose diet caused an enhancement of total caloric intake compared to the solid high-sucrose diet and the control diet. In addition, the liquid high-sucrose diet increased expression of GLUT2, GLUT5, and cholecystokinin expression in the ileum (P<0.001. Enhanced liver triglyceride accumulation was observed in mice being fed the liquid high-sucrose or -fructose, and the solid high-sucrose diet compared to controls. In obese, GLUT2 and GLUT5 mRNA expression was enhanced in comparison to lean individuals. CONCLUSIONS: We show that the form of sugar intake (liquid versus solid is presumably more important than the type of sugar, with regard to feeding behavior, intestinal sugar uptake and liver fat accumulation in mice. Interestingly, in obese individuals, an intestinal sugar transporter modulation also occurred when compared to lean individuals.

Performance of the majority voting rule in solving the density classification problem in high dimensions

Energy Technology Data Exchange (ETDEWEB)

Gomez Soto, Jose Manuel [Unidad Academica de Matematicas, Universidad Autonoma de Zacatecas, Calzada Solidaridad entronque Paseo a la Bufa, Zacatecas, Zac. (Mexico); Fuks, Henryk, E-mail: jmgomezgoo@gmail.com, E-mail: hfuks@brocku.ca [Department of Mathematics, Brock University, St. Catharines, ON (Canada)

2011-11-04

The density classification problem (DCP) is one of the most widely studied problems in the theory of cellular automata. After it was shown that the DCP cannot be solved perfectly, the research in this area has been focused on finding better rules that could solve the DCP approximately. In this paper, we argue that the majority voting rule in high dimensions can achieve high performance in solving the DCP, and that its performance increases with dimension. We support this conjecture with arguments based on the mean-field approximation and direct computer simulations. (paper)

Performance of the majority voting rule in solving the density classification problem in high dimensions

International Nuclear Information System (INIS)

Gomez Soto, Jose Manuel; Fuks, Henryk

2011-01-01

The density classification problem (DCP) is one of the most widely studied problems in the theory of cellular automata. After it was shown that the DCP cannot be solved perfectly, the research in this area has been focused on finding better rules that could solve the DCP approximately. In this paper, we argue that the majority voting rule in high dimensions can achieve high performance in solving the DCP, and that its performance increases with dimension. We support this conjecture with arguments based on the mean-field approximation and direct computer simulations. (paper)

Oxidation of cholesterol moiety of low density lipoprotein in the presence of human endothelial cells or Cu+2 ions: identification of major products and their effects.

Science.gov (United States)

Bhadra, S; Arshad, M A; Rymaszewski, Z; Norman, E; Wherley, R; Subbiah, M T

1991-04-15

Oxidation of lipoproteins is believed to play a key role in atherogenesis. In this study, low density lipoproteins (LDL) was subjected to oxidation in the presence of either human umbilical vein endothelial cells or with Cu+2 ions and the major oxides formed were identified. While cholesterol-alpha-epoxide (C-alpha EP) was the major product of cholesterol peroxidation in the presence of endothelial cells, cholest-3,5-dien-7-one (CD) predominated in the presence of Cu+2 ion. Both steroids were identified by gas chromatography/mass spectrometry. HDL cholesterol was resistant to oxidation. When tested on human skin fibroblasts in culture C-alpha EP (10 micrograms/ml) caused marked stimulation of 14C-oleate incorporation into cholesterol esters, while CD stimulated cholesterol esterification only mildly. These studies show that a) C-alpha EP is the major peroxidation product of LDL cholesterol moiety in the presence of endothelial cells and b) it causes marked stimulation of cholesterol esterification in cells. C-alpha EP may play a key role in increasing cholesterol esterification noted in atherogenesis.

Anal high-risk human papillomavirus infection and high-grade anal intraepithelial neoplasia detected in women and heterosexual men infected with human immunodeficiency virus

Directory of Open Access Journals (Sweden)

Gandra S

2015-01-01

Full Text Available Sumanth Gandra, Aline Azar, Mireya WessolosskyDivision of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, MA, USABackground: Although anal high-risk human papillomavirus (HR-HPV infection and anal cytological abnormalities are highly prevalent among human immunodeficiency virus (HIV-infected men who have sex with men (MSM, there are insufficient data on these abnormalities among HIV-infected heterosexual men (HSM and women. In this study, we evaluated the prevalence of anal HR-HPV, cytological abnormalities, and performance of these screening tests in detecting high-grade anal intraepithelial neoplasia (AIN2+ among our cohort of HIV-infected MSM and non-MSM (HSM and women.Methods: A single-center, retrospective cohort study was conducted with HIV-infected individuals who underwent anal cancer screening with anal cytology and HR-HPV testing from January 2011 to January 31, 2013.Results: Screening of 221 HIV-infected individuals for both HR-HPV and anal cytology showed the presence of HR-HPV in 54% (abnormal anal cytology 48% of MSM, 28% (abnormal anal cytology 28% of HSM, and 27% (abnormal anal cytology 34% of women. Among 117 (53% individuals with abnormal results (HR-HPV-positive and/or cytology was atypical squamous cells of undetermined significance or above, 67 underwent high resolution anoscopy. Of these 67 individuals, 22 individuals had AIN2+ (17 MSM, four women, and one HSM. HR-HPV correlated better with AIN2+ than with anal cytology on biopsy in both MSM (r=0.29 versus r=0.10; P=0.05 versus P=0.49 and non-MSM (r=0.36 versus r=-0.34; P=0.08 versus P=0.09.Conclusion: Given the presence of AIN2+ in screened HIV-infected HSM and women, routine anal cancer screening in all HIV-infected individuals should be considered. HR-HPV merits further evaluation for anal cancer screening among non-MSM.Keywords: human immunodeficiency virus, anal human papillomavirus, heterosexual men, women, anal cancer

A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System.

Science.gov (United States)

Beliveau, Vincent; Ganz, Melanie; Feng, Ling; Ozenne, Brice; Højgaard, Liselotte; Fisher, Patrick M; Svarer, Claus; Greve, Douglas N; Knudsen, Gitte M

2017-01-04

The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT 1A , 5-HT 1B , 5-HT 2A , and 5-HT 4 ) and the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance imaging (MRI) scans acquired in a total of 210 healthy individuals. Comparison of the regional PET binding measures with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system of the human brain. We present a high-resolution positron emission tomography (PET)- and magnetic resonance imaging-based human brain atlas of important serotonin receptors and the transporter. The regional PET-derived binding measures correlate strongly with the corresponding autoradiography protein levels. The strong correlation enables the transformation of the PET-derived human brain atlas into a protein density map of the serotonin (5-hydroxytryptamine, 5-HT) system. Next, we compared the regional receptor/transporter protein densities with mRNA levels and uncovered unique associations between protein expression and density at high detail. This new in vivo neuroimaging atlas of the 5-HT system not only provides insight in the human brain's regional protein

Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

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Robin Mesnage

2014-01-01

Full Text Available Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3. Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.

Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

Science.gov (United States)

Spiroux de Vendômois, Joël; Séralini, Gilles-Eric

2014-01-01

Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone. PMID:24719846

Enhancing the water management schemes of H08 global hydrological model to attribute human water use to six major water sources

Science.gov (United States)

Hanasaki, N.; Yoshikawa, S.; Pokhrel, Y. N.; Kanae, S.

2017-12-01

Humans abstract water from various sources to sustain their livelihood and society. Some global hydrological models (GHMs) include explicit schemes of human water management, but the representation and performance of these schemes remain limited. We substantially enhanced the human water management schemes of the H08 GHM by incorporating the latest data and techniques. The model enables us to estimate water abstraction from six major water sources, namely, river flow regulated by global reservoirs (i.e., reservoirs regulating the flow of the world's major rivers), aqueduct water transfer, local reservoirs, seawater desalination, renewable groundwater, and nonrenewable groundwater. All the interactions were simulated in a single computer program and the water balance was always strictly closed at any place and time during the simulation period. Using this model, we first conducted a historical global hydrological simulation at a spatial resolution of 0.5 x 0.5 degree to specify the sources of water for humanity. The results indicated that, in 2000, of the 3628 km3yr-1 global freshwater requirement, 2839 km3yr-1 was taken from surface water and 789 km3yr-1 from groundwater. Streamflow, aqueduct water transfer, local reservoirs, and seawater desalination accounted for 1786, 199, 106, and 1.8 km3yr-1 of the surface water, respectively. The remaining 747 km3yr-1 freshwater requirement was unmet, or surface water was not available when and where it was needed in our simulation. Renewable and nonrenewable groundwater accounted for 607 and 182 km3yr-1 of the groundwater total, respectively. Second, we evaluated the water stress using our simulations and contrasted it with earlier global assessments based on empirical water scarcity indicators, namely, the Withdrawal to Availability ratio and the Falkenmark index (annual renewable water resources per capita). We found that inclusion of water infrastructures in our model diminished water stress in some parts of the world, on

Silver and lead in high-altitude lake sediments: Proxies for climate changes and human activities

International Nuclear Information System (INIS)

Garçon, Marion; Chauvel, Catherine; Chapron, Emmanuel; Faïn, Xavier; Lin, Mingfang; Campillo, Sylvain; Bureau, Sarah; Desmet, Marc; Bailly-Maître, Marie-Christine; Charlet, Laurent

2012-01-01

High-altitude lake sediments are often used as archives for environmental changes and their chemical and isotopic compositions provide significant constraints on natural and anthropogenic long-term changes that have occurred in their catchment area. Here, trace-element concentrations and Pb isotopes are presented for two sedimentary cores from Lake Blanc Huez in the French Alps, to trace the impact of climate changes and human activities over the Holocene. Lead and Ag contents are very high and clearly dominated by input from a Pb–Ag vein located a few meters from the lakeshore, a vein that also buffers the Pb isotopes. Mining of this vein in medieval times is recorded in the corresponding lake sediments with high Ag content coupled with high Pb/U ratio. These chemical characteristics can be used to constrain the major Holocene climate changes. Significant advances of glaciers next to the lake produced sediments with Ag and Pb concentration peaks and high Pb/U ratios due to accelerated erosion of the Pb–Ag vein, similar to the effects of the medieval mining. In contrast, reduced glacier activity led to the formation of organic-rich sediments with high U and As contents and low Pb/U ratios. More generally, the observed combination of chemical changes could be used elsewhere to decipher environmental changes over long periods of time.

Hybridization of two major termite invaders as a consequence of human activity.

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Chouvenc, Thomas; Helmick, Ericka E; Su, Nan-Yao

2015-01-01

While hybridization of an invasive species with a native species is a common occurrence, hybridization between two invasive species is rare. Formosan subterranean termites (Coptotermes formosanus) and Asian subterranean termites (C. gestroi) are both ecologically successful and are the two most economically important termite pests in the world. Both species have spread throughout many areas of the world due to human activity; however, their distributions overlap in only three narrow areas because of distinct ecological requirements. In south Florida, where C. formosanus and C. gestroi are both invasive, the dispersal flight seasons of both species overlapped for the first time on record in 2013 and 2014. Pairings of heterospecific individuals were readily observed in the field and C. gestroi males preferentially engaged in mating behavior with C. formosanus females rather than females from their own species. In the laboratory, heterospecific and conspecific pairings had an equal colony establishment rate, but heterospecific incipient colonies had twice the growth rate of conspecific incipient colonies, suggesting a potential case of hybrid vigor. As all pre-zygotic barriers were lifted between the two species in the field, the apparent absence of post-zygotic barriers in the laboratory raises the possibility for introgressive hybridization in south Florida. While laboratory observations remain to be confirmed in the field, and the alate hybrid fertility is currently unknown, our results raise a tangible concern about the hybridization of two major destructive pest species. Such hybridization would likely be associated with a new economic impact.

The Effective Practices and Beliefs of School Principals in High Achieving Hispanic Majority Mid-Level Schools

Science.gov (United States)

Briseno, Johnny

2010-01-01

This qualitative phenomenological research study used narrative inquiry to investigate the effective practices and beliefs of 10 Texas principals in high achieving majority Hispanic mid-level schools. Participant interviews were analyzed using the Creswell (2007) six step method for analyzing phenomenological studies. Findings from this study…

Transcriptome analysis of exosome-compromised human cells using high-density tiling arrays

DEFF Research Database (Denmark)

Jensen, Torben Heick

The extent of RNA degradation in the nucleus has traditionally been underestimated. However, all major RNA species are synthesized, processed and can be degraded in this compartment and consequently an enormous amount of nucleosides are turned over and recycled. The RNA exosome, a multisubunit co......) tiling array that covers discrete regions from different chromosomes to represent a range of gene content and exonic/nonexonic conservation grades of the human genome....

High-field fMRI unveils orientation columns in humans.

Science.gov (United States)

Yacoub, Essa; Harel, Noam; Ugurbil, Kâmil

2008-07-29

Functional (f)MRI has revolutionized the field of human brain research. fMRI can noninvasively map the spatial architecture of brain function via localized increases in blood flow after sensory or cognitive stimulation. Recent advances in fMRI have led to enhanced sensitivity and spatial accuracy of the measured signals, indicating the possibility of detecting small neuronal ensembles that constitute fundamental computational units in the brain, such as cortical columns. Orientation columns in visual cortex are perhaps the best known example of such a functional organization in the brain. They cannot be discerned via anatomical characteristics, as with ocular dominance columns. Instead, the elucidation of their organization requires functional imaging methods. However, because of insufficient sensitivity, spatial accuracy, and image resolution of the available mapping techniques, thus far, they have not been detected in humans. Here, we demonstrate, by using high-field (7-T) fMRI, the existence and spatial features of orientation- selective columns in humans. Striking similarities were found with the known spatial features of these columns in monkeys. In addition, we found that a larger number of orientation columns are devoted to processing orientations around 90 degrees (vertical stimuli with horizontal motion), whereas relatively similar fMRI signal changes were observed across any given active column. With the current proliferation of high-field MRI systems and constant evolution of fMRI techniques, this study heralds the exciting prospect of exploring unmapped and/or unknown columnar level functional organizations in the human brain.

Human Contamination in Public Genome Assemblies.

Science.gov (United States)

Kryukov, Kirill; Imanishi, Tadashi

2016-01-01

Contamination in genome assembly can lead to wrong or confusing results when using such genome as reference in sequence comparison. Although bacterial contamination is well known, the problem of human-originated contamination received little attention. In this study we surveyed 45,735 available genome assemblies for evidence of human contamination. We used lineage specificity to distinguish between contamination and conservation. We found that 154 genome assemblies contain fragments that with high confidence originate as contamination from human DNA. Majority of contaminating human sequences were present in the reference human genome assembly for over a decade. We recommend that existing contaminated genomes should be revised to remove contaminated sequence, and that new assemblies should be thoroughly checked for presence of human DNA before submitting them to public databases.

Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

Directory of Open Access Journals (Sweden)

Claudia Mastroeni

Full Text Available Repetitive transcranial magnetic stimulation (rTMS of the human motor hand area (M1HAND can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66met polymorphism in the brain-derived neurotrophic factor (BDNF gene. Here we used theta burst stimulation (TBS to examine whether the BDNF val(66met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS usually inducing a lasting increase and continuous TBS (cTBS a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66met (n = 12 and val(66val (n = 17 carriers received neuronavigated cTBS followed by cTBS (n = 27, cTBS followed by iTBS (n = 29, and iTBS followed by iTBS (n = 28. Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS and increase (iTBS in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66met carriers and val(66val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66met polymorphism, our results do not support the notion that the BDNF val(66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

Science.gov (United States)

Mastroeni, Claudia; Bergmann, Til Ole; Rizzo, Vincenzo; Ritter, Christoph; Klein, Christine; Pohlmann, Ines; Brueggemann, Norbert; Quartarone, Angelo; Siebner, Hartwig Roman

2013-01-01

Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val(66)met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

Observations on the expression of human papillomavirus major capsid protein in HeLa cells.

Science.gov (United States)

Xiao, Chang-Yi; Fu, Bing-Bing; Li, Zhi-Ying; Mushtaq, Gohar; Kamal, Mohammad Amjad; Li, Jia-Hua; Tang, Gui-Cheng; Xiao, Shuo-Shuang

2015-01-01

The goal of this study was to identify the nature of the inclusion bodies that have been found in HeLa cells (cervical cancer immortal cell line) by electron microscope and to determine whether the major capsid protein (L1) of human papillomavirus (HPV) can be expressed in HPV-positive uterine cervix cancer cells. HPV L1 protein expression in HeLa cells was detected with anti-HPV L1 multivalent mice monoclonal antibody and rabbit polyclonal anti-HPV L1 antibody by ELISA, light microscope immunohistochemistry, electron microscope immunocytochemistry and Western blotting assays. Reverse transcriptional PCR (RT-PCR) was performed to detect the transcription of L1 mRNA in HeLa cells. The immortalized human keratinocyte HeCat was used as the negative control. HPV L1 proteins reacted positively in the lysate of HeLa cells by ELISA assays. HRP labeled light microscope immunohistochemistry assay showed that there was a strong HPV L1 positive reaction in HeLa cells. Under the electron microscope, irregular shaped inclusion bodies, assembled by many small and uniform granules, had been observed in the cytoplasm of some HeLa cells. These granules could be labeled by the colloidal gold carried by HPV L1 antibody. The Western blotting assay showed that there was a L1 reaction strap at 80-85 kDa in the HeLa cell lysates, hence demonstrating the existence of HPV18 L1 in HeLa cells. RT-PCR assay showed that the L1 mRNA was transcribed in HeLa cells. The inclusion bodies found in the cytoplasm of HeLa cells are composed of HPV18 L1 protein. Since HeLa cell line is a type of cervical cancer cells, this implies that HeLa cells have the ability to express HPV L1 proteins.

A study of particulate emissions during 23 major industrial fires: Implications for human health.

Science.gov (United States)

Griffiths, Simon D; Chappell, Philip; Entwistle, Jane A; Kelly, Frank J; Deary, Michael E

2018-03-01

Public exposure to significantly elevated levels of particulate matter (PM) as a result of major fires at industrial sites is a worldwide problem. Our paper describes how the United Kingdom developed its Air Quality in Major Incidents (AQinMI) service to provide fire emission plume concentration data for use by managers at the time of the incident and to allow an informed public health response. It is one of the first civilian services of its type anywhere in the world. Based on the involvement of several of the authors in the AQinMI service, we describe the service's function, detail the nature of fires covered by the service, and report for the first time on the concentration ranges of PM to which populations may be exposed in major incident fires. We also consider the human health impacts of short-term exposure to significantly elevated PM concentrations and reflect on the appropriateness of current short-term guideline values in providing public health advice. We have analysed monitoring data for airborne PM (≤10μm, PM 10 ;≤2.5μm, PM 2.5 and ≤1.0μm, PM 1 ) collected by AQinMI teams using an Osiris laser light scattering monitor, the UK Environment Agency's 'indicative standard' equipment, during deployment to 23 major incident industrial fires. In this context, 'indicative' is applied to monitoring equipment that provides confirmation of the presence of particulates and indicates a measured mass concentration value. Incident-averaged concentrations ranged from 38 to 1450μgm -3 for PM 10 and 7 to 258μgm -3 for PM 2.5 . Of concern was that, for several incidents, 15-min averaged concentrations reached >6500μgm -3 for PM 10 and 650μgm -3 for PM 2.5 , though such excursions tended to be of relatively short duration. In the absence of accepted very short-term (15-min to 1-h) guideline values for PM 10 and PM 2.5, we have analysed the relationship between the 1-h and 24-h threshold values and whether the former can be used as a predictor of longer

High protective efficacy of probiotics and rice bran against human norovirus infection and diarrhea in gnotobiotic pigs

Directory of Open Access Journals (Sweden)

Shaohua Lei

2016-11-01

Full Text Available Probiotics have been recognized as vaccine adjuvants and therapeutic agents to treat acute gastroenteritis in children. We previously showed that rice bran reduced human rotavirus diarrhea in gnotobiotic pigs. Human noroviruses (HuNoVs are the major pathogens causing nonbacterial acute gastroenteritis worldwide. In this study, Lactobacillus rhamnosus GG (LGG and Escherichia coli Nissle 1917 (EcN were first screened for their ability to bind HuNoV P particles and virions derived from clinical samples containing HuNoV genotype GII.3 and GII.4, then the effects of LGG+EcN and rice bran on HuNoV infection and diarrhea were investigated using the gnotobiotic pig model. While LGG+EcN colonization inhibited HuNoV shedding, probiotic cocktail regimens in which rice bran feeding started 7 days prior to or 1 day after viral inoculation in the LGG+EcN colonized gnotobiotic pigs exhibited high protection against HuNoV diarrhea and shedding, characterized by significantly reduced incidence (89% versus 20% and shorter mean duration of diarrhea (2.2 versus 0.2 days, as well as shorter mean duration of virus shedding (3.2 versus 1.0 days. In both probiotic cocktail groups, the diarrhea reduction rates were 78% compared with the control group, and diarrhea severity was reduced as demonstrated by the significantly lower cumulative fecal scores. The high protective efficacy of the probiotic cocktail regimens was attributed to stimulation of IFN-γ+ T cell responses, increased production of intestinal IgA and IgG, and maintenance of healthy intestinal morphology (manifested as longer villi compared with the control group. Therefore, probiotic cocktail regimens containing LGG+EcN and rice bran may represent highly efficacious strategies to prevent and treat HuNoV gastroenteritis, and potentially other human enteric pathogens.

Cooking and the human commitment to a high-quality diet.

Science.gov (United States)

Carmody, R N; Wrangham, R W

2009-01-01

For our body size, humans exhibit higher energy use yet reduced structures for mastication and digestion of food compared to chimpanzees, our closest living relatives. This suite of features suggests that humans are adapted to a high-quality diet. Although increased consumption of meat during human evolution certainly contributed to dietary quality, meat-eating alone appears to be insufficient to support the evolution of these traits, because modern humans fare poorly on raw diets that include meat. Here, we suggest that cooking confers physical and chemical benefits to food that are consistent with observed human dietary adaptations. We review evidence showing that cooking facilitates mastication, increases digestibility, and otherwise improves the net energy value of plant and animal foods regularly consumed by humans. We also address the likelihood that cooking was adopted more than 250,000 years ago (kya), a period that we believe is sufficient in length for the proposed adaptations to have occurred. Additional experimental work is needed to help discriminate the relative contributions of cooking, meat eating, and other innovations such as nonthermal food processing in supporting the human transition toward dietary quality.

Antibody responses to a major Pneumocystis carinii antigen in human immunodeficiency virus-infected patients with and without P. carinii pneumonia

DEFF Research Database (Denmark)

Lundgren, Bettina; Lundgren, Jens Dilling; Nielsen, T

1992-01-01

of pulmonary symptoms. Significantly more patients with P. carinii pneumonia (PCP) had detectable antibodies compared with HIV-infected patients without PCP and with HIV-negative controls (50 [66%] of 76 vs. 18 [34%] of 53 and 7 [35%] of 20, respectively; P less than .001), and the level of antibody response......Antibody responses to a major purified human Pneumocystis carinii surface antigen (gp95) were determined by ELISA in human immunodeficiency virus (HIV)-infected patients. Serum IgG directed against gp95 was measured in 129 consecutive HIV-infected patients who underwent bronchoscopy for evaluation...... response, compared with only 1 (3%) of 31 patients without PCP (P less than .001). This patient had PCP on the basis of clinical criteria, including response to therapy. Thus, despite severe immunosuppression, a proportion of HIV-infected patients with PCP can mount a specific IgG-mediated antibody...

Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons

OpenAIRE

Morelli, Annamaria; Comeglio, Paolo; Sarchielli, Erica; Cellai, Ilaria; Vignozzi, Linda; Vannelli, Gabriella B.; Maggi, Mario

2013-01-01

Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose...

Climate change and human health

International Nuclear Information System (INIS)

Sanderson, G.

1991-01-01

Changes in the earth's climate, stemming from the greenhouse effect, are highly likely to damage human health. As well as the disruptions to food and fresh water supplies, there is the prospect of major diseases flourishing in warmer conditions, in addition the decrease in the ozone layer is causing an increased incidence of skin cancer

Plasma fibronectin in patients undergoing major surgery

International Nuclear Information System (INIS)

Sallam, M.H.M.

2003-01-01

Plasma fibronectin in patients undergoing major surgery had been determined before and after operation. The study was done on 15 patients and 15 normal healthy individuals. The study revealed that patients subjected to major operation, their fibronectin level was normal before operation followed by reduction one day post-operation. After one week, fibronectin level raised again nearly to the pre-operations levels. The probable mechanisms of fibronectin in healing processes were discussed. Fibronectin (FN) is a family of structurally and immunologically related high molecular weight glycoproteins that are present in many cell surfaces, in extracellular fluids, in connective tissues and in most membranes. Interaction with certain discrete extracellular substances, such as a glucosaminoglycans (e.g. heparin), fibrin and collagen and with cell surface structure seem to account for many of its biological activities, among which are regulation of adhesion, spreading and locomotion (Mosesson and amrani, 1980). The concentration of Fn in human plasma decreases after extensive destruction such as that occurs in major surgery, burns or other trauma. This decrease has been generally though to be due to increased consumption of soluble plasma Fn in opsonization of particulate and soluble debris from circulation by the reticuloendothelial (RE) system. Fn rapidly appears in injury areas, in experimentally induced blisters, wounded and epithelium tissues (Petersen et al., 1985). Fn accumulates at times of increased vascular permeability and it is produced by cell of blood vessels in response to injury

High pressure treatment of human norovirus virus-like particles: factors affecting destruction efficacy

Science.gov (United States)

Human norovirus (NoV) accounts for more than 90% of nonbacterial gastroenteritis. To date, the efficacy of human NoV inactivation interventions cannot be accurately evaluated because the virus is nonculturable. In this study, we aimed to estimate inactivation of human NoV by high pressure processing...

Distortion product otoacoustic emissions in college music majors and nonmusic majors

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Rebecca L. Warner Henning

2016-01-01

Full Text Available The presence and absence of distortion product otoacoustic emissions (DPOAEs as well as DPOAE amplitudes were compared between college music majors and a control group of nonmusic majors. Participants included 28 music majors and 35 nonmusic majors enrolled at a university with ages ranging from 18-25 years. DPOAEs and hearing thresholds were measured bilaterally on all the participants. DPOAE amplitudes were analyzed at the following f2 frequencies: 1,187 Hz, 1,500 Hz, 1,906 Hz, 2,531 Hz, 3,031 Hz, 3812 Hz, 4,812 Hz, and 6,031 Hz. Significantly more music majors (7/28 than nonmusic majors (0/35 exhibited absent DPOAEs for at least one frequency in at least one ear. Both groups of students reported similar histories of recreational and occupational noise exposures that were unrelated to studying music, and none of the students reported high levels of noise exposure within the previous 48 h. There were no differences in audiometric thresholds between the groups at any frequency. At DPOAE f2 frequencies from 3,031 Hz to 6,031 Hz, nonsignificantly lower amplitudes of 2-4 dB were seen in the right ears of music majors versus nonmajors, and in the right ears of music majors playing brass instruments compared to music majors playing nonbrass instruments. Given the greater prevalence of absent DPOAEs in university music majors compared to nonmusic majors, it appears that early stages of cochlear damage may be occurring in this population. Additional research, preferably longitudinal and across multiple colleges/universities, would be beneficial to more definitively determine when the music students begin to show signs of cochlear damage, and to identify whether any particular subgroups of music majors are at a greater risk of cochlear damage.

The human factor in operation and maintenance of complex high-reliability systems

International Nuclear Information System (INIS)

Ryan, T.G.

1989-01-01

Human factors issues in probabilistic risk assessment (PRAs) of complex high-reliability systems are addressed. These PRAs influence system operation and technical support programs such as maintainability, test, and surveillance. Using the U.S. commercial nuclear power industry as the setting, the paper addresses the manner in which PRAs currently treat human performance, the state of quantification methods and source data for analyzing human performance, and the role of human factors specialist in the analysis. The paper concludes with a presentation of TALENT, an emerging concept for fully integrating broad-based human factors expertise into the PRA process, is presented. 47 refs

Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons

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Annamaria Morelli

2013-01-01

Full Text Available Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose effects in the human GnRH-secreting FNC-B4 cells. Gene expression profiling by qRT-PCR, confirmed that FNC-B4 cells express GnRH and several genes relevant for GnRH neuron function (KISS1R, KISS1, sex steroid and leptin receptors, FGFR1, neuropilin 2, and semaphorins, along with glucose transporters (GLUT1, GLUT3, and GLUT4. High glucose exposure (22 mM; 40 mM significantly reduced gene and protein expression of GnRH, KISS1R, KISS1, and leptin receptor, as compared to normal glucose (5 mM. Consistent with previous studies, leptin treatment significantly induced GnRH mRNA expression at 5 mM glucose, but not in the presence of high glucose concentrations. In conclusion, our findings demonstrate a deleterious direct contribution of high glucose on human GnRH neurons, thus providing new insights into pathogenic mechanisms linking metabolic disorders to reproductive dysfunctions.

Incidence of high-level evernimicin resistance in Enterococcus faecium among food animals and humans

DEFF Research Database (Denmark)

Aarestrup, Frank Møller; McNicholas, P. M.

2002-01-01

Six high-level evernimicin-resistant Enterococcus faecium isolates were identified among 304 avilarnycin-resistant E. faecium isolates from animals and 404 stool samples from humans with diarrhea. All four animal isolates, and one of the human isolates, were able to transfer resistance...... to a susceptible E. faecium strain. The resulting transconjugants all tested positive for the presence of emtA, a gene encoding a methyltransferase previously linked with high-level evernimicin resistance. The four transconjugants derived from animal isolates all carried the same plasmid, while a differently sized...... plasmid was found in the isolate from humans. This study demonstrated a low incidence of high-level evernimicin resistance mediated by the emtA gene in different E. faecium isolates of animal and human origin....

Hybridization of two major termite invaders as a consequence of human activity.

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Thomas Chouvenc

Full Text Available While hybridization of an invasive species with a native species is a common occurrence, hybridization between two invasive species is rare. Formosan subterranean termites (Coptotermes formosanus and Asian subterranean termites (C. gestroi are both ecologically successful and are the two most economically important termite pests in the world. Both species have spread throughout many areas of the world due to human activity; however, their distributions overlap in only three narrow areas because of distinct ecological requirements. In south Florida, where C. formosanus and C. gestroi are both invasive, the dispersal flight seasons of both species overlapped for the first time on record in 2013 and 2014. Pairings of heterospecific individuals were readily observed in the field and C. gestroi males preferentially engaged in mating behavior with C. formosanus females rather than females from their own species. In the laboratory, heterospecific and conspecific pairings had an equal colony establishment rate, but heterospecific incipient colonies had twice the growth rate of conspecific incipient colonies, suggesting a potential case of hybrid vigor. As all pre-zygotic barriers were lifted between the two species in the field, the apparent absence of post-zygotic barriers in the laboratory raises the possibility for introgressive hybridization in south Florida. While laboratory observations remain to be confirmed in the field, and the alate hybrid fertility is currently unknown, our results raise a tangible concern about the hybridization of two major destructive pest species. Such hybridization would likely be associated with a new economic impact.

Electromagnetic Modeling of Human Body Using High Performance Computing

Science.gov (United States)

Ng, Cho-Kuen; Beall, Mark; Ge, Lixin; Kim, Sanghoek; Klaas, Ottmar; Poon, Ada

Realistic simulation of electromagnetic wave propagation in the actual human body can expedite the investigation of the phenomenon of harvesting implanted devices using wireless powering coupled from external sources. The parallel electromagnetics code suite ACE3P developed at SLAC National Accelerator Laboratory is based on the finite element method for high fidelity accelerator simulation, which can be enhanced to model electromagnetic wave propagation in the human body. Starting with a CAD model of a human phantom that is characterized by a number of tissues, a finite element mesh representing the complex geometries of the individual tissues is built for simulation. Employing an optimal power source with a specific pattern of field distribution, the propagation and focusing of electromagnetic waves in the phantom has been demonstrated. Substantial speedup of the simulation is achieved by using multiple compute cores on supercomputers.

Seroprevalence of Toxoplasma gondii in humans and pigs in North Sulawesi, Indonesia.

Science.gov (United States)

Tuda, Josef; Adiani, Sri; Ichikawa-Seki, Madoka; Umeda, Kousuke; Nishikawa, Yoshifumi

2017-10-01

Toxoplasma gondii, an intracellular protozoan parasite, is a major public health concern throughout the world. Importantly, toxoplasmosis has several adverse effects, including neurological and ocular diseases. There are currently no data on the prevalence of T. gondii infection in humans or animals in North Sulawesi, although Indonesia is known to have a high seroprevalence of this parasite. In this study, the prevalence of T. gondii was determined in samples of humans and pigs from North Sulawesi using the latex agglutination test. In total, 856 human were sampled and 58.5% of whom were positive for T. gondii. Although the antibody prevalence in male and female children aged 0-9years was 40% in both sexes, suggesting that the transmission rate of the parasite to humans is extremely high in this area. However, the overall prevalence of T. gondii in pigs was only 2.3%. Our study indicates a high incidence of T. gondii infection in humans. Therefore, a survey of the prevalence of T. gondii among different infection sources is required to determine the major risk factors for infection in North Sulawesi. Copyright © 2017 Elsevier B.V. All rights reserved.

High-temperature superconductors make major progress

CERN Multimedia

CERN Bulletin

2014-01-01

This month's Nature Materials featured an important breakthrough for high-temperature superconductors. A new method has been found for processing Bi-2212 high-temperature superconducting round wire in order to drastically increase its critical current density. The result confirms that this conductor is a serious candidate for future very-high-field magnets.   This image shows the cross-section of two Bi-2212 wires. The bottom wire has less leakage and void porosity due to a heat treatment done at an overpressure of 100 bar - about 100 times the pressure used to produce the top wire (image from [Nature Materials, Vol. 13 (2014), 10.1038/nmat3887]). The workhorse for building superconducting accelerator magnets has been, so far, the Niobium-Titanium (Nb-Ti) alloy superconductor. But with Nb-Ti having reached its full potential, other conductors must be used to operate in higher magnetic fields beyond those reached with the LHC magnets. Today, the intermetallic Niobium-Tin (Nb3Sn) is th...

A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System

DEFF Research Database (Denmark)

Beliveau, Vincent; Ganz-Benjaminsen, Melanie; Feng, Ling

2017-01-01

The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4...... with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human...... brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system...

Development of a new high-affinity human antibody with antitumor activity against solid and blood malignancies.

Science.gov (United States)

Sioud, Mouldy; Westby, Phuong; Vasovic, Vlada; Fløisand, Yngvar; Peng, Qian

2018-04-16

mAbs have emerged as a promising strategy for the treatment of cancer. However, in several malignancies, no effective antitumor mAbs are yet available. Identifying therapeutic mAbs that recognize common tumor antigens could render the treatment widely applicable. Here, a human single-chain variable fragment (scFv) antibody library was sequentially affinity selected against a panel of human cancer cell lines and an antibody fragment (named MS5) that bound to solid and blood cancer cells was identified. The MS5 scFv was fused to the human IgG1 Fc domain to generate an antibody (MS5-Fc fusion) that induced antibody-dependent cellular cytotoxicity and phagocytosis of cancer cells by macrophages. In addition, the MS5-Fc antibody bound to primary leukemia cells and induced antibody-dependent cellular cytotoxicity. In the majority of analyzed cancer cells, the MS5-Fc antibody induced cell surface redistribution of the receptor complexes, but not internalization, thus maximizing the accessibility of the IgG1 Fc domain to immune effector cells. In vitro stability studies showed that the MS5-Fc antibody was stable after 6 d of incubation in human serum, retaining ∼60% of its initial intact form. After intravenous injections, the antibody localized into tumor tissues and inhibited the growth of 3 different human tumor xenografts (breast, lymphoma, and leukemia). These antitumor effects were associated with tumor infiltration by macrophages and NK cells. In the Ramos B-cell lymphoma xenograft model, the MS5-Fc antibody exhibited a comparable antitumor effect as rituximab, a chimeric anti-CD20 IgG1 mAb. These results indicate that human antibodies with pan-cancer abilities can be generated from phage display libraries, and that the engineered MS5-Fc antibody could be an attractive agent for further clinical investigation.-Sioud, M., Westby, P., Vasovic, V., Fløisand, Y., Peng, Q. Development of a new high-affinity human antibody with antitumor activity against solid and

Ontology-Based High-Level Context Inference for Human Behavior Identification

Science.gov (United States)

Villalonga, Claudia; Razzaq, Muhammad Asif; Khan, Wajahat Ali; Pomares, Hector; Rojas, Ignacio; Lee, Sungyoung; Banos, Oresti

2016-01-01

Recent years have witnessed a huge progress in the automatic identification of individual primitives of human behavior, such as activities or locations. However, the complex nature of human behavior demands more abstract contextual information for its analysis. This work presents an ontology-based method that combines low-level primitives of behavior, namely activity, locations and emotions, unprecedented to date, to intelligently derive more meaningful high-level context information. The paper contributes with a new open ontology describing both low-level and high-level context information, as well as their relationships. Furthermore, a framework building on the developed ontology and reasoning models is presented and evaluated. The proposed method proves to be robust while identifying high-level contexts even in the event of erroneously-detected low-level contexts. Despite reasonable inference times being obtained for a relevant set of users and instances, additional work is required to scale to long-term scenarios with a large number of users. PMID:27690050

Ontology-Based High-Level Context Inference for Human Behavior Identification

Directory of Open Access Journals (Sweden)

Claudia Villalonga

2016-09-01

Full Text Available Recent years have witnessed a huge progress in the automatic identification of individual primitives of human behavior, such as activities or locations. However, the complex nature of human behavior demands more abstract contextual information for its analysis. This work presents an ontology-based method that combines low-level primitives of behavior, namely activity, locations and emotions, unprecedented to date, to intelligently derive more meaningful high-level context information. The paper contributes with a new open ontology describing both low-level and high-level context information, as well as their relationships. Furthermore, a framework building on the developed ontology and reasoning models is presented and evaluated. The proposed method proves to be robust while identifying high-level contexts even in the event of erroneously-detected low-level contexts. Despite reasonable inference times being obtained for a relevant set of users and instances, additional work is required to scale to long-term scenarios with a large number of users.

Coping with ecological catastrophe: crossing major thresholds

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John Cairns, Jr.

2004-08-01

Full Text Available The combination of human population growth and resource depletion makes catastrophes highly probable. No long-term solutions to the problems of humankind will be discovered unless sustainable use of the planet is achieved. The essential first step toward this goal is avoiding or coping with global catastrophes that result from crossing major ecological thresholds. Decreasing the number of global catastrophes will reduce the risks associated with destabilizing ecological systems, which could, in turn, destabilize societal systems. Many catastrophes will be local, regional, or national, but even these upheavals will have global consequences. Catastrophes will be the result of unsustainable practices and the misuse of technology. However, avoiding ecological catastrophes will depend on the development of eco-ethics, which is subject to progressive maturation, comments, and criticism. Some illustrative catastrophes have been selected to display some preliminary issues of eco-ethics.

Computer-aided method for identification of major flavone/flavonol glycosides by high-performance liquid chromatography-diode array detection-tandem mass spectrometry (HPLC-DAD-MS/MS).

Science.gov (United States)

Wang, Zhengfang; Lin, Longze; Harnly, James M; Harrington, Peter de B; Chen, Pei

2014-11-01

A new computational tool is proposed here for tentatively identifying major (UV quantifiable) flavone/flavonol glycoside peaks of high performance liquid chromatogram (HPLC)-diode array detection (DAD)-tandem mass spectrometry (MS/MS) profiles based on a MATLAB-based script implementing an in-house algorithm. The HPLC-DAD-MS/MS profiles of red onion, Chinese lettuce, carrot leaf, and celery seed extracts were analyzed by the proposed computer-aided screening method for identifying possible flavone/flavonol glycoside peaks from the HPLC-UV and MS total ion current (TIC) chromatograms. The number of identified flavone/flavonol glycoside peaks of the HPLC-UV chromatograms is four, four, six, and nine for red onion, Chinese lettuce, carrot leaf, and celery seed, respectively. These results have been validated by human(s) experts. For the batch processing of nine HPLC-DAD-MS/MS profiles of celery seed extract, the entire script execution time was within 15 s while manual calculation of only one HPLC-DAD-MS/MS profile by a flavonoid expert could take hours. Therefore, this MATLAB-based screening method is able to facilitate the HPLC-DAD-MS/MS analysis of flavone/flavonol glycosides in plants to a large extent.

Mixtures of endocrine disrupting contaminants modelled on human high end exposures

DEFF Research Database (Denmark)

Christiansen, Sofie; Kortenkamp, A.; Petersen, Marta Axelstad

2012-01-01

exceeding 1 is expected to lead to effects in the rat, a total dose more than 62 times higher than human exposures should lead to responses. Considering the high uncertainty of this estimate, experience on lowest‐observed‐adverse‐effect‐level (LOAEL)/NOAEL ratios and statistical power of rat studies, we...... expected that combined doses 150 times higher than high end human intake estimates should give no, or only borderline effects, whereas doses 450 times higher should produce significant responses. Experiments indeed showed clear developmental toxicity of the 450‐fold dose in terms of increased nipple...... though each individual chemical is present at low, ineffective doses, but the effects of mixtures modelled based on human intakes have not previously been investigated. To address this issue for the first time, we selected 13 chemicals for a developmental mixture toxicity study in rats where data about...

An integrated tool to study MHC region: accurate SNV detection and HLA genes typing in human MHC region using targeted high-throughput sequencing.

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Hongzhi Cao

Full Text Available The major histocompatibility complex (MHC is one of the most variable and gene-dense regions of the human genome. Most studies of the MHC, and associated regions, focus on minor variants and HLA typing, many of which have been demonstrated to be associated with human disease susceptibility and metabolic pathways. However, the detection of variants in the MHC region, and diagnostic HLA typing, still lacks a coherent, standardized, cost effective and high coverage protocol of clinical quality and reliability. In this paper, we presented such a method for the accurate detection of minor variants and HLA types in the human MHC region, using high-throughput, high-coverage sequencing of target regions. A probe set was designed to template upon the 8 annotated human MHC haplotypes, and to encompass the 5 megabases (Mb of the extended MHC region. We deployed our probes upon three, genetically diverse human samples for probe set evaluation, and sequencing data show that ∼97% of the MHC region, and over 99% of the genes in MHC region, are covered with sufficient depth and good evenness. 98% of genotypes called by this capture sequencing prove consistent with established HapMap genotypes. We have concurrently developed a one-step pipeline for calling any HLA type referenced in the IMGT/HLA database from this target capture sequencing data, which shows over 96% typing accuracy when deployed at 4 digital resolution. This cost-effective and highly accurate approach for variant detection and HLA typing in the MHC region may lend further insight into immune-mediated diseases studies, and may find clinical utility in transplantation medicine research. This one-step pipeline is released for general evaluation and use by the scientific community.

A multi-sample based method for identifying common CNVs in normal human genomic structure using high-resolution aCGH data.

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Chihyun Park

Full Text Available BACKGROUND: It is difficult to identify copy number variations (CNV in normal human genomic data due to noise and non-linear relationships between different genomic regions and signal intensity. A high-resolution array comparative genomic hybridization (aCGH containing 42 million probes, which is very large compared to previous arrays, was recently published. Most existing CNV detection algorithms do not work well because of noise associated with the large amount of input data and because most of the current methods were not designed to analyze normal human samples. Normal human genome analysis often requires a joint approach across multiple samples. However, the majority of existing methods can only identify CNVs from a single sample. METHODOLOGY AND PRINCIPAL FINDINGS: We developed a multi-sample-based genomic variations detector (MGVD that uses segmentation to identify common breakpoints across multiple samples and a k-means-based clustering strategy. Unlike previous methods, MGVD simultaneously considers multiple samples with different genomic intensities and identifies CNVs and CNV zones (CNVZs; CNVZ is a more precise measure of the location of a genomic variant than the CNV region (CNVR. CONCLUSIONS AND SIGNIFICANCE: We designed a specialized algorithm to detect common CNVs from extremely high-resolution multi-sample aCGH data. MGVD showed high sensitivity and a low false discovery rate for a simulated data set, and outperformed most current methods when real, high-resolution HapMap datasets were analyzed. MGVD also had the fastest runtime compared to the other algorithms evaluated when actual, high-resolution aCGH data were analyzed. The CNVZs identified by MGVD can be used in association studies for revealing relationships between phenotypes and genomic aberrations. Our algorithm was developed with standard C++ and is available in Linux and MS Windows format in the STL library. It is freely available at: http://embio.yonsei.ac.kr/~Park/mgvd.php.

Roles of different IRES-dependent FGF2 isoforms in the acquisition of the major aggressive features of human metastatic melanoma.

Science.gov (United States)

Andreucci, Elena; Bianchini, Francesca; Biagioni, Alessio; Del Rosso, Mario; Papucci, Laura; Schiavone, Nicola; Magnelli, Lucia

2017-01-01

Fibroblast growth factor 2 (FGF2) is involved in many physiological and pathological processes. Fgf2 deregulation contributes to the acquisition of malignant features of melanoma and other cancers. FGF2 is an alternative translation product expressed as five isoforms, a low-molecular-weight (18 KDa) and four high-molecular-weight (22, 22.5, 24, 34 KDa) isoforms, with different subcellular distributions. An internal ribosomal entry site (IRES) in its mRNA controls the translation of all the isoforms with the exception for the cap-dependent 34 KDa. The 18-KDa isoform has been extensively studied, while very few is known about the roles of high molecular weight isoforms. FGF2 is known to promote melanoma development and progression. To disclose the differential contribution of FGF2 isoforms in melanoma, we forced the expression of IRES-dependent low-molecular-weight (LMW, 18 KDa) and high-molecular-weight (HMW, 22, 22.5, 24 KDa) isoforms in a human metastatic melanoma cell line. This comparative study highlights that, while LMW isoform confers stem-like features to melanoma cells and promotes angiogenesis, HMW isoforms induce higher migratory ability and contribute to tumor perfusion by promoting vasculogenic mimicry (VM) when endothelial cell-driven angiogenesis is lacking. To conclude, FGF2 isoforms mainly behave in specific, antithetical manners, but can cooperate in different steps of tumor progression, providing melanoma cells with major malignant features. FGF2 is an alternative translation product expressed as different isoforms termed LMW and HMW. FGF2 is involved in melanoma development and progression. HMW FGF2 isoforms enhance in vitro motility of melanoma cells. LMW FGF2 confers stem-like features and increases in vivo metastasization. LMW FGF2 promotes angiogenesis while HMW FGF2 induces vasculogenic mimicry.

Post-mortem inference of the human hippocampal connectivity and microstructure using ultra-high field diffusion MRI at 11.7 T.

Science.gov (United States)

Beaujoin, Justine; Palomero-Gallagher, Nicola; Boumezbeur, Fawzi; Axer, Markus; Bernard, Jeremy; Poupon, Fabrice; Schmitz, Daniel; Mangin, Jean-François; Poupon, Cyril

2018-06-01

The human hippocampus plays a key role in memory management and is one of the first structures affected by Alzheimer's disease. Ultra-high magnetic resonance imaging provides access to its inner structure in vivo. However, gradient limitations on clinical systems hinder access to its inner connectivity and microstructure. A major target of this paper is the demonstration of diffusion MRI potential, using ultra-high field (11.7 T) and strong gradients (750 mT/m), to reveal the extra- and intra-hippocampal connectivity in addition to its microstructure. To this purpose, a multiple-shell diffusion-weighted acquisition protocol was developed to reach an ultra-high spatio-angular resolution with a good signal-to-noise ratio. The MRI data set was analyzed using analytical Q-Ball Imaging, Diffusion Tensor Imaging (DTI), and Neurite Orientation Dispersion and Density Imaging models. High Angular Resolution Diffusion Imaging estimates allowed us to obtain an accurate tractography resolving more complex fiber architecture than DTI models, and subsequently provided a map of the cross-regional connectivity. The neurite density was akin to that found in the histological literature, revealing the three hippocampal layers. Moreover, a gradient of connectivity and neurite density was observed between the anterior and the posterior part of the hippocampus. These results demonstrate that ex vivo ultra-high field/ultra-high gradients diffusion-weighted MRI allows the mapping of the inner connectivity of the human hippocampus, its microstructure, and to accurately reconstruct elements of the polysynaptic intra-hippocampal pathway using fiber tractography techniques at very high spatial/angular resolutions.

Variable high pressure processing sensitivities for GII human noroviruses

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Human norovirus (HuNoV) is the leading cause of foodborne diseases worldwide. High pressure processing (HPP) is one of the most promising non-thermal technologies for decontamination of viral pathogens in foods. However, the survival of HuNoVs by HPP is poorly understood because these viruses cann...

Whole high-quality light environment for humans and plants

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Sharakshane, Anton

2017-11-01

Plants sharing a single light environment on a spaceship with a human being and bearing a decorative function should look as natural and attractive as possible. And consequently they can be illuminated only with white light with a high color rendering index. Can lighting optimized for a human eye be effective and appropriate for plants? Spectrum-based effects have been compared under artificial lighting of plants by high-pressure sodium lamps and general-purpose white LEDs. It has been shown that for the survey sample phytochrome photo-equilibria does not depend significantly on the parameters of white LED light, while the share of phytoactive blue light grows significantly as the color temperature increases. It has been revealed that yield photon flux is proportional to luminous efficacy and increases as the color temperature decreases, general color rendering index Ra and the special color rendering index R14 (green leaf) increase. General-purpose white LED lamps with a color temperature of 2700 K, Ra > 90 and luminous efficacy of 100 lm/W are as efficient as the best high-pressure sodium lamps, and at a higher luminous efficacy their yield photon flux per joule is even bigger in proportion. Here we show that demand for high color rendering white LED light is not contradictory to the agro-technical objectives.

High-content screening of small compounds on human embryonic stem cells.

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Barbaric, Ivana; Gokhale, Paul J; Andrews, Peter W

2010-08-01

Human ES (embryonic stem) cells and iPS (induced pluripotent stem) cells have been heralded as a source of differentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson's disease or diabetes. Despite the great potential for their use in regenerative therapy, the challenge remains to understand the basic biology of these remarkable cells, in order to differentiate them into any functional cell type. Given the scale of the task, high-throughput screening of agents and culture conditions offers one way to accelerate these studies. The screening of small-compound libraries is particularly amenable to such high-throughput methods. Coupled with high-content screening technology that enables simultaneous assessment of multiple cellular features in an automated and quantitative way, this approach is proving powerful in identifying both small molecules as tools for manipulating stem cell fates and novel mechanisms of differentiation not previously associated with stem cell biology. Such screens performed on human ES cells also demonstrate the usefulness of human ES/iPS cells as cellular models for pharmacological testing of drug efficacy and toxicity, possibly a more imminent use of these cells than in regenerative medicine.

Boundary Conditions of the High-Investment Human Resource Systems-Small-Firm Labor Productivity Relationship

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Chadwick, Clint; Way, Sean A.; Kerr, Gerry; Thacker, James W.

2013-01-01

Although a few published, multiindustry, firm-level, empirical studies have linked systems of high-investment or high-performance human resource management practices to enhanced small-firm performance, this stream of strategic human resource management research is underdeveloped and equivocal. Accordingly, in this study, we use a sample of…

A high content screening assay to predict human drug-induced liver injury during drug discovery.

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Persson, Mikael; Løye, Anni F; Mow, Tomas; Hornberg, Jorrit J

2013-01-01

Adverse drug reactions are a major cause for failures of drug development programs, drug withdrawals and use restrictions. Early hazard identification and diligent risk avoidance strategies are therefore essential. For drug-induced liver injury (DILI), this is difficult using conventional safety testing. To reduce the risk for DILI, drug candidates with a high risk need to be identified and deselected. And, to produce drug candidates without that risk associated, risk factors need to be assessed early during drug discovery, such that lead series can be optimized on safety parameters. This requires methods that allow for medium-to-high throughput compound profiling and that generate quantitative results suitable to establish structure-activity-relationships during lead optimization programs. We present the validation of such a method, a novel high content screening assay based on six parameters (nuclei counts, nuclear area, plasma membrane integrity, lysosomal activity, mitochondrial membrane potential (MMP), and mitochondrial area) using ~100 drugs of which the clinical hepatotoxicity profile is known. We find that a 100-fold TI between the lowest toxic concentration and the therapeutic Cmax is optimal to classify compounds as hepatotoxic or non-hepatotoxic, based on the individual parameters. Most parameters have ~50% sensitivity and ~90% specificity. Drugs hitting ≥2 parameters at a concentration below 100-fold their Cmax are typically hepatotoxic, whereas non-hepatotoxic drugs typically hit based on nuclei count, MMP and human Cmax, we identified an area without a single false positive, while maintaining 45% sensitivity. Hierarchical clustering using the multi-parametric dataset roughly separates toxic from non-toxic compounds. We employ the assay in discovery projects to prioritize novel compound series during hit-to-lead, to steer away from a DILI risk during lead optimization, for risk assessment towards candidate selection and to provide guidance of safe

A Phosphorylcholine-Containing Glycolipid-like Antigen Present on the Surface of Infective Stage Larvae of Ascaris spp. Is a Major Antibody Target in Infected Pigs and Humans.

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Johnny Vlaminck

2016-12-01

Full Text Available The pig parasite Ascaris suum plays and important role in veterinary medicine and represents a suitable model for A. lumbricoides, which infects over 800 million people. In pigs, continued exposure to Ascaris induces immunity at the level of the gut, protecting the host against migrating larvae. The objective of this study was to identify and characterize parasite antigens targeted by this local immune response that may be crucial for parasite invasion and establishment and to evaluate their protective and diagnostic potential.Pigs were immunized by trickle infection for 30 weeks, challenged with 2,000 eggs at week 32 and euthanized two weeks after challenge. At necropsy, there was a 100% reduction in worms recovered from the intestine and a 97.2% reduction in liver white spots in comparison with challenged non-immune control animals. Antibodies purified from the intestinal mucus or from the supernatant of cultured antibody secreting cells from mesenteric lymph nodes of immune pigs were used to probe L3 extracts to identify antibody targets. This resulted in the recognition of a 12kDa antigen (As12 that is actively shed from infective Ascaris L3. As12 was characterized as a phosphorylcholine-containing glycolipid-like antigen that is highly resistant to different enzymatic and chemical treatments. Vaccinating pigs with an As12 fraction did not induce protective immunity to challenge infection. However, serological analysis using sera or plasma from experimentally infected pigs or naturally infected humans demonstrated that the As12 ELISA was able to detect long-term exposure to Ascaris with a high diagnostic sensitivity (98.4% and 92%, respectively and specificity (95.5% and 90.0% in pigs and humans, respectively.These findings show the presence of a highly stage specific, glycolipid-like component (As12 that is actively secreted by infectious Ascaris larvae and which acts as a major antibody target in infected humans and pigs.

Types of Language Learning Strategies Used by Tertiary English Majors

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Chuin, Tan Khye; Kaur, Sarjit

2015-01-01

This study investigated the types of language learning strategies used by 73 English majors from the School of Humanities in Universiti Sains Malaysia. Using questionnaires adopted from Oxford's (1990) Strategy Inventory of Language Learning (SILL) and focus group interviews, the study also examined the English major students' perceptions of using…

Friends-enemies: endogenous retroviruses are major transcriptional regulators of human DNA

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Buzdin, Anton A.; Prassolov, Vladimir; Garazha, Andrew V.

2017-06-01

Endogenous retroviruses are mobile genetic elements hardly distinguishable from infectious, or “exogenous”, retroviruses at the time of insertion in the host DNA. Human endogenous retroviruses (HERVs) are not rare. They gave rise to multiple families of closely related mobile elements that occupy 8% of the human genome. Together, they shape genomic regulatory landscape by providing at least 320,000 human transcription factor binding sites (TFBS) located on 110,000 individual HERV elements. The HERVs host as many as 155,000 mapped DNaseI hypersensitivity sites, which denote loci active in the regulation of gene expression or chromatin structure. The contemporary view of the HERVs evolutionary dynamics suggests that at the early stages after insertion, the HERV is treated by the host cells as a foreign genetic element, and is likely to be suppressed by the targeted methylation and mutations. However, at the later stages, when significant number of mutations has been already accumulated and when the retroviral genes are broken, the regulatory potential of a HERV may be released and recruited to modify the genomic balance of transcription factor binding sites. This process goes together with further accumulation and selection of mutations, which reshape the regulatory landscape of the human DNA. However, developmental reprogramming, stress or pathological conditions like cancer, inflammation and infectious diseases, can remove the blocks limiting expression and HERV-mediated host gene regulation. This, in turn, can dramatically alter the gene expression equilibrium and shift it to a newer state, thus further amplifying instability and exacerbating the stressful situation.

Prevention of Major Accident Hazards (MAHs) in major Hazard Installation (MHI) premises via land use planning (LUP): a review

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Khudbiddin, M. Q.; Rashid, Z. A.; Yeong, A. F. M. S.; Alias, A. B.; Irfan, M. F.; Fuad, M.; Hayati, H.

2018-03-01

For a number of years, there is a concern about the causes of major hazards, their identification, risk assessment and the process of its management from the global perspective on the activities of the industries due to the protection of the environment, human and property. Though, industries cannot take pleasure in their business by harming the nature of the land, there are a number of measures that need to be put into consideration by the industries. Such measures are in terms of management and safety for the businesses, lives, properties, as well as the environment. The lack of consideration in the selected appropriate criteria can result in major accidental hazards (MAHs). This paper will review the land use planning (LUP) methods used in the past and present to prevent major accident hazards at major hazard installation (MHI).

Multi-scale motility amplitude associated with suicidal thoughts in major depression.

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Premananda Indic

Full Text Available Major depression occurs at high prevalence in the general population, often starts in juvenile years, recurs over a lifetime, and is strongly associated with disability and suicide. Searches for biological markers in depression may have been hindered by assuming that depression is a unitary and relatively homogeneous disorder, mainly of mood, rather than addressing particular, clinically crucial features or diagnostic subtypes. Many studies have implicated quantitative alterations of motility rhythms in depressed human subjects. Since a candidate feature of great public-health significance is the unusually high risk of suicidal behavior in depressive disorders, we studied correlations between a measure (vulnerability index [VI] derived from multi-scale characteristics of daily-motility rhythms in depressed subjects (n = 36 monitored with noninvasive, wrist-worn, electronic actigraphs and their self-assessed level of suicidal thinking operationalized as a wish to die. Patient-subjects had a stable clinical diagnosis of bipolar-I, bipolar-II, or unipolar major depression (n = 12 of each type. VI was associated inversely with suicidal thinking (r = -0.61 with all subjects and r = -0.73 with bipolar disorder subjects; both p<0.0001 and distinguished patients with bipolar versus unipolar major depression with a sensitivity of 91.7% and a specificity of 79.2%. VI may be a useful biomarker of characteristic features of major depression, contribute to differentiating bipolar and unipolar depression, and help to detect risk of suicide. An objective biomarker of suicide-risk could be advantageous when patients are unwilling or unable to share suicidal thinking with clinicians.

Major proteins in normal human lymphocyte subpopulations separated by fluorescence-activated cell sorting and analyzed by two-dimensional gel electrophoresis

DEFF Research Database (Denmark)

Madsen, P S; Hokland, M; Ellegaard, J

1988-01-01

markers were observed in all cell types. All the putative protein markers have been identified in the protein database of human peripheral blood mononuclear cells (PBMCs) (see accompanying article by Celis et al.). Comparison of the overall patterns of protein synthesis of the unsorted PBMCs with those...... of the four subpopulations showed that the synthesis of some major PBMC proteins decreased substantially in the sorted subsets. These proteins are most likely not of monocyte origin, as these cells constituted only about 15% of the total PBMCs. Also, the inhibition does not seem to be due to the addition...

Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells

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Pfeiffer, Elisa; Zeilinger, Katrin; Seehofer, Daniel; Damm, Georg

2016-01-01

Beside parenchymal hepatocytes, the liver consists of non-parenchymal cells (NPC) namely Kupffer cells (KC), liver endothelial cells (LEC) and hepatic Stellate cells (HSC). Two-dimensional (2D) culture of primary human hepatocyte (PHH) is still considered as the "gold standard" for in vitro testing of drug metabolism and hepatotoxicity. It is well-known that the 2D monoculture of PHH suffers from dedifferentiation and loss of function. Recently it was shown that hepatic NPC play a central role in liver (patho-) physiology and the maintenance of PHH functions. Current research focuses on the reconstruction of in vivo tissue architecture by 3D- and co-culture models to overcome the limitations of 2D monocultures. Previously we published a method to isolate human liver cells and investigated the suitability of these cells for their use in cell cultures in Experimental Biology and Medicine1. Based on the broad interest in this technique the aim of this article was to provide a more detailed protocol for the liver cell isolation process including a video, which will allow an easy reproduction of this technique. Human liver cells were isolated from human liver tissue samples of surgical interventions by a two-step EGTA/collagenase P perfusion technique. PHH were separated from the NPC by an initial centrifugation at 50 x g. Density gradient centrifugation steps were used for removal of dead cells. Individual liver cell populations were isolated from the enriched NPC fraction using specific cell properties and cell sorting procedures. Beside the PHH isolation we were able to separate KC, LEC and HSC for further cultivation. Taken together, the presented protocol allows the isolation of PHH and NPC in high quality and quantity from one donor tissue sample. The access to purified liver cell populations could allow the creation of in vivo like human liver models. PMID:27077489

Prevalence of high-risk human papilloma virus among women with hepatitis C virus before liver transplantation.

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Tarallo, P A; Smolowitz, J; Carriero, D; Tarallo, J; Siegel, A; Jia, H; Emond, J C

2013-08-01

We sought to assess the prevalence and risk factors for high-risk human papillomavirus (HPV) infection among female liver transplant (LT) candidates. Traditional health screening before LT listing has included Pap smear and is typically carried out by the patient's local provider. The prevalence of high-risk HPV in this population has not been studied. With Institutional Review Board approval, 62 LT candidates received a liquid-based Pap smear with high-risk HPV testing as part of their pre-transplant evaluation by a single provider. Clinical variables included age, ethnicity, insurance status, prior Pap smear, and HPV results, HPV risk factors including age of first intercourse, number of lifetime partners, last sexual activity, smoking, birth control pill use, history of sexually transmitted infections, human immunodeficiency virus status, immunosuppressive medication, medical diagnoses, prescribed medications, and history of hepatitis A, B, C, or D. The 62 women had a median age of 56 years, and 39% had high-risk behavior known to be associated with HPV. Ten of 62 patients (16.1%) had high-risk HPV at baseline screening, 5 of whom had atypical cytology. All of the patients who were positive for high-risk HPV had an etiology of hepatitis C virus (HCV) as the underlying cause of liver disease, with the majority (90%) having no history of high-risk behavior for HPV. In contrast, all patients with high-risk behavior who were HCV negative were HPV negative. Fisher's exact test demonstrated a statistically significant relationship between HPV and HCV; odds ratio = 24.4, 95% confidence interval, 1.4, 438.7, P-value = 0.0013. None of the other potential risk factors were associated with HPV in this cohort. In this study, we provide evidence of a strong association between HCV and HPV in LT candidates, which has not been previously reported. HPV positivity was observed in non-sexually active women, suggesting a reactivation of dormant HPV. An association between

Identification of geographically distributed sub-populations of Leishmania (Leishmania major by microsatellite analysis

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Schwenkenbecher Jan

2008-06-01

Full Text Available Abstract Background Leishmania (Leishmania major, one of the agents causing cutaneous leishmaniasis (CL in humans, is widely distributed in the Old World where different species of wild rodent and phlebotomine sand fly serve as animal reservoir hosts and vectors, respectively. Despite this, strains of L. (L. major isolated from many different sources over many years have proved to be relatively uniform. To investigate the population structure of the species highly polymorphic microsatellite markers were employed for greater discrimination among it's otherwise closely related strains, an approach applied successfully to other species of Leishmania. Results Multilocus Microsatellite Typing (MLMT based on 10 different microsatellite markers was applied to 106 strains of L. (L. major from different regions where it is endemic. On applying a Bayesian model-based approach, three main populations were identified, corresponding to three separate geographical regions: Central Asia (CA; the Middle East (ME; and Africa (AF. This was congruent with phylogenetic reconstructions based on genetic distances. Re-analysis separated each of the populations into two sub-populations. The two African sub-populations did not correlate well with strains' geographical origin. Strains falling into the sub-populations CA and ME did mostly group according to their place of isolation although some anomalies were seen, probably, owing to human migration. Conclusion The model- and distance-based analyses of the microsatellite data exposed three main populations of L. (L. major, Central Asia, the Middle East and Africa, each of which separated into two sub-populations. This probably correlates with the different species of rodent host.

A major QTL controls susceptibility to spinal curvature in the curveback guppy

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Dreyer Christine

2011-01-01

Full Text Available Abstract Background Understanding the genetic basis of heritable spinal curvature would benefit medicine and aquaculture. Heritable spinal curvature among otherwise healthy children (i.e. Idiopathic Scoliosis and Scheuermann kyphosis accounts for more than 80% of all spinal curvatures and imposes a substantial healthcare cost through bracing, hospitalizations, surgery, and chronic back pain. In aquaculture, the prevalence of heritable spinal curvature can reach as high as 80% of a stock, and thus imposes a substantial cost through production losses. The genetic basis of heritable spinal curvature is unknown and so the objective of this work is to identify quantitative trait loci (QTL affecting heritable spinal curvature in the curveback guppy. Prior work with curveback has demonstrated phenotypic parallels to human idiopathic-type scoliosis, suggesting shared biological pathways for the deformity. Results A major effect QTL that acts in a recessive manner and accounts for curve susceptibility was detected in an initial mapping cross on LG 14. In a second cross, we confirmed this susceptibility locus and fine mapped it to a 5 cM region that explains 82.6% of the total phenotypic variance. Conclusions We identify a major QTL that controls susceptibility to curvature. This locus contains over 100 genes, including MTNR1B, a candidate gene for human idiopathic scoliosis. The identification of genes associated with heritable spinal curvature in the curveback guppy has the potential to elucidate the biological basis of spinal curvature among humans and economically important teleosts.

The Virome and Its Major Component, Anellovirus, a Convoluted System Molding Human Immune Defenses and Possibly Affecting the Development of Asthma and Respiratory Diseases in Childhood

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Giulia Freer

2018-04-01

Full Text Available The microbiome, a thriving and complex microbial community colonizing the human body, has a broad impact on human health. Colonization is a continuous process that starts very early in life and occurs thanks to shrewd strategies microbes have evolved to tackle a convoluted array of anatomical, physiological, and functional barriers of the human body. Cumulative evidence shows that viruses are part of the microbiome. This part, called virome, has a dynamic composition that reflects what we eat, how and where we live, what we do, our genetic background, and other unpredictable variables. Thus, the virome plays a chief role in shaping innate and adaptive host immune defenses. Imbalance of normal microbial flora is thought to trigger or exacerbate many acute and chronic disorders. A compelling example can be found in the respiratory apparatus, where early-life viral infections are major determinants for the development of allergic diseases, like asthma, and other non-transmissible diseases. In this review, we focus on the virome and, particularly, on Anelloviridae, a recently discovered virus family. Anelloviruses are major components of the virome, present in most, if not all, human beings, where they are acquired early in life and replicate persistently without causing apparent disease. We will discuss how modulation of innate and adaptive immune systems by Anelloviruses can influence the development of respiratory diseases in childhood and provide evidence for the use of Anelloviruses as useful and practical molecular markers to monitor inflammatory processes and immune system competence.

High Performace Liquid Chromtographic Determination of Nicardipine Hydrochloride in Human Plasma

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Y. S. R. Krishnaiah

2004-01-01

Full Text Available A sensitive high-performance liquid chromatographic method was developed for the estimation of nicardipine hydrochloride in human plasma. Varying amount of nicardipine hydrochloride (2.5 to 150 ng/0.5 mL and fixed quantity (100 ng/0.5 mL of nifedipine (internal standard was added to blank human plasma, and a single step extraction was carried out with ethyl acetate. The mixture was centrifuged, ethyl acetate layer separated, dried and reconstituted with 100 μL of acetonitrile. Twenty microliters of this solution was injected into a reverse phase C-18 column using a mobile phase consisting of acetonitrile: 0.02 M potassium dihydrogen phosphate (pH 4.0 in the ratio of 60:40 v/v and the eluents were monitored at 239 nm. The method was validated for its linearity, precision and accuracy. The calibration curve was linear in the range of 5-150 ng/0.5 mL of plasma and the lower detection limit was 2.5 ng/0.5 mL of plasma. The intra- and inter-day variation was found to be less than 2.5% indicating that the method is highly precise. The mean recovery of nicardipine hydrochloride from plasma samples was 89.6±2.60%. The proposed HPLC method was applied for the estimation of nicardipine hydrochloride in human plasma after oral administration of an immediate release nicardipine hydrochloride capsule (dose 30 mg to 6 adult male volunteers. There was no interference of either the drug metabolites or other plasma components with the proposed HPLC method for the estimation of nicardipine hydrochloride in human plasma. Due to its simplicity, sensitivity, high precision and accuracy, the proposed HPLC method may be used for biopharmaceutical and pharmacokinetic evaluation of nicardipine hydrochloride and its formulations in humans

Brain-Derived Neurotrophic Factor – A Major Player in Stimulation-Induced Homeostatic Metaplasticity of Human Motor Cortex?

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Rizzo, Vincenzo; Ritter, Christoph; Klein, Christine; Pohlmann, Ines; Brueggemann, Norbert; Quartarone, Angelo; Siebner, Hartwig Roman

2013-01-01

Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val66met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val66met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val66met (n = 12) and val66val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val66met carriers and val66val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val66met polymorphism, our results do not support the notion that the BDNF val66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND. PMID:23469118

High Prevalence of Hyper-Aerotolerant Campylobacter jejuni in Retail Poultry with Potential Implication in Human Infection.

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Oh, Euna; McMullen, Lynn; Jeon, Byeonghwa

2015-01-01

Campylobacter jejuni is a leading cause of foodborne illnesses around the world. Since C. jejuni is microaerophilic and sensitive to oxygen, aerotolerance is important in the transmission of C. jejuni to humans via foods under aerobic conditions. In this study, 70 C. jejuni strains were isolated from retail raw chicken meats and were subject to multilocus sequence typing (MLST) analysis. In the aerotolerance testing by aerobic shaking at 200 rpm, 50 (71.4%) isolates survived after 12 h (i.e., aerotolerant), whereas 20 (28.6%) isolates did not (i.e., aerosensitive). Interestingly, further aerobic cultivation showed that 25 (35.7%) isolates still survived even after 24 h of vigorous aerobic shaking (i.e., hyper-aerotolerant). Compared to aerosensitive strains, the hyper-aerotolerant strains exhibited increased resistance to oxidative stress, both peroxide and superoxide. A mutation of ahpC in hyper-aerotolerant strains significantly impaired aerotolerance, indicating oxidative stress defense plays an important role in hyper-aerotolerance. The aerotolerant and hyper-aerotolerant strains were primarily classified into MLST clonal complexes (CCs)-21 and -45, which are known to be the major CCs implicated in human gastroenteritis. Compared to the aerosensitive strains, CC-21 was more dominant than CC-45 in aerotolerant and hyper-aerotolerant strains. The findings in this study revealed that hyper-aerotolerant C. jejuni is highly prevalent in raw chicken meats. The enhanced aerotolerance in C. jejuni would impact human infection by increasing possibilities of the foodborne transmission of C. jejuni under aerobic conditions.

Wide Variability in Caloric Density of Expressed Human Milk Can Lead to Major Underestimation or Overestimation of Nutrient Content.

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Sauer, Charles W; Boutin, Mallory A; Kim, Jae H

2017-05-01

Very-low-birth-weight infants continue to face significant difficulties with postnatal growth. Human milk is the optimal form of nutrition for infants but may exhibit variation in nutrient content. This study aimed to perform macronutrient analysis on expressed human milk from mothers whose babies are hospitalized in the neonatal intensive care unit. Up to five human milk samples per participant were analyzed for protein, carbohydrate, and fat content using reference chemical analyses (Kjeldahl for protein, high pressure liquid chromatography for carbohydrates, and Mojonnier for fat). Calorie content was calculated. A total of 64 samples from 24 participants was analyzed. Wide variability was found in calorie, protein, carbohydrate, and fat composition. The authors found an average of 17.9 kcal/ounce, with only 34% of samples falling within 10% of the expected caloric density. The assumption that human milk contains 20 kcal/ounce is no longer supported based on this study. This supports promoting an individualized nutrition strategy as a crucial aspect to optimal nutrition.

Major advances associated with reproduction in dairy cattle.

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Moore, K; Thatcher, W W

2006-04-01

The purpose of this overview is to review some of the major advances in reproductive technologies, and how they may be applied to meet the challenge of enhancing reproductive efficiency in the high-producing dairy cow of the 21st century. The current population of high-producing dairy cows is considered to be subfertile, as characterized by low pregnancy rates and high rates of embryonic mortality. Coordinated systems of reproductive management have been developed based upon a thorough understanding of the endocrine, cellular, and molecular factors controlling ovarian and uterine function. These systems will partially restore herd reproductive performance. Advances in other reproductive technologies offer possibilities for wider use of superior germplasm. Technologies such as sexed semen, cloning, transgenesis, and preimplantation genetic diagnosis offer the potential to enhance the influence of superior animals on production of food for human consumption. However, at this time, additional research is needed to counteract the higher rates of embryonic and fetal mortality associated with some of these technologies. Furthermore, use of genomics, proteomics, and bioinformatics in the study of reproduction will undoubtedly provide investigators with a greater understanding of the limitations to efficient reproductive processes in the subfertile lactating dairy cow.

Dichotomy of the human T cell response to Leishmania antigens. I. Th1-like response to Leishmania major promastigote antigens in individuals recovered from cutaneous leishmaniasis

DEFF Research Database (Denmark)

Kemp, M; Hey, A S; Kurtzhals, J A

1994-01-01

of skin lesions, and in Danes without known exposure to Leishmania parasites. Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in antigen-stimulated cultures was measured. Lymphocytes from individuals with a history of CL proliferated vigorously and produced IFN-gamma after...... the unexposed Danes were not activated by gp63. The cells from Danish donors produced either IFN-gamma or IL-4, but not both cytokines after incubation with the crude preparation of L. major antigens. The data show that the T cell response to Leishmania antigens in humans who have had uncomplicated CL...... stimulation with either a crude preparation of L. major antigens or the major surface protease gp63. These cultures produced no or only little IL-4. Also cells from leishmanin skin test-positive donors with no history of CL produced IFN-gamma and no IL-4 in response to L. major antigens. Cells from...

Moral Disengagement in Business and Humanities Majors: An Exploratory Study

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Cory, Suzanne N.; Hernandez, Abigail R.

2014-01-01

This study measures moral disengagement of undergraduate business and humanities students with a focus on differences in moral disengagement between genders. Students completed a survey that consisted of 32 statements and were asked to determine the degree to which they agreed with each, using a 7-point Likert scale. The questions measured moral…

Comparative Analysis of Human and Canine Campylobacter upsaliensis Isolates by Amplified Fragment Length Polymorphism

DEFF Research Database (Denmark)

Damborg, Peter; Guardabassi, Luca; Pedersen, Karl

2008-01-01

Human (n = 33) and canine (n = 53) Campylobacter upsaliensis isolates from seven countries were genotyped by a new amplified fragment length polymorphism method. We observed 100% typeability and high overall diversity. The majority of human strains (23/33) clustered separately from canine strains...

Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

DEFF Research Database (Denmark)

Sørensen, A L; Hey, A S; Kharazmi, A

1994-01-01

In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes...... towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63...... in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished...

Aspects of animal models for major neuropsychiatric disorders

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Lefter Radu

2014-01-01

Full Text Available We will review the main animal models for the major neuropsychiatric disorders, focusing on schizophrenia, Alzheimer’s disease, Parkinson’s disease, depression, anxiety and autism. Although these mental disorders are specifically human pathologies and therefore impossible to perfectly replicate in animals, the use of experimental animals is based on the physiological and anatomical similarities between humans and animals such as the rat, and mouse, and on the fact that 99% of human and murine genomes are shared. Pathological conditions in animals can be assessed by manipulating the metabolism of neurotransmitters, through various behavioral tests, and by determining biochemical parameters that can serve as important markers of disorders.

Structures of the major capsid proteins of the human Karolinska Institutet and Washington University polyomaviruses.

Science.gov (United States)

Neu, Ursula; Wang, Jianbo; Macejak, Dennis; Garcea, Robert L; Stehle, Thilo

2011-07-01

The Karolinska Institutet and Washington University polyomaviruses (KIPyV and WUPyV, respectively) are recently discovered human viruses that infect the respiratory tract. Although they have not yet been linked to disease, they are prevalent in populations worldwide, with initial infection occurring in early childhood. Polyomavirus capsids consist of 72 pentamers of the major capsid protein viral protein 1 (VP1), which determines antigenicity and receptor specificity. The WUPyV and KIPyV VP1 proteins are distant in evolution from VP1 proteins of known structure such as simian virus 40 or murine polyomavirus. We present here the crystal structures of unassembled recombinant WUPyV and KIPyV VP1 pentamers at resolutions of 2.9 and 2.55 Å, respectively. The WUPyV and KIPyV VP1 core structures fold into the same β-sandwich that is a hallmark of all polyomavirus VP1 proteins crystallized to date. However, differences in sequence translate into profoundly different surface loop structures in KIPyV and WUPyV VP1 proteins. Such loop structures have not been observed for other polyomaviruses, and they provide initial clues about the possible interactions of these viruses with cell surface receptors.

The High-mountain Cryosphere: Environmental Changes and Human Risks

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Maria Shahgedanova

2016-08-01

Full Text Available Reviewed: The High-mountain Cryosphere: Environmental Changes and Human Risks Edited by Christian Huggel, Mark Carey, John J. Clague, and Andreas Kääb. Cambridge, UK: Cambridge University Press, 2015. xii + 363 pp. Hardcover: US$ 140.00, ISBN 978-1-107-06584-0. E-book: US$ 112.00, ISBN 978-1-316-35515-2.

Identification and Characterization of Plasma Cells in Normal Human Bone Marrow by High-Resolution Flow Cytometry

NARCIS (Netherlands)

Terstappen, Leonardus Wendelinus Mathias Marie; Johnsen, Steen; Segers-Nolten, Gezina M.J.; Loken, Michael R.

1990-01-01

The low frequency of plasma cells and the lack of specific cell surface markers has been a major obstacle for a detailed characterization of plasma cells in normal human bone marrow. Multiparameter flow cytometry enabled the identification of plasma cells in normal bone marrow aspirates. The plasma

Galleria mellonella model identifies highly virulent strains among all major molecular types of Cryptococcus gattii.

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Carolina Firacative

Full Text Available Cryptococcosis is mainly caused by Cryptococcus neoformans. However, the number of cases due to C. gattii is increasing, affecting mainly immunocompetent hosts. C. gattii is divided into four major molecular types, VGI to VGIV, which differ in their host range, epidemiology, antifungal susceptibility and geographic distribution. Besides studies on the Vancouver Island outbreak strains, which showed that the subtype VGIIa is highly virulent compared to the subtype VGIIb, little is known about the virulence of the other major molecular types. To elucidate the virulence potential of the major molecular types of C. gattii, Galleria mellonella larvae were inoculated with ten globally selected strains per molecular type. Survival rates were recorded and known virulence factors were studied. One VGII, one VGIII and one VGIV strain were more virulent (p 0.05, 21 (five VGI, five VGII, four VGIII and seven VGIV were less virulent (p <0.05 while one strain of each molecular type were avirulent. Cell and capsule size of all strains increased markedly during larvae infection (p <0.001. No differences in growth rate at 37°C were observed. Melanin synthesis was directly related with the level of virulence: more virulent strains produced more melanin than less virulent strains (p <0.05. The results indicate that all C. gattii major molecular types exhibit a range of virulence, with some strains having the potential to be more virulent. The study highlights the necessity to further investigate the genetic background of more and less virulent strains in order to recognize critical features, other than the known virulence factors (capsule, melanin and growth at mammalian body temperature, that maybe crucial for the development and progression of cryptococcosis.

Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC and its application for DNA methylation analysis

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Ottaviani Diego

2008-05-01

Full Text Available Abstract Background The major histocompatibility complex (MHC is essential for human immunity and is highly associated with common diseases, including cancer. While the genetics of the MHC has been studied intensively for many decades, very little is known about the epigenetics of this most polymorphic and disease-associated region of the genome. Methods To facilitate comprehensive epigenetic analyses of this region, we have generated a genomic tiling array of 2 Kb resolution covering the entire 4 Mb MHC region. The array has been designed to be compatible with chromatin immunoprecipitation (ChIP, methylated DNA immunoprecipitation (MeDIP, array comparative genomic hybridization (aCGH and expression profiling, including of non-coding RNAs. The array comprises 7832 features, consisting of two replicates of both forward and reverse strands of MHC amplicons and appropriate controls. Results Using MeDIP, we demonstrate the application of the MHC array for DNA methylation profiling and the identification of tissue-specific differentially methylated regions (tDMRs. Based on the analysis of two tissues and two cell types, we identified 90 tDMRs within the MHC and describe their characterisation. Conclusion A tiling array covering the MHC region was developed and validated. Its successful application for DNA methylation profiling indicates that this array represents a useful tool for molecular analyses of the MHC in the context of medical genomics.

Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

International Nuclear Information System (INIS)

Rajasekaran, Maheswari; Brents, Lisa K.; Franks, Lirit N.; Moran, Jeffery H.; Prather, Paul L.

2013-01-01

K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB 1 Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB 2 Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB 2 Rs (hCB 2 Rs). The affinity of cannabinoids for hCB 2 Rs was determined by competition binding studies employing CHO-hCB 2 membranes. Intrinsic activity of compounds was assessed by G-protein activation and adenylyl cyclase (AC)-inhibition in CHO-hCB 2 cells. JWH-073, JWH-018 and several of their human metabolites exhibit nanomolar affinity and act as potent agonists at hCB 2 Rs. Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to CB 2 Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. Finally, when compared to CP-55,940 and Δ 9 -tetrahydrocannabinol (Δ 9 -THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB 2 R occupancy to produce similar levels of AC-inhibition, indicating that these compounds may more efficiently couple CB 2 Rs to AC than the well characterized cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB 2 Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB 1 and CB 2 Rs. - Highlights: • JWH-018 and JWH-073 are synthetic cannabinoids present in abused K2

Omega-oxidation is the major pathway for the catabolism of leukotriene B4 in human polymorphonuclear leukocytes.

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Shak, S; Goldstein, I M

1984-08-25

Leukotriene B4 (LTB4), formed by the 5-lipoxygenase pathway in human polymorphonuclear leukocytes (PMN), may be an important mediator of inflammation. Recent studies suggest that human leukocytes can convert LTB4 to products that are less biologically active. To examine the catabolism of LTB4, we developed (using high performance liquid chromatography) a sensitive, reproducible assay for this mediator and its omega-oxidation products (20-OH- and 20-COOH-LTB4). With this assay, we have found that human PMN (but not human monocytes, lymphocytes, or platelets) convert exogenous LTB4 almost exclusively to 20-OH- and 20-COOH-LTB4 (identified by gas chromatography-mass spectrometry). Catabolism of exogenous LTB4 by omega-oxidation is rapid (t1/2 approximately 4 min at 37 degrees C in reaction mixtures containing 1.0 microM LTB4 and 20 X 10(6) PMN/ml), temperature-dependent (negligible at 0 degrees C), and varies with cell number as well as with initial substrate concentration. The pathway for omega-oxidation in PMN is specific for LTB4 and 5(S),12(S)-dihydroxy-6,8,10,14-eicosatetraenoic acid (only small amounts of other dihydroxylated-derivatives of arachidonic acid are converted to omega-oxidation products). Even PMN that are stimulated by phorbol myristate acetate to produce large amounts of superoxide anion radicals catabolize exogenous leukotriene B4 primarily by omega-oxidation. Finally, LTB4 that is generated when PMN are stimulated with the calcium ionophore, A23187, is rapidly catabolized by omega-oxidation. Thus, human PMN not only generate and respond to LTB4, but also rapidly and specifically catabolize this mediator by omega-oxidation.

High school and college introductory science education experiences: A study regarding perceptions of university students persisting in science as a major area of study

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Fredrick, L. Denise

The focus of this study was to investigate college students' perception of high school and college introductory science learning experiences related to persistence in science as a major area of study in college. The study included students' perceptions of the following areas of science education: (1) teacher interpersonal relationship with students, (2) teacher personality styles, (3) teacher knowledge of the content, (4) instructional methods, and (5) science course content. A survey research design was employed in the investigative study to collect and analyze data. One hundred ninety two students participated in the research study. A survey instrument entitled Science Education Perception Survey was used to collect data. The researcher sought to reject or support three null hypotheses as related to participants' perceptions of high school and college introductory science education experiences. Using binomial regression analysis, this study analyzed differences between students persisting in science and students not persisting in science as a major. The quantitative research indicated that significant differences exist between persistence in science as a major and high school science teacher traits and college introductory science instructional methods. Although these variables were found to be significant predictors, the percent variance was low and should be considered closely before concluded these as strong predictors of persistence. Major findings of the qualitative component indicated that students perceived that: (a) interest in high school science course content and high school science teacher personality and interpersonal relationships had the greatest effect on students' choice of major area of study; (b) interest in college introductory science course content had the greatest effect on students' choice of major area of study; (c) students recalled laboratory activities and overall good teaching as most meaningful to their high school science

Bipolar cell gap junctions serve major signaling pathways in the human retina.

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Kántor, Orsolya; Varga, Alexandra; Nitschke, Roland; Naumann, Angela; Énzsöly, Anna; Lukáts, Ákos; Szabó, Arnold; Németh, János; Völgyi, Béla

2017-08-01

Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models. Furthermore, a number of unique features (e.g. fovea, trichromacy, midget system) necessitate a reexamination of the animal model results in the human retina. Well-preserved postmortem human samples of this study are allowed to identify Cx36 expressing BCs neurochemically. Results reveal that both rod and cone pathway interneurons display strong Cx36 expression. Rod BC inputs to AII amacrine cells (AC) appear in juxtaposition to AII GJs, thus suggesting a strategic AII cell targeting by rod BCs. Cone BCs serving midget, parasol or koniocellular signaling pathways display a wealth of Cx36 expression to form homologously coupled arrays. In addition, they also establish heterologous GJ contacts to serve an exchange of information between parallel signaling streams. Interestingly, a prominent Cx36 expression was exhibited by midget system BCs that appear to maintain intimate contacts with bistratified BCs serving other pathways. These findings suggest that BC GJs in parallel signaling streams serve both an intra- and inter-pathway exchange of signals in the human retina.

High-Yield Purification, Preservation, and Serial Transplantation of Human Satellite Cells

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Steven M. Garcia

2018-03-01

Full Text Available Summary: Investigation of human muscle regeneration requires robust methods to purify and transplant muscle stem and progenitor cells that collectively constitute the human satellite cell (HuSC pool. Existing approaches have yet to make HuSCs widely accessible for researchers, and as a result human muscle stem cell research has advanced slowly. Here, we describe a robust and predictable HuSC purification process that is effective for each human skeletal muscle tested and the development of storage protocols and transplantation models in dystrophin-deficient and wild-type recipients. Enzymatic digestion, magnetic column depletion, and 6-marker flow-cytometric purification enable separation of 104 highly enriched HuSCs per gram of muscle. Cryostorage of HuSCs preserves viability, phenotype, and transplantation potential. Development of enhanced and species-specific transplantation protocols enabled serial HuSC xenotransplantation and recovery. These protocols and models provide an accessible system for basic and translational investigation and clinical development of HuSCs. : Garcia and colleagues report methods for efficient purification of satellite cells from human skeletal muscle. They use their approaches to demonstrate stem cell functions of endogenous satellite cells and to make human satellite cells accessible for sharing among researchers. Keywords: human satellite cell purification, serial transplantation, satellite cell cryopreservation

How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans

OpenAIRE

Cartmell, Alan; Lowe, Elisabeth C.; Basl?, Arnaud; Firbank, Susan J.; Ndeh, Didier A.; Murray, Heath; Terrapon, Nicolas; Lombard, Vincent; Henrissat, Bernard; Turnbull, Jeremy E.; Czjzek, Mirjam; Gilbert, Harry J.; Bolam, David N.

2017-01-01

The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron, a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases...

LncRNA Expression Profile of Human Thoracic Aortic Dissection by High-Throughput Sequencing.

Science.gov (United States)

Sun, Jie; Chen, Guojun; Jing, Yuanwen; He, Xiang; Dong, Jianting; Zheng, Junmeng; Zou, Meisheng; Li, Hairui; Wang, Shifei; Sun, Yili; Liao, Wangjun; Liao, Yulin; Feng, Li; Bin, Jianping

2018-01-01

In this study, the long non-coding RNA (lncRNA) expression profile in human thoracic aortic dissection (TAD), a highly lethal cardiovascular disease, was investigated. Human TAD (n=3) and normal aortic tissues (NA) (n=3) were examined by high-throughput sequencing. Bioinformatics analyses were performed to predict the roles of aberrantly expressed lncRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results. A total of 269 lncRNAs (159 up-regulated and 110 down-regulated) and 2, 255 mRNAs (1 294 up-regulated and 961 down-regulated) were aberrantly expressed in human TAD (fold-change> 1.5, PTAD than in NA. The predicted binding motifs of three up-regulated lncRNAs (ENSG00000248508, ENSG00000226530, and EG00000259719) were correlated with up-regulated RUNX1 (R=0.982, PTAD. These findings suggest that lncRNAs are novel potential therapeutic targets for human TAD. © 2018 The Author(s). Published by S. Karger AG, Basel.

Polymorphic Human Sulfotransferase 2A1 Mediates the Formation of 25-Hydroxyvitamin D3-3-O-Sulfate, a Major Circulating Vitamin D Metabolite in Humans.

Science.gov (United States)

Wong, Timothy; Wang, Zhican; Chapron, Brian D; Suzuki, Mizuki; Claw, Katrina G; Gao, Chunying; Foti, Robert S; Prasad, Bhagwat; Chapron, Alenka; Calamia, Justina; Chaudhry, Amarjit; Schuetz, Erin G; Horst, Ronald L; Mao, Qingcheng; de Boer, Ian H; Thornton, Timothy A; Thummel, Kenneth E

2018-04-01

Metabolism of 25-hydroxyvitamin D 3 (25OHD 3 ) plays a central role in regulating the biologic effects of vitamin D in the body. Although cytochrome P450-dependent hydroxylation of 25OHD 3 has been extensively investigated, limited information is available on the conjugation of 25OHD 3 In this study, we report that 25OHD 3 is selectively conjugated to 25OHD 3 -3- O -sulfate by human sulfotransferase 2A1 (SULT2A1) and that the liver is a primary site of metabolite formation. At a low (50 nM) concentration of 25OHD 3 , 25OHD 3 -3- O -sulfate was the most abundant metabolite, with an intrinsic clearance approximately 8-fold higher than the next most efficient metabolic route. In addition, 25OHD 3 sulfonation was not inducible by the potent human pregnane X receptor agonist, rifampicin. The 25OHD 3 sulfonation rates in a bank of 258 different human liver cytosols were highly variable but correlated with the rates of dehydroepiandrosterone sulfonation. Further analysis revealed a significant association between a common single nucleotide variant within intron 1 of SULT2A1 (rs296361; minor allele frequency = 15% in whites) and liver cytosolic SULT2A1 content as well as 25OHD 3 -3- O -sulfate formation rate, suggesting that variation in the SULT2A1 gene contributes importantly to interindividual differences in vitamin D homeostasis. Finally, 25OHD 3 -3- O -sulfate exhibited high affinity for the vitamin D binding protein and was detectable in human plasma and bile but not in urine samples. Thus, circulating concentrations of 25OHD 3 -3- O -sulfate appear to be protected from rapid renal elimination, raising the possibility that the sulfate metabolite may serve as a reservoir of 25OHD 3 in vivo, and contribute indirectly to the biologic effects of vitamin D. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Bacterial translational regulations: high diversity between all mRNAs and major role in gene expression

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Picard Flora

2012-10-01

Full Text Available Abstract Background In bacteria, the weak correlations at the genome scale between mRNA and protein levels suggest that not all mRNAs are translated with the same efficiency. To experimentally explore mRNA translational level regulation at the systemic level, the detailed translational status (translatome of all mRNAs was measured in the model bacterium Lactococcus lactis in exponential phase growth. Results Results demonstrated that only part of the entire population of each mRNA species was engaged in translation. For transcripts involved in translation, the polysome size reached a maximum of 18 ribosomes. The fraction of mRNA engaged in translation (ribosome occupancy and ribosome density were not constant for all genes. This high degree of variability was analyzed by bioinformatics and statistical modeling in order to identify general rules of translational regulation. For most of the genes, the ribosome density was lower than the maximum value revealing major control of translation by initiation. Gene function was a major translational regulatory determinant. Both ribosome occupancy and ribosome density were particularly high for transcriptional regulators, demonstrating the positive role of translational regulation in the coordination of transcriptional networks. mRNA stability was a negative regulatory factor of ribosome occupancy and ribosome density, suggesting antagonistic regulation of translation and mRNA stability. Furthermore, ribosome occupancy was identified as a key component of intracellular protein levels underlining the importance of translational regulation. Conclusions We have determined, for the first time in a bacterium, the detailed translational status for all mRNAs present in the cell. We have demonstrated experimentally the high diversity of translational states allowing individual gene differentiation and the importance of translation-level regulation in the complex process linking gene expression to protein

Human biosample authentication using the high-throughput, cost-effective SNPtrace(TM system.

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May M Y Liang-Chu

Full Text Available Cell lines are the foundation for much of the fundamental research into the mechanisms underlying normal biologic processes and disease mechanisms. It is estimated that 15%-35% of human cell lines are misidentified or contaminated, resulting in a huge waste of resources and publication of false or misleading data. Here we evaluate a panel of 96 single-nucleotide polymorphism (SNP assays utilizing Fluidigm microfluidics technology for authentication and sex determination of human cell lines. The SNPtrace Panel was tested on 907 human cell lines. Pairwise comparison of these data show the SNPtrace Panel discriminated among identical, related and unrelated pairs of samples with a high degree of confidence, equivalent to short tandem repeat (STR profiling. We also compared annotated sex calls with those determined by the SNPtrace Panel, STR and Illumina SNP arrays, revealing a high number of male samples are identified as female due to loss of the Y chromosome. Finally we assessed the sensitivity of the SNPtrace Panel to detect intra-human cross-contamination, resulting in detection of as little as 2% contaminating cell population. In conclusion, this study has generated a database of SNP fingerprints for 907 cell lines used in biomedical research and provides a reliable, fast, and economic alternative to STR profiling which can be applied to any human cell line or tissue sample.

A review of human leptospirosis in Malaysia.

Science.gov (United States)

El Jalii, I M; Bahaman, A R

2004-12-01

This paper reviews the literature on human leptospirosis in Malaysia from its first description in 1925 until the present day. Fletcher diagnosed the first case of human leptospirosis in Malaysia in 1925. Following Fletcher, many investigations on human leptospirosis in Malaysia disclosed a high prevalence of infection. These investigations indicated that the disease was endemic in the country. Examination of 1993 suspected human cases of leptospirosis by Tan indicated 28 % of the cases were positive. In a recent survey, 2190 serum samples from patients with different clinical manifestations in the country disclosed 12.6% were positive for antibodies to leptospires. The risk to leptospiral infection with respect to occupation, location, sex, race and age groups was demonstrated. Both civilians and military personnel were affected. Thirty-seven serovars from thirteen serogroups have been identified in the country. Recent studies on animal leptospirosis showed that the disease was highly endemic in the animal population. It is considered that the majority of leptospirosis cases in humans were due to association of man with animals and disease-infected environment.

A human monoclonal antibody with neutralizing activity against highly divergent influenza subtypes.

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Nicola Clementi

Full Text Available The interest in broad-range anti-influenza A monoclonal antibodies (mAbs has recently been strengthened by the identification of anti-hemagglutinin (HA mAbs endowed with heterosubtypic neutralizing activity to be used in the design of "universal" prophylactic or therapeutic tools. However, the majority of the single mAbs described to date do not bind and neutralize viral isolates belonging to highly divergent subtypes clustering into the two different HA-based influenza phylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and H9 and the group 2 including, among others, H3 subtype. Here, we describe a human mAb, named PN-SIA28, capable of binding and neutralizing all tested isolates belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes and several isolates belonging to group 2, including H3N2 isolates from the first period of the 1968 pandemic. Therefore, PN-SIA28 is capable of neutralizing isolates belonging to subtypes responsible of all the reported pandemics, as well as other subtypes with pandemic potential. The region recognized by PN-SIA28 has been identified on the stem region of HA and includes residues highly conserved among the different influenza subtypes. A deep characterization of PN-SIA28 features may represent a useful help in the improvement of available anti-influenza therapeutic strategies and can provide new tools for the development of universal vaccinal strategies.

High-energy x-ray grating-based phase-contrast radiography of human anatomy

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Horn, Florian; Hauke, Christian; Lachner, Sebastian; Ludwig, Veronika; Pelzer, Georg; Rieger, Jens; Schuster, Max; Seifert, Maria; Wandner, Johannes; Wolf, Andreas; Michel, Thilo; Anton, Gisela

2016-03-01

X-ray grating-based phase-contrast Talbot-Lau interferometry is a promising imaging technology that has the potential to raise soft tissue contrast in comparison to conventional attenuation-based imaging. Additionally, it is sensitive to attenuation, refraction and scattering of the radiation and thus provides complementary and otherwise inaccessible information due to the dark-field image, which shows the sub-pixel size granularity of the measured object. Until recent progress the method has been mainly limited to photon energies below 40 keV. Scaling the method to photon energies that are sufficient to pass large and spacious objects represents a challenging task. This is caused by increasing demands regarding the fabrication process of the gratings and the broad spectra that come along with the use of polychromatic X-ray sources operated at high acceleration voltages. We designed a setup that is capable to reach high visibilities in the range from 50 to 120 kV. Therefore, spacious and dense parts of the human body with high attenuation can be measured, such as a human knee. The authors will show investigations on the resulting attenuation, differential phase-contrast and dark-field images. The images experimentally show that X-ray grating-based phase-contrast radiography is feasible with highly absorbing parts of the human body containing massive bones.

Human-Specific Endogenous Retroviruses

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Anton Buzdin

2007-01-01

Full Text Available This review focuses on a small family of human-specific genomic repetitive elements, presented by 134 members that shaped ~330 kb of the human DNA. Although modest in terms of its copy number, this group appeared to modify the human genome activity by endogenizing ~50 functional copies of viral genes that may have important implications in the immune response, cancer progression, and antiretroviral host defense. A total of 134 potential promoters and enhancers have been added to the human DNA, about 50% of them in the close gene vicinity and 22% in gene introns. For 60 such human-specific promoters, their activity was confirmed by in vivo assays, with the transcriptional level varying ~1000-fold from hardly detectable to as high as ~3% of β-actin transcript level. New polyadenylation signals have been provided to four human RNAs, and a number of potential antisense regulators of known human genes appeared due to human-specific retroviral insertional activity. This information is given here in the context of other major genomic changes underlining differences between human and chimpanzee DNAs. Finally, a comprehensive database, is available for download, of human-specific and polymorphic endogenous retroviruses is presented, which encompasses the data on their genomic localization, primary structure, encoded viral genes, human gene neighborhood, transcriptional activity, and methylation status.

Persistence and reappearance of high-risk human papillomavirus after conization

DEFF Research Database (Denmark)

Gosvig, Camilla Flarup; Huusom, Lene Drasbek; Andersen, Klaus Kaae

2013-01-01

Women with early cervical cancer or intraepithelial neoplasia grades 2 and 3 (CIN2+) are treated by conization; however, they still have a higher risk for subsequent CIN2+ than the general female population. Persistence of high-risk (HR) human papillomavirus (HPV) is a key factor in the development...

Quantitative Profiling of Major Neutral Lipid Classes in Human Meibum by Direct Infusion Electrospray Ionization Mass Spectrometry

Science.gov (United States)

Chen, Jianzhong; Green, Kari B.; Nichols, Kelly K.

2013-01-01

Purpose. The purpose of this investigation was to better understand lipid composition in human meibum. Methods. Intact lipids in meibum samples were detected by direct infusion electrospray ionization mass spectrometry (ESI-MS) analysis in positive detection mode using sodium iodide (NaI) as an additive. The peak intensities of all major types of lipid species, that is, wax esters (WEs), cholesteryl esters (CEs), and diesters (DEs) were corrected for peak overlapping and isotopic distribution; an additional ionization efficiency correction was performed for WEs and CEs, which was simplified by the observation that the corresponding ionization efficiency was primarily dependent on the specific lipid class and saturation degree of the lipids while independent of the carbon chain length. A set of WE and CE standards was spiked in meibum samples for ionization efficiency determination and absolute quantitation. Results. The absolute amount (μmol/mg) for each of 51 WEs and 31 CEs in meibum samples was determined. The summed masses for 51 WEs and 31 CEs accounted for 48 ± 4% and 40 ± 2%, respectively, of the total meibum lipids. The mass percentages of saturated and unsaturated species were determined to be 75 ± 2% and 25 ± 1% for CEs and 14 ± 1% and 86 ± 1% for WEs. The profiles for two types of DEs were also obtained, which include 42 α,ω Type II DEs, and 21 ω Type I-St DEs. Conclusions. Major neutral lipid classes in meibum samples were quantitatively profiled by ESI-MS analysis with NaI additive. PMID:23847307

A highly selective CCR2 chemokine agonist encoded by human herpesvirus 6

DEFF Research Database (Denmark)

Lüttichau, Hans R; Clark-Lewis, Ian; Jensen, Peter Østrup

2003-01-01

The chemokine-like, secreted protein product of the U83 gene from human herpesvirus 6, here named vCCL4, was chemically synthesized to be characterized in a complete library of the 18 known human chemokine receptors expressed individually in stably transfected cell lines. vCCL4 was found to cause...... being equally or more efficacious in causing cell migration than CCL2 and CCL7 and considerably more efficacious than CCL8 and CCL13. It is concluded that human herpesvirus 6 encodes a highly selective and efficacious CCR2 agonist, which will attract CCR2 expressing cells, for example macrophages...

Escitalopram for the management of major depressive disorder: a review of its efficacy, safety, and patient acceptability

OpenAIRE

Kirino, Eiji

2012-01-01

Eiji Kirino1,21Department of Psychiatry, Juntendo University Shizuoka Hospital, Shizuoka, Japan; 2Department of Psychiatry, Juntendo University School of Medicine, Tokyo, JapanAbstract: Escitalopram (escitalopram oxalate; Cipralex®, Lexapro®) is a selective serotonin reuptake inhibitor (SSRI) used for the treatment of major depressive disorder (MDD) and anxiety disorder. This drug exerts a highly selective, potent, and dose-dependent inhibitory effect on the human serotonin tr...

Ultra-high field MRI: Advancing systems neuroscience towards mesoscopic human brain function

NARCIS (Netherlands)

Dumoulin, Serge O; Fracasso, A.; Van der Zwaag, W.; Siero, Jeroen C W; Petridou, Natalia

2018-01-01

Human MRI scanners at ultra-high magnetic field strengths of 7 T and higher are increasingly available to the neuroscience community. A key advantage brought by ultra-high field MRI is the possibility to increase the spatial resolution at which data is acquired, with little reduction in image

The "Discouraged-Business-Major" Hypothesis: Policy Implications

Science.gov (United States)

Marangos, John

2012-01-01

This paper uses a relatively large dataset of the stated academic major preferences of economics majors at a relatively large, not highly selective, public university in the USA to identify the "discouraged-business-majors" (DBMs). The DBM hypothesis addresses the phenomenon where students who are screened out of the business curriculum often…

Livestock-Associated Methicillin Resistant and Methicillin Susceptible Staphylococcus aureus Sequence Type (CC1 in European Farmed Animals: High Genetic Relatedness of Isolates from Italian Cattle Herds and Humans.

Directory of Open Access Journals (Sweden)

Patricia Alba

Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA Sequence Type (ST1, Clonal Complex(CC1, SCCmec V is one of the major Livestock-Associated (LA- lineages in pig farming industry in Italy and is associated with pigs in other European countries. Recently, it has been increasingly detected in Italian dairy cattle herds. The aim of this study was to analyse the differences between ST1 MRSA and methicillin-susceptible S. aureus (MSSA from cattle and pig herds in Italy and Europe and human isolates. Sixty-tree animal isolates from different holdings and 20 human isolates were characterized by pulsed-field gel electrophoresis (PFGE, spa-typing, SCCmec typing, and by micro-array analysis for several virulence, antimicrobial resistance, and strain/host-specific marker genes. Three major PFGE clusters were detected. The bovine isolates shared a high (≥90% to 100% similarity with human isolates and carried the same SCCmec type IVa. They often showed genetic features typical of human adaptation or present in human-associated CC1: Immune evasion cluster (IEC genes sak and scn, or sea; sat and aphA3-mediated aminoglycoside resistance. Contrary, typical markers of porcine origin in Italy and Spain, like erm(A mediated macrolide-lincosamide-streptograminB, and of vga(A-mediated pleuromutilin resistance were always absent in human and bovine isolates. Most of ST(CC1 MRSA from dairy cattle were multidrug-resistant and contained virulence and immunomodulatory genes associated with full capability of colonizing humans. As such, these strains may represent a greater human hazard than the porcine strains. The zoonotic capacity of CC1 LA-MRSA from livestock must be taken seriously and measures should be implemented at farm-level to prevent spill-over.

Livestock-Associated Methicillin Resistant and Methicillin Susceptible Staphylococcus aureus Sequence Type (CC)1 in European Farmed Animals: High Genetic Relatedness of Isolates from Italian Cattle Herds and Humans.

Science.gov (United States)

Alba, Patricia; Feltrin, Fabiola; Cordaro, Gessica; Porrero, María Concepción; Kraushaar, Britta; Argudín, María Angeles; Nykäsenoja, Suvi; Monaco, Monica; Stegger, Marc; Aarestrup, Frank M; Butaye, Patrick; Franco, Alessia; Battisti, Antonio

2015-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) Sequence Type (ST)1, Clonal Complex(CC)1, SCCmec V is one of the major Livestock-Associated (LA-) lineages in pig farming industry in Italy and is associated with pigs in other European countries. Recently, it has been increasingly detected in Italian dairy cattle herds. The aim of this study was to analyse the differences between ST1 MRSA and methicillin-susceptible S. aureus (MSSA) from cattle and pig herds in Italy and Europe and human isolates. Sixty-tree animal isolates from different holdings and 20 human isolates were characterized by pulsed-field gel electrophoresis (PFGE), spa-typing, SCCmec typing, and by micro-array analysis for several virulence, antimicrobial resistance, and strain/host-specific marker genes. Three major PFGE clusters were detected. The bovine isolates shared a high (≥90% to 100%) similarity with human isolates and carried the same SCCmec type IVa. They often showed genetic features typical of human adaptation or present in human-associated CC1: Immune evasion cluster (IEC) genes sak and scn, or sea; sat and aphA3-mediated aminoglycoside resistance. Contrary, typical markers of porcine origin in Italy and Spain, like erm(A) mediated macrolide-lincosamide-streptograminB, and of vga(A)-mediated pleuromutilin resistance were always absent in human and bovine isolates. Most of ST(CC)1 MRSA from dairy cattle were multidrug-resistant and contained virulence and immunomodulatory genes associated with full capability of colonizing humans. As such, these strains may represent a greater human hazard than the porcine strains. The zoonotic capacity of CC1 LA-MRSA from livestock must be taken seriously and measures should be implemented at farm-level to prevent spill-over.

Influence of HLA on human partnership and sexual satisfaction.

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Kromer, J; Hummel, T; Pietrowski, D; Giani, A S; Sauter, J; Ehninger, G; Schmidt, A H; Croy, I

2016-08-31

The major histocompatibility complex (MHC, called HLA in humans) is an important genetic component of the immune system. Fish, birds and mammals prefer mates with different genetic MHC code compared to their own, which they determine using olfactory cues. This preference increases the chances of high MHC variety in the offspring, leading to enhanced resilience against a variety of pathogens. Humans are also able to discriminate HLA related olfactory stimuli, however, it is debated whether this mechanism is of behavioural relevance. We show on a large sample (N = 508), with high-resolution typing of HLA class I/II, that HLA dissimilarity correlates with partnership, sexuality and enhances the desire to procreate. We conclude that HLA mediates mate behaviour in humans.

Managing human fallibility in critical aerospace situations

Science.gov (United States)

Tew, Larry

2014-11-01

Human fallibility is pervasive in the aerospace industry with over 50% of errors attributed to human error. Consider the benefits to any organization if those errors were significantly reduced. Aerospace manufacturing involves high value, high profile systems with significant complexity and often repetitive build, assembly, and test operations. In spite of extensive analysis, planning, training, and detailed procedures, human factors can cause unexpected errors. Handling such errors involves extensive cause and corrective action analysis and invariably schedule slips and cost growth. We will discuss success stories, including those associated with electro-optical systems, where very significant reductions in human fallibility errors were achieved after receiving adapted and specialized training. In the eyes of company and customer leadership, the steps used to achieve these results lead to in a major culture change in both the workforce and the supporting management organization. This approach has proven effective in other industries like medicine, firefighting, law enforcement, and aviation. The roadmap to success and the steps to minimize human error are known. They can be used by any organization willing to accept human fallibility and take a proactive approach to incorporate the steps needed to manage and minimize error.

High-risk human papillomavirus clearance in pregnant women: trends for lower clearance during pregnancy with a catch-up postpartum

OpenAIRE

Nobbenhuis, M A E; Helmerhorst, T J M; van den Brule, A J C; Rozendaal, L; Bezemer, P D; Voorhorst, F J; Meijer, C J L M

2002-01-01

We followed 353 women referred with abnormal cervical cytology in a non-intervention cohort study. In 91 pregnant women we compared high-risk human papilloma virus rates in the subsequent trimesters and postpartum in comparison to 262 non-pregnant women. High-risk human papilloma virus clearance was compared with 179 high-risk human papilloma virus positive non-pregnant women. Our main questions were: (1) do high-risk human papilloma virus rates change during pregnancy?; and (2) is there any ...

Systematic high-yield production of human secreted proteins in Escherichia coli

International Nuclear Information System (INIS)

Dai Xueyu; Chen Qiang; Lian Min; Zhou Yanfeng; Zhou Mo; Lu Shanyun; Chen Yunjia; Luo Jingchu; Gu Xiaocheng; Jiang Ying; Luo Ming; Zheng Xiaofeng

2005-01-01

Human secreted proteins play a very important role in signal transduction. In order to study all potential secreted proteins identified from the human genome sequence, systematic production of large amounts of biologically active secreted proteins is a prerequisite. We selected 25 novel genes as a trial case for establishing a reliable expression system to produce active human secreted proteins in Escherichia coli. Expression of proteins with or without signal peptides was examined and compared in E. coli strains. The results indicated that deletion of signal peptides, to a certain extent, can improve the expression of these proteins and their solubilities. More importantly, under expression conditions such as induction temperature, N-terminus fusion peptides need to be optimized in order to express adequate amounts of soluble proteins. These recombinant proteins were characterized as well-folded proteins. This system enables us to rapidly obtain soluble and highly purified human secreted proteins for further functional studies

Frequency variations of discrete cranial traits in major human populations. I. Supernumerary ossicle variations.

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Hanihara, T; Ishida, H

2001-06-01

Four supernumerary ossicle variations-the ossicle at the lambda, the parietal notch bone, the asterionic bone, and the occipitomastoid bone-were examined for laterality differences, intertrait correlations, sex differences, and between group variations in the samples from around the world. Significant laterality differences were not detected in almost all samples. In some pairs of traits, significant association of occurrence were found. Several geographic samples were sexually dimorphic with respect to the asterionic bone and to a lesser extent for the parietal notch bone. East/Northeast Asians including the Arctic populations in general had lower frequencies of the 4 accessory ossicles. Australians, Melanesians and the majority of the New World peoples, on the other hand, generally had high frequencies. In the western hemisphere of the Old World, Subsaharan Africans had relatively high frequencies. Except for the ossicle at the lambda, the distribution pattern in incidence showed clinal variation from south to north. Any identifiable adaptive value related to environmental or subsistence factors may be expressed in such clinal variation. This may allow us to hypothesise that not only mechanical factors but a founder effect, genetic drift, and population structure could have been the underlying causes for interregional variation and possible clines in the incidences of the accessory ossicles.

High cell density suppresses BMP4-induced differentiation of human pluripotent stem cells to produce macroscopic spatial patterning in a unidirectional perfusion culture chamber.

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Tashiro, Shota; Le, Minh Nguyen Tuyet; Kusama, Yuta; Nakatani, Eri; Suga, Mika; Furue, Miho K; Satoh, Taku; Sugiura, Shinji; Kanamori, Toshiyuki; Ohnuma, Kiyoshi

2018-04-19

Spatial pattern formation is a critical step in embryogenesis. Bone morphogenetic protein 4 (BMP4) and its inhibitors are major factors for the formation of spatial patterns during embryogenesis. However, spatial patterning of the human embryo is unclear because of ethical issues and isotropic culture environments resulting from conventional culture dishes. Here, we utilized human pluripotent stem cells (hiPSCs) and a simple anisotropic (unidirectional perfusion) culture chamber, which creates unidirectional conditions, to measure the cell community effect. The influence of cell density on BMP4-induced differentiation was explored during static culture using a conventional culture dish. Immunostaining of the early differentiation marker SSEA-1 and the mesendoderm marker BRACHYURY revealed that high cell density suppressed differentiation, with small clusters of differentiated and undifferentiated cells formed. Addition of five-fold higher concentration of BMP4 showed similar results, suggesting that suppression was not caused by depletion of BMP4 but rather by high cell density. Quantitative RT-PCR array analysis showed that BMP4 induced multi-lineage differentiation, which was also suppressed under high-density conditions. We fabricated an elongated perfusion culture chamber, in which proteins were transported unidirectionally, and hiPSCs were cultured with BMP4. At low density, the expression was the same throughout the chamber. However, at high density, SSEA-1 and BRACHYURY were expressed only in upstream cells, suggesting that some autocrine/paracrine factors inhibited the action of BMP4 in downstream cells to form the spatial pattern. Human iPSCs cultured in a perfusion culture chamber might be useful for studying in vitro macroscopic pattern formation in human embryogenesis. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

In normal human fibroblasts variation in DSB repair capacity cannot be ascribed to radiation-induced changes in the localisation, expression or activity of major NHEJ proteins

DEFF Research Database (Denmark)

Kasten-Pisula, Ulla; Vronskaja, Svetlana; Overgaard, Jens

2008-01-01

in the activity of the DNA-PK complex induced upon irradiation. CONCLUSIONS: For normal human fibroblasts, the level or activity of NHEJ proteins measured prior to or after irradiation cannot be used to predict the DSB repair capacity or cellular radiosensitivity. Udgivelsesdato: 2008-Mar......BACKGROUND AND PURPOSE: The aim of the present study was to test whether for normal human fibroblasts the variation in double-strand break (DSB) repair capacity results from radiation-induced differences in localisation, expression or activity of major non-homologous end-joining (NHEJ) proteins....... MATERIALS AND METHODS: Experiments were performed with 11 normal human fibroblast strains AF01-11. NHEJ proteins were determined by Western blot and DNA-PK activity by pulldown-assay. RESULTS: The four NHEJ proteins tested (Ku70, Ku80, XRCC4 and DNA-PKcs) were found to be localised almost exclusively...

A high confidence, manually validated human blood plasma protein reference set

DEFF Research Database (Denmark)

Schenk, Susann; Schoenhals, Gary J; de Souza, Gustavo

2008-01-01

BACKGROUND: The immense diagnostic potential of human plasma has prompted great interest and effort in cataloging its contents, exemplified by the Human Proteome Organization (HUPO) Plasma Proteome Project (PPP) pilot project. Due to challenges in obtaining a reliable blood plasma protein list......-trap-Fourier transform (LTQ-FT) and a linear ion trap-Orbitrap (LTQ-Orbitrap) for mass spectrometry (MS) analysis. Both instruments allow the measurement of peptide masses in the low ppm range. Furthermore, we employed a statistical score that allows database peptide identification searching using the products of two...... consecutive stages of tandem mass spectrometry (MS3). The combination of MS3 with very high mass accuracy in the parent peptide allows peptide identification with orders of magnitude more confidence than that typically achieved. RESULTS: Herein we established a high confidence set of 697 blood plasma proteins...

Interaction patterns of major air pollutants in Hong Kong territory

International Nuclear Information System (INIS)

Lu, W.Z.; Wang, X.K.

2004-01-01

Air pollution in a metropolitan city like Hong Kong is a major obstacle to improve air quality and living environment due to the high population density and the vehicle emission increases. The high air pollutant levels impose harm to the human health and impair the city image. The characteristic analysis of air pollutants is very important and necessary to pollutant monitoring, forecasting and controlling. In this study, the interaction patterns of principle air pollutants, e.g. nitrogen dioxide (NO 2 ), nitric oxide (NO), nitric oxides (NO x ) and ozone (O 3 ), a secondary pollutant, are investigated based on the measured database in four selected areas, which covers two urban types (i.e. residential area, mixed residential/commercial/industrial area) in Hong Kong, during the period of 1999-2001. The study involves analyzing the chemical and physical properties, the characteristics of air pollutants and the factors affecting such interactions using statistical method. The results reveal several routines in urban air pollutants' variations, interaction and trends from macro aspect

Expression and proteasomal degradation of the major vault protein (MVP) in mammalian oocytes and zygotes.

Science.gov (United States)

Sutovsky, Peter; Manandhar, Gaurishankar; Laurincik, Jozef; Letko, Juraj; Caamaño, Jose Nestor; Day, Billy N; Lai, Liangxue; Prather, Randall S; Sharpe-Timms, Kathy L; Zimmer, Randall; Sutovsky, Miriam

2005-03-01

Major vault protein (MVP), also called lung resistance-related protein is a ribonucleoprotein comprising a major part (>70%) of the vault particle. The function of vault particle is not known, although it appears to be involved in multi-drug resistance and cellular signaling. Here we show that MVP is expressed in mammalian, porcine, and human ova and in the porcine preimplantation embryo. MVP was identified by matrix-assisted laser-desorption ionization-time-of-flight (MALDI-TOF) peptide sequencing and Western blotting as a protein accumulating in porcine zygotes cultured in the presence of specific proteasomal inhibitor MG132. MVP also accumulated in poor-quality human oocytes donated by infertile couples and porcine embryos that failed to develop normally after in vitro fertilization or somatic cell nuclear transfer. Normal porcine oocytes and embryos at various stages of preimplantation development showed mostly cytoplasmic labeling, with increased accumulation of vault particles around large cytoplasmic lipid inclusions and membrane vesicles. Occasionally, MVP was associated with the nuclear envelope and nucleolus precursor bodies. Nucleotide sequences with a high degree of homology to human MVP gene sequence were identified in porcine oocyte and endometrial cell cDNA libraries. We interpret these data as the evidence for the expression and ubiquitin-proteasome-dependent turnover of MVP in the mammalian ovum. Similar to carcinoma cells, MVP could fulfill a cell-protecting function during early embryonic development.

Human CD4+ T cell responses to the dog major allergen Can f 1 and its human homologue tear lipocalin resemble each other.

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Aino L K Liukko

Full Text Available Lipocalin allergens form a notable group of proteins, as they contain most of the significant respiratory allergens from mammals. The basis for the allergenic capacity of allergens in the lipocalin family, that is, the development of T-helper type 2 immunity against them, is still unresolved. As immunogenicity has been proposed to be a decisive feature of allergens, the purpose of this work was to examine human CD4+ T cell responses to the major dog allergen Can f 1 and to compare them with those to its human homologue, tear lipocalin (TL. For this, specific T cell lines were induced in vitro from the peripheral blood mononuclear cells of Can f 1-allergic and healthy dog dust-exposed subjects with peptides containing the immunodominant T cell epitopes of Can f 1 and the corresponding TL peptides. We found that the frequency of Can f 1 and TL-specific T cells in both subject groups was low and close to each other, the difference being about two-fold. Importantly, we found that the proliferative responses of both Can f 1 and TL-specific T cell lines from allergic subjects were stronger than those from healthy subjects, but that the strength of the responses within the subject groups did not differ between these two antigens. Moreover, the phenotype of the Can f 1 and TL-specific T cell lines, determined by cytokine production and expression of cell surface markers, resembled each other. The HLA system appeared to have a minimal role in explaining the allergenicity of Can f 1, as the allergic and healthy subjects' HLA background did not differ, and HLA binding was very similar between Can f 1 and TL peptides. Along with existing data on lipocalin allergens, we conclude that strong antigenicity is not decisive for the allergenicity of Can f 1.

Temporally delineated sources of major chemical species in high Arctic snow

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K. M. Macdonald

2018-03-01

Full Text Available Long-range transport of aerosol from lower latitudes to the high Arctic may be a significant contributor to climate forcing in the Arctic. To identify the sources of key contaminants entering the Canadian High Arctic an intensive campaign of snow sampling was completed at Alert, Nunavut, from September 2014 to June 2015. Fresh snow samples collected every few days were analyzed for black carbon, major ions, and metals, and this rich data set provided an opportunity for a temporally refined source apportionment of snow composition via positive matrix factorization (PMF in conjunction with FLEXPART (FLEXible PARTicle dispersion model potential emission sensitivity analysis. Seven source factors were identified: sea salt, crustal metals, black carbon, carboxylic acids, nitrate, non-crustal metals, and sulfate. The sea salt and crustal factors showed good agreement with expected composition and primarily northern sources. High loadings of V and Se onto Factor 2, crustal metals, was consistent with expected elemental ratios, implying these metals were not primarily anthropogenic in origin. Factor 3, black carbon, was an acidic factor dominated by black carbon but with some sulfate contribution over the winter-haze season. The lack of K+ associated with this factor, a Eurasian source, and limited known forest fire events coincident with this factor's peak suggested a predominantly anthropogenic combustion source. Factor 4, carboxylic acids, was dominated by formate and acetate with a moderate correlation to available sunlight and an oceanic and North American source. A robust identification of this factor was not possible; however, atmospheric photochemical reactions, ocean microlayer reaction, and biomass burning were explored as potential contributors. Factor 5, nitrate, was an acidic factor dominated by NO3−, with a likely Eurasian source and mid-winter peak. The isolation of NO3− on a separate factor may reflect its complex atmospheric

Meat consumption is a major risk factor for hepatitis E virus infection.

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Ed Slot

Full Text Available The incidence of autochthonous hepatitis E virus genotype 3 (HEV gt3 infections in Western Europe is high. Although pigs are a major reservoir of the virus, the exact sources and transmission route(s of HEV gt3 to humans remain unclear.To determine the role of meat consumption at a population level, the seroprevalence of anti-HEV IgG antibodies was compared between Dutch blood donors with a vegetarian lifestyle and donors who consume meat on a daily basis.The age-weighted anti-HEV IgG seroprevalence among donors not eating meat was significantly lower than among meat-eating donors (12.4% vs 20.5%, p = 0.002. For both groups the prevalence strongly increased with age and the difference in prevalence was apparent for all age groups.Compared with meat-eating donors, the incidence of HEV infection is significantly lower among donors not eating meat, indicating that meat consumption is a major risk factor for HEV infection.

A half-century ago physicists missed a major public service opportunity, costing the human race widespread chronic illness and many deaths!

Science.gov (United States)

Lundquist, Marjorie

2005-03-01

Radar-pulsed microwave (MW) radiation-helped the Allies win World War II but health concerns soon arose. Alerted to a syndrome resembling mild radiation poisoning,^1 a worried M.D. surveyed radar-exposed workers, finding a high incidence of internal bleeding, 2 leukemia cases in 600 radar operators, 2 brain tumor cases in a 5-man MW research team and many complaints of headache. He sent his report^2 to the Pentagon in 1953. Alarmed Navy officers convened a meeting^3 [mostly of electrical engineers (EEs)] to identify a safe level of MW exposure for servicemen. Biophysicist Herman Schwan attended, playing a major role in establishing 10 mW/cm^2 as a thermally safe MW exposure limit. The IEEE became sole sponsor of ANSI C95 [an early health standard for radiofrequency (RF) exposure] with negative long-term consequences for human health! I review RF health standards development since 1953, comparing what physicists might have done, had they-not EEs-had this responsibility! [See also my technical abstract.] ^1 N.H. Steneck, The Microwave Debate, Cambridge, MA: MIT Press, 1984; p. 33. ^2 J.T. McLaughlin, A Study of Possible Health Hazards from Exposure to Microwave Radiation (Hughes Aircraft, Culver City CA, Feb. 9, 1953). ^3 Biological Effects of Microwaves, meeting minutes (Navy Dept. Conference, Naval Medical Research Institute, Bethesda MD, Apr. 29, 1953).

Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells

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Ben Chung Lap Chan

2015-09-01

Full Text Available Atopic dermatitis (AD is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC culture model coupled with the high-speed counter-current chromatography (HSCCC, high pressure liquid chromatography (HPLC and Liquid Chromatography-Mass Spectrometry (LCMS analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL-12 p40 and the functional cluster of differentiation (CD surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC.

Mitochondrial function in human skeletal muscle following high-altitude exposure

DEFF Research Database (Denmark)

Jacobs, Robert A; Boushel, Robert; Wright-Paradis, Cynthia

2013-01-01

Studies regarding mitochondrial modifications in human skeletal muscle following acclimatization to high altitude are conflicting, and these inconsistencies may be due to the prevalence of representing mitochondrial function through static and isolated measurements of specific mitochondrial...... characteristics. The aim of this study, therefore, was to investigate mitochondrial function in response to high-altitude acclimatization through measurements of respiratory control in the vastus lateralis muscle. Skeletal muscle biopsies were obtained from 10 lowland natives prior to and again after a total of 9......-11 days of exposure to 4559 m. High-resolution respirometry was performed on the muscle samples to compare respiratory chain function and respiratory capacities. Respirometric analysis revealed that mitochondrial function was largely unaffected, because high-altitude exposure did not affect the capacity...

High prevalence of human anti-bovine IgG antibodies as the major cause of false positive reactions in two-site immunoassays based on monoclonal antibodies

DEFF Research Database (Denmark)

Andersen, Ditte C; Koch, Claus; Jensen, Charlotte H

2004-01-01

were purified by protein G affinity chromatography from culture supernatant containing 10% (v/v) fetal calf serum (FCS). Human anti-animal IgG (bovine, mouse, horse, and swine) antibodies and human anti-bovine serum albumin antibodies were measured using an ELISA design, with direct bridging...... of the solid phase and biotinylated antigens. The false positive reactions were abolished by addition of 1% (v/v) bovine serum to the dilution buffer (DB). Human anti-bovine IgG antibodies (HABIA) were detected in 99 out of 104 sera from blood donors (50 females; 54 males). HABIA levels in male sera (n = 54......) were positively correlated to the false positive signals in the PP14 ELISA (r = 0.923; p detected in the donor sera, but levels and frequencies were lower compared to that of HABIA. Furthermore, HABIA were...

Evaluation of molecular brain changes associated with environmental stress in rodent models compared to human major depressive disorder: A proteomic systems approach.

Science.gov (United States)

Cox, David Alan; Gottschalk, Michael Gerd; Stelzhammer, Viktoria; Wesseling, Hendrik; Cooper, Jason David; Bahn, Sabine

2016-11-25

Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue (n = 12) and matched controls (n = 23) were compared with equivalent data from three commonly used preclinical models exposed to environmental stressors (chronic mild stress, prenatal stress and social defeat). Functional pathophysiological features associated with depression-like behaviour were identified in these models through enrichment of protein-protein interaction networks. A cross-species comparison evaluated which model(s) represent human MDD pathology most closely. Seven functional domains associated with MDD and represented across at least two models such as "carbohydrate metabolism and cellular respiration" were identified. Through statistical evaluation using kernel-based machine learning techniques, the social defeat model was found to represent MDD brain changes most closely for four of the seven domains. This is the first study to apply a method for directly evaluating the relevance of the molecular pathology of multiple animal models to human MDD on the functional level. The methodology and findings outlined here could help to overcome translational obstacles of preclinical psychiatric research.

Leishmania major infection in a dog with cutaneous manifestations

OpenAIRE

Baneth, Gad; Nachum-Biala, Yaarit; Shabat Simon, Maytal; Brenner, Ori; Gaier, Sarit; Rojas, Alicia; Yasur-Landau, Daniel

2016-01-01

Background Leishmania major is a main cause of cutaneous leishmaniasis in humans in an area that stretches from India through Central Asia, the Middle East, to North and West Africa. In Israel, it is a common infection of humans with rodents as the reservoir hosts and Phlebotomus papatasi as its sand fly vector. Findings A 6?months old spayed female mixed breed dog was referred to the Hebrew University Veterinary Teaching Hospital with a large ulcerative dermal lesion on the muzzle, and lesio...

Beta-lipotropin is the major component of the plasma opioid response to surgical stress in humans

Energy Technology Data Exchange (ETDEWEB)

Porro, C.A.; Facchinetti, F.; Bertellini, E.; Petraglia, F.; Stacca, R.; Barbieri, G.C.; Genazzani, A.R.

1987-12-07

There is growing experimental evidence that beta-endorphin immunoreactivity is raised by surgical stress in patients undergoing general anesthesia. As the assay methods employed to date did not allow to fully discriminate between beta-endorphin and its immediate precursor, beta-lipotropin, the authors have investigated in the present study plasma levels of these two peptides by separating them by chromatography on plasma extracts prior to radioimmunoassay. Beta-lipotropin, but not beta-endorphin, plasma levels were found to be significantly elevated during surgery in the general anesthesia group, while no change was found in either peptide concentration in the spinal one. Cortisol plasma levels also increased significantly 90 minutes after the beginning of surgery. Although the sampling time they adopted may have prevented them from detecting an early peak of beta-endorphin during the first 30 minutes of surgery, the major component of the pituitary opioid response to surgical stress appears to be related to beta-lipotropin. This is in agreement with results of experimental work on various kinds of stress in animals and humans and seems to rule out a role for plasma beta-endorphin in post-operative analgesia. 38 references, 1 figure, 1 table.

Neurotensin receptors in human neoplasms: high incidence in Ewing's sarcomas.

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Reubi, J C; Waser, B; Schaer, J C; Laissue, J A

1999-07-19

Receptors for regulatory peptides, such as somatostatin or vasoactive intestinal peptide (VIP), expressed at high density by neoplastic cells, can be instrumental for tumor diagnosis and therapy. Little is known about the expression of neurotensin receptors in human tumors. In the present study, 464 human neoplasms of various types were investigated for their neurotensin receptor content by in vitro receptor autoradiography on tissue sections using 125I-[Tyr3]-neurotensin as radioligand. Neurotensin receptors were identified and localized in tumor cells of 11/17 Ewing's sarcomas, 21/40 meningiomas, 10/23 astrocytomas, 5/13 medulloblastomas, 7/24 medullary thyroid cancers and 2/8 small cell lung cancers. They were rarely found in non-small cell lung cancers and breast carcinomas; they were absent in prostate, ovarian, renal cell and hepatocellular carcinomas, neuroendocrine gut tumors, pituitary adenomas, schwannomas, neuroblastomas and lymphomas. When present, the receptors bound with nanomolar affinity neurotensin and acetyl-neurotensin-(8-13), with lower affinity neuromedin N, diethylenetriamine penta-acetic acidneurotensin-(8-13) and SR 48692, but not neurotensin-(1-11). They were all of the NT1 type, without high affinity for levocabastine. Further, in 2 receptor-positive Ewing's sarcomas, neurotensin mRNA was detected by in situ hybridization techniques. Since neurotensin is known to stimulate cell proliferation, the presence of neurotensin receptors in human neoplasia may be of biological relevance, possibly as an integrative part of an autocrine feedback mechanism of tumor growth stimulation.

Degrees of reality: airway anatomy of high-fidelity human patient simulators and airway trainers.

Science.gov (United States)

Schebesta, Karl; Hüpfl, Michael; Rössler, Bernhard; Ringl, Helmut; Müller, Michael P; Kimberger, Oliver

2012-06-01

Human patient simulators and airway training manikins are widely used to train airway management skills to medical professionals. Furthermore, these patient simulators are employed as standardized "patients" to evaluate airway devices. However, little is known about how realistic these patient simulators and airway-training manikins really are. This trial aimed to evaluate the upper airway anatomy of four high-fidelity patient simulators and two airway trainers in comparison with actual patients by means of radiographic measurements. The volume of the pharyngeal airspace was the primary outcome parameter. Computed tomography scans of 20 adult trauma patients without head or neck injuries were compared with computed tomography scans of four high-fidelity patient simulators and two airway trainers. By using 14 predefined distances, two cross-sectional areas and three volume parameters of the upper airway, the manikins' similarity to a human patient was assessed. The pharyngeal airspace of all manikins differed significantly from the patients' pharyngeal airspace. The HPS Human Patient Simulator (METI®, Sarasota, FL) was the most realistic high-fidelity patient simulator (6/19 [32%] of all parameters were within the 95% CI of human airway measurements). The airway anatomy of four high-fidelity patient simulators and two airway trainers does not reflect the upper airway anatomy of actual patients. This finding may impact airway training and confound comparative airway device studies.

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord.

Directory of Open Access Journals (Sweden)

David G Brohawn

Full Text Available ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned >50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR for identification of differentially expressed genes (DEG's. Ingenuity Pathways Analysis (IPA and Weighted Gene Co-expression Network Analysis (WGCNA identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF found to be a major pathway regulator (IPA and TNFα-induced protein 2 (TNFAIP2 as a major network "hub" gene (WGCNA. Using the oPOSSUM algorithm, we analyzed transcription factors (TF controlling expression of the nine DEG/hub genes in the ALS samples and identified TF's involved in inflammation (NFkB, REL, NFkB1 and macrophage function (NR1H2::RXRA heterodimer. Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be

Human Use Index

Data.gov (United States)

U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

A translatable predictor of human radiation exposure.

Science.gov (United States)

Lucas, Joseph; Dressman, Holly K; Suchindran, Sunil; Nakamura, Mai; Chao, Nelson J; Himburg, Heather; Minor, Kerry; Phillips, Gary; Ross, Joel; Abedi, Majid; Terbrueggen, Robert; Chute, John P

2014-01-01

Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

A translatable predictor of human radiation exposure.

Directory of Open Access Journals (Sweden)

Joseph Lucas

Full Text Available Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB and humans treated with total body irradiation (TBI. Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

A Simple and Sensitive LC-MS/MS Method for Determination of Four Major Active Diterpenoids from Andrographis paniculata in Human Plasma and Its Application to a Pilot Study.

Science.gov (United States)

Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Satayavivad, Jutamaad

2016-01-01

Andrographis paniculata contains four major active diterpenoids, including andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4), which exhibit differences in types and/or degrees of their pharmacological activity. Previous pharmacokinetic studies in humans reported only the parameters of compound 1 and its analytical method in human plasma. The purpose of this study was to develop a simple, sensitive, and selective liquid chromatography tandem-mass spectrometry technique for the simultaneous determination of all four major active diterpenoids in the A. paniculata product in human plasma. These four diterpenoids in plasma samples were extracted by a simple protein precipitation method with methanol and separated on a Kinetex C18 column using a gradient system with a mobile phase of acetonitrile and water. The liquid chromatography tandem-mass spectrometry was performed in the negative mode, and the multiple reaction monitoring mode was used for the quantitation. The method showed a good linearity over a wide concentration range of 2.50-500 ng/mL for 1 and over the range of 1.00-500 ng/mL for the other diterpenoids with a correlation coefficient R(2) > 0.995. The lower limit of quantification of 1 was found to be 2.50 ng/mL, while those of the other diterpenoids were 1.00 ng/mL. The intraday and interday accuracy (relative error) ranged from 0.03 % to 10.03 %, and the intraday and interday precisions (relative standard deviation) were in the range of 2.05-9.67 %. The extraction recovery (86.54-111.56 %) with a relative standard deviation of 2.78-8.61 % and the matrix effect (85.15-112.36 %) were within the acceptance criteria. Moreover, these four major active diterpenoids were stable in plasma samples at the studied storage conditions with a relative error ≤-9.79 % and a relative standard deviation ≤ 9.26 %. Hence, this present method was successfully validated

Requirements for growth and IL-10 expression of highly purified human T regulatory cells

OpenAIRE

Bonacci, Benedetta; Edwards, Brandon; Jia, Shuang; Williams, Calvin; Hessner, Martin J.; Gauld, Stephen; Verbsky, James

2012-01-01

Human regulatory T cells (TR) cells have potential for the treatment of a variety of immune mediated diseases but the anergic phenotype of these cells makes them difficult to expand in vitro. We have examined the requirements for growth and cytokine expression from highly purified human TR cells, and correlated these findings with the signal transduction events of these cells. We demonstrate that these cells do not proliferate or secrete IL-10 even in the presence of high doses of IL-2. Stimu...

Human adipocytes are highly sensitive to intermittent hypoxia induced NF-kappaB activity and subsequent inflammatory gene expression

International Nuclear Information System (INIS)

Taylor, Cormac T.; Kent, Brian D.; Crinion, Sophie J.; McNicholas, Walter T.; Ryan, Silke

2014-01-01

Highlights: • Intermittent hypoxia (IH) leads to NF-κB activation in human primary adipocytes. • Adipocytes bear higher pro-inflammatory potential than other human primary cells. • IH leads to upregulation of multiple pro-inflammatory genes in human adipocytes. - Abstract: Introduction: Intermittent hypoxia (IH)-induced activation of pro-inflammatory pathways is a major contributing factor to the cardiovascular pathophysiology associated with obstructive sleep apnea (OSA). Obesity is commonly associated with OSA although it remains unknown whether adipose tissue is a major source of inflammatory mediators in response to IH. The aim of this study was to test the hypothesis that IH leads to augmented inflammatory responses in human adipocytes when compared to cells of non-adipocyte lineages. Methods and results: Human primary subcutaneous and visceral adipocytes, human primary microvascular pulmonary endothelial cells (HUMEC-L) and human primary small airway epithelial cells (SAEC) were exposed to 0, 6 or 12 cycles of IH or stimulated with tumor necrosis factor (TNF)-α. IH led to a robust increase in NF-κB DNA-binding activity in adipocytes compared with normoxic controls regardless of whether the source of adipocytes was visceral or subcutaneous. Notably, the NF-κB response of adipocytes to both IH and TNF-α was significantly greater than that in HUMEC-L and SAEC. Western blotting confirmed enhanced nuclear translocation of p65 in adipocytes in response to IH, accompanied by phosphorylation of I-κB. Parallel to p65 activation, we observed a significant increase in secretion of the adipokines interleukin (IL)-8, IL-6 and TNF-α with IH in adipocytes accompanied by significant upregulation of mRNA expression. PCR-array suggested profound influence of IH on pro-inflammatory gene expression in adipocytes. Conclusion: Human adipocytes demonstrate strong sensitivity to inflammatory gene expression in response to acute IH and hence, adipose tissue may be a key

Human adipocytes are highly sensitive to intermittent hypoxia induced NF-kappaB activity and subsequent inflammatory gene expression

Energy Technology Data Exchange (ETDEWEB)

Taylor, Cormac T. [School of Medicine and Medical Science, The Conway Institute, University College Dublin (Ireland); Kent, Brian D.; Crinion, Sophie J.; McNicholas, Walter T. [School of Medicine and Medical Science, The Conway Institute, University College Dublin (Ireland); Pulmonary and Sleep Disorders Unit, St. Vincent’s University Hospital, Dublin (Ireland); Ryan, Silke, E-mail: silke.ryan@ucd.ie [School of Medicine and Medical Science, The Conway Institute, University College Dublin (Ireland); Pulmonary and Sleep Disorders Unit, St. Vincent’s University Hospital, Dublin (Ireland)

2014-05-16

Highlights: • Intermittent hypoxia (IH) leads to NF-κB activation in human primary adipocytes. • Adipocytes bear higher pro-inflammatory potential than other human primary cells. • IH leads to upregulation of multiple pro-inflammatory genes in human adipocytes. - Abstract: Introduction: Intermittent hypoxia (IH)-induced activation of pro-inflammatory pathways is a major contributing factor to the cardiovascular pathophysiology associated with obstructive sleep apnea (OSA). Obesity is commonly associated with OSA although it remains unknown whether adipose tissue is a major source of inflammatory mediators in response to IH. The aim of this study was to test the hypothesis that IH leads to augmented inflammatory responses in human adipocytes when compared to cells of non-adipocyte lineages. Methods and results: Human primary subcutaneous and visceral adipocytes, human primary microvascular pulmonary endothelial cells (HUMEC-L) and human primary small airway epithelial cells (SAEC) were exposed to 0, 6 or 12 cycles of IH or stimulated with tumor necrosis factor (TNF)-α. IH led to a robust increase in NF-κB DNA-binding activity in adipocytes compared with normoxic controls regardless of whether the source of adipocytes was visceral or subcutaneous. Notably, the NF-κB response of adipocytes to both IH and TNF-α was significantly greater than that in HUMEC-L and SAEC. Western blotting confirmed enhanced nuclear translocation of p65 in adipocytes in response to IH, accompanied by phosphorylation of I-κB. Parallel to p65 activation, we observed a significant increase in secretion of the adipokines interleukin (IL)-8, IL-6 and TNF-α with IH in adipocytes accompanied by significant upregulation of mRNA expression. PCR-array suggested profound influence of IH on pro-inflammatory gene expression in adipocytes. Conclusion: Human adipocytes demonstrate strong sensitivity to inflammatory gene expression in response to acute IH and hence, adipose tissue may be a key

Harmfulness of smoking among high school students

Directory of Open Access Journals (Sweden)

Iwona Rotter

2013-03-01

Full Text Available Introduction: The aim of the study was to assess the level of awareness of smoking and non smoking students on harmful impact of nicotine and cigarette smoke on human body. Material and methods: The study was carried out in March 2011 in high schools in Szczecin. Own elaborated questionnaire was used. 288 students from high school, technical college and vocational school were tested. Results: The majority of responders (95,1% claimed that cigarette smoke is harmful both for passive and active smokers. They most often pinpoint the direct cause connected with smoking to pulmonary diseases (264 persons and cancers (240 persons. Almost 90% of students found negative impact of tobacco products on development of fetus of pregnant women. Overwhelming majority of respondents (83,2% feels anxious if it comes to stay in a room filled with smoke. Conclusions: The awareness of high school students on negative influence of smoking on human body is quite satisfactory, but there is still a need for more education in the range of diseases and symptoms connected with smoking.

Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

Energy Technology Data Exchange (ETDEWEB)

Rajasekaran, Maheswari; Brents, Lisa K.; Franks, Lirit N. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Moran, Jeffery H. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Arkansas Department of Public Health, Public Health Laboratory, Little Rock, AR 72205 (United States); Prather, Paul L., E-mail: pratherpaull@uams.edu [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

2013-06-01

K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB{sub 1}Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB{sub 2}Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB{sub 2}Rs (hCB{sub 2}Rs). The affinity of cannabinoids for hCB{sub 2}Rs was determined by competition binding studies employing CHO-hCB{sub 2} membranes. Intrinsic activity of compounds was assessed by G-protein activation and adenylyl cyclase (AC)-inhibition in CHO-hCB{sub 2} cells. JWH-073, JWH-018 and several of their human metabolites exhibit nanomolar affinity and act as potent agonists at hCB{sub 2}Rs. Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to CB{sub 2}Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. Finally, when compared to CP-55,940 and Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB{sub 2}R occupancy to produce similar levels of AC-inhibition, indicating that these compounds may more efficiently couple CB{sub 2}Rs to AC than the well characterized cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB{sub 2}Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB{sub 1} and CB{sub 2}Rs. - Highlights: • JWH-018

Correlation of maternal age, gravida status, major malformations, stillbirth and sex ratio in high level natural radiation areas of Kerala coast

International Nuclear Information System (INIS)

Sudheer, K.R.; Koya, P.K.M.; Jaikrishan, G.; Das, Birajalaxmi

2016-01-01

As a part of the ongoing study on biological and health effects of chronic low dose and/or dose rate on human population, consecutive births were monitored in selected Govt. hospitals located in normal and high level natural radiation areas (HLNRA) of Kerala coast. This area is unique because of its vast population size and varied range of background radiation level due to natural deposit of monazite containing thorium. The objective is to elucidate the role of chronic low dose radiation, if any, on the adverse pregnancy outcome. Since 1995, ∼1,70,000 newborns were monitored in this area, of which 74,238 singleton first births were monitored. Of these, 634 (0.85%) cases were observed with detectable major congenital malformations (that include serious structural, functional or cosmetic disability requiring surgical or medical management) and 240 (0.32%) cases were stillborn. Sex ratio at first birth was observed in the ratio of 1050 males to 1000 females. The distribution of age at marriage of the mothers was stratified into the following groups: d"18 years (15.5%), 19 20 years (25.9%), 21 22 years (25.6%), 23 24 years (17.2%) and >25 years (15.8%). It was observed that about 78.9% mothers had their first birth within one year of marriage, 13.7% had their first birth within 1.1 2 years and 5.2% within 2.1 4 years. About 2.2% (1613) mothers had their first child after 4 years or more. Individual, combined and interactive effects of age at marriage, first birth interval (first gravida status), background radiation levels and gender of the newborn on major congenital malformation and stillbirth will be discussed. (author)

MAJOR AND LYMPHOCYTE POPULATIONS OF HUMAN PERIPHERAL BLOOD LYMPHOCYTES AND THEIR REFERENCE VALUES, AS ASSAYED BY MULTI-COLOUR CYTOMETRY

Directory of Open Access Journals (Sweden)

S. V. Khaidukov

2009-01-01

Full Text Available Abstract. Determination of lymphocyte subpopulations and their phenotypes is an important diagnostic feature, in order to elucidate some disturbances connected with immune system functioning. However, insufficient data are obtained when analyzing only major populations of peripheral lymphocytes. In order to perform clinical diagnostics, the data about minor lymphocytic populations and activated cellular pools seem to be more pertinent.Studies of peripheral blood cell subpopulations of healthy donors performed in different Russian regions allowed to assess quantitative distribution intervals for both major and minor immune cell subpopulations in humans. The results obtained, as compared with data from literature, provide an evidence for similar reference intervals for main immune cell subpopulations in healthy donors, independent on their habitation area.Present work has resulted into development of algorithms for cytometric studies and generation of certain panels of monoclonal antibodies enabling evaluation of all main lymphocyte subpopulations, as well as their minor subsets participating in emerging immune response. The distribution intervals have been estimated for such minor subpopulations, as B1- and B2-lymphocytes, memory B-cells, γδ- and αβT-cells, regulatory and naїve T-cells, cytotoxic and secretory NK-cell polupations.The results of present study, while been performed with peripheral blood of healthy donors, may provide a basis of reference values when studying subpopulation profile of immune cells.

Major intrinsic proteins (MIPs) in plants: a complex gene family with major impacts on plant phenotype.

Science.gov (United States)

Forrest, Kerrie L; Bhave, Mrinal

2007-10-01

The ubiquitous cell membrane proteins called aquaporins are now firmly established as channel proteins that control the specific transport of water molecules across cell membranes in all living organisms. The aquaporins are thus likely to be of fundamental significance to all facets of plant growth and development affected by plant-water relations. A majority of plant aquaporins have been found to share essential structural features with the human aquaporin and exhibit water-transporting ability in various functional assays, and some have been shown experimentally to be of critical importance to plant survival. Furthermore, substantial evidence is now available from a number of plant species that shows differential gene expression of aquaporins in response to abiotic stresses such as salinity, drought, or cold and clearly establishes the aquaporins as major players in the response of plants to conditions that affect water availability. This review summarizes the function and regulation of these genes to develop a greater understanding of the response of plants to water insufficiency, and particularly, to identify tolerant genotypes of major crop species including wheat and rice and plants that are important in agroforestry.

Human interest meets biodiversity hotspots: A new systematic approach for urban ecosystem conservation.

Science.gov (United States)

Kasada, Minoru; Matsuba, Misako; Miyashita, Tadashi

2017-01-01

Creating a win-win relationship between biodiversity and human well-being is one of the major current challenges for environmental policy. One way to approach this challenge is to identify sites with both high biodiversity and high human interest in urban areas. Here, we propose a new systematic approach to identify such sites by using land prices and biodiversity indexes for butterflies and birds from a nationwide perspective. As a result, we found sites that are valuable to humans and to other organisms, including national red-list species, and they are located in sites with cultural heritages and near seaside. By referencing the habitat features and landscape characteristics of these sites, we can establish high quality environments that provide a benefit to both humans and biodiversity in urban landscapes.

High-precision Pb isotopic measurements of teeth and environmental samples from Sofia (Bulgaria): insights for regional lead sources and possible pathways to the human body

Science.gov (United States)

Kamenov, George D.

2008-08-01

High-precision Pb isotopic measurements on teeth and possible sources in a given area can provide important insights for the lead (Pb) sources and pathways in the human body. Pb isotopic analyses on soils from the area of Sofia, Bulgaria show that Pb is contributed by three end-members represented by two natural sources and leaded gasoline. Sequential leaching experiments reveal that the alumosilicate fraction of the soils is mainly controlled by natural Pb derived from two mountain massifs bordering the city. Around 1/3 to a half of the Pb in the soil leachates, however, can be explained by contamination from leaded gasoline. Contemporary teeth from Sofia residents show very similar Pb isotopic compositions to the soil leachates, also indicating that around 1/3 to a half of the Pb can be explained by derivation from leaded gasoline. The remarkable isotopic similarities between the teeth and the most labile fractions of the local soils suggest that the lead can be derived from the latter. Pb incorporation in the human body via soil-plant-human or soil-plant-animal-human chains is unlikely due to the fact that no significant farming occurs in the city area. The isotopic compositions of the local soil labile fractions can be used as approximation of the bioaccessible lead for humans. Considering all possible scenarios it appears that soil and/or soil-born dust inhalation and/or ingestion is the most probable pathway for incorporation of local soil lead in the local population. The high-precision Pb isotope data presented in this work indicate that apparently the local soil is what plays major role in the human Pb exposure.

A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei.

Science.gov (United States)

Pauli, Wolfgang M; Nili, Amanda N; Tyszka, J Michael

2018-04-17

Recent advances in magnetic resonance imaging methods, including data acquisition, pre-processing and analysis, have benefited research on the contributions of subcortical brain nuclei to human cognition and behavior. At the same time, these developments have led to an increasing need for a high-resolution probabilistic in vivo anatomical atlas of subcortical nuclei. In order to address this need, we constructed high spatial resolution, three-dimensional templates, using high-accuracy diffeomorphic registration of T 1 - and T 2 - weighted structural images from 168 typical adults between 22 and 35 years old. In these templates, many tissue boundaries are clearly visible, which would otherwise be impossible to delineate in data from individual studies. The resulting delineations of subcortical nuclei complement current histology-based atlases. We further created a companion library of software tools for atlas development, to offer an open and evolving resource for the creation of a crowd-sourced in vivo probabilistic anatomical atlas of the human brain.

Human colon cancers as a major problem in poland and in the world – medical and environmental issues

Directory of Open Access Journals (Sweden)

Sylwia Katarzyna Król

2011-12-01

Full Text Available Many epidemiological data have shown an increasing incidence and mortality of colon cancer cases in the past several years, not only in Poland but all over the world as well. Each year, approximately a million new cases of colon cancer are diagnosed and that is the cause of death of almost half a million patients in the world. The aim of this article is to present the epidemiology and the current state of scientific knowledge concerning etiology and pathogenesis of neoplastic diseases in human large intestine. Furthermore, this short review describes the essential risk factors and suggests the simple and effective ways of colon cancer prevention.Colorectal cancer is one of the most frequently diagnosed cancers in EU countries. Scientific studies have proved that genetic and hereditary factors have a strong influence on carcinogenesis in human colon. Moreover, environmental factors, such as dietary contribute to the development of colon neoplasm. The most useful tool to reduce high morbidity and mortality is a prevention. Screening tests in nonsymptomatic people from high-risk groups or populations enable diagnosis in the early stage of colorectal cancer. Many publications have reported that modification of lifestyle and daily diet also play a significant role in prevention.

Seroprevalence of Leptospira infection in bats roosting in human ...

African Journals Online (AJOL)

Leptospirosis is a neglected emerging infectious disease with high burden in Africa. Major reservoirs of leptospirosis are rodents and other small mammals. Studies of leptospirosis in bats and the extent to which they contribute to its transmission to humans and domestic animals in Tanzania are lacking. The objective of this ...

Concept Design of High Power Solar Electric Propulsion Vehicles for Human Exploration

Science.gov (United States)

Hoffman, David J.; Kerslake, Thomas W.; Hojnicki, Jeffrey S.; Manzella, David H.; Falck, Robert D.; Cikanek, Harry A., III; Klem, Mark D.; Free, James M.

2011-01-01

Human exploration beyond low Earth orbit will require enabling capabilities that are efficient, affordable and reliable. Solar electric propulsion (SEP) has been proposed by NASA s Human Exploration Framework Team as one option to achieve human exploration missions beyond Earth orbit because of its favorable mass efficiency compared to traditional chemical propulsion systems. This paper describes the unique challenges associated with developing a large-scale high-power (300-kWe class) SEP vehicle and design concepts that have potential to meet those challenges. An assessment of factors at the subsystem level that must be considered in developing an SEP vehicle for future exploration missions is presented. Overall concepts, design tradeoffs and pathways to achieve development readiness are discussed.

Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans.

Directory of Open Access Journals (Sweden)

Michelle D Leach

Full Text Available Eukaryotic cells have evolved mechanisms to sense and adapt to dynamic environmental changes. Adaptation to thermal insults, in particular, is essential for their survival. The major fungal pathogen of humans, Candida albicans, is obligately associated with warm-blooded animals and hence occupies thermally buffered niches. Yet during its evolution in the host it has retained a bona fide heat shock response whilst other stress responses have diverged significantly. Furthermore the heat shock response is essential for the virulence of C. albicans. With a view to understanding the relevance of this response to infection we have explored the dynamic regulation of thermal adaptation using an integrative systems biology approach. Our mathematical model of thermal regulation, which has been validated experimentally in C. albicans, describes the dynamic autoregulation of the heat shock transcription factor Hsf1 and the essential chaperone protein Hsp90. We have used this model to show that the thermal adaptation system displays perfect adaptation, that it retains a transient molecular memory, and that Hsf1 is activated during thermal transitions that mimic fever. In addition to providing explanations for the evolutionary conservation of the heat shock response in this pathogen and the relevant of this response to infection, our model provides a platform for the analysis of thermal adaptation in other eukaryotic cells.

Assuring human operator alertness at night in power plants

International Nuclear Information System (INIS)

Moore-Ede, M.C.

1988-01-01

The human body is not designed for peak alertness and performance at night, nor is it well-equipped to cope with the frequent day-night inversions required by rotating shift work schedules. As a result, the human operator can become the weak link in a complex technological operation such as a nuclear power plant. The high degree of dependence on human operator vigilance, decision-making ability and performance that is required in nuclear power plant operations can conflict with the human sleepiness and error-proneness which naturally occur during the night shift or after extended periods without adequate sleep. An opportunity to address these problems has come from a series of major research advances in basic circadian physiology

High-level transfer and long-term expression of the human beta-globin gene in a mouse transplant model.

Science.gov (United States)

Raftopoulos, H; Ward, M; Bank, A

1998-06-30

Insertion of a normally functioning human beta-globin gene into the hematopoietic stem cells (HSC) of patients with beta-thalassemia may be an effective approach to the therapy of this disorder. Safe, efficient gene transfer and long-term, high-level expression of the transferred human beta-globin gene in animal models are prerequisites for HSC somatic gene therapy. We have recently shown for the first time that, using a modified beta-globin retroviral vector in a mouse transplant model, long-term, high-level expression of a transferred human beta-globin gene is possible. The human beta-globin gene continues to be detected up to eight months post-transplantation of beta-globin-transduced hematopoietic cells into lethally irradiated mice. The transferred human beta-globin gene is detected in three of five mice surviving long-term (> 4 months) transplanted with bone marrow cells transduced with high-titer virus. The unrearranged 5.1 kb human beta-globin gene-containing provirus is seen by Southern blotting in two of these mice. More importantly, long-term expression of the transferred gene is seen in two mice at levels of 5% and 20% that of endogenous murine beta-globin. We document stem cell transduction by showing continued high-level expression of the human beta-globin gene in secondarily transplanted recipient mice. These results provide evidence of HSC transduction with a human beta-globin gene in animals and demonstrate that retroviral-mediated unrearranged human beta-globin gene transfer leads to a high level of human beta-globin gene expression in the long term for the first time. A gene therapy strategy may be a feasible therapeutic approach to the beta-thalassemias if consistent human beta-globin gene transfer and expression into HSC can be achieved.

High Leptospira Diversity in Animals and Humans Complicates the Search for Common Reservoirs of Human Disease in Rural Ecuador.

Science.gov (United States)

Barragan, Veronica; Chiriboga, Jorge; Miller, Erin; Olivas, Sonora; Birdsell, Dawn; Hepp, Crystal; Hornstra, Heidie; Schupp, James M; Morales, Melba; Gonzalez, Manuel; Reyes, Soraya; de la Cruz, Carmen; Keim, Paul; Hartskeerl, Rudy; Trueba, Gabriel; Pearson, Talima

2016-09-01

Leptospirosis is a zoonotic disease responsible for high morbidity around the world, especially in tropical and low income countries. Rats are thought to be the main vector of human leptospirosis in urban settings. However, differences between urban and low-income rural communities provide additional insights into the epidemiology of the disease. Our study was conducted in two low-income rural communities near the coast of Ecuador. We detected and characterized infectious leptospira DNA in a wide variety of samples using new real time quantitative PCR assays and amplicon sequencing. We detected infectious leptospira in a high percentage of febrile patients (14.7%). In contrast to previous studies on leptospirosis risk factors, higher positivity was not found in rats (3.0%) but rather in cows (35.8%) and pigs (21.1%). Six leptospira species were identified (L. borgpetersenii, L kirschnerii, L santarosai, L. interrogans, L noguchii, and an intermediate species within the L. licerasiae and L. wolffii clade) and no significant differences in the species of leptospira present in each animal species was detected (χ2 = 9.89, adj.p-value = 0.27). A large portion of the world's human population lives in low-income, rural communities, however, there is limited information about leptospirosis transmission dynamics in these settings. In these areas, exposure to peridomestic livestock is particularly common and high prevalence of infectious leptospira in cows and pigs suggest that they may be the most important reservoir for human transmission. Genotyping clinical samples show that multiple species of leptospira are involved in human disease. As these genotypes were also detected in samples from a variety of animals, genotype data must be used in conjunction with epidemiological data to provide evidence of transmission and the importance of different potential leptospirosis reservoirs.

Annotating DNA variants is the next major goal for human genetics.

Science.gov (United States)

Cutting, Garry R

2014-01-02

Clinical genetic testing has undergone a dramatic transformation in the past two decades. Diagnostic laboratories that previously tested for well-established disease-causing DNA variants in a handful of genes have evolved into sequencing factories identifying thousands of variants of known and unknown medical consequence. Sorting out what does and does not cause disease in our genomes is the next great challenge in making genetics a central feature of healthcare. I propose that closing the gap in our ability to interpret variation responsible for Mendelian disorders provides a grand and unprecedented opportunity for geneticists. Human geneticists are well placed to coordinate a systematic evaluation of variants in collaboration with basic scientists and clinicians. Sharing of knowledge, data, methods, and tools will aid both researchers and healthcare workers in achieving their common goal of defining the pathogenic potential of variants. Generation of variant annotations will inform genetic testing and will deepen our understanding of gene and protein function, thereby aiding the search for molecular targeted therapies. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver.

Science.gov (United States)

Papageorgiou, Ioannis; Freytsis, Marina; Court, Michael H

2016-10-01

Acetaminophen is the leading cause of acute liver failure (ALF) in many countries including the United States. Hepatic glucuronidation by UDP-glucuronosyltransferase (UGT) 1A subfamily enzymes is the major route of acetaminophen elimination. Reduced glucuronidation may predispose some individuals to acetaminophen-induced ALF, but mechanisms underlying reduced glucuronidation are poorly understood. We hypothesized that specific microRNAs (miRNAs) may reduce UGT1A activity by direct effects on the UGT1A 3'-UTR shared by all UGT1A enzyme transcripts, or by indirect effects on transcription factors regulating UGT1A expression. We performed an unbiased miRNA whole transcriptome association analysis using a bank of human livers with known acetaminophen glucuronidation activities. Of 754 miRNAs evaluated, 9 miRNAs were identified that were significantly overexpressed (p2-fold) in livers with low acetaminophen glucuronidation activities compared with those with high activities. miR-375 showed the highest difference (>10-fold), and was chosen for further mechanistic validation. We demonstrated using in silico analysis and luciferase reporter assays that miR-375 has a unique functional binding site in the 3'-UTR of the aryl hydrocarbon receptor (AhR) gene. Furthermore overexpression of miR-375 in LS180 cells demonstrated significant repression of endogenous AhR protein (by 40%) and mRNA (by 10%), as well as enzyme activity and/or mRNA of AhR regulated enzymes including UGT1A1, UGT1A6, and CYP1A2, without affecting UGT2B7, which is not regulated by AhR. Thus miR-375 is identified as a novel repressor of UGT1A-mediated hepatic acetaminophen glucuronidation through reduced AhR expression, which could predispose some individuals to increased risk for acetaminophen-induced ALF. Published by Elsevier Inc.

Meiotic faults as a major cause of offspring inviability

DEFF Research Database (Denmark)

Levitis, Daniel; Zimmerman, Kolea; Pringle, Anne

2014-01-01

, this result demonstrates that failures associated with meiosis are a major cause of offspring inviability not only for meiotic parthenogenesis, but for sexual reproducers such as humans. Meiosis is necessary for genetic recombination in eukaryotes, but is vestigial, and costly, in parthenogens. The question...... range of organisms....

T wave abnormalities, high body mass index, current smoking and high lipoprotein (a levels predict the development of major abnormal Q/QS patterns 20 years later. A population-based study

Directory of Open Access Journals (Sweden)

Sundstrom Johan

2006-03-01

Full Text Available Abstract Background Most studies on risk factors for development of coronary heart disease (CHD have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome. Methods Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later. Results At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18–8.17, high lipoprotein (a levels, high body mass index (BMI and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern. Conclusion T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a levels may be a stronger risk factor for silent myocardial infarction (MI compared to clinically recognized MI.

The Major Histocompatibility Complex in Transplantation

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Marco Antonio Ayala García

2012-01-01

Full Text Available The transplant of organs is one of the greatest therapeutic achievements of the twentieth century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the principal target of the immune response is the MHC (major histocompatibility complex molecules expressed on the surface of donor cells. However, we should not forget that the innate and adaptive immunities are closely interrelated and should be viewed as complementary and cooperating. When a human transplant is performed, HLA (human leukocyte antigens molecules from a donor are recognized by the recipient's immune system triggering an alloimmune response Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. This paper will present MHC, the innate and adaptive immunities, and clinical HLA testing.

A hybrid CPU-GPU accelerated framework for fast mapping of high-resolution human brain connectome.

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Yu Wang

Full Text Available Recently, a combination of non-invasive neuroimaging techniques and graph theoretical approaches has provided a unique opportunity for understanding the patterns of the structural and functional connectivity of the human brain (referred to as the human brain connectome. Currently, there is a very large amount of brain imaging data that have been collected, and there are very high requirements for the computational capabilities that are used in high-resolution connectome research. In this paper, we propose a hybrid CPU-GPU framework to accelerate the computation of the human brain connectome. We applied this framework to a publicly available resting-state functional MRI dataset from 197 participants. For each subject, we first computed Pearson's Correlation coefficient between any pairs of the time series of gray-matter voxels, and then we constructed unweighted undirected brain networks with 58 k nodes and a sparsity range from 0.02% to 0.17%. Next, graphic properties of the functional brain networks were quantified, analyzed and compared with those of 15 corresponding random networks. With our proposed accelerating framework, the above process for each network cost 80∼150 minutes, depending on the network sparsity. Further analyses revealed that high-resolution functional brain networks have efficient small-world properties, significant modular structure, a power law degree distribution and highly connected nodes in the medial frontal and parietal cortical regions. These results are largely compatible with previous human brain network studies. Taken together, our proposed framework can substantially enhance the applicability and efficacy of high-resolution (voxel-based brain network analysis, and have the potential to accelerate the mapping of the human brain connectome in normal and disease states.

High-energy phosphate transfer in human muscle: diffusion of phosphocreatine.

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Gabr, Refaat E; El-Sharkawy, Abdel-Monem M; Schär, Michael; Weiss, Robert G; Bottomley, Paul A

2011-07-01

The creatine kinase (CK) reaction is central to muscle energetics, buffering ATP levels during periods of intense activity via consumption of phosphocreatine (PCr). PCr is believed to serve as a spatial shuttle of high-energy phosphate between sites of energy production in the mitochondria and sites of energy utilization in the myofibrils via diffusion. Knowledge of the diffusion coefficient of PCr (D(PCr)) is thus critical for modeling and understanding energy transport in the myocyte, but D(PCr) has not been measured in humans. Using localized phosphorus magnetic resonance spectroscopy, we measured D(PCr) in the calf muscle of 11 adults as a function of direction and diffusion time. The results show that the diffusion of PCr is anisotropic, with significantly higher diffusion along the muscle fibers, and that the diffusion of PCr is restricted to a ∼28-μm pathlength assuming a cylindrical model, with an unbounded diffusion coefficient of ∼0.69 × 10(-3) mm(2)/s. This distance is comparable in size to the myofiber radius. On the basis of prior measures of CK reaction kinetics in human muscle, the expected diffusion distance of PCr during its half-life in the CK reaction is ∼66 μm. This distance is much greater than the average distances between mitochondria and myofibrils. Thus these first measurements of PCr diffusion in human muscle in vivo support the view that PCr diffusion is not a factor limiting high-energy phosphate transport between the mitochondria and the myofibrils in healthy resting myocytes.

The catalytic chain of human complement subcomponent C1r. Purification and N-terminal amino acid sequences of the major cyanogen bromide-cleavage fragments.

Science.gov (United States)

Arlaud, G J; Gagnon, J; Porter, R R

1982-01-01

1. The a- and b-chains of reduced and alkylated human complement subcomponent C1r were separated by high-pressure gel-permeation chromatography and isolated in good yield and in pure form. 2. CNBr cleavage of C1r b-chain yielded eight major peptides, which were purified by gel filtration and high-pressure reversed-phase chromatography. As determined from the sum of their amino acid compositions, these peptides accounted for a minimum molecular weight of 28 000, close to the value 29 100 calculated from the whole b-chain. 3. N-Terminal sequence determinations of C1r b-chain and its CNBr-cleavage peptides allowed the identification of about two-thirds of the amino acids of C1r b-chain. From our results, and on the basis of homology with other serine proteinases, an alignment of the eight CNBr-cleavage peptides from C1r b-chain is proposed. 4. The residues forming the 'charge-relay' system of the active site of serine proteinases (His-57, Asp-102 and Ser-195 in the chymotrypsinogen numbering) are found in the corresponding regions of C1r b-chain, and the amino acid sequence around these residues has been determined. 5. The N-terminal sequence of C1r b-chain has been extended to residue 60 and reveals that C1r b-chain lacks the 'histidine loop', a disulphide bond that is present in all other known serine proteinases.

Habitability and Human Factors Contributions to Human Space Flight

Science.gov (United States)

Sumaya, Jennifer Boyer

2011-01-01

This slide presentation reviews the work of the Habitability and Human Factors Branch in support of human space flight in two main areas: Applied support to major space programs, and Space research. The field of Human Factors applies knowledge of human characteristics for the design of safer, more effective, and more efficient systems. This work is in several areas of the human space program: (1) Human-System Integration (HSI), (2) Orion Crew Exploration Vehicle, (3) Extravehicular Activity (EVA), (4) Lunar Surface Systems, (5) International Space Station (ISS), and (6) Human Research Program (HRP). After detailing the work done in these areas, the facilities that are available for human factors work are shown.

Finite element analysis of high modal dynamic responses of a composite floor subjected to human motion under passive live load

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Arash Behnia

Full Text Available Light weight and long span composite floors are common place in modern construction. A critical consequence of this application is undesired vibration which may cause excessive discomfort to occupants. This work investigates the composite floor vibration behavior of an existing building based on a comprehensive study of high modal dynamic responses, the range of which has been absent in previous studies and major analytical templates, of different panels under the influence of loads induced by human motion. The resulting fundamental natural frequency and vibration modes are first validated with respect to experimental and numerical evidences from literature. Departing from close correlation established in comparison, this study explores in detail the effects of intensity of passive live load as additional stationary mass due to crowd jumping as well as considering human structure interaction. From observation, a new approach in the simulation of passive live load through the consideration of human structure interaction and human body characteristics is proposed. It is concluded that higher vibration modes are essential to determine the minimum required modes and mass participation ratio in the case of vertical vibration. The results indicate the need to consider 30 modes of vibration to obtain all possible important excitations and thereby making third harmonic of load frequency available to excite the critical modes. In addition, presence of different intensities of passive live load on the composite floor showed completely different behavior in each particular panel associated with load location of panel and passive live load intensity. Furthermore, implementing human body characteristics in simulation causes an obvious increase in modal damping and hence better practicality and economical presentation can be achieved in structural dynamic behavior.

Major congenital malformations in the high and normal level radiation areas of southwest coast of Kerala

International Nuclear Information System (INIS)

Sudheer, K.R.; Jaikrishan, G.; Andrews, V.J.; Koya, P.K.M.; Seshadri, M.; Jagadeesan, C.K.; Madhusoodhanan, M.

2012-01-01

Congenital malformations are defects in organogenesis during the fetal periods and its influence on the individual may vary according to the type of malformation. Some congenital malformations are trivial and may not have any significance but for a minimal cosmetic deformity. Major malformations on the contrary may be severe enough to be life-threatening with serious structural, functional or cosmetic disability requiring surgical or medical management and are an important cause of mortality and morbidity all over the world. The present paper analyses the major malformations detected during the monitoring of newborns in selected government hospitals in and around the high level natural radiation areas of Kerala, a narrow strip of land in the southwest coast extending from Purakkad panchayat of Alapuzha district in the north to Neendakara Panchayat of Quilon district in the south. The coastal area has natural deposits of Monazite sand containing Thorium. Thorium together with its daughter products accounts for the elevated levels of natural radiation. The finding in general was in conformity with similar works on malformations

Genetic Divergence of the Rhesus Macaque Major Histocompatibility Complex

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Daza-Vamenta, Riza; Glusman, Gustavo; Rowen, Lee; Guthrie, Brandon; Geraghty, Daniel E.

2004-01-01

The major histocompatibility complex (MHC) is comprised of the class I, class II, and class III regions, including the MHC class I and class II genes that play a primary role in the immune response and serve as an important model in studies of primate evolution. Although nonhuman primates contribute significantly to comparative human studies, relatively little is known about the genetic diversity and genomics underlying nonhuman primate immunity. To address this issue, we sequenced a complete rhesus macaque MHC spanning over 5.3 Mb, and obtained an additional 2.3 Mb from a second haplotype, including class II and portions of class I and class III. A major expansion of from six class I genes in humans to as many as 22 active MHC class I genes in rhesus and levels of sequence divergence some 10-fold higher than a similar human comparison were found, averaging from 2% to 6% throughout extended portions of class I and class II. These data pose new interpretations of the evolutionary constraints operating between MHC diversity and T-cell selection by contrasting with models predicting an optimal number of antigen presenting genes. For the clinical model, these data and derivative genetic tools can be implemented in ongoing genetic and disease studies that involve the rhesus macaque. PMID:15289473

High yield of recombinant human Apolipoprotein A-I expressed in Pichia pastoris by using mixed-mode chromatography.

Science.gov (United States)

Narasimhan Janakiraman, Vignesh; Noubhani, Abdelmajid; Venkataraman, Krishnan; Vijayalakshmi, Mookambeswaran; Santarelli, Xavier

2016-01-01

A vast majority of the cardioprotective properties exhibited by High-Density Lipoprotein (HDL) is mediated by its major protein component Apolipoprotein A-I (ApoA1). In order to develop a simplified bioprocess for producing recombinant human Apolipoprotein A-I (rhApoA1) in its near-native form, rhApoA1was expressed without the use of an affinity tag in view of its potential therapeutic applications. Expressed in Pichia pastoris at expression levels of 58.2 mg ApoA1 per litre of culture in a reproducible manner, the target protein was purified by mixed-mode chromatography using Capto™ MMC ligand with a purity and recovery of 84% and 68%, respectively. ApoA1 purification was scaled up to Mixed-mode Expanded Bed Adsorption chromatography to establish an 'on-line' process for the efficient capture of rhApoA1 directly from the P. pastoris expression broth. A polishing step using anion exchange chromatography enabled the recovery of ApoA1 up to 96% purity. Purified ApoA1 was identified and verified by RPLC-ESI-Q-TOF mass spectrometry. This two-step process would reduce processing times and therefore costs in comparison to the twelve-step procedure currently used for recovering rhApoA1 from P. pastoris. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human intrusion

International Nuclear Information System (INIS)

Hora, S.; Neill, R.; Williams, R.; Bauser, M.; Channell, J.

1993-01-01

This paper focused on the possible approaches to evaluating the impacts of human intrusion on nuclear waste disposal. Several major issues were reviewed. First, it was noted that human intrusion could be addressed either quantitatively through performance assessments or qualitatively through design requirements. Second, it was decided that it was impossible to construct a complete set of possible future human intrusion scenarios. Third, the question of when the effect of possible human intrusion should be considered, before or after site selection was reviewed. Finally, the time frame over which human intrusion should be considered was discussed

Controlling major cellular processes of human mesenchymal stem cells using microwell structures.

Science.gov (United States)

Xu, Xun; Wang, Weiwei; Kratz, Karl; Fang, Liang; Li, Zhengdong; Kurtz, Andreas; Ma, Nan; Lendlein, Andreas

2014-12-01

Directing stem cells towards a desired location and function by utilizing the structural cues of biomaterials is a promising approach for inducing effective tissue regeneration. Here, the cellular response of human adipose-derived mesenchymal stem cells (hADSCs) to structural signals from microstructured substrates comprising arrays of square-shaped or round-shaped microwells is explored as a transitional model between 2D and 3D systems. Microwells with a side length/diameter of 50 μm show advantages over 10 μm and 25 μm microwells for accommodating hADSCs within single microwells rather than in the inter-microwell area. The cell morphologies are three-dimensionally modulated by the microwell structure due to differences in focal adhesion and consequent alterations of the cytoskeleton. In contrast to the substrate with 50 μm round-shaped microwells, the substrate with 50 μm square-shaped microwells promotes the proliferation and osteogenic differentiation potential of hADSCs but reduces the cell migration velocity and distance. Such microwell shape-dependent modulatory effects are highly associated with Rho/ROCK signaling. Following ROCK inhibition, the differences in migration, proliferation, and osteogenesis between cells on different substrates are diminished. These results highlight the possibility to control stem cell functions through the use of structured microwells combined with the manipulation of Rho/ROCK signaling. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improving Saliency Models by Predicting Human Fixation Patches

KAUST Repository

Dubey, Rachit

2015-04-16

There is growing interest in studying the Human Visual System (HVS) to supplement and improve the performance of computer vision tasks. A major challenge for current visual saliency models is predicting saliency in cluttered scenes (i.e. high false positive rate). In this paper, we propose a fixation patch detector that predicts image patches that contain human fixations with high probability. Our proposed model detects sparse fixation patches with an accuracy of 84 % and eliminates non-fixation patches with an accuracy of 84 % demonstrating that low-level image features can indeed be used to short-list and identify human fixation patches. We then show how these detected fixation patches can be used as saliency priors for popular saliency models, thus, reducing false positives while maintaining true positives. Extensive experimental results show that our proposed approach allows state-of-the-art saliency methods to achieve better prediction performance on benchmark datasets.

Improving Saliency Models by Predicting Human Fixation Patches

KAUST Repository

Dubey, Rachit; Dave, Akshat; Ghanem, Bernard

2015-01-01

There is growing interest in studying the Human Visual System (HVS) to supplement and improve the performance of computer vision tasks. A major challenge for current visual saliency models is predicting saliency in cluttered scenes (i.e. high false positive rate). In this paper, we propose a fixation patch detector that predicts image patches that contain human fixations with high probability. Our proposed model detects sparse fixation patches with an accuracy of 84 % and eliminates non-fixation patches with an accuracy of 84 % demonstrating that low-level image features can indeed be used to short-list and identify human fixation patches. We then show how these detected fixation patches can be used as saliency priors for popular saliency models, thus, reducing false positives while maintaining true positives. Extensive experimental results show that our proposed approach allows state-of-the-art saliency methods to achieve better prediction performance on benchmark datasets.

A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol

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Norrie John

2010-04-01

Full Text Available Abstract Background Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. Methods/Design A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. Discussion We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. Trial Registration Trial registration number - ISRCTN32188676

Role of high-risk human papillomavirus in the etiology of oral and oropharyngeal cancers in Thailand: A case-control study.

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Chotipanich, Adit; Siriarechakul, Surattaya; Mungkung, On-Ong

2018-01-01

Among developing countries, Thailand shows no increase in the incidence of human papillomavirus-driven oropharyngeal cancer. The causal role of human papillomavirus infection in this pathology has not been researched thoroughly. A hospital-based, case-control study was performed which included 104 patients with newly diagnosed oral and oropharyngeal squamous cell carcinomas and 104 individuals without cancer. The Cervista high-risk human papillomavirus and 16/18 assays were used to detect human papillomavirus. Odds ratios were used to assess the association between high-risk genotypes of human papillomavirus and the cancers. High-risk human papillomavirus was detected in 4 of 52 (7.7%) oral cancer cases, 6 of 52 (11.5%) oropharyngeal cancer cases, and 1 of 104 (0.96%) control subjects. Of 104 cancer patients in the study, 83 were smokers. High-risk human papillomavirus was significantly associated with oropharyngeal cancer (odds ratio = 13.44, 95% confidence interval = 1.6-114.8) but was nonsignificantly associated with oral cancer (odds ratio = 8.58, 95% confidence interval = 0.9-78.9). However, after adjustment for smoking, high-risk human papillomavirus was determined to be nonsignificantly associated with oropharyngeal cancer (adjusted odds ratio = 5.83, 95% confidence interval = 0.8-43.5). Although low human papillomavirus prevalence was observed, the rate of high-risk human papillomavirus infection in the cancer group was still higher than that in the control group. Smoking may have an influence on the etiology of human papillomavirus-related cancers. However, the study is underpowered to clarify the role of human papillomavirus as the independent risk factor for oral and oropharyngeal cancers in the Thai population.

High-frequency oscillations in human and monkey neocortex during the wake-sleep cycle.

Science.gov (United States)

Le Van Quyen, Michel; Muller, Lyle E; Telenczuk, Bartosz; Halgren, Eric; Cash, Sydney; Hatsopoulos, Nicholas G; Dehghani, Nima; Destexhe, Alain

2016-08-16

Beta (β)- and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake-sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β- and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β- and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β- and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS.

High-frequency oscillations in human and monkey neocortex during the wake–sleep cycle

Science.gov (United States)

Le Van Quyen, Michel; Muller, Lyle E.; Telenczuk, Bartosz; Halgren, Eric; Cash, Sydney; Hatsopoulos, Nicholas G.; Dehghani, Nima; Destexhe, Alain

2016-01-01

Beta (β)- and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake–sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β- and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β- and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β- and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS. PMID:27482084

Human rights and the requirement for international medical aid.

Science.gov (United States)

Tolchin, Benjamin

2008-08-01

Every year approximately 18 million people die prematurely from treatable medical conditions including infectious diseases and nutritional deficiencies. The deaths occur primarily amongst the poorest citizens of poor developing nations. Various groups and individuals have advanced plans for major international medical aid to avert many of these unnecessary deaths. For example, the World Health Organization's Commission on Macroeconomics and Health estimated that eight million premature deaths could be prevented annually by interventions costing roughly US$57 bn per year. This essay advances an argument that human rights require high-income nations to provide such aid. The essay briefly examines John Rawls' obligations of justice and the reasons that their applicability to cases of international medical aid remains controversial. Regardless, the essay argues that purely humanitarian obligations bind the governments and citizens of high-income liberal democracies at a minimum to provide major medical aid to avert premature deaths in poor nations. In refusing to undertake such medical relief efforts, developed nations fail to adequately protect a fundamental human right to life.

The Microbiota of the Human Skin.

Science.gov (United States)

Egert, Markus; Simmering, Rainer

2016-01-01

The aim of this chapter is to sum up important progress in the field of human skin microbiota research that was achieved over the last years.The human skin is one of the largest and most versatile organs of the human body. Owing to its function as a protective interface between the largely sterile interior of the human body and the highly microbially contaminated outer environment, it is densely colonized with a diverse and active microbiota. This skin microbiota is of high importance for human health and well-being. It is implicated in several severe skin diseases and plays a major role in wound infections. Many less severe, but negatively perceived cosmetic skin phenomena are linked with skin microbes, too. In addition, skin microorganisms, in particular on the human hands, are crucial for the field of hygiene research. Notably, apart from being only a potential source of disease and contamination, the skin microbiota also contributes to the protective functions of the human skin in many ways. Finally, the analysis of structure and function of the human skin microbiota is interesting from a basic, evolutionary perspective on human microbe interactions.Key questions in the field of skin microbiota research deal with (a) a deeper understanding of the structure (species inventory) and function (physiology) of the healthy human skin microbiota in space and time, (b) the distinction of resident and transient skin microbiota members, (c) the distinction of beneficial skin microorganisms from microorganisms or communities with an adverse or sickening effect on their hosts, (d) factors shaping the skin microbiota and its functional role in health and disease, (e) strategies to manipulate the skin microbiota for therapeutic reasons.

First-void urine: A potential biomarker source for triage of high-risk human papillomavirus infected women.

Science.gov (United States)

Van Keer, Severien; Pattyn, Jade; Tjalma, Wiebren A A; Van Ostade, Xaveer; Ieven, Margareta; Van Damme, Pierre; Vorsters, Alex

2017-09-01

Great interest has been directed towards the use of first-void urine as a liquid biopsy for high-risk human papillomavirus DNA testing. Despite the high correlations established between urinary and cervical infections, human papillomavirus testing is unable to distinguish between productive and transforming high-risk infections that have the tendency to progress to cervical cancer. Thus far, investigations have been primarily confined to the identification of biomarkers for triage of high-risk human papillomavirus-positive women in cervicovaginal specimens and tissue biopsies. This paper reviews urinary biomarkers for cervical cancer and triage of high-risk human papillomavirus infections and elaborates on the opportunities and challenges that have emerged regarding the use of first-void urine as a liquid biopsy for the analysis of both morphological- (conventional cytology and novel immunohistochemical techniques) and molecular-based (HPV16/18 genotyping, host/viral gene methylation, RNA, and proteins) biomarkers. A literature search was performed in PubMed and Web of Science for studies investigating the use of urine as a biomarker source for cervical cancer screening. Five studies were identified reporting on biomarkers that are still in preclinical exploratory or clinical assay development phases and on assessments of non-invasive (urine) samples. Although large-scale validation studies are still needed, we conclude that methylation of both host and viral genes in urine has been proven feasible for use as a molecular cervical cancer triage and screening biomarker in phase two studies. This is especially promising and underscores our hypothesis that human papillomavirus DNA and candidate human and viral biomarkers are washed away with the initial, first-void urine, together with exfoliated cells, debris and impurities that line the urethra opening. Similar to the limitations of self-collected cervicovaginal samples, first-void urine will likely not fulfil the

Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism*

Science.gov (United States)

Gunawardane, Ruwanthi N.; Fordstrom, Preston; Piper, Derek E.; Masterman, Stephanie; Siu, Sophia; Liu, Dongming; Brown, Mike; Lu, Mei; Tang, Jie; Zhang, Richard; Cheng, Janet; Gates, Andrew; Meininger, David; Chan, Joyce; Carlson, Tim; Walker, Nigel; Schwarz, Margrit; Delaney, John; Zhou, Mingyue

2016-01-01

Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouseTM platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 Å LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease. PMID:26644477

Rabbit IgG directed to a synthetic C-terminal peptide of the major grass pollen allergen Lol p I inhibits human basophil histamine release induced by natural Lol p I

NARCIS (Netherlands)

van Ree, R.; Aalberse, R. C.

1995-01-01

The potential role of allergen-specific IgG antibodies as 'blocking' antibodies in allergen-induced human basophil histamine release was investigated. This was studied in a model with the major grass pollen allergen Lol p I and polyclonal rabbit antisera directed against this allergen and against a

Novel mutations in scavenger receptor BI associated with high HDL cholesterol in humans

NARCIS (Netherlands)

Brunham, Liam R.; Tietjen, Ian; Bochem, Andrea E.; Singaraja, Roshni R.; Franchini, Patrick L.; Radomski, Chris; Mattice, Maryanne; Legendre, Annick; Hovingh, G. Kees; Kastelein, John J. P.; Hayden, Michael R.

2011-01-01

The scavenger receptor class B, member 1 (SR-BI), is a key cellular receptor for high-density lipoprotein (HDL) in mice, but its relevance to human physiology has not been well established. Recently a family was reported with a mutation in the gene encoding SR-BI and high HDL cholesterol (HDL-C).

Multiple genes encode the major surface glycoprotein of Pneumocystis carinii

DEFF Research Database (Denmark)

Kovacs, J A; Powell, F; Edman, J C

1993-01-01

The major surface antigen of Pneumocystis carinii, a life-threatening opportunistic pathogen in human immunodeficiency virus-infected patients, is an abundant glycoprotein that functions in host-organism interactions. A monoclonal antibody to this antigen is protective in animals, and thus this a...

Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis.

Science.gov (United States)

Moretti, Michele; Buiatti, Alessandra; Merlo, Marco; Massa, Laura; Fabris, Enrico; Pinamonti, Bruno; Sinagra, Gianfranco

2013-11-01

The management of refractory recurrent pericarditis is challenging. Previous clinical reports have noted a beneficial effect of high-dose intravenous human immunoglobulins (IvIgs) in isolated and systemic inflammatory disease-related forms. In this article, we analyzed retrospectively our clinical experience with IvIg therapy in a series of clinical cases of pericarditis refractory to conventional treatment. We retrospectively analyzed 9 patients (1994 to 2010) with refractory recurrent pericarditis, who received high-dose IvIg as a part of their medical treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine treatment was not discontinued during IvIg treatment. No patients had a history of autoimmune or connective tissue diseases. During an average period of 11 months from the first recurrence, patients had experienced a mean of 5 relapses before the first IvIg treatment. In 4 cases, patients showed complete clinical remission with no further relapse after the first IvIg cycle. Two patients experienced a single minor relapse, responsive to short-term nonsteroidal anti-inflammatory drugs. In 2 patients, we performed a second cycle of IvIg after a recurrence of pericarditis, with subsequent complete remission. One patient did not respond to 3 cycles of IvIg and subsequently underwent pericardial window and long-term immunosuppressive treatment. No major adverse effect was observed in consequence of IvIg administration in all the cases. In conclusion, although IvIg mode of action is still poorly understood in this setting, this treatment can be considered as an option in patients with recurrent pericarditis refractory to conventional medical treatment and, in our small series, has proved to be effective in 8 of 9 cases. Copyright © 2013 Elsevier Inc. All rights reserved.

Gardening as vector of a humanization of high-rise building

Science.gov (United States)

Lekareva, Nina; Zaslavskaya, Anna

2018-03-01

Article is devoted to issue of integration of vertical gardening into structure of high-rise building in the conditions of the constrained town-planning situation. On the basis of the analysis of the existing experience of design and building of "biopositive" high-rise building ecological, town-planning, social and constructive advantages of the organization of gardens on roofs and vertical gardens are considered [1]. As the main mechanism of increase in investment appeal of high-rise building the principle of a humanization due to gardening of high-rise building taking into account requirements of ecology, energy efficiency of buildings and improvement of quality of construction with minimization of expenses and maximizing comfort moves forward. The National Standards of Green construction designed to adapt the international requirements of architecture and construction of the energy efficient, eco-friendly and comfortable building or a complex to local conditions are considered [2,3].

High Diversity of Myocyanophage in Various Aquatic Environments Revealed by High-Throughput Sequencing of Major Capsid Protein Gene With a New Set of Primers

Directory of Open Access Journals (Sweden)

Weiguo Hou

2018-05-01

Full Text Available Myocyanophages, a group of viruses infecting cyanobacteria, are abundant and play important roles in elemental cycling. Here we investigated the particle-associated viral communities retained on 0.2 μm filters and in sediment samples (representing ancient cyanophage communities from four ocean and three lake locations, using high-throughput sequencing and a newly designed primer pair targeting a gene fragment (∼145-bp in length encoding the cyanophage gp23 major capsid protein (MCP. Diverse viral communities were detected in all samples. The fragments of 142-, 145-, and 148-bp in length were most abundant in the amplicons, and most sequences (>92% belonged to cyanophages. Additionally, different sequencing depths resulted in different diversity estimates of the viral community. Operational taxonomic units obtained from deep sequencing of the MCP gene covered the majority of those obtained from shallow sequencing, suggesting that deep sequencing exhibited a more complete picture of cyanophage community than shallow sequencing. Our results also revealed a wide geographic distribution of marine myocyanophages, i.e., higher dissimilarities of the myocyanophage communities corresponded with the larger distances between the sampling sites. Collectively, this study suggests that the newly designed primer pair can be effectively used to study the community and diversity of myocyanophage from different environments, and the high-throughput sequencing represents a good method to understand viral diversity.

Habitat selection of a large carnivore along human-wildlife boundaries in a highly modified landscape.

Directory of Open Access Journals (Sweden)

Chihiro Takahata

Full Text Available When large carnivores occupy peripheral human lands conflict with humans becomes inevitable, and the reduction of human-carnivore interactions must be the first consideration for those concerned with conflict mitigation. Studies designed to identify areas of high human-bear interaction are crucial for prioritizing management actions. Due to a surge in conflicts, against a background of social intolerance to wildlife and the prevalent use of lethal control throughout Japan, Asiatic black bears (Ursus thibetanus are now threatened by high rates of mortality. There is an urgent need to reduce the frequency of human-bear encounters if bear populations are to be conserved. To this end, we estimated the habitats that relate to human-bear interactions by sex and season using resource selection functions (RSF. Significant seasonal differences in selection for and avoidance of areas by bears were estimated by distance-effect models with interaction terms of land cover and sex. Human-bear boundaries were delineated on the basis of defined bear-habitat edges in order to identify areas that are in most need of proactive management strategies. Asiatic black bears selected habitats in close proximity to forest edges, forest roads, rivers, and red pine and riparian forests during the peak conflict season and this was correctly predicted in our human-bear boundary maps. Our findings demonstrated that bears selected abandoned forests and agricultural lands, indicating that it should be possible to reduce animal use near human lands by restoring season-specific habitat in relatively remote areas. Habitat-based conflict mitigation may therefore provide a practical means of creating adequate separation between humans and these large carnivores.

Habitat selection of a large carnivore along human-wildlife boundaries in a highly modified landscape.

Science.gov (United States)

Takahata, Chihiro; Nielsen, Scott Eric; Takii, Akiko; Izumiyama, Shigeyuki

2014-01-01

When large carnivores occupy peripheral human lands conflict with humans becomes inevitable, and the reduction of human-carnivore interactions must be the first consideration for those concerned with conflict mitigation. Studies designed to identify areas of high human-bear interaction are crucial for prioritizing management actions. Due to a surge in conflicts, against a background of social intolerance to wildlife and the prevalent use of lethal control throughout Japan, Asiatic black bears (Ursus thibetanus) are now threatened by high rates of mortality. There is an urgent need to reduce the frequency of human-bear encounters if bear populations are to be conserved. To this end, we estimated the habitats that relate to human-bear interactions by sex and season using resource selection functions (RSF). Significant seasonal differences in selection for and avoidance of areas by bears were estimated by distance-effect models with interaction terms of land cover and sex. Human-bear boundaries were delineated on the basis of defined bear-habitat edges in order to identify areas that are in most need of proactive management strategies. Asiatic black bears selected habitats in close proximity to forest edges, forest roads, rivers, and red pine and riparian forests during the peak conflict season and this was correctly predicted in our human-bear boundary maps. Our findings demonstrated that bears selected abandoned forests and agricultural lands, indicating that it should be possible to reduce animal use near human lands by restoring season-specific habitat in relatively remote areas. Habitat-based conflict mitigation may therefore provide a practical means of creating adequate separation between humans and these large carnivores.

Purification and characterization of a major human Pneumocystis carinii surface antigen

DEFF Research Database (Denmark)

Lundgren, B; Lipschik, G Y; Kovacs, J A

1991-01-01

. To evaluate humoral immune responses to the human P. carinii protein, an enzyme-linked immunosorbent assay using purified protein was developed. Some, but not all, patients who subsequently developed P. carinii pneumonia demonstrated a serum antibody response to the surface antigen. Nearly all subjects...... without a history of P. carinii pneumonia had no detectable antibodies. Purified P. carinii proteins will greatly facilitate the investigation of host-P. carinii interactions....

Majoring in Selection, and Minoring in Socialization: The Role of the College Experience in Goal Change Post-High School.

Science.gov (United States)

Hill, Patrick L; Jackson, Joshua J; Nagy, Nicole; Nagy, Gabriel; Roberts, Brent W; Lüdtke, Oliver; Trautwein, Ulrich

2016-04-01

Though it is frequently assumed that the college experience can influence our life goals, this claim has been relatively understudied. The current study examined the role of goals in college major selection, as well as whether major selection influences later goal change. In addition, we examined whether a person's perceptions of his or her peers' goals influence goal setting. Using a sample of German students (Mage  = 19 years; n = 3,023 at Wave 1), we assessed life goal levels and changes from high school into college across three assessment occasions. Participants reported their current aspirations, along with the perceived goals of their peers during the college assessments. Using latent growth curve models, findings suggest that life goals upon entering college significantly predict the majors students select. However, this major selection had limited influence on later changes in life goals. Stronger effects were found with respect to perceptions of peers' goals, with students tending to change their goals to better align with their peers. The current study provides evidence that life goals are relatively stable and yet can change during the emerging adult years, in ways that demonstrate the potential influence of the college experience. © 2014 Wiley Periodicals, Inc.

Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

DEFF Research Database (Denmark)

Pedersen, Lasse Eggers; Harndahl, Mikkel; Rasmussen, Michael

2011-01-01

a HLA-I molecule (HLA-A*11:01), thereby generating recombinant human/swine chimeric MHC-I molecules as well as the intact SLA-1*0401 molecule. Biochemical peptide-binding assays and positional scanning combinatorial peptide libraries were used to analyze the peptide-binding motifs of these molecules....... A pan-specific predictor of peptide–MHC-I binding, NetMHCpan, which was originally developed to cover the binding specificities of all known HLA-I molecules, was successfully used to predict the specificities of the SLA-1*0401 molecule as well as the porcine/human chimeric MHC-I molecules. These data......In all vertebrate animals, CD8+ cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules. These are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating CTLs. The polymorphism of the MHC...

Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo.

Science.gov (United States)

Apelgren, Peter; Amoroso, Matteo; Lindahl, Anders; Brantsing, Camilla; Rotter, Nicole; Gatenholm, Paul; Kölby, Lars

2017-01-01

Cartilage repair and replacement is a major challenge in plastic reconstructive surgery. The development of a process capable of creating a patient-specific cartilage framework would be a major breakthrough. Here, we described methods for creating human cartilage in vivo and quantitatively assessing the proliferative capacity and cartilage-formation ability in mono- and co-cultures of human chondrocytes and human mesenchymal stem cells in a three-dimensional (3D)-bioprinted hydrogel scaffold. The 3D-bioprinted constructs (5 × 5 × 1.2 mm) were produced using nanofibrillated cellulose and alginate in combination with human chondrocytes and human mesenchymal stem cells using a 3D-extrusion bioprinter. Immediately following bioprinting, the constructs were implanted subcutaneously on the back of 48 nude mice and explanted after 30 and 60 days, respectively, for morphological and immunohistochemical examination. During explantation, the constructs were easy to handle, and the majority had retained their macroscopic grid appearance. Constructs consisting of human nasal chondrocytes showed good proliferation ability, with 17.2% of the surface areas covered with proliferating chondrocytes after 60 days. In constructs comprising a mixture of chondrocytes and stem cells, an additional proliferative effect was observed involving chondrocyte production of glycosaminoglycans and type 2 collagen. This clinically highly relevant study revealed 3D bioprinting as a promising technology for the creation of human cartilage.

Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo.

Directory of Open Access Journals (Sweden)

Peter Apelgren

Full Text Available Cartilage repair and replacement is a major challenge in plastic reconstructive surgery. The development of a process capable of creating a patient-specific cartilage framework would be a major breakthrough. Here, we described methods for creating human cartilage in vivo and quantitatively assessing the proliferative capacity and cartilage-formation ability in mono- and co-cultures of human chondrocytes and human mesenchymal stem cells in a three-dimensional (3D-bioprinted hydrogel scaffold. The 3D-bioprinted constructs (5 × 5 × 1.2 mm were produced using nanofibrillated cellulose and alginate in combination with human chondrocytes and human mesenchymal stem cells using a 3D-extrusion bioprinter. Immediately following bioprinting, the constructs were implanted subcutaneously on the back of 48 nude mice and explanted after 30 and 60 days, respectively, for morphological and immunohistochemical examination. During explantation, the constructs were easy to handle, and the majority had retained their macroscopic grid appearance. Constructs consisting of human nasal chondrocytes showed good proliferation ability, with 17.2% of the surface areas covered with proliferating chondrocytes after 60 days. In constructs comprising a mixture of chondrocytes and stem cells, an additional proliferative effect was observed involving chondrocyte production of glycosaminoglycans and type 2 collagen. This clinically highly relevant study revealed 3D bioprinting as a promising technology for the creation of human cartilage.

Human Use Index (Future)

Data.gov (United States)

U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

[High oncogenic risk human papillomavirus and urinary bladder cancer].

Science.gov (United States)

Loran, O B; Sinyakova, L A; Gundorova, L V; Kosov, V A; Kosova, I V; Pogodina, I E; Kolbasov, D N

2017-07-01

To determine the role of human papillomavirus (HPV) of high oncogenic risk in the development of urinary bladder cancer. 100 patients (72 men and 28 women) aged 38 to 90 years (mean age 65+/-10 years) diagnosed with bladder cancer were examined and underwent treatment. Clinical assessment was complemented by enzyme-linked immunosorbent assays for the presence of antiviral antibodies to herpes simplex virus (HSV) type 1 and type 2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), urethra scraping for detecting high oncogenic risk HPV. Tumor tissue was sampled for PCR virus detection. Semi-quantitative analysis was used to evaluate the components of lymphocyte-plasmocyte and leukocyte infiltrates and cytopathic changes in tumor tissue. There were positive correlations between cytopathic cell changes (koylocytosis and intranuclear inclusions, as manifestations of HPV) and the level of antiviral antibodies, the presence of viruses in the tumor, as well as with the components of the lymphoid-plasmocyte infiltrate. Negative correlations were found between the presence of papillomatosis and the above changes. Human papillomavirus is believed to be a trigger for the initiation of a tumor in young patients with a latent infection (CMV and EBV, HSV, HPV). Cytopathic changes (kylocytosis and intranuclear inclusions) were associated with the activity and morphological features of herpes-viral infections. Their degree varied depending on the stage of the process, but not on the anaplasia degree. Papillomatosis is associated with a more favorable course of the tumor process.

Four-dimensional maps of the human somatosensory system.

Science.gov (United States)

Avanzini, Pietro; Abdollahi, Rouhollah O; Sartori, Ivana; Caruana, Fausto; Pelliccia, Veronica; Casaceli, Giuseppe; Mai, Roberto; Lo Russo, Giorgio; Rizzolatti, Giacomo; Orban, Guy A

2016-03-29

A fine-grained description of the spatiotemporal dynamics of human brain activity is a major goal of neuroscientific research. Limitations in spatial and temporal resolution of available noninvasive recording and imaging techniques have hindered so far the acquisition of precise, comprehensive four-dimensional maps of human neural activity. The present study combines anatomical and functional data from intracerebral recordings of nearly 100 patients, to generate highly resolved four-dimensional maps of human cortical processing of nonpainful somatosensory stimuli. These maps indicate that the human somatosensory system devoted to the hand encompasses a widespread network covering more than 10% of the cortical surface of both hemispheres. This network includes phasic components, centered on primary somatosensory cortex and neighboring motor, premotor, and inferior parietal regions, and tonic components, centered on opercular and insular areas, and involving human parietal rostroventral area and ventral medial-superior-temporal area. The technique described opens new avenues for investigating the neural basis of all levels of cortical processing in humans.

Detecting Site-Specific Physicochemical Selective Pressures: Applications to the Class I HLA of the Human Major Histocompatibility Complex and the SRK of the Plant Sporophytic Self-Incompatibility System

DEFF Research Database (Denmark)

Sainudiin, Raazesh; Wong, Wendy Shuk Wan; Yogeeswaran, Krithika

2005-01-01

:transversion biases. Here, we apply this method to two positively selected receptors involved in ligand-recognition: the class I alleles of the human major histocompatibility complex (MHC) of known structure and the S-locus receptor kinase (SRK) of the sporophytic self-incompatibility system (SSI) in cruciferous...... Bayes approach is used to identify sites that may be important for ligand recognition in these proteins....

Sequencing of 50 human exomes reveals adaptation to high altitude

DEFF Research Database (Denmark)

Yi, Xin; Liang, Yu; Huerta-Sanchez, Emilia

2010-01-01

Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which repres...... in genetic adaptation to high altitude.......Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which...... represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involved in response to hypoxia. One single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency...

One lesion, one virus: individual components of high-grade anal intraepithelial neoplasia in HIV-positive men contain a single HPV type

NARCIS (Netherlands)

Richel, Olivier; Quint, Koen D.; Lindeman, Jan; van Noesel, Carel J. M.; de Koning, Maurits N. C.; van den Munckhof, Henk A. M.; de Vries, Henry J. C.; Prins, Jan M.; Quint, Wim G. V.

2014-01-01

High-grade anal intraepithelial neoplasia (AIN) is present in many human immunodeficiency virus (HIV)-positive men who have sex with men. The major etiologic factor is infection with an oncogenic human papillomavirus (HPV) genotype. We investigated whether individual components of high-grade AIN are

Contribution of Personality to Self-Efficacy and Outcome Expectations in Selecting a High School Major among Adolescents with Learning Disabilities

Science.gov (United States)

Brown, Dikla; Cinamon, Rachel Gali

2016-01-01

The current study focuses on the contribution of five personality traits to the development of self-efficacy and outcome expectations regarding selecting a high school major among adolescents with learning disabilities (LD). Social cognitive career theory and the Big Five personality traits model served as the theoretical framework. Participants…

Should humans interfere in the lives of elephants?

Directory of Open Access Journals (Sweden)

H.P.P. Lötter

2005-07-01

Full Text Available Culling seems to be a cruel method of human interference in the lives of elephants. Culling is generally used to control population numbers of highly developed mammals to protect vegetation and habitat for other species. Many people are against human interference in the lives of elephants. In this article aspects of this highly controversial issue are explored. Three fascinating characteristics of this ethical dilemma are discussed in the introductory part, and then the major arguments raised against human interference in the lives of elephants are evaluated. These arguments are the following: First, that nature should be allowed to run its course and establish its own balance; nature will thus solve the problem of elephant over-population. The second argument raised by animal-rights activists as well as by animal-welfare groups either claim that animals have rights that humans must respect at all times, or that all sentient beings have interests that humans ought to respect, as those beings can experience pleasure or pain. The third argument often associates culling elephants as method for population control with the commercial use and exploitation of wilderness areas. Many people argue that it is unethical to use wildlife as a sustainable resource for fighting poverty. In conclusion it is stated that despite these arguments human

High-risk regions and outbreak modelling of tularemia in humans.

Science.gov (United States)

Desvars-Larrive, A; Liu, X; Hjertqvist, M; Sjöstedt, A; Johansson, A; Rydén, P

2017-02-01

Sweden reports large and variable numbers of human tularemia cases, but the high-risk regions are anecdotally defined and factors explaining annual variations are poorly understood. Here, high-risk regions were identified by spatial cluster analysis on disease surveillance data for 1984-2012. Negative binomial regression with five previously validated predictors (including predicted mosquito abundance and predictors based on local weather data) was used to model the annual number of tularemia cases within the high-risk regions. Seven high-risk regions were identified with annual incidences of 3·8-44 cases/100 000 inhabitants, accounting for 56·4% of the tularemia cases but only 9·3% of Sweden's population. For all high-risk regions, most cases occurred between July and September. The regression models explained the annual variation of tularemia cases within most high-risk regions and discriminated between years with and without outbreaks. In conclusion, tularemia in Sweden is concentrated in a few high-risk regions and shows high annual and seasonal variations. We present reproducible methods for identifying tularemia high-risk regions and modelling tularemia cases within these regions. The results may help health authorities to target populations at risk and lay the foundation for developing an early warning system for outbreaks.

Major depression as a risk factor for high blood pressure: epidemiologic evidence from a national longitudinal study.

Science.gov (United States)

Patten, Scott B; Williams, Jeanne V A; Lavorato, Dina H; Campbell, Norman R C; Eliasziw, Michael; Campbell, Tavis S

2009-04-01

To determine whether major depression (MD) leads to an increased risk of new-onset high blood pressure diagnoses. The data source was the Canadian National Population Health Survey (NPHS). The NPHS included a short-form version of the Composite International Diagnostic Interview (CIDI-SF) to assess MD and collected self-report data about professionally diagnosed high blood pressure and the use of antihypertensive medications. The analysis included 12,270 respondents who did not report high blood pressure or the use of antihypertensive medications at a baseline interview conducted in 1994. Proportional hazards models were used to compare the incidence of high blood pressure in respondents with and without MD during 10 years of subsequent follow-up. After adjustment for age, the risk of developing high blood pressure was elevated in those with MD. The hazard ratio was 1.6 (95% Confidence Interval = 1.2-2.1), p = .001, indicating a 60% increase in risk. Adjustment for additional covariates did not alter the association. MD may be a risk factor for new-onset high blood pressure. Epidemiologic data cannot definitely confirm a causal role, and the association may be due to shared etiologic factors. However, the increased risk may warrant closer monitoring of blood pressure in people with depressive disorders.

Requirements for growth and IL-10 expression of highly purified human T regulatory cells

Science.gov (United States)

Bonacci, Benedetta; Edwards, Brandon; Jia, Shuang; Williams, Calvin; Hessner, Martin J.; Gauld, Stephen; Verbsky, James

2013-01-01

Human regulatory T cells (TR) cells have potential for the treatment of a variety of immune mediated diseases but the anergic phenotype of these cells makes them difficult to expand in vitro. We have examined the requirements for growth and cytokine expression from highly purified human TR cells, and correlated these findings with the signal transduction events of these cells. We demonstrate that these cells do not proliferate or secrete IL-10 even in the presence of high doses of IL-2. Stimulation with a superagonistic anti-CD28 antibody (clone 9D4) and IL-2 partially reversed the proliferative defect, and this correlated with reversal of the defective calcium mobilization in these cells. Dendritic cells were effective at promoting TR cell proliferation, and under these conditions the proliferative capacity of TR cells was comparable to conventional CD4 lymphocytes. Blocking TGF-β activity abrogated IL-10 expression from these cells, while addition of TGF-β resulted in IL-10 production. These data demonstrate that highly purified populations of TR cells are anergic even in the presence of high doses of IL-2. Furthermore, antigen presenting cells provide proper co-stimulation to overcome the anergic phenotype of TR cells, and under these conditions they are highly sensitive to IL-2. In addition, these data demonstrate for the first time that TGF-β is critical to enable human TR cells to express IL-10. PMID:22562448

Human Rights: The Essential Reference.

Science.gov (United States)

Devine, Carol; Hansen, Carol Rae; Wilde, Ralph; Bronkhorst, Daan; Moritz, Frederic A.; Rolle, Baptiste; Sherman, Rebecca; Southard, Jo Lynn; Wilkinson, Robert; Poole, Hilary, Ed.

This reference work documents the history of human rights theory, explains each article of the Universal Declaration of Human Rights, explores the contemporary human rights movement, and examines the major human rights issues facing the world today. This book is the first to combine historical and contemporary perspectives on these critical…

Region and cell-type resolved quantitative proteomic map of the human heart

DEFF Research Database (Denmark)

Doll, Sophia; Dreßen, Martina; Geyer, Philipp E

2017-01-01

The heart is a central human organ and its diseases are the leading cause of death worldwide, but an in-depth knowledge of the identity and quantity of its constituent proteins is still lacking. Here, we determine the healthy human heart proteome by measuring 16 anatomical regions and three major...... cardiac cell types by high-resolution mass spectrometry-based proteomics. From low microgram sample amounts, we quantify over 10,700 proteins in this high dynamic range tissue. We combine copy numbers per cell with protein organellar assignments to build a model of the heart proteome at the subcellular...

Selectable high-yield recombinant protein production in human cells using a GFP/YFP nanobody affinity support.

Science.gov (United States)

Schellenberg, Matthew J; Petrovich, Robert M; Malone, Christine C; Williams, R Scott

2018-03-25

Recombinant protein expression systems that produce high yields of pure proteins and multi-protein complexes are essential to meet the needs of biologists, biochemists, and structural biologists using X-ray crystallography and cryo-electron microscopy. An ideal expression system for recombinant human proteins is cultured human cells where the correct translation and chaperone machinery are present. However, compared to bacterial expression systems, human cell cultures present several technical challenges to their use as an expression system. We developed a method that utilizes a YFP fusion-tag to generate recombinant proteins using suspension-cultured HEK293F cells. YFP is a dual-function tag that enables direct visualization and fluorescence-based selection of high expressing clones for and rapid purification using a high-stringency, high-affinity anti-GFP/YFP nanobody support. We demonstrate the utility of this system by expressing two large human proteins, TOP2α (340 KDa dimer) and a TOP2β catalytic core (260 KDa dimer). This robustly and reproducibly yields >10 mg/L liter of cell culture using transient expression or 2.5 mg/L using stable expression. Published 2018. This article is a US Government work and is in the public domain in the USA.

Nuclear Regulatory Commission Human Factors Program Plan. Revision 2

International Nuclear Information System (INIS)

1986-04-01

This document is the Second Annual Revision to the NRC Human Factors Program Plan. The first edition was published in August 1983. Revision 1 was published in July of 1984. Purpose of the NRC Human Factors Program is to ensure that proper consideration is given to human factors in the design and operation of nuclear power plants. This document describes the plans of the Office of Nuclear Reactor Regulation to address high priority human factors concerns of importance to reactor safety in FY 1986 and FY 1987. Revision 2 of the plan incorporates recent Commission decisions and policies bearing on the human factors aspects of reactor safety regulation. With a few exceptions, the principal changes from prior editions reflect a shift from developing new requirements to staff evaluation of industry progress in resolving human factors issues. The plan addresses seven major program elements: (1) Training, (2) Licensing Examinations, (3) Procedures, (4) Man-Machine Interface, (5) Staffing and Qualifications, (6) Management and Organization, and (7) Human Performance

High-resolution copy-number variation map reflects human olfactory receptor diversity and evolution.

Directory of Open Access Journals (Sweden)

Yehudit Hasin

2008-11-01

Full Text Available Olfactory receptors (ORs, which are involved in odorant recognition, form the largest mammalian protein superfamily. The genomic content of OR genes is considerably reduced in humans, as reflected by the relatively small repertoire size and the high fraction ( approximately 55% of human pseudogenes. Since several recent low-resolution surveys suggested that OR genomic loci are frequently affected by copy-number variants (CNVs, we hypothesized that CNVs may play an important role in the evolution of the human olfactory repertoire. We used high-resolution oligonucleotide tiling microarrays to detect CNVs across 851 OR gene and pseudogene loci. Examining genomic DNA from 25 individuals with ancestry from three populations, we identified 93 OR gene loci and 151 pseudogene loci affected by CNVs, generating a mosaic of OR dosages across persons. Our data suggest that approximately 50% of the CNVs involve more than one OR, with the largest CNV spanning 11 loci. In contrast to earlier reports, we observe that CNVs are more frequent among OR pseudogenes than among intact genes, presumably due to both selective constraints and CNV formation biases. Furthermore, our results show an enrichment of CNVs among ORs with a close human paralog or lacking a one-to-one ortholog in chimpanzee. Interestingly, among the latter we observed an enrichment in CNV losses over gains, a finding potentially related to the known diminution of the human OR repertoire. Quantitative PCR experiments performed for 122 sampled ORs agreed well with the microarray results and uncovered 23 additional CNVs. Importantly, these experiments allowed us to uncover nine common deletion alleles that affect 15 OR genes and five pseudogenes. Comparison to the chimpanzee reference genome revealed that all of the deletion alleles are human derived, therefore indicating a profound effect of human-specific deletions on the individual OR gene content. Furthermore, these deletion alleles may be used

High-throughput gene expression profiling of memory differentiation in primary human T cells

Directory of Open Access Journals (Sweden)

Russell Kate

2008-08-01

Full Text Available Abstract Background The differentiation of naive T and B cells into memory lymphocytes is essential for immunity to pathogens. Therapeutic manipulation of this cellular differentiation program could improve vaccine efficacy and the in vitro expansion of memory cells. However, chemical screens to identify compounds that induce memory differentiation have been limited by 1 the lack of reporter-gene or functional assays that can distinguish naive and memory-phenotype T cells at high throughput and 2 a suitable cell-line representative of naive T cells. Results Here, we describe a method for gene-expression based screening that allows primary naive and memory-phenotype lymphocytes to be discriminated based on complex genes signatures corresponding to these differentiation states. We used ligation-mediated amplification and a fluorescent, bead-based detection system to quantify simultaneously 55 transcripts representing naive and memory-phenotype signatures in purified populations of human T cells. The use of a multi-gene panel allowed better resolution than any constituent single gene. The method was precise, correlated well with Affymetrix microarray data, and could be easily scaled up for high-throughput. Conclusion This method provides a generic solution for high-throughput differentiation screens in primary human T cells where no single-gene or functional assay is available. This screening platform will allow the identification of small molecules, genes or soluble factors that direct memory differentiation in naive human lymphocytes.

A high-resolution comparative map between pig chromosome 17 and human chromosomes 4, 8, and 20: Identification of synteny breakpoints

DEFF Research Database (Denmark)

Lahbib-Mansais, Yvette; Karlskov-Mortensen, Peter; Mompart, Florence

2005-01-01

We report on the construction of a high-resolution comparative map of porcine chromosome 17 (SSC17) focusing on evolutionary breakpoints with human chromosomes. The comparative map shows high homology with human chromosome 20 but suggests more limited homologies with other human chromosomes. SSC1...

Feasibility of creating a high-resolution 3D diffusion tensor imaging based atlas of the human brainstem: a case study at 11.7 T.

Science.gov (United States)

Aggarwal, Manisha; Zhang, Jiangyang; Pletnikova, Olga; Crain, Barbara; Troncoso, Juan; Mori, Susumu

2013-07-01

A three-dimensional stereotaxic atlas of the human brainstem based on high resolution ex vivo diffusion tensor imaging (DTI) is introduced. The atlas consists of high resolution (125-255 μm isotropic) three-dimensional DT images of the formalin-fixed brainstem acquired at 11.7 T. The DTI data revealed microscopic neuroanatomical details, allowing three-dimensional visualization and reconstruction of fiber pathways including the decussation of the pyramidal tract fibers, and interdigitating fascicles of the corticospinal and transverse pontine fibers. Additionally, strong gray-white matter contrasts in the apparent diffusion coefficient (ADC) maps enabled precise delineation of gray matter nuclei in the brainstem, including the cranial nerve and the inferior olivary nuclei. Comparison with myelin-stained histology shows that at the level of resolution achieved in this study, the structural details resolved with DTI contrasts in the brainstem were comparable to anatomical delineation obtained with histological sectioning. Major neural structures delineated from DTI contrasts in the brainstem are segmented and three-dimensionally reconstructed. Further, the ex vivo DTI data are nonlinearly mapped to a widely-used in vivo human brain atlas, to construct a high-resolution atlas of the brainstem in the Montreal Neurological Institute (MNI) stereotaxic coordinate space. The results demonstrate the feasibility of developing a 3D DTI based atlas for detailed characterization of brainstem neuroanatomy with high resolution and contrasts, which will be a useful resource for research and clinical applications. Copyright © 2013 Elsevier Inc. All rights reserved.

Do Biology Majors Really Differ from Non–STEM Majors?

Science.gov (United States)

Cotner, Sehoya; Thompson, Seth; Wright, Robin

2017-01-01

Recent calls to action urge sweeping reform in science education, advocating for improved learning for all students—including those majoring in fields beyond the sciences. However, little work has been done to characterize the differences—if any exist—between students planning a career in science and those studying other disciplines. We describe an attempt to clarify, in broad terms, how non–STEM (science, technology, engineering, and mathematics) majors differ from life sciences majors, and how they are similar. Using survey responses and institutional data, we find that non–STEM majors are not unilaterally science averse; non–STEM majors are more likely than biology majors to hold misconceptions about the nature of science, yet they are not completely ignorant of how science works; non–STEM majors are less likely than biology majors to see science as personally relevant; and non–STEM majors populations are likely to be more diverse—with respect to incoming knowledge, perceptions, backgrounds, and skills—than a biology majors population. We encourage science educators to consider these characteristics when designing curricula for future scientists or simply for a well-informed citizenry. PMID:28798210

HLA-G in human reproduction

DEFF Research Database (Denmark)

Hviid, Thomas Vauvert F

2005-01-01

The non-classical human leukocyte antigen (HLA) class Ib genes, HLA-E, -G and -F, are located on chromosome 6 in the human major histocompatibility complex (MHC). HLA class Ib antigens resemble the HLA class Ia antigens in many ways, but several major differences have been described. This review ...... transplantation and in inflammatory or autoimmune disease, and of HLA-G in an evolutionary context, are also briefly examined....

Targeting allergenic fungi in agricultural environments aids the identification of major sources and potential risks for human health.

Science.gov (United States)

Weikl, F; Radl, V; Munch, J C; Pritsch, K

2015-10-01

Fungi are, after pollen, the second most important producers of outdoor airborne allergens. To identify sources of airborne fungal allergens, a workflow for qPCR quantification from environmental samples was developed, thoroughly tested, and finally applied. We concentrated on determining the levels of allergenic fungi belonging to Alternaria, Cladosporium, Fusarium, and Trichoderma in plant and soil samples from agricultural fields in which cereals were grown. Our aims were to identify the major sources of allergenic fungi and factors potentially influencing their occurrence. Plant materials were the main source of the tested fungi at and after harvest. Amounts of A. alternata and C. cladosporioides varied significantly in fields under different management conditions, but absolute levels were very high in all cases. This finding suggests that high numbers of allergenic fungi may be an inevitable side effect of farming in several crops. Applied in large-scale studies, the concept described here may help to explain the high number of sensitization to airborne fungal allergens. Copyright © 2015 Elsevier B.V. All rights reserved.

Improvements and impacts of GRCh38 human reference on high throughput sequencing data analysis.

Science.gov (United States)

Guo, Yan; Dai, Yulin; Yu, Hui; Zhao, Shilin; Samuels, David C; Shyr, Yu

2017-03-01

Analyses of high throughput sequencing data starts with alignment against a reference genome, which is the foundation for all re-sequencing data analyses. Each new release of the human reference genome has been augmented with improved accuracy and completeness. It is presumed that the latest release of human reference genome, GRCh38 will contribute more to high throughput sequencing data analysis by providing more accuracy. But the amount of improvement has not yet been quantified. We conducted a study to compare the genomic analysis results between the GRCh38 reference and its predecessor GRCh37. Through analyses of alignment, single nucleotide polymorphisms, small insertion/deletions, copy number and structural variants, we show that GRCh38 offers overall more accurate analysis of human sequencing data. More importantly, GRCh38 produced fewer false positive structural variants. In conclusion, GRCh38 is an improvement over GRCh37 not only from the genome assembly aspect, but also yields more reliable genomic analysis results. Copyright © 2017. Published by Elsevier Inc.

Long-Term Bird Assemblage Trends in Areas of High and Low Human Population Density

International Nuclear Information System (INIS)

Barrett, K.; Romagosa, C.M.; Williams, M.I.

2008-01-01

Urban areas are expanding globally, and the impact of high human population density (HHPD) on bird species richness remains unresolved. Studies primarily focus on species richness along an urban-to-rural gradient; however, some studies have analyzed larger-scale patterns and found results that contrast with those obtained at smaller scales. To move the discussion beyond static species richness patterns, we analyzed the effect of HHPD on bird assemblage dynamics (year-to-year extinction probability, turnover, changes in species richness) across the United States over a 25-year period. We found that bird assemblages in both high and low human population density areas changed significantly over the period of record. Specifically, bird assemblages increased in species richness on average. Assemblage change in areas of HHPD was not significantly different from assemblage change in areas with LHPD. These results suggest that human population density alone does not alter the persistence of avian assemblage patterns.

High energy radiation effects on the human body

International Nuclear Information System (INIS)

Kato, Kazuaki

1977-01-01

High-energy radiation injuries and their risks were recognized, information on low-energy radiation injuries was also arranged, and with these backgrounds, countermeasures against prevention of radiation injuries were considered. Redintegration of DNA and mutation by radiation were described, and relationship between radiation injuries and dose was considered. Interaction of high-energy radiation and substances in the living body and injuries by the interaction were also considered. Expression method of risk was considered, and a concept of protection dose was suggested. Protection dose is dose equivalent which is worthy of value at the point where the ratio to permissible dose distributed among each part of the body is at its maximum in the distribution of dose equivalent formed within the body when standard human body is placed at a certain radiation field for a certain time. Significance and countermeasures of health examination which is under an abligation to make radiation workers receive health check were thought, and problems were proposed on compensation when radiation injuries should appear actually. (Tsunoda, M.)

High volume hydraulic fracturing operations: potential impacts on surface water and human health.

Science.gov (United States)

Mrdjen, Igor; Lee, Jiyoung

2016-08-01

High volume, hydraulic fracturing (HVHF) processes, used to extract natural gas and oil from underground shale deposits, pose many potential hazards to the environment and human health. HVHF can negatively affect the environment by contaminating soil, water, and air matrices with potential pollutants. Due to the relatively novel nature of the process, hazards to surface waters and human health are not well known. The purpose of this article is to link the impacts of HVHF operations on surface water integrity, with human health consequences. Surface water contamination risks include: increased structural failure rates of unconventional wells, issues with wastewater treatment, and accidental discharge of contaminated fluids. Human health risks associated with exposure to surface water contaminated with HVHF chemicals include increased cancer risk and turbidity of water, leading to increased pathogen survival time. Future research should focus on modeling contamination spread throughout the environment, and minimizing occupational exposure to harmful chemicals.

High pressure treatment of human norovirus-like particles: factors affecting destruction efficacy

Science.gov (United States)

Human norovirus (HuNoV) is the leading cause of foodborne diseases worldwide. High pressure processing (HPP) is considered a promising non-thermal technology to inactivate viral pathogens in foods. However, the effectiveness of HPP on inactivating HuNoV remains poorly understood because it cannot be...

Characteristics of high affinity and low affinity adenosine binding sites in human cerebral cortex

International Nuclear Information System (INIS)

John, D.; Fox, I.V.

1986-01-01

The binding characteristics of human brain cortical membrane fractions were evaluated to test the hypothesis that there are A 1 and A 2 adenosine binding sites. The ligands used were 2-chloro(8- 3 H) adenosine and N 6 -(adenine-2, 8- 3 H) cyclohexayladenosine. Binding of chloroadenosine to human brain cortical membranes was time dependent, reversible and concentration dependent. The kinetic constant determinations from binding studies of the adenosine receptor are presented. Utilizing tritium-cyclohexyladenosine as ligand the authors observed evidence for a high affinity binding site in human brain cortical membranes with a kd of 5 nM

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery--the FOCCUS study.

Science.gov (United States)

Cuthbertson, Brian H; Campbell, Marion K; Stott, Stephen A; Elders, Andrew; Hernández, Rodolfo; Boyers, Dwayne; Norrie, John; Kinsella, John; Brittenden, Julie; Cook, Jonathan; Rae, Daniela; Cotton, Seonaidh C; Alcorn, David; Addison, Jennifer; Grant, Adrian

2011-01-01

Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Prospective Clinical Trials, ISRCTN32188676.

Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging

OpenAIRE

Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R.; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

2017-01-01

Summary Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in?age from 16 to 106 years. We show that astrocyte-?and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional express...

Olfactory cues associated with the major histocompatibility complex.

Science.gov (United States)

Eggert, F; Müller-Ruchholtz, W; Ferstl, R

Besides its immunological function of self/non-self discrimination the major histocompatibility complex (MHC) has been recognized as a possible source of individual specific body odors. Dating back to speculations on the role of the extraordinary polymorphism of the MHC as background of an individual chemosensory identity and to early observations of MHC-dependent mate choice in inbred strains of mice, systematic experimental studies revealed a first evidence for H-2 related body odors in this species. Meanwhile a large number of animal studies with rodents and a series of field studies and experiments with humans have extended our knowledge of MHC-related odor signals and substantiated the hypothesis of immunogenetic associated odor types. These results suggest that the most prominent feature of the MHC, its extraordinary genetic diversity, seems in part to be selectively maintained by behavioral mechanisms which operate in contemporary natural populations. The high degree of heterozygosity found in natural populations of most species seems to be promoted by non-disease-based selection such as mating preferences and selective block of pregnancy.

Jammed Humans in High-Density Crowd Disasters

Science.gov (United States)

Bottinelli, Arianna; Sumpter, David; Silverberg, Jesse

When people gather in large groups like those found at Black Friday sales events, pilgrimages, heavy metal concerts, and parades, crowd density often becomes exceptionally high. As a consequence, these events can produce tragic outcomes such as stampedes and ''crowd crushes''. While human collective motion has been studied with active particle simulations, the underlying mechanisms for emergent behavior are less well understood. Here, we use techniques developed to study jammed granular materials to analyze an active matter model inspired by large groups of people gathering at a point of common interest. In the model, a single behavioral rule combined with body-contact interactions are sufficient for the emergence of a self-confined steady state, where particles fluctuate around a stable position. Applying mode analysis to this system, we find evidence for Goldstone modes, soft spots, and stochastic resonance, which may be the preferential mechanisms for dangerous emergent collective motions in crowds.

An agent-based model for Leishmania major infection

Science.gov (United States)

Dancik, Garrett M.; Jones, Douglas E.; Dorman, Karin S.

Leishmania are protozoan parasites transmitted by bites of infected sandflies. Over 20 species of Leishmania, endemic in 88 countries, are capable of causing human disease. Disease is either cutaneous, where skin ulcers occur on exposed surfaces of the body, or visceral, with near certain mortality if untreated. C3HeB/FeJ mice are resistant to L. major, but develop chronic cutaneous lesions when infected with another species L. amazonensis. The well-characterized mechanism of resistance to L. major depends on a CD4+ Thl immune response, macrophage activation, and elimination of the parasite [Sacks 2002]. The factors that account for host susceptibility to L. Amazonensis, however, are not completely understood, despite being generally attributed to a weakened Th1 response [Vanloubbeck 2004].

Persistently High Hip Circumference after Bariatric Surgery Is a Major Hurdle to Successful Hip Replacement

Directory of Open Access Journals (Sweden)

Menachem M. Meller

2014-01-01

Full Text Available The prevalence of class III obesity (BMI≥40 kg/m2 in black women is 18%. As class III obesity leads to hip joint deterioration, black women frequently present for orthopedic care. Weight loss associated with bariatric surgery should lead to enhanced success of hip replacements. However, we present a case of a black woman who underwent Roux-en-Y gastric bypass with the expectation that weight loss would make her a better surgical candidate for hip replacement. Her gastric bypass was successful as her BMI declined from 52.0 kg/m2 to 33.7 kg/m2. However, her hip circumference after weight loss remained persistently high. Therefore, at surgery the soft tissue tunnel geometry presented major challenges. Tunnel depth and immobility of the soft tissue interfered with retractor placement, tissue reflection, and surgical access to the acetabulum. Therefore a traditional cup placement could not be achieved. Instead, a hemiarthroplasty was performed. After surgery her pain and reliance on external support decreased. But her functional independence never improved. This case demonstrates that a lower BMI after bariatric surgery may improve the metabolic profile and decrease anesthesia risk, but the success of total hip arthroplasties remains problematic if fat mass in the operative field (i.e., high hip circumference remains high.

Environmental impacts of polluted effluents on human health

International Nuclear Information System (INIS)

Ahmad, M.S.

2005-01-01

One of the major environmental problems confronting Pakistan is water pollution. Human health is being affected by water pollution. The major sources of pollution for surface and groundwater resources are municipal sewage and industrial wastewater. The indiscriminate discharges of untreated sewage and industrial effluents into the water bodies have affected not only the water quality but also human health. Groundwater is also being contaminated by the discharge of untreated sewage into land. Water pollution is responsible for water borne diseases such as hepatitis, dysentery, typhoid, cholera, paratyphoid fever etc. This paper presents a general overview of the wastewater pollution in Pakistan, an evaluation and a specific reference to Lahore city and the effects on human health. Finally, sustainable treatment methods have been proposed to mitigate the water pollution problem. The analysis of water bodies at wastewater discharge points shows depletion of Dissolved Oxygen (DO) and high levels of E. Coli. There is an evidence of groundwater pollution in many areas due to the discharge of wastewater on open land. To protect the water sources from contamination, appropriate treatment methods/treatment technologies have also been discussed in this paper. In the end conclusion and recommendations are given. (author)

Environmental impacts of polluted effluents on human health

Energy Technology Data Exchange (ETDEWEB)

Ahmad, M S [NESPAK, Lahore (Pakistan). Geo-Environmental Engineering Div.

2005-07-15

One of the major environmental problems confronting Pakistan is water pollution. Human health is being affected by water pollution. The major sources of pollution for surface and groundwater resources are municipal sewage and industrial wastewater. The indiscriminate discharges of untreated sewage and industrial effluents into the water bodies have affected not only the water quality but also human health. Groundwater is also being contaminated by the discharge of untreated sewage into land. Water pollution is responsible for water borne diseases such as hepatitis, dysentery, typhoid, cholera, paratyphoid fever etc. This paper presents a general overview of the wastewater pollution in Pakistan, an evaluation and a specific reference to Lahore city and the effects on human health. Finally, sustainable treatment methods have been proposed to mitigate the water pollution problem. The analysis of water bodies at wastewater discharge points shows depletion of Dissolved Oxygen (DO) and high levels of E. Coli. There is an evidence of groundwater pollution in many areas due to the discharge of wastewater on open land. To protect the water sources from contamination, appropriate treatment methods/treatment technologies have also been discussed in this paper. In the end conclusion and recommendations are given. (author)

Parasites of importance for human health in Nigerian dogs: high prevalence and limited knowledge of pet owners.

Science.gov (United States)

Ugbomoiko, Uade Samuel; Ariza, Liana; Heukelbach, Jorg

2008-12-09

Dogs are the most common pet animals worldwide. They may harbour a wide range of parasites with zoonotic potential, thus causing a health risk to humans. In Nigeria, epidemiological knowledge on these parasites is limited. In a community-based study, we examined 396 dogs in urban and rural areas of Ilorin (Kwara State, Central Nigeria) for ectoparasites and intestinal helminths. In addition, a questionnaire regarding knowledge and practices was applied to pet owners. Nine ectoparasite species belonging to four taxa and six intestinal helminth species were identified: fleas (Ctenocephalides canis, Pulex irritans, Tunga penetrans), mites (Demodex canis, Otodectes sp., Sarcoptes scabiei var. canis), ticks (Rhipicephalus sanguineus, Ixodes sp.), and lice (Trichodectes canis); and Toxocara canis, Ancylostoma sp., Trichuris vulpis, Dipylidium caninum, Taenidae and Strongyloides sp. Overall prevalence of ectoparasites was 60.4% and of intestinal helminths 68.4%. The occurrence of C. canis, R. sanguineus, T. canis, Ancylostoma sp. and T. vulpis was most common (prevalence 14.4% to 41.7%). Prevalence patterns in helminths were age-dependent, with T. canis showing a decreasing prevalence with age of host, and a reverse trend in other parasite species. Knowledge regarding zoonoses was very limited and the diseases not considered a major health problem. Treatment with antiparasitic drugs was more frequent in urban areas. Parasites of importance for human health were highly prevalent in Nigerian dogs. Interventions should include health education provided to dog owners and the establishment of a program focusing on zoonotic diseases.

Extremely stable soluble high molecular mass multi-protein complex with DNase activity in human placental tissue.

Directory of Open Access Journals (Sweden)

Evgeniya E Burkova

Full Text Available Human placenta is an organ which protects, feeds, and regulates the grooving of the embryo. Therefore, identification and characterization of placental components including proteins and their multi-protein complexes is an important step to understanding the placenta function. We have obtained and analyzed for the first time an extremely stable multi-protein complex (SPC, ∼ 1000 kDa from the soluble fraction of three human placentas. By gel filtration on Sepharose-4B, the SPC was well separated from other proteins of the placenta extract. Light scattering measurements and gel filtration showed that the SPC is stable in the presence of NaCl, MgCl2, acetonitrile, guanidinium chloride, and Triton in high concentrations, but dissociates efficiently in the presence of 8 M urea, 50 mM EDTA, and 0.5 M NaCl. Such a stable complex is unlikely to be a casual associate of different proteins. According to SDS-PAGE and MALDI mass spectrometry data, this complex contains many major glycosylated proteins with low and moderate molecular masses (MMs 4-14 kDa and several moderately abundant (79.3, 68.5, 52.8, and 27.2 kDa as well as minor proteins with higher MMs. The SPC treatment with dithiothreitol led to a disappearance of some protein bands and revealed proteins with lower MMs. The SPCs from three placentas efficiently hydrolyzed plasmid supercoiled DNA with comparable rates and possess at least two DNA-binding sites with different affinities for a 12-mer oligonucleotide. Progress in study of placental protein complexes can promote understanding of their biological functions.

Prototype Systems Containing Human Cytochrome P450 for High-Throughput Real-Time Detection of DNA Damage by Compounds That Form DNA-Reactive Metabolites.

Science.gov (United States)

Brito Palma, Bernardo; Fisher, Charles W; Rueff, José; Kranendonk, Michel

2016-05-16

The formation of reactive metabolites through biotransformation is the suspected cause of many adverse drug reactions. Testing for the propensity of a drug to form reactive metabolites has increasingly become an integral part of lead-optimization strategy in drug discovery. DNA reactivity is one undesirable facet of a drug or its metabolites and can lead to increased risk of cancer and reproductive toxicity. Many drugs are metabolized by cytochromes P450 in the liver and other tissues, and these reactions can generate hard electrophiles. These hard electrophilic reactive metabolites may react with DNA and may be detected in standard in vitro genotoxicity assays; however, the majority of these assays fall short due to the use of animal-derived organ extracts that inadequately represent human metabolism. The current study describes the development of bacterial systems that efficiently detect DNA-damaging electrophilic reactive metabolites generated by human P450 biotransformation. These assays use a GFP reporter system that detects DNA damage through induction of the SOS response and a GFP reporter to control for cytotoxicity. Two human CYP1A2-competent prototypes presented here have appropriate characteristics for the detection of DNA-damaging reactive metabolites in a high-throughput manner. The advantages of this approach include a short assay time (120-180 min) with real-time measurement, sensitivity to small amounts of compound, and adaptability to a microplate format. These systems are suitable for high-throughput assays and can serve as prototypes for the development of future enhanced versions.

A geophysical tour of high background radiation areas of the world

International Nuclear Information System (INIS)

Krishnan, D.; Kher, R.K.; Nambi, K.S.V.

1995-01-01

A comparison of the findings including health effects in four major high natural background areas of the world are given. Such high background areas could prove to be a radiation ecology laboratory gifted by nature and provide further insight in the relation of radiation, natural or otherwise and human health. 3 refs., 2 tabs

Quality assurance of human error modelling in a major probabilistic risk assessment programme

International Nuclear Information System (INIS)

Rycraft, H.S.

1990-01-01

A method of incorporating the consideration of operator error within a major PRA exercise is described along with the quality assurance procedures employed to ensure a quality product. The exercise was undertaken at the Sellafield Reprocessing Plant. (author)

CityMobil : Human factor issues regarding highly automated vehicles on eLane

NARCIS (Netherlands)

Toffetti, A.; Wilschut, E.S.; Martens, M.H.; Schieben, A.; Rambaldini, A.; Merat, N.; Flemisch, F.

2009-01-01

There are several human factor concerns with highly autonomous or semiautonomous driving, such as transition of control, loss of skill, and dealing with automated system errors. Four CityMobil experiments studied the eLane concept for dual-mode cars, and the results of one are described. The open

April 2006. 32 Major Orthopaedic Procedures

African Journals Online (AJOL)

user

2006-04-01

Apr 1, 2006 ... Major Orthopaedic Procedures: 17 Year Trends. Biruk Lambisso Wamisho1 ... financial and logistic constraints with poor compliance of ... Modern orthopaedic surgery is very expensive. A highly ..... Case management. Tribury.

Comparative distribution of human and avian type sialic acid influenza receptors in the pig

Directory of Open Access Journals (Sweden)

Perez Belinda

2010-01-01

Full Text Available Abstract Background A major determinant of influenza infection is the presence of virus receptors on susceptible host cells to which the viral haemagglutinin is able to bind. Avian viruses preferentially bind to sialic acid α2,3-galactose (SAα2,3-Gal linked receptors, whereas human strains bind to sialic acid α2,6-galactose (SAα2,6-Gal linked receptors. To date, there has been no detailed account published on the distribution of SA receptors in the pig, a model host that is susceptible to avian and human influenza subtypes, thus with potential for virus reassortment. We examined the relative expression and spatial distribution of SAα2,3-GalG(1-3GalNAc and SAα2,6-Gal receptors in the major organs from normal post-weaned pigs by binding with lectins Maackia amurensis agglutinins (MAA II and Sambucus nigra agglutinin (SNA respectively. Results Both SAα2,3-Gal and SAα2,6-Gal receptors were extensively detected in the major porcine organs examined (trachea, lung, liver, kidney, spleen, heart, skeletal muscle, cerebrum, small intestine and colon. Furthermore, distribution of both SA receptors in the pig respiratory tract closely resembled the published data of the human tract. Similar expression patterns of SA receptors between pig and human in other major organs were found, with exception of the intestinal tract. Unlike the limited reports on the scarcity of influenza receptors in human intestines, we found increasing presence of SAα2,3-Gal and SAα2,6-Gal receptors from duodenum to colon in the pig. Conclusions The extensive presence of SAα2,3-Gal and SAα2,6-Gal receptors in the major organs examined suggests that each major organ may be permissive to influenza virus entry or infection. The high similarity of SA expression patterns between pig and human, in particular in the respiratory tract, suggests that pigs are not more likely to be potential hosts for virus reassortment than humans. Our finding of relative abundance of SA receptors

Identification and quantification of six major α-dicarbonyl process contaminants in high-fructose corn syrup.

Science.gov (United States)

Gensberger, Sabrina; Mittelmaier, Stefan; Glomb, Marcus A; Pischetsrieder, Monika

2012-07-01

High-fructose corn syrup (HFCS) is a widely used liquid sweetener produced from corn starch by hydrolysis and partial isomerization of glucose to fructose. During these processing steps, sugars can be considerably degraded, leading, for example, to the formation of reactive α-dicarbonyl compounds (α-DCs). The present study performed targeted screening to identify the major α-DCs in HFCS. For this purpose, α-DCs were selectively converted with o-phenylendiamine to the corresponding quinoxaline derivatives, which were analyzed by liquid chromatography with hyphenated diode array-tandem mass spectrometry (LC-DAD-MS/MS) detection. 3-Deoxy-D-erythro-hexos-2-ulose (3-deoxyglucosone), D-lyxo-hexos-2-ulose (glucosone), 3-deoxy-D-threo-hexos-2-ulose (3-deoxygalactosone), 1-deoxy-D-erythro-hexos-2,3-diulose (1-deoxyglucosone), 3,4-dideoxyglucosone-3-ene, methylglyoxal, and glyoxal were identified by enhanced mass spectra as well as MS/MS product ion spectra using the synthesized standards as reference. Addition of diethylene triamine pentaacetic acid and adjustment of the derivatization conditions ensured complete derivatization without de novo formation for all identified α-DCs in HFCS matrix except for glyoxal. Subsequently, a ultra-high performance LC-DAD-MS/MS method was established to quantify 3-deoxyglucosone, glucosone, 3-deoxygalactosone, 1-deoxyglucosone, 3,4-dideoxyglucosone-3-ene, and methylglyoxal in HFCS. Depending on the α-DC compound and concentration, the recovery ranged between 89.2% and 105.8% with a relative standard deviation between 1.9% and 6.5%. Subsequently, the α-DC profiles of 14 commercial HFCS samples were recorded. 3-Deoxyglucosone was identified as the major α-DC with concentrations up to 730 μg/mL HFCS. The total α-DC content ranged from 293 μg/mL to 1,130 μg/mL HFCS. Significantly different α-DC levels were not detected between different HFCS specifications, but between samples of various manufacturers indicating that the �

High adult mortality among Hiwi hunter-gatherers: implications for human evolution.

Science.gov (United States)

Hill, Kim; Hurtado, A M; Walker, R S

2007-04-01

Extant apes experience early sexual maturity and short life spans relative to modern humans. Both of these traits and others are linked by life-history theory to mortality rates experienced at different ages by our hominin ancestors. However, currently there is a great deal of debate concerning hominin mortality profiles at different periods of evolutionary history. Observed rates and causes of mortality in modern hunter-gatherers may provide information about Upper Paleolithic mortality that can be compared to indirect evidence from the fossil record, yet little is published about causes and rates of mortality in foraging societies around the world. To our knowledge, interview-based life tables for recent hunter-gatherers are published for only four societies (Ache, Agta, Hadza, and Ju/'hoansi). Here, we present mortality data for a fifth group, the Hiwi hunter-gatherers of Venezuela. The results show comparatively high death rates among the Hiwi and highlight differences in mortality rates among hunter-gatherer societies. The high levels of conspecific violence and adult mortality in the Hiwi may better represent Paleolithic human demographics than do the lower, disease-based death rates reported in the most frequently cited forager studies.

Successful implementation of inquiry-based physiology laboratories in undergraduate major and nonmajor courses.

Science.gov (United States)

Casotti, G; Rieser-Danner, L; Knabb, M T

2008-12-01

Recent evidence has demonstrated that inquiry-based physiology laboratories improve students' critical- and analytical-thinking skills. We implemented inquiry-based learning into three physiology courses: Comparative Vertebrate Physiology (majors), Human Physiology (majors), and Human Anatomy and Physiology (nonmajors). The aims of our curricular modifications were to improve the teaching of physiological concepts, teach students the scientific approach, and promote creative and critical thinking. We assessed our modifications using formative (laboratory exams, oral presentations, and laboratory reports) and summative evaluations (surveys, laboratory notebook, and an end of semester project). Students appreciated the freedom offered by the new curriculum and the opportunity to engage in the inquiry process. Results from both forms of evaluation showed a marked improvement due to the curricular revisions. Our analyses indicate an increased confidence in students' ability to formulate questions and hypotheses, design experiments, collect and analyze data, and make conclusions. Thus, we have successfully incorporated inquiry-based laboratories in both major and nonmajor courses.

Inactivation of Staphylococcus aureus and native microflora in human milk by high pressure processing