Helpers' Self-Assessment Biases Before and after Helping Skills Training

Science.gov (United States)

Jaeken, Marine; Zech, Emmanuelle; Brison, Céline; Verhofstadt, Lesley L.; Van Broeck, Nady; Mikolajczak, Moïra

2017-01-01

Several studies have shown that therapists are generally biased concerning their performed helping skills, as compared to judges' ratings. As clients' ratings of therapists' performance are better predictors of psychotherapy effectiveness than judges' ratings, this study examined the validity and effectiveness of a helping skills training program at reducing novice helpers' self-enhancement biases concerning their helping skills, in comparison to their clients' ratings. Helping skills were assessed by three objective measures (a knowledge multiple choice test, a video test and a role play), as well as by a self- and peer-reported questionnaire. In addition, some performed helping skills' correlates (relationship quality, session quality, and helpers' therapeutic attitudes) were assessed both by helpers and their simulated helpees. Seventy-two sophomores in psychology participated to this study, 37 being assigned to a 12-h helping skills training program, and 35 to a control group. Helpers were expected to assess the aforementioned performed helping skills and correlates as being better than their helpees' assessments at pretest, thus revealing a self-enhancement bias. At posttest, we expected that trained helpers would objectively exhibit better helping skills than untrained helpers while beginning to underestimate their performance, thus indexing a self-diminishment bias. In contrast, we hypothesized that untrained helpers would continue to overestimate their performance. Our hypotheses were only partly confirmed but results reflected a skilled-unaware pattern among trainees. Trained helpers went either from a pretest overestimation to a posttest equivalence (performed helping skills and performed therapeutic attitudes), or from a pretest equivalence to a posttest underestimation (performed session quality and performed therapeutic relationship), as compared to helpees' ratings. Results showed that trained helpers improved on all helping skills objective measures

Helpers' Self-Assessment Biases Before and after Helping Skills Training.

Science.gov (United States)

Jaeken, Marine; Zech, Emmanuelle; Brison, Céline; Verhofstadt, Lesley L; Van Broeck, Nady; Mikolajczak, Moïra

2017-01-01

Several studies have shown that therapists are generally biased concerning their performed helping skills, as compared to judges' ratings. As clients' ratings of therapists' performance are better predictors of psychotherapy effectiveness than judges' ratings, this study examined the validity and effectiveness of a helping skills training program at reducing novice helpers' self-enhancement biases concerning their helping skills, in comparison to their clients' ratings. Helping skills were assessed by three objective measures (a knowledge multiple choice test, a video test and a role play), as well as by a self- and peer-reported questionnaire. In addition, some performed helping skills' correlates (relationship quality, session quality, and helpers' therapeutic attitudes) were assessed both by helpers and their simulated helpees. Seventy-two sophomores in psychology participated to this study, 37 being assigned to a 12-h helping skills training program, and 35 to a control group. Helpers were expected to assess the aforementioned performed helping skills and correlates as being better than their helpees' assessments at pretest, thus revealing a self-enhancement bias. At posttest, we expected that trained helpers would objectively exhibit better helping skills than untrained helpers while beginning to underestimate their performance, thus indexing a self-diminishment bias. In contrast, we hypothesized that untrained helpers would continue to overestimate their performance. Our hypotheses were only partly confirmed but results reflected a skilled-unaware pattern among trainees. Trained helpers went either from a pretest overestimation to a posttest equivalence (performed helping skills and performed therapeutic attitudes), or from a pretest equivalence to a posttest underestimation (performed session quality and performed therapeutic relationship), as compared to helpees' ratings. Results showed that trained helpers improved on all helping skills objective measures

Optimized quantization in Zero Leakage Helper data systems

NARCIS (Netherlands)

Stanko, T.; Andini, F.N.; Skoric, B.

2017-01-01

Helper data systems are a cryptographic primitive that allows for the reproducible extraction of secrets from noisy measurements. Redundancy data called helper data makes it possible to do error correction while leaking little or nothing (Zero Leakage) about the extracted secret string. We study the

Comparison of gray matter and metabolic reduction in mild Alzheimer's disease using FDG-PET and voxel-based morphometric MR studies

Energy Technology Data Exchange (ETDEWEB)

Ishii, Kazunari; Sasaki, Hiroki; Kono, Atsushi K.; Miyamoto, Naokazu; Fukuda, Tetsuya [Hyogo Brain and Heart Center, Department of Radiology and Nuclear Medicine, Himeji, Hyogo (Japan); Mori, Etsuro [Hyogo Brain and Heart Center, Institute for Aging Brain and Cognitive Disorders, Himeji, Hyogo (Japan)

2005-08-01

The aim of this study was to investigate regional differences between morphologic and functional changes in the same patients with mild Alzheimer's disease (AD) using statistical parametric mapping (SPM) and voxel-based morphometry (VBM). Thirty patients with very mild AD (mean age 66.8 years, mean MMSE score 24.0) and 30 age- and sex-matched normal volunteers underwent both{sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and three-dimensional spoiled gradient echo (SPGR) magnetic resonance imaging (MRI). Statistical parametric mapping was used to conduct VBM analysis of the morphological data, which were compared voxel by voxel with the results of a similar analysis of the glucose metabolic data. In AD patients, VBM data indicated a significant gray matter volume density decrease in bilateral amygdala/hippocampus complex (p<0.05, corrected), while FDG-PET analysis showed significant glucose metabolic reductions in the posterior cingulate gyri and the right parietal lobule, compared with those in the normal control group. In very mild AD, morphological change occurs in the medial temporal lobes, while in contrast, metabolic changes occur in the posterior cingulate gyri and parietal lobule. (orig.)

Impact of sodium butyrate and mild hypothermia on metabolic and physiological behaviour of CHO TF 70R cells

Directory of Open Access Journals (Sweden)

Veronica Avello

2017-05-01

Conclusions: The combination of NaBu addition and mild hypothermic condition causes an impact on physiological and metabolic state of CHO TF 70R cells, decreasing cell growth rate and improving glucose consumption efficiency. These results therefore provide a promising strategy to increase specific productivity of rh-tPA.

Suppression induction in vivo by a T helper clone?

DEFF Research Database (Denmark)

Crispe, I N; Owens, T

1985-01-01

We have previously described a helper T cell clone which augments in vivo cytotoxic T cell responses when injected at 10(4) cells per mouse, but not at 10(5) per mouse (Crispe, I. N. et al., Immunology 1984. 52:55). To test whether this dose-response relationship was due to the induction...... of suppression, naive syngeneic mice were injected with 10(5) cloned T helper cells, and their spleen cells were subsequently assayed for suppressive activity in adoptive transfer experiments. Lymphocytes from such mice indeed suppressed an antigen-specific cytotoxic response, but only in the presence...... of the same T helper cell clone freshly added at the time of adoptive transfer. On this basis we argue that the distinction between T helper cell activity and T suppressor-inducer activity corresponds to differences in cell numbers, rather than to two separate cell lineages....

Characterization of a human antigen specific helper factor

International Nuclear Information System (INIS)

Richardson, B.

1986-01-01

While antigen (Ag) specific helper factors have been characterized in mice, similar molecules have not been identified in humans. To characterize human antigen specific helper molecules, an IL-2 dependent tetanus toxoid (T.T.) reactive T cell line was fused with a 6-thioguanine resistant CEM line, and hybrids selected in medium containing hypoxanthine and azaserine. Hybrids were screened by culturing the cells with 35 S-Met then reacting the supernatants with T.T. or hepatitis vaccine immobilized on nitrocellulose. One hybrid, TT6BA-O, was identified which secreted a Met-containing molecule which bound T.T. but not hepatitis vaccine. Supernatants from TT6BA-O, but not the parent CEM line, when added to autologous peripheral blood mononuclear cells (PBMC's) stimulated secretion of T.T. specific antibodies (Abs). Specificity controls demonstrated that TT6BA-O supernatant did not induce antibodies to diphtheria toxoid, hepatitis vaccine or pneumococcal polysaccharide, and total immunoglobulin (lg) synthesis was minimally increased. In contrast, pokeweed mitogen stimulated significant lg synthesis as well as Ab's to pneumococcal polysaccharide and T.T. TT6BA-O supernatant induced anti-T.T.Ab's in autologous PBMC's but not PBMC's from 3 unrelated donors, suggesting that the activity of the helper factor is restricted, possibly by the MHC. The molecular weight of the helper factor was estimated at 100,000-150,000 by Sephacryl S-300 chromatography. Finally, the helper factor could be demonstrated to bind and elute from sephorose-immobilized T.T. and anti-DR antisera, but not anti-lg antisera or the T40/25 monoclonal antibody, which binds a nonpolymorphic determinant on the human T cell receptor. These results demonstrate that human Ag specific helper factors exist, bind antigen and bear class II MHC determinants

Longitudinal brain metabolic changes from amnestic mild cognitive impairment to Alzheimer's disease

Science.gov (United States)

Fouquet, Marine; Desgranges, Béatrice; Landeau, Brigitte; Duchesnay, Edouard; Mézenge, Florence; De La Sayette, Vincent; Viader, Fausto; Baron, Jean-Claude; Eustache, Francis; Chételat, Gaël

2009-01-01

A sensitive marker for monitoring progression of early Alzheimer’s Disease (AD) would help to develop and test new therapeutic strategies. The present study aimed at investigating brain metabolism changes over time, as potential monitoring marker, in patients with amnestic Mild Cognitive Impairment (aMCI), according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen aMCI patients underwent MRI and 18FDG-PET scans both at inclusion and 18 months later. Baseline and follow-up PET data were corrected for partial volume effects and spatially normalized using MRI data, scaled to the vermis and compared using SPM2. ‘PET-PAC’ maps reflecting metabolic percent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than nonconverters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18FDG-PET for monitoring early AD progression. PMID:19477964

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial.

Science.gov (United States)

Rijpma, Anne; van der Graaf, Marinette; Lansbergen, Marieke M; Meulenbroek, Olga; Cetinyurek-Yavuz, Aysun; Sijben, John W; Heerschap, Arend; Olde Rikkert, Marcel G M

2017-07-26

Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer's disease. Thirty-four drug-naive patients with mild Alzheimer's disease (Mini Mental State Examination score ≥20) were enrolled in this exploratory, double-blind, randomized controlled study. Before and after 4-week intervention with Souvenaid or an isocaloric control product, phosphorus and proton magnetic resonance spectroscopy (MRS) was performed to assess surrogate measures of phospholipid synthesis and breakdown (phosphomonoesters [PME] and phosphodiesters [PDEs]), neural integrity (N-acetyl aspartate), gliosis (myo-inositol), and choline metabolism (choline-containing compounds [tCho]). The main outcome parameters were PME and PDE signal intensities and the PME/PDE ratio. MRS data from 33 patients (60-86 years old; 42% males; Souvenaid arm n = 16; control arm n = 17) were analyzed. PME/PDE and tCho were higher after 4 weeks of Souvenaid compared with control (PME/PDE least squares [LS] mean difference [95% CI] 0.18 [0.06-0.30], p = 0.005; tCho LS mean difference [95% CI] 0.01 [0.00-0.02], p = 0.019). No significant differences were observed in the other MRS outcome parameters. MRS reveals that Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease, in line with findings in preclinical studies. Netherlands Trial Register, NTR3346 . Registered on 13 March 2012.

Bluetooth helper environment

Science.gov (United States)

Zhang, Junbiao

2001-10-01

Handheld devices are gaining great popularity and becoming a common commodity on the market primarily due to their small sizes and mobile nature. However, these devices are all limited in capabilities, especially in terms of screen display, processing power, storage space and network access. Some of these limitations, such as the small screen sizes, are inherently difficult to improve given the usage model of these devices. In this paper, we propose a framework in which small handheld devices can use their environment, the devices around them, to expand their limited capabilities. Such an environment can be deployed in the office, at home for user convenience or in a public access area as a revenue generating service. A handheld device interacts with the helper environment through several essential steps including device discovery, service query, request transfer and remote control. In order to ensure the proper operation of such an environment, the framework provides essential system components for admission control, resource allocation, task scheduling and device coordination. We refer to such a framework as the device helper environment and discuss its system architecture and usage scenarios in this paper.

Synergism between two helper cell subpopulations characterized by different radiosensitivity and nylon adherence

International Nuclear Information System (INIS)

Agarossi, G.; Mancini, C.; Doria, G.

1981-01-01

The present work extends our previous results on the radiosensitivity of the helper cell function. Two helper cell subpopulations, 1 radiosensitive and the other radioresistant, have been demonstrated in the spleen of mice at different times after priming with HRBC. The radiosensitive subpopulation increases with the increasing time interval between carrier-priming and irradiation. The 2 cell subpopulations have been further characterized by different nylon adherence properties: radioresistant helper cells adhere to nylon wool, whereas radiosensitive cells pass through. The 2 cell subpopulations were separated by x-irradiation and nylon wool filtration, and their helper activity was assessed separately or after recombination. The results favor the notion that 2 functionally independent helper T cells, as characterized by different radiosensitivity and nylon adherence, participate synergistically in the helper activity of primed spleen cells

Managing Stress and Burnout among Helpers in Rural Areas.

Science.gov (United States)

Reed, John C.

Individuals who work in the helping professions (physicians, counselors, nurses, pastors, and social workers) often work with individuals in stressful crisis situations. In addition to working in high stress situations, helpers in rural areas also suffer from isolation from support networks and peers that are available to urban helpers. This…

Association between cardiorespiratory fitness and metabolic risk factors in a population with mild to severe obesity.

Science.gov (United States)

Do, Kathy; Brown, Ruth E; Wharton, Sean; Ardern, Chris I; Kuk, Jennifer L

2018-01-01

Previous literature suggests the beneficial effects of fitness on abdominal obesity may be attenuated in obesity and abolished in severe obesity. It is unclear whether the beneficial association between fitness and health is similarly present in those with mild and severe obesity. Patients from the Wharton Medical Clinic ( n  = 853) completed a clinical examination and maximal treadmill test. Patients were categorized into fit and unfit based on age- and sex-categories and body mass index (BMI) class (mild: ≤ 34.9 kg/m 2 , moderate: 35-39.9 kg/m 2 or severe obesity: ≥ 40 kg/m 2 ). Within the sample, 41% of participants with mild obesity had high fitness whereas only 25% and 11% of the participants with moderate and severe obesity, respectively, had high fitness. BMI category was independently associated with most of the metabolic risk factors, while fitness was only independently associated with systolic blood pressure and triglycerides ( P  fitness groups were only significantly different in their relative risk for prevalent pre-clinical hypertension within the severe obesity group ( p  = 0.03). High fitness was associated with smaller waist circumferences, with differences between high and low fitness being larger in those with severe obesity than mild obesity (Men: P  = 0.06, Women: P  = 0.0005). Thus, in contrast to previous observations, the favourable associations of having high fitness and health may be similar if not augmented in individuals with severe compared to mild obesity.

Refeeding and metabolic syndromes: two sides of the same coin

Science.gov (United States)

Obeid, O A; Hachem, D H; Ayoub, J J

2014-01-01

Refeeding syndrome describes the metabolic and clinical changes attributed to aggressive rehabilitation of malnourished subjects. The metabolic changes of refeeding are related to hypophosphatemia, hypokalemia, hypomagnesemia, sodium retention and hyperglycemia, and these are believed to be mainly the result of increased insulin secretion following high carbohydrate intake. In the past few decades, increased consumption of processed food (refined cereals, oils, sugar and sweeteners, and so on) lowered the intake of several macrominerals (mainly phosphorus, potassium and magnesium). This seems to have compromised the postprandial status of these macrominerals, in a manner that mimics low grade refeeding syndrome status. At the pathophysiological level, this condition favored the development of the different components of the metabolic syndrome. Thus, it is reasonable to postulate that metabolic syndrome is the result of long term exposure to a mild refeeding syndrome. PMID:24979149

Crisis Intervention Strategies for School-Based Helpers. Second Edition.

Science.gov (United States)

Fairchild, Thomas N., Ed.

School-based helpers are helping professionals who work within educational settings and whose training and primary responsibility is to promote the mental health of students. Few resource materials provide these helpers with needed information and practical strategies--this text tries to meet that need. The 12 chapters here cover a wide range of…

Longitudinal PET evaluation of cerebral glucose metabolism in rivastigmine treated patients with mild Alzheimer's disease

International Nuclear Information System (INIS)

Stefanova, E.; Forsberg, A.; Wall, A.; Nilsson, A.; Langstroem, B.; Almkvist, O.; Nordberg, A.

2006-01-01

In this study 11 patients with mild Alzheimer's disease (AD) were treated with the cholinesterase inhibitor rivastigmine (mean dose 8.6 ± 1.3 mg) for 12 months and underwent positron emission tomography (PET) studies of cerebral glucose metabolism (CMRglc) and neuropsychological testing at baseline and after 12 months. An untreated group of 10 AD patients served as control group. While the untreated AD patients showed a significant decline of CMRglc in the temporo-parietal and frontal cortical regions after 12 months follow-up the rivastigmine-treated patients showed no decline in CMRglc in corresponding cortical brain regions. Furthermore, a significant dose-related increase in CMRglc was recorded in the right frontal association region after 12 months rivastigmine treatment. A positive correlation was observed between changes in CMRglc and several cognitive tests in patients receiving higher doses (10.5-12 mg) of rivastigmine. These results suggest a stabilization effect of rivastigmine on CMRglc in mild AD patients receiving long-term rivastigmine treatment. (author)

Helper contributions in the cooperatively breeding laughing kookaburra: feeding young is no laughing matter.

Science.gov (United States)

Legge

2000-05-01

I studied the contributions of individuals to incubation and nestling feeding in a population of cooperatively breeding laughing kookaburras, Dacelo novaeguineae. In most cooperatively breeding birds where nest success is limited by nestling starvation, related helpers increase the overall level of provisioning to the nest, thus boosting the production of nondescendent kin. However, although partial brood loss is the largest cause of lost productivity in kookaburra nests, additional helpers failed to increase overall provisioning. Instead, all group members, but especially helpers, reduced their feeding contributions as group size increased. Breeders and helpers reduced the size of prey delivered, and helpers also reduced the number of feeding visits. An important benefit of helping in kookaburras may be to allow all group members to reduce their effort. Within groups, contributions to care depended on status, sex, group size and the brood size. Breeding males delivered the most food. Breeding females provisioned less than their partner, but their effort was comparable to that of male helpers. Female helpers contributed the least food. Incubation effort followed similar patterns. The relatedness of helpers to the brood had no impact on their provisioning. Across all group sizes, helpers generally brought larger items to the nest than breeders. Copyright 2000 The Association for the Study of Animal Behaviour.

[Recovering helpers in the addiction treatment system in Hungary: an interpretative phenomenological analysis].

Science.gov (United States)

Kassai, Szilvia; Pintér, Judit Nóra; Rácz, József

2015-01-01

The work of recovering helpers who work in the addiction rehabilitation centres was studied. The aim was to investigate the process of addicts becoming recovering helpers, and to study what peer help means to them. According to interpretative phenomenological analysis (IPA) design, subjects were selected, data were collected and analysed. 6 (5 males, 1 female), working as recovering helpers at least one year at addiction rehabilitation centres. Semi-structured life interviews were carried out and analysed according to IPA. Emerging themes from the interviews were identified and summarized, then interpreted as central themes: important periods and turning points of the life story interviews: the experience of psychoactive drugs use, the development of the addiction (which became " Turning Point No 1") then the "rock bottom" experience ("Turning Point No 2"). Then the experience of the helping process was examined: here four major themes were identified: the development of the recovering self and the helping self, the wounded helper and the skilled helper, the experience of the helping process. IPA was found to be a useful method for idiographic exploration of the development and the work of the recovering helpers. The work of the recovering helpers can be described as mentoring of the addict clients. Our experiences might be used for the training programs for recovering helpers as well as to adopt their professional role in addiction services.

From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation revisited

NARCIS (Netherlands)

Boniface, Katia; Blom, Bianca; Liu, Yong-Jun; de Waal Malefyt, René

2008-01-01

Protracted inflammation leading to dysregulation of effector T-cell responses represents a common feature of a wide range of autoimmune diseases. The interleukin-12 (IL-12)/T-helper 1 (Th1) pathway was thought to be responsible for the pathogenesis of multiple chronic inflammatory diseases,

Adeno-associated virus vectors can be efficiently produced without helper virus.

Science.gov (United States)

Matsushita, T; Elliger, S; Elliger, C; Podsakoff, G; Villarreal, L; Kurtzman, G J; Iwaki, Y; Colosi, P

1998-07-01

The purpose of this work was to develop an efficient method for the production of adeno-associated virus (AAV) vectors in the absence of helper virus. The adenovirus regions that mediate AAV vector replication were identified and assembled into a helper plasmid. These included the VA, E2A and E4 regions. When this helper plasmid was cotransfected into 293 cells, along with plasmids encoding the AAV vector, and rep and cap genes, AAV vector was produced as efficiently as when using adenovirus infection as a source of help. CMV-driven constructs expressing the E4orf6 and the 72-M(r), E2A proteins were able to functionally replace the E4 and E2A regions, respectively. Therefore the minimum set of genes required to produce AAV helper activity equivalent to that provided by adenovirus infection consists of, or is a subset of, the following genes: the E4orf6 gene, the 72-M(r), E2A protein gene, the VA RNA genes and the E1 region. AAV vector preparations made with adenovirus and by the helper virus-free method were essentially indistinguishable with respect to particle density, particle to infectivity ratio, capsimer ratio and efficiency of muscle transduction in vivo. Only AAV vector preparations made by the helper virus-free method were not reactive with anti-adenovirus sera.

Peer Helping Programs: Helper Role, Supervisor Training, and Suicidal Behavior.

Science.gov (United States)

Lewis, Max W.; Lewis, Arleen C.

1996-01-01

Presents results of a survey of Washington State school counselors concerning peer helper programs. Descriptive analyses indicate that peer helper counseling programs are widely used and that they are often supervised by noncounseling professionals. The analysis also revealed greater numbers of completed suicides at those schools with the…

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Self-Help Groups and Professional Helpers.

Science.gov (United States)

Balgopal, Pallassana R.; And Others

1986-01-01

Suggests innovative solutions for mutual benefits for self-help groups and the professionals. Through a derivative paradigm the role of the professional helper within self-help groups is presented. (Author/BL)

Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles

Directory of Open Access Journals (Sweden)

Xiaoxia Gao

2018-01-01

Full Text Available The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS (with depression and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC- Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future.

File list: Oth.Bld.10.AllAg.Follicular_helper_T_cells [Chip-atlas[Archive

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File list: Oth.Bld.50.AllAg.Follicular_helper_T_cells [Chip-atlas[Archive

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File list: Oth.Bld.05.AllAg.Follicular_helper_T_cells [Chip-atlas[Archive

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Changes in helper and suppressor T lymphocytes following radiotherapy for breast cancer

International Nuclear Information System (INIS)

Newman, G.H.; Rees, G.J.G.; Jones, R.S.J.; Grove, E.A.; Preece, A.W.

1987-01-01

Changes in total lymphocyte, T lymphocyte, T helper and T suppressor lymphocyte numbers were studied in 22 patients with breast cancer before and after radiotherapy. T lymphocyte subsets were measured using monoclonal antibodies and fluorescence microscopy. After treatment the total lymphocyte count fell significantly and was still reduced 9 months later, but the proportion of cells labelled as T lymphocytes was unchanged during this period. The helper-suppressor ratio, which was within the normal range before radiotherapy, was significantly reduced at 3 months and 9 months after. Following treatment both T helper and T suppressor cell numbers were significantly reduced. T helper cell numbers remained reduced throughout the study period but T suppressor cell numbers showed a recovery to normal values 9 months after radiotherapy. (author)

Antigen-primed helper T cell function in CBA/N mice is radiosensitive

International Nuclear Information System (INIS)

Phillips, N.E.; Campbell, P.A.

1981-01-01

CBA/N mice have an X-linked immunodeficiency that includes a deficient humoral response to sheep red blood cells (SRBC). In order to study the cellular mechanisms of this deficiency we have examined helper T cell function to SRBC in an adoptive transfer system by using 2 different sources of helper T cells. When thymocytes were used as the source of helper T cell precursors in an adoptive transfer system, CBA/N thymocytes were as effective as CBA/Ca thymocytes in inducing CBA/Ca bone marrow cells to develop into both direct and indirect anti-SRBC plaque-forming cells (PFC). However, when SRBC-primed, irradiated recipient mice were used as the source of helper T cells, primed and irradiated CBA/N recipiets developed significantly fewer direct and indirect anti-SRBC PFC than similarly treated CBA/CA recipients when reconstituted with CBA/Ca bone marrow cells and challenged with SRBC. We conclude that antigen-primed helper T cell function in CBA/N mice is radiosensitive. Possible reasons for this are evaluated and discussed

Egg size investment in superb fairy-wrens: helper effects are modulated by climate

Science.gov (United States)

Heinsohn, R. G.; Russell, A. F.; Kilner, R. M.

2016-01-01

Natural populations might exhibit resilience to changing climatic conditions if they already show adaptive flexibility in their reproductive strategies. In cooperative breeders, theory predicts that mothers with helpers should provide less care when environmental conditions are favourable, but maintain high investment when conditions are challenging. Here, we test for evidence of climate-mediated flexibility in maternal investment in the cooperatively breeding superb fairy-wren Malurus cyaneus. We focus on egg size because in this species egg size influences offspring size, and females reduce egg investment when there are helpers at the nest. We report that females lay larger eggs during dry, hot conditions. However, the effect of temperature is modulated by the presence of helpers: the average egg size of females with helpers is reduced during cooler conditions but increased during hot conditions relative to females without helpers. This appears to reflect plasticity in egg investment rather than among female differences. Analysis of maternal survival suggests that helped females are better able to withstand the costs of breeding in hot conditions than females without helpers. Our study suggests that females can use multiple, independent cues to modulate egg investment flexibly in a variable environment. PMID:27903872

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Figuring out whether they can be trusted: older widows' intentions relative to hired non-professional home-care helpers.

Science.gov (United States)

Porter, Eileen J; Lasiter, Sue; Poston, Emily

2005-01-01

The purpose of this phenomenological study was to describe the experience of older women relative to trusting hired non-professional home-care helpers. Open-ended interviews were done about the home-care experience with 25 women over three years, and 14 women (age 80-93) shared data about hiring and trusting helpers. The women perceived risks to personal safety that adversely influenced willingness to seek new helpers. After hiring a helper, the women were still trying to discern whether the helper could be trusted. Primary-care providers should enable older women to recognize and reduce the risk of having helpers and to monitor helpers' behavior, as well as assessing the psychosocial status of women who have such helpers.

Development of Empathy in Helpers.

Science.gov (United States)

Fretz, Bruce R.

A trait measure of empathy, a skill measure of empathy and an attitude scale on psychological effectiveness were administered to both counselor trainees and "natural helpers", i.e. persons in helping relationships who have not been formally trained as mental health professionals or paraprofessionals. The results indicated that the measures of…

The role of the paid non-professional nursing helper: a review of the literature.

Science.gov (United States)

Dewar, B J; Clark, J M

1992-01-01

This paper presents an overview of research into the role of paid non-professional nursing helpers. This term refers to auxiliaries, ward clerks, healthcare assistants and support workers. The focus of the review is on work carried out on attitudes of qualified staff to the role of the helper, role descriptions and the role of the helper in different organizational modes of work. Some of the research reviewed in relation to the role description and attitudes to the helper date back to 1978. However, the emphasis of the paper is on research published in the past 3 years. The research is reviewed against the background of two theoretical frameworks, both of which are perceived to be useful in analysing the division of labour between the nurse, the patient and the helper.

Neuron-astrocyte interaction enhance GABAergic synaptic transmission in a manner dependent on key metabolic enzymes.

Directory of Open Access Journals (Sweden)

Przemysław eKaczor

2015-04-01

Full Text Available GABA is the major inhibitory neurotransmitter in the adult brain and mechanisms of GABAergic inhibition have been intensely investigated in the past decades. Recent studies provided evidence for an important role of astrocytes in shaping GABAergic currents. One of the most obvious, but yet poorly understood, mechanisms of the cross-talk between GABAergic currents and astrocytes is metabolism including neurotransmitter homeostasis. In particular, how modulation of GABAergic currents by astrocytes depends on key enzymes involved in cellular metabolism remains largely unknown. To address this issue, we have considered two simple models of neuronal cultures: nominally astrocyte-free neuronal culture (NC and neuronal-astrocytic co-cultures (ANCC and miniature Inhibitory Postsynaptic Currents (mIPSCs were recorded in control conditions and in the presence of respective enzyme blockers. We report that enrichment of neuronal culture with astrocytes results in a marked increase in mIPSC frequency. This enhancement of GABAergic activity was accompanied by increased number of GAD65 and vGAT puncta, indicating that at least a part of the frequency enhancement was due to increased number of synaptic contacts. Inhibition of glutamine synthetase (with MSO strongly reduced mIPSC frequency in ANCC but had no effect in NC. Moreover, treatment of ANCC with inhibitor of glycogen phosphorylase (BAYU6751 or with selective inhibitor of astrocytic Krebs cycle,fluoroacetate, resulted in a marked reduction of mIPSC frequency in ANCC having no effect in NC. We conclude that GABAergic synaptic transmission strongly depends on neuron-astrocyte interaction in a manner dependent on key metabolic enzymes as well as on the Krebs cycle.

Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.

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Kimberly B Zumbrennen-Bullough

Full Text Available Iron Regulatory Protein 2 (Irp2, Ireb2 is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2-/- mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc, expression are increased and decreased, respectively, in the brain from Irp2-/- mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.

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Becoming a Helper. Third Edition.

Science.gov (United States)

Corey, Marianne Schneider; Corey, Gerald

The problems involved in becoming an effective helper and the personal difficulties of working with others are addressed. A discussion of motivations for seeking a career in the helping professions is followed by an overview of the helping process. Chapter topics include: (1) "Are the Helping Professions for You?"; (2) "Getting the Most from Your…

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Memory T follicular helper CD4 T cells

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J. Scott eHale

2015-02-01

Full Text Available T follicular helper (Tfh cells are the subset of CD4 T helper cells that are required for generation and maintenance of germinal center reactions and the generation of long-lived humoral immunity. This specialized T helper subset provides help to cognate B cells via their expression of CD40 ligand, IL-21, IL-4, and other molecules. Tfh cells are characterized by their expression of the chemokine receptor CXCR5, expression of the transcriptional repressor Bcl6, and their capacity to migrate to the follicle and promote germinal center B cell responses. Until recently, it remained unclear whether Tfh cells differentiated into memory cells and whether they maintain their Tfh commitment at the memory phase. This review will highlight several recent studies that support the idea of Tfh-committed CD4 T cells at the memory stage of the immune response. The implication of these findings is that memory Tfh cells retain their capacity to recall their Tfh-specific effector functions upon reactivation to provide help for B cell responses and play an important role in prime and boost vaccination or during recall responses to infection. The markers that are useful for distinguishing Tfh effector and memory cells, as well as the limitations of using these markers will be discussed. Tfh effector and memory generation, lineage maintenance, and plasticity relative to other T helper lineages (Th1, Th2, Th17, etc will also be discussed. Ongoing discoveries regarding the maintenance and lineage stability versus plasticity of memory Tfh cells will improve strategies that utilize CD4 T cell memory to modulate antibody responses during prime and boost vaccination.

"Little Helper" - An Autonomous Industrial Mobile Manipulator Concept

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Mads Hvilshoj

2011-06-01

Full Text Available This paper presents the concept "autonomous industrial mobile manipulation" (AIMM based on the mobile manipulator "Little Helper" - an ongoing research project at Aalborg University, Denmark, concerning the development of an autonomous and flexible manufacturing assistant. The paper focuses on the contextual aspects and the working principles of AIMM. Furthermore, the paper deals with the design principles and overall hardware and software architectures of "Little Helper" from a functional and modular mechatronics point of view, in order to create a generic AIMM platform. The design challenges faced in the project is to integrate commercial off‐the‐shelf (COTS and dedicated highly integrated systems into an autonomous mobile manipulator system with the ability to perform diverse tasks in industrial environments. We propose an action based domain specific communication language for AIMM for routine and task definition, in order to lower the entry barriers for the users of the technology. To demonstrate the "Little Helper" concept a full‐scale prototype has been built and different application examples carried out. Experiences and knowledge gained from this show promising results regarding industrial integration, exploitation and maturation of the AIMM technology.

Distinct pattern of lesion distribution in multiple sclerosis is associated with different circulating T-helper and helper-like innate lymphoid cell subsets.

Science.gov (United States)

Gross, Catharina C; Schulte-Mecklenbeck, Andreas; Hanning, Uta; Posevitz-Fejfár, Anita; Korsukewitz, Catharina; Schwab, Nicholas; Meuth, Sven G; Wiendl, Heinz; Klotz, Luisa

2017-06-01

Distinct lesion topography in relapsing-remitting multiple sclerosis (RRMS) might be due to different antigen presentation and/or trafficking routes of immune cells into the central nervous system (CNS). To investigate whether distinct lesion patterns in multiple sclerosis (MS) might be associated with a predominance of distinct circulating T-helper cell subset as well as their innate counterparts. Flow cytometric analysis of lymphocytes derived from the peripheral blood of patients with exclusively cerebral (n = 20) or predominantly spinal (n = 12) disease manifestation. Patients with exclusively cerebral or preferential spinal lesion manifestation were associated with increased proportions of circulating granulocyte-macrophage colony-stimulating factor (GM-CSF) producing T H 1 cells or interleukin (IL)-17-producing T H 17 cells, respectively. In contrast, proportions of peripheral IL-17/IL-22-producing lymphoid tissue inducer (LTi), the innate counterpart of T H 17 cells, were enhanced in RRMS patients with exclusively cerebral lesion topography. Distinct T-helper and T-helper-like innate lymphoid cell (ILC) subsets are associated with different lesion topography in RRMS.

Effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury

Institute of Scientific and Technical Information of China (English)

WANG Qiong; LI Ai-lin; ZHI Da-shi; HUANG Hui-ling

2007-01-01

Objective:To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (STBI) using clinical microdialysis.Methods: Thirty-one patients with STBI ( GCS ≤8) were randomly divided into hypothermic group (Group A) and control group (Group B). Microdialysis catheters were inserted into the cerebral cortex of perilesional and normal brain tissue. All samples were analyzed using CMA microdialysis analyzer.Results: In comparison with the control group, lactate/glucose ratio ( L/G) , lactate/pyruvate ratio ( L/P) and glycerol (Gly) in perilensional tissue were significantly decreased; L/P in normal brain tissue was significantly decreased. In control group, L/G, L/P and Gly in perilensional tissue were higher than that in normal brain tissue. In the hypothermic group, L/P in perilensional tissue was higher than that in relative normal brain.Conclusions: Mild hypothermia protects brain tissues by decreasing L/G, L/P and Gly in perilensional tissue and L/P in "normal brain" tissues. The energy crisis and membrane phospholipid degradation in perilensional tissue are easier to happen after traumatic brain injury, and mild hypothermia protects brain better in perilensional tissue than in normal brain tissue.

Consequences of 'load-lightening' for future indirect fitness gains by helpers in a cooperatively breeding bird.

Science.gov (United States)

Meade, Jessica; Nam, Ki-Baek; Beckerman, Andrew P; Hatchwell, Ben J

2010-05-01

1. Helpers that invest energy in provisioning the offspring of related individuals stand to gain indirect fitness benefits from doing so. First, if the helper's effort is additional to that of the parents (additive) the productivity of the current breeding attempt can be increased. Secondly, if the parents reduce their workload (compensation) this can result in future indirect fitness gains to the helper via increased breeder survival; termed 'load-lightening'. 2. Long-tailed tits (Aegithalos caudatus) have a cooperative breeding system in which helpers assist kin and parents exhibit both additive and compensatory reactions in the presence of helpers. Offspring from helped nests are heavier and more likely to recruit into the breeding population, thus helpers gain indirect fitness benefits from increasing the productivity of the current breeding attempt. Despite breeders' reduction of feeding effort in the presence of helpers, previous investigations found no subsequent increase in breeder survival. 3. The aim of this study was to test the hypothesis that load-lightening resulted in indirect fitness benefits for helpers. We used data from a 14-year study to investigate the provisioning rate, survival and future fecundity of male and female long-tailed tits that did and did not receive help at the nest. 4. We found an asymmetrical response to the presence of helpers at large brood sizes. Males reduced their feeding rate more than females, and this differential response was reflected in a significant increase in male survival when provisioning large broods assisted by helpers. We found no evidence of any increase in future fecundity for helped breeders. 5. The finding that males reduce their provisioning rate in the presence of helpers (at large brood sizes) to a greater degree than females, and that this is reflected in an increase in survival rate for males only, implies that the survival increase is caused by the reduction in work-rate rather than a non

Peer Helpers: Encouraging Kids to Confide.

Science.gov (United States)

Tanaka, Gail; Reid, Kelley

1997-01-01

In peer-helping programs, a professional counselor or teacher trains a group of students who then help other students by listening, providing information, and referring them to others with the necessary expertise. Peer helpers can help improve the school climate by contributing to its health and security. Since 1979, Seattle's Natural Helpers…

Identification of altered metabolic pathways in plasma and CSF in mild cognitive impairment and Alzheimer's disease using metabolomics.

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Eugenia Trushina

Full Text Available Alzheimer's Disease (AD currently affects more than 5 million Americans, with numbers expected to grow dramatically as the population ages. The pathophysiological changes in AD patients begin decades before the onset of dementia, highlighting the urgent need for the development of early diagnostic methods. Compelling data demonstrate that increased levels of amyloid-beta compromise multiple cellular pathways; thus, the investigation of changes in various cellular networks is essential to advance our understanding of early disease mechanisms and to identify novel therapeutic targets. We applied a liquid chromatography/mass spectrometry-based non-targeted metabolomics approach to determine global metabolic changes in plasma and cerebrospinal fluid (CSF from the same individuals with different AD severity. Metabolic profiling detected a total of significantly altered 342 plasma and 351 CSF metabolites, of which 22% were identified. Based on the changes of >150 metabolites, we found 23 altered canonical pathways in plasma and 20 in CSF in mild cognitive impairment (MCI vs. cognitively normal (CN individuals with a false discovery rate <0.05. The number of affected pathways increased with disease severity in both fluids. Lysine metabolism in plasma and the Krebs cycle in CSF were significantly affected in MCI vs. CN. Cholesterol and sphingolipids transport was altered in both CSF and plasma of AD vs. CN. Other 30 canonical pathways significantly disturbed in MCI and AD patients included energy metabolism, Krebs cycle, mitochondrial function, neurotransmitter and amino acid metabolism, and lipid biosynthesis. Pathways in plasma that discriminated between all groups included polyamine, lysine, tryptophan metabolism, and aminoacyl-tRNA biosynthesis; and in CSF involved cortisone and prostaglandin 2 biosynthesis and metabolism. Our data suggest metabolomics could advance our understanding of the early disease mechanisms shared in progression from CN to

Knowledge and Practices About the Subject Emergency Contraception of the Pharmacists and Their Helpers in the Pharmacies in Manisa

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Ayten Taspinar

2012-08-01

Full Text Available AIM: The study was carried out as descriptive to determine the knowledge and practices about the subject emergency contraception of the pharmacists and their helpers in the pharmacies in central Manisa. METHOD: The universe of the research was formed by the 113 pharmacies registered to Manisa chamber of pharmacists in the year 2008 and all the pharmacies were included in the study. 47 pharmacists and 88 helpers agreed to join the study. The research which was planned to be descriptive March-to-June 2008. A questionnaire was produced by researchers and filled in during face-to face interviews with the pharmacists and their helpers. RESULTS: The pharmacists and their helpers stated that combined pills (46.8% and 44.5% and condoms (41.5% and 42.7% the most requested family planning methods their pharmacy. It was determined that 48.9% of the pharmacists, 33% of the pharmacist’s helpers gave information to customers about their use of family planning methods, 38.3% of the pharmacists, 23.9 % of the pharmacist’s helpers gave information what to do in case of failure to use/ where to apply to. 91.5% of the pharmacists, 95.5% of the pharmacist’s helpers stated that they had emergency contraception (EC purpose pills in their pharmacies. It was determined that 61.7% of the pharmacists, 28.4% of the pharmacist’s helpers had the knowledge about EC, 61.7% of the pharmacists, 52.3% of the pharmacist’s helpers could consider the EC methods true, 68.1% of the pharmacists, 70.5% of the pharmacist’s helpers gave the correct answers to the question of when the EC – purpose pills would be used. 68.1% of the pharmacists, 45.5% of the pharmacist’s helpers stated that EC methods might have adverse effects, 14.9% of the pharmacists, 25% of the pharmacist’s helpers stated that EC methods were protect agains to STD or not information about it, 12.8% of the pharmacists, 9.1% of the pharmacist’s helpers stated that these pills might be effective after the

Die posisie van die Helper in die sending

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I. J. van der Walt

1972-05-01

Full Text Available Gedurende die aanvangsjare van die sending het die helper ’n onmisbare funksie vervul. Hulle het die onherbergsame binnelande geken, waardevolle kontakpunte vir die sendelinge geopen en hulle mense geestelik help voorlig en voorberei.

Follicular helper T cell in immunity and autoimmunity

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D. Mesquita Jr

2016-01-01

Full Text Available The traditional concept that effector T helper (Th responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17 and the follicular helper T cells (Tfh. These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R, the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases.

Essential competencies for the education of nursing assistants and care helpers in elderly care.

Science.gov (United States)

Oeseburg, Barth; Hilberts, Rudi; Roodbol, Petrie F

2015-10-01

The Dutch health care system faces huge challenges with regard to the demand on elderly care and the competencies of professionals required to meet this demand. However, a recent study showed that the curricula in vocational education for nursing assistants and care helpers remains inadequate to prepare them for the social and healthcare needs of the elderly. To determine the essential competencies for the initial education of nursing assistants and care helpers in elderly care. First, a draft version of essential competencies for the education of nursing assistants and care helpers in elderly care (N=120) was developed and approved by experts, also members of the project steering committee. Second, a Delphi survey was conducted to determine the essential competencies. The Delphi panel consisted of eleven field experts (teachers/educational developers) working for different vocational education training colleges in the Netherlands. Ten panel members participated in a two-round consensus building process via email. A definitive set of 116 essential competencies for the initial education of nursing assistants and 42 essential competencies for the initial education of care helpers were determined. The competencies in the definitive set are more in line with social and healthcare needs of the elderly like: autonomy, daily functioning prevention of health problems, healthy ageing and wellbeing, involvement of informal care, collaboration between professionals and informal care. The main challenge now is to translate these competencies into educational programmes for vocational education training colleges for care helpers and nursing assistants. Recommendations are made for the implementation of these competencies in the Dutch vocational education training colleges for care helpers and nursing assistants. Copyright © 2015 Elsevier Ltd. All rights reserved.

General pathologist-helper: The new medical app about general pathology

Directory of Open Access Journals (Sweden)

Iván Fernandez-Vega

2015-01-01

Full Text Available Introduction: Smartphone applications (apps have become increasingly prevalent in medicine. Due to most pathologists, pathology trainees, technicians, and medical students use smartphones; apps can be a different way for general pathology education. “General pathologist-helper (GP-HELPER” is a novel app developed as a reference tool in general pathology and especially for general pathologists, developed for Android and iOS platforms. Materials and Methods: “GP-HELPER,” was created using Mobincube website platform. This tool also integrates “FORUM GP-HELPER,” an external website created using Miarroba website (http://forum-gp-helper.mboards.com and “COMMUNITY GP-HELPER” a multichannel chat created using Chatango website platform. Results: The application was released in July 2015, and it is been periodically updated since then. The app has permanent information (offline data about different pathology protocols (TNM latest edition, protocols regarding management of tumors of unknown primary origin, and flowcharts for some of the most difficult tumors to diagnose and a database with more than 5000 immunohistochemistry results from different tumors. Online data have links to more than 1100 reference pathology video lectures, 250 antibodies information, more than 70 pathology association websites, 46 pathology providers, and 78 outstanding pathology journal websites. Besides this information, the app has two interactive places such as “FORUM GP-HELPER” and “COMMUNITY GP-HELPER” that let users to stay in touch everywhere and every time. Expert consult section is also available. Conclusions: “GP-HELPER” pretends to integrate offline and online data about pathology with two interactive external places in order to represent a reference tool for general pathologists and associate members.

Interleukin 2 is not sufficient as helper component for the activation of cytotoxic T lymphocytes but synergizes with a late helper effect that is provided by irradiated T-region-incompatible stimulator cells

Energy Technology Data Exchange (ETDEWEB)

Reddehase, M.; Suessmith, W.; Moyers, C.; Falk, W.; Droege, W.

1982-01-01

Interleukin 2-containing supernatants from concanavalin A-activated spleen cells (CSCS) were found to provide strong helper activity for cytotoxic T lymphocyte (CTL) responses against allogeneic stimulator cells in microculture systems, but provided usually insufficient help for CTL responses against l-region compatible allogeneic or TNP-haptenated syngeneic stimulator cells. The interleukin 2-containing supernatant from HGG-activated AODH 7.1 hybridoma cells also mediated only relatively weak CTL responses against TNP-haptenated syngeneic cells in microcultures. Both types of supernatants, however, supported substantial responses against TNP-haptenated syngeneic stimulator cells if irradiated allogeneically activated syngeneic T cells or irradiated allogeneic spleen cells were added to the cultures. The allogeneic cells and the activated syngeneic T cells provided little helper activity if they were added in the absence of the interleukin 2-containing supernatants, thus demonstrating a synergistic effect between these 2 helper components. An l-region difference was sufficient for the helper effect of the allogeneic cells and control experiments showed that the presence of foreign l-region determinants could not be substituted for the TNP-haptenated stimulator cells.

Interleukin 2 is not sufficient as helper component for the activation of cytotoxic T lymphocytes but synergizes with a late helper effect that is provided by irradiated T-region-incompatible stimulator cells

International Nuclear Information System (INIS)

Reddehase, M.; Suessmith, W.; Moyers, C.; Falk, W.; Droege, W.

1982-01-01

Interleukin 2-containing supernatants from concanavalin A-activated spleen cells (CSCS) were found to provide strong helper activity for cytotoxic T lymphocyte (CTL) responses against allogeneic stimulator cells in microculture systems, but provided usually insufficient help for CTL responses against l-region compatible allogeneic or TNP-haptenated syngeneic stimulator cells. The interleukin 2-containing supernatant from HGG-activated AODH 7.1 hybridoma cells also mediated only relatively weak CTL responses against TNP-haptenated syngeneic cells in microcultures. Both types of supernatants, however, supported substantial responses against TNP-haptenated syngeneic stimulator cells if irradiated allogeneically activated syngeneic T cells or irradiated allogeneic spleen cells were added to the cultures. The allogeneic cells and the activated syngeneic T cells provided little helper activity if they were added in the absence of the interleukin 2-containing supernatants, thus demonstrating a synergistic effect between these 2 helper components. An l-region difference was sufficient for the helper effect of the allogeneic cells and control experiments showed that the presence of foreign l-region determinants could not be substituted for the TNP-haptenated stimulator cells

Personal experience in professional narratives: the role of helpers' families in their work with terror victims.

Science.gov (United States)

Shamai, Michal

2005-06-01

This article describes research on the narratives of social workers who help terror victims, focusing on the relationship between the helpers' families and their work. Qualitative analysis of three training groups of social workers who are responsible for helping in the event of terror attacks in different parts of Israel, and of three debriefing groups for social workers after terror attacks, reveals that the helpers' families play a role in the narratives constructed by the helpers. Two main themes were identified. The first centers on the interaction between work and the family, and shows that in the situation of a terror attack, the conflict between the two disappears and the family often serves as a support system for the helpers. The second theme refers to the family dimension alone, and focuses on the dichotomy between vitality and loss. The way that family life events affect helpers'professional intervention is described. The findings are discussed in light of Conservation of Resources Theory, the fight-flight response to threat, and the concept of the family as a source of safety and risk taking.

Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch

NARCIS (Netherlands)

Amsen, Derk; Antov, Andrey; Jankovic, Dragana; Sher, Alan; Radtke, Freddy; Souabni, Abdallah; Busslinger, Meinrad; McCright, Brent; Gridley, Thomas; Flavell, Richard A.

2007-01-01

CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using

Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment

NARCIS (Netherlands)

Bosch, A.M.; Abeling, N.G.G.M.; Ijlst, L.; Knoester, H.; van der Pol, W.L.; Stroomer, A.E.M.; Wanders, R.J.; Visser, G.; Wijburg, F.A.; Duran, M.; Waterham, H.R.

2011-01-01

We report on three patients (two siblings and one unrelated) presenting in infancy with progressive muscle weakness and paralysis of the diaphragm. Metabolic studies revealed a profile of plasma acylcarnitines and urine organic acids suggestive of a mild form of the multiple acyl-CoA dehydrogenation

Central role of T helper 17 cells in chronic hypoxia-induced pulmonary hypertension.

Science.gov (United States)

Maston, Levi D; Jones, David T; Giermakowska, Wieslawa; Howard, Tamara A; Cannon, Judy L; Wang, Wei; Wei, Yongyi; Xuan, Weimin; Resta, Thomas C; Gonzalez Bosc, Laura V

2017-05-01

Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4 + T cells are required for initiating and maintaining inflammation, suggesting that these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension. Our objective was to test the hypothesis that CD4 + T cells, specifically the T helper 17 subset, contribute to chronic hypoxia-induced pulmonary hypertension. We compared indices of pulmonary hypertension resulting from chronic hypoxia (3 wk) in wild-type mice and recombination-activating gene 1 knockout mice (RAG1 -/- , lacking mature T and B cells). Separate sets of mice were adoptively transferred with CD4 + , CD8 + , or T helper 17 cells before normoxic or chronic hypoxic exposure to evaluate the involvement of specific T cell subsets. RAG1 -/- mice had diminished right ventricular systolic pressure and arterial remodeling compared with wild-type mice exposed to chronic hypoxia. Adoptive transfer of CD4 + but not CD8 + T cells restored the hypertensive phenotype in RAG1 -/- mice. Interestingly, RAG1 -/- mice receiving T helper 17 cells displayed evidence of pulmonary hypertension independent of chronic hypoxia. Supporting our hypothesis, depletion of CD4 + cells or treatment with SR1001, an inhibitor of T helper 17 cell development, prevented increased pressure and remodeling responses to chronic hypoxia. We conclude that T helper 17 cells play a key role in the development of chronic hypoxia-induced pulmonary hypertension. Copyright © 2017 the American Physiological Society.

The SOS Club: A Practical Peer Helper Program.

Science.gov (United States)

Scarborough, Janna L.

1997-01-01

Describes a peer helper program developed for students in grades K-5. The program applies the concept that each student has something positive to offer the school and is responsible for providing that service. Discusses program goals and objectives, ways to gain support for the program, training, implementation, and evaluation. (RJM)

Symptoms of thyrotoxicosis, bone metabolism and occult atrial fibrillation in older women with mild endogenous subclinical hyperthyroidism.

Science.gov (United States)

Rosario, Pedro Weslley; Carvalho, Marina; Calsolari, Maria Regina

2016-07-01

The objective of this study was to evaluate symptoms of thyrotoxicosis, bone turnover, bone mineral density (BMD) and occult atrial fibrillation (AF) in women ≥65 years with mild endogenous subclinical hyperthyroidism (SCH). Cross-sectional and case-control study. Signs and symptoms of thyrotoxicosis, serum carboxyterminal telopeptide (CTx) and procollagen type I N-terminal propeptide (PINP), BMD, resting electrocardiogram (ECG) and 72-h ECG monitoring were evaluated in 180 women ≥65 years, including 90 with mild SCH (TSH between 0·1 and 0·4 mIU/l) and 90 euthyroid controls matched for age and body mass index. Symptom Rating Scale scores did not differ between patients and controls. None of the patients with SCH scored 20 points, a score compatible with clinical thyrotoxicosis. Eighty patients with SCH (89%) obtained seven or fewer points, a score compatible with euthyroidism. No difference in serum CTx or PINP concentrations was observed between patients and controls. There was also no correlation between these markers and TSH, free T4 or total T3 levels. Finally, no difference in femoral neck or lumbar spine BMD was observed between patients with SCH and controls. Three patients with SCH (3·3%) and two euthyroid women (2·2%) had known AF or AF in the resting ECG. ECG monitoring for 72 h revealed episodes of occult AF in 1/87 patients with SCH and in 1/88 euthyroid women (1·1%). Mild endogenous SCH (TSH between 0·1 and 0·4 mIU/l) was not associated with symptoms of thyrotoxicosis, altered bone metabolism or a higher prevalence of occult AF in women ≥65 years. © 2015 John Wiley & Sons Ltd.

Individual cerebral metabolic deficits in Alzheimer's disease and amnestic mild cognitive impairment: an FDG PET study

International Nuclear Information System (INIS)

Del Sole, Angelo; Lecchi, Michela; Lucignani, Giovanni; Clerici, Francesca; Mariani, Claudio; Maggiore, Laura; Chiti, Arturo; Mosconi, Lisa

2008-01-01

The purpose of the study was the identification of group and individual subject patterns of cerebral glucose metabolism (CMRGlu) in patients with Alzheimer's disease (AD) and with amnestic mild cognitive impairment (aMCI). [ 18 F]fluorodeoxyglucose positron emission tomography (PET) studies and neuropsychological tests were performed in 16 aMCI patients (ten women, age 75 ± 8 years) and in 14 AD patients (ten women, age 75 ± 9 years). Comparisons between patient subgroups and with a control population were performed using Statistical Parametric Mapping. Clusters of low CMRGlu were observed bilaterally in the posterior cingulate cortex (PCC), in the precuneus, in the inferior parietal lobule and middle temporal gyrus of AD patients. In aMCI patients, reduced CMRGlu was found only in PCC. Areas of low CMRGlu in PCC were wider in AD compared to aMCI and extended to the precuneus, while low CMRGlu was found in the lateral parietal cortex in AD but not in aMCI patients. Individual subject pattern analysis revealed that 86% of AD patients had low CMRGlu in the PCC (including the precuneus in 71%), 71% in the temporal cortex, 64% in the parietal cortex and 35% in the frontal cortex. Among the aMCI patients, 56% had low CMRGlu in the PCC, 44% in the temporal cortex, 18% in the frontal cortex and none in the parietal cortex. This study demonstrates that both AD and aMCI patients have highly heterogeneous metabolic impairment. This potential of individual metabolic PET imaging in patients with AD and aMCI may allow timely identification of brain damage on individual basis and possibly help planning tailored early interventions. (orig.)

Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

Directory of Open Access Journals (Sweden)

Khedr LH

2015-11-01

Full Text Available Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally. Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c, caspase-3 (Casp-3, as well as nitric oxide metabolites (NOx were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001 as well as the changes in adenosine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001. Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression. Keywords: rats, CMS, hippocampus, paroxetine, apoptosis, adenine nucleotides, cytochrome-c, caspase-3

PubstractHelper: A Web-based Text-Mining Tool for Marking Sentences in Abstracts from PubMed Using Multiple User-Defined Keywords.

Science.gov (United States)

Chen, Chou-Cheng; Ho, Chung-Liang

2014-01-01

While a huge amount of information about biological literature can be obtained by searching the PubMed database, reading through all the titles and abstracts resulting from such a search for useful information is inefficient. Text mining makes it possible to increase this efficiency. Some websites use text mining to gather information from the PubMed database; however, they are database-oriented, using pre-defined search keywords while lacking a query interface for user-defined search inputs. We present the PubMed Abstract Reading Helper (PubstractHelper) website which combines text mining and reading assistance for an efficient PubMed search. PubstractHelper can accept a maximum of ten groups of keywords, within each group containing up to ten keywords. The principle behind the text-mining function of PubstractHelper is that keywords contained in the same sentence are likely to be related. PubstractHelper highlights sentences with co-occurring keywords in different colors. The user can download the PMID and the abstracts with color markings to be reviewed later. The PubstractHelper website can help users to identify relevant publications based on the presence of related keywords, which should be a handy tool for their research. http://bio.yungyun.com.tw/ATM/PubstractHelper.aspx and http://holab.med.ncku.edu.tw/ATM/PubstractHelper.aspx.

Mycorrhiza helper bacteria

Energy Technology Data Exchange (ETDEWEB)

Deveau, Aurelie [French National Insitute for Agricultural Research (INRA); Labbe, Jessy [ORNL

2016-10-01

This chapter focuses on the Mycorrhiza Helper Bacteria (MHB), a generic name given to bacteria which stimulate the formation of mycorrhizal symbiosis. By extension, some bacterial strains that positively impact the functioning of mycorrhizal symbiosis are also called MHB. These bacteria have applicative interests, as they indirectly improve the health and growth of tree seedlings. MHB are not restricted to a specific type of ecosystem, but are rather generalist in the way that they associate with both herbaceous and woody mycorrhizal plants from boreal, temperate, arid and tropical ecosystems. However, understanding the molecular mechanisms and their specificities will help us to know more about the ecology of the MHB. The process of acquisition varies between fungal species; while ectomycorrhizal fungi most probably recurrently acquire them from the environment, the association between bacterial endosymbionts and Glomeromycota probably dates back to very ancient times, and has since been vertically transmitted.

Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

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Jessica M. V. Pino

2017-05-01

Full Text Available Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR or with normal diet (CTL for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological

When helping helps: autonomous motivation for prosocial behavior and its influence on well-being for the helper and recipient.

Science.gov (United States)

Weinstein, Netta; Ryan, Richard M

2010-02-01

Self-determination theory posits that the degree to which a prosocial act is volitional or autonomous predicts its effect on well-being and that psychological need satisfaction mediates this relation. Four studies tested the impact of autonomous and controlled motivation for helping others on well-being and explored effects on other outcomes of helping for both helpers and recipients. Study 1 used a diary method to assess daily relations between prosocial behaviors and helper well-being and tested mediating effects of basic psychological need satisfaction. Study 2 examined the effect of choice on motivation and consequences of autonomous versus controlled helping using an experimental design. Study 3 examined the consequences of autonomous versus controlled helping for both helpers and recipients in a dyadic task. Finally, Study 4 manipulated motivation to predict helper and recipient outcomes. Findings support the idea that autonomous motivation for helping yields benefits for both helper and recipient through greater need satisfaction. Limitations and implications are discussed. Copyright 2009 APA, all rights reserved

Potential role of non-antibiotics (helper compounds) in the treatment of multidrug-resistant Gram-negative infections

DEFF Research Database (Denmark)

Martins, Marta; Dastidar, Sujata G; Fanning, Seamus

2008-01-01

that have been shown to be efflux pump inhibitors (EPIs) and which, if used as 'helper compounds' in combination with antibiotics to which the organism is initially resistant, may produce the required cure. Although not all of the EPIs may serve a helper role owing to their toxicity, they may nevertheless...

Systemic frequencies of T helper 1 and T helper 17 cells in patients with age-related macular degeneration: A case-control study

DEFF Research Database (Denmark)

Singh, Amardeep; Subhi, Yousif; Nielsen, Marie Krogh

2017-01-01

Age-related macular degeneration (AMD) is a degenerative disease of the retina and a leading cause of irreversible vision loss. We investigated the systemic differences in the frequency of T helper (Th) 1 and Th17 cells in patients with non-exudative and exudative AMD and compared to age...

Alteration patterns of brain glucose metabolism: comparisons of healthy controls, subjective memory impairment and mild cognitive impairment.

Science.gov (United States)

Song, In-Uk; Choi, Eun Kyoung; Oh, Jin Kyoung; Chung, Yong-An; Chung, Sung-Woo

2016-01-01

Some groups have focused on the detection and management of subjective memory impairment (SMI) as the stage that precedes mild cognitive impairment (MCI). However, there have been few clinical studies that have examined biomarkers of SMI to date. To investigate the differences in glucose metabolism as a prodromal marker of dementia in patients with SMI, MCI, and healthy controls using brain F-18 fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Sixty-eight consecutive patients with SMI, 47 patients with MCI, and 42 age-matched healthy subjects were recruited. All subjects underwent FDG-PET and detailed neuropsychological testing. FDG-PET images were analyzed using the statistical parametric mapping (SPM) program. FDG-PET analysis showed glucose hypometabolism in the periventricular regions of patients with SMI and in the parietal, precentral frontal, and periventricular regions of patients with MCI compared with healthy controls. Interestingly, hypometabolism on FDG-PET was noted in the parietal and precentral frontal regions in MCI patients compared to SMI patients. The results suggest that hypometabolism in the periventricular regions as seen on FDG-PET may play a role as a predictive biomarker of pre-dementia, and the extension of reduced glucose metabolism into parietal regions likely reflects progression of cognitive deterioration. © The Foundation Acta Radiologica 2014.

Geriatric Helper: An mHealth Application to Support Comprehensive Geriatric Assessment

Directory of Open Access Journals (Sweden)

Samuel Silva

2018-04-01

Full Text Available The Comprehensive Geriatric Assessment (CGA is a multidisciplinary diagnosis approach that considers several dimensions of fragility in older adults to develop an individualized plan to improve their overall health. Despite the evidence of its positive impact, CGA is still applied by a reduced number of professionals in geriatric care in many countries, mostly using a paper-based approach. In this context, we collaborate with clinicians to bring CGA to the attention of more healthcare professionals and to enable its easier application in clinical settings by proposing a mobile application, Geriatric Helper, to act as a pocket guide that is easy to update remotely with up-to-date information, and that acts as a tool for conducting CGA. This approach reduces the time spent on retrieving the scales documentation, the overhead of calculating the results, and works as a source of information for non-specialists. Geriatric Helper is a tool for the health professionals developed considering an iterative, User-Centred Design approach, with extensive contributions from a broad set of users including domain experts, resulting in a highly usable and accepted system. Geriatric Helper is currently being tested in Portuguese healthcare units allowing for any clinician to apply the otherwise experts-limited geriatric assessment.

Cholesterol metabolism as a prognostic marker in patients with mildly symptomatic nonischemic dilated cardiomyopathy.

Science.gov (United States)

Sawamura, Akinori; Okumura, Takahiro; Hiraiwa, Hiroaki; Aoki, Soichiro; Kondo, Toru; Ichii, Takeo; Furusawa, Kenji; Watanabe, Naoki; Kano, Naoaki; Fukaya, Kenji; Morimoto, Ryota; Bando, Yasuko K; Murohara, Toyoaki

2017-06-01

Little is known about whether the alteration of cholesterol metabolism reflects abdominal organ impairments due to heart failure. Therefore, we investigated the prognostic value of cholesterol metabolism by evaluating serum campesterol and lathosterol levels in patients with early-stage nonischemic dilated cardiomyopathy (NIDCM). We enrolled 64 patients with NIDCM (median age 57.5 years, 31% female) with New York Heart Association functional class I/II. Serum campesterol and lathosterol levels were measured in all patients. The patients were then divided into four subsets based on the median non-cholesterol sterol levels (campesterol 3.6μg/mL, lathosterol 1.4μg/mL): reference (R-subset), high-campesterol/high-lathosterol; absorption-reduced (A-subset), low-campesterol/high-lathosterol; synthesis-reduced (S-subset), high-campesterol/low-lathosterol; double-reduced (D-subset), low-campesterol/low-lathosterol. Endpoint was a composite of cardiac events, including cardiac-related death, hospitalization for worsening heart failure, and lethal arrhythmia. Median brain natriuretic peptide (BNP) level was 114pg/mL. Mean left ventricular ejection fraction was 31.4%. D-subset had the lowest total cholesterol level and cardiac index and the highest BNP level and pulmonary capillary wedge pressure. D-subset also had the highest cardiac event rate during the mean 3.8 years of follow-up (log-rank p=0.001). Multivariate regression analysis showed that D-subset was an independent determinant of cardiac events. The receiver operating characteristic curve analysis revealed that total cholesterol cholesterol absorption and liver synthesis predicts future cardiac events in patients with mildly symptomatic NIDCM. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Effects of Aerobic Training on Cognition and Brain Glucose Metabolism in Subjects with Mild Cognitive Impairment.

Science.gov (United States)

Porto, Fábio Henrique de Gobbi; Coutinho, Artur Martins Novaes; Pinto, Ana Lucia de Sá; Gualano, Bruno; Duran, Fabio Luís de Souza; Prando, Silvana; Ono, Carla Rachel; Spíndola, Lívia; de Oliveira, Maira Okada; do Vale, Patrícia Helena Figuerêdo; Nitrini, Ricardo; Buchpiguel, Carlos Alberto; Brucki, Sonia Maria Dozzi

2015-01-01

Aerobic training (AT) is a promising intervention for mild cognitive impairment (MCI). To evaluate the effects of AT on cognition and regional brain glucose metabolism (rBGM) in MCI patients. Subjects performed a twice-a-week, moderate intensity, AT program for 24 weeks. Assessment with ADAS-cog, a comprehensive neuropsychological battery, and evaluation of rBGM with positron emission tomography with 18F-fluorodeoxyglucose ([18F]FDG-PET) were performed before and after the intervention. Aerobic capacity was compared using the maximal oxygen consumption VO2max (mL/Kg/min). [18F]FDG-PET data were analyzed on a voxel-by-voxel basis with SPM8 software. Forty subjects were included, with a mean (M) age of 70.3 (5.4) years and an initial Mini-Mental State Exam score of 27.4 (1.7). Comparisons using paired t-tests revealed improvements in the ADAS-cog (M difference: -2.7 (3.7), p <  0.001) and VO2max scores (M difference: 1.8 (2.0) mL/kg/min, p <  0.001). Brain metabolic analysis revealed a bilateral decrease in the rBGM of the dorsal anterior cingulate cortex, pFWE = 0.04. This rBGM decrease was negatively correlated with improvement in a visuospatial function/attentional test (rho =-0.31, p = 0.04). Several other brain areas also showed increases or decreases in rBGM. Of note, there was an increase in the retrosplenial cortex, an important node of the default mode network, that was negatively correlated with the metabolic decrease in the dorsal anterior cingulate cortex (r =-0.51, p = 0.001). AT improved cognition and changed rBGM in areas related to cognition in subjects with MCI.

Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity

NARCIS (Netherlands)

L.Y.A. Chai (Louis); F. van de Veerdonk (Frank); R.J. Marijnissen (Renoud); S.C. Cheng (Shih-Chin); A.L. Khoo; M. Hectors (Magda); K. Lagrou (Katrien); A.G. Vonk (Alieke); J. Maertens (Johan); L.A.B. Joosten (Leo); B.J. Kullberg (Bart Jan); M.G. Netea (Mihai)

2010-01-01

textabstractSummary Both interferon-γ-producing type 1 T helper (Th1)- and interleukin-17 (IL-17)-producing Th17 cells have been proposed to be involved in anti-fungal host defence. Although invasive aspergillosis is one of the most severe human fungal infections, little is known regarding the

Females increase reproductive investment in response to helper-mediated improvements in allo-feeding, nest survival, nestling provisioning and post-fledging survival in the Karoo scrub-robin Cercotrichas coryphaeus

Science.gov (United States)

Lloyd, P.; Andrew, Taylor W.; du Plessis, Morné A.; Martin, T.E.

2009-01-01

In many cooperatively-breeding species, the presence of one or more helpers improves the reproductive performance of the breeding pair receiving help. Helper contributions can take many different forms, including allo-feeding, offspring provisioning, and offspring guarding or defence. Yet, most studies have focussed on single forms of helper contribution, particularly offspring provisioning, and few have evaluated the relative importance of a broader range of helper contributions to group reproductive performance. We examined helper contributions to multiple components of breeding performance in the Karoo scrub-robin Cercotrichas coryphaeus, a facultative cooperative breeder. We also tested a prediction of increased female investment in reproduction when helpers improve conditions for rearing young. Helpers assisted the breeding male in allo-feeding the incubating female, increasing allo-feeding rates. Greater allo-feeding correlated with greater female nest attentiveness during incubation. Nest predation was substantially lower among pairs breeding with a helper, resulting in a 74% increase in the probability of nest survival. Helper contributions to offspring provisioning increased nestling feeding rates, resulting in a reduced incidence of nestling starvation and increased nestling mass. Nestling mass had a strong, positive effect on post-fledging survival. Controlling for female age and habitat effects, annual production of fledged young was 130% greater among pairs breeding with a helper, and was influenced most strongly by helper correlates with nest survival, despite important helper effects on offspring provisioning. Females breeding with a helper increased clutch size, supporting the prediction of increased female investment in reproduction in response to helper benefits. ?? 2009 J. Avian Biol.

The helper component-proteinase of cowpea aphid-borne mosaic virus

NARCIS (Netherlands)

Mlotshwa, S.

2000-01-01

Cowpea aphid-borne mosaic potyvirus causes severe yield losses in cowpea, an important legume crop in semi-arid regions of Africa. We have elucidated the genomic sequence of the virus and subsequently focused our attention on the so-called helper component-proteinase (HC-Pro), a

Natural Helpers: A Study of Primary Caregivers among Migrant Women.

Science.gov (United States)

Greenfield, Wilma L.

Natural helpers exist even among the most oppressed populations in this country, particularly migrant women, and recognition of their helping networks can give professional caregivers access to a resource that is often more adaptive, more efficient, and more humane than many static, impersonal, and obsolete human service bureaucracies. Migrant…

The progress of functional neuroimaging in the study of mild cognitive impairment

International Nuclear Information System (INIS)

Li Zugui

2006-01-01

Mild cognitive impairment (MCI) represents a transitional state between healthy aging and very mild Alzheimer's disease. MCI patients have a substantially higher rate of progression to Alzheimer's disease compared with cognitively normal elderly people. Functional neutroimaging modalities, including PET, SPECT and functional MRI show that MCI patients have special abnormalities in brain metabolism and perfusion, so they can offer great value in the predicting cognitive decline and early diagnosis of dementia. (authors)

The figure of the helper advisor in cases of sexual abuse against people with intellectual disabilities

Directory of Open Access Journals (Sweden)

Almudena MARTORELL CAFRANGA

2017-09-01

Full Text Available In this paper we analyse the main barriers that people with intellectual disabilities who have suffered sexual abuse have to face when they access the Justice system. Regarding these barriers, the Victim Support Unit for People with Intellectual Disabilities of the Fundación Carmen Pardo-Valcarce proposes the inclusion in the judicial process of a helper advisor. The entry into force in 2015 of the Law 4/2015, in 27 April, the Statute of the crime victim represents an exemplary opportunity to ensure the incorporation of support proposals involving the insertion of the helper advisor in the judicial process in cases where the victim is a person with intellectual disabilities. In this paper we analyse the impact of the helper advisor, with particular emphasis on cases that have been dismissed under instruction.

Contaminants and energy expenditure in an Arctic seabird: Organochlorine pesticides and perfluoroalkyl substances are associated with metabolic rate in a contrasted manner.

Science.gov (United States)

Blévin, Pierre; Tartu, Sabrina; Ellis, Hugh I; Chastel, Olivier; Bustamante, Paco; Parenteau, Charline; Herzke, Dorte; Angelier, Frédéric; Gabrielsen, Geir W

2017-08-01

Basal metabolic rate (BMR), the minimal energetic cost of living in endotherms, is known to be influenced by thyroid hormones (THs) which are known to stimulate in vitro oxygen consumption of tissues in birds and mammals. Several environmental contaminants may act on energy expenditure through their thyroid hormone-disrupting properties. However, the effect of contaminants on BMR is still poorly documented for wildlife. Here, we investigated the relationships between three groups of contaminants (organochlorines (OCs), perfluoroalkyl substances (PFASs), and mercury) with metabolic rate (MR), considered here as a proxy of BMR and also with circulating total THs (thyroxine (TT4) and triiodothyronine (TT3)) in Arctic breeding adult black-legged kittiwakes (Rissa tridactyla) from Svalbard, during the chick rearing period. Our results indicate a negative relationship between the sum of all detected chlordanes (∑CHLs) and MR in both sexes whereas perfluorotridecanoate (PFTrA) and MR were positively related in females only. MR was not associated with mercury. Additionally, levels of TT3 were negatively related to ∑CHLs but not to PFTrA. The findings from the present study indicate that some OCs (in both sexes) and some PFASs (only in females) could disrupt fine adjustment of BMR during reproduction in adult kittiwakes. Importantly, highly lipophilic OCs and highly proteinophilic PFASs appear, at least in females, to have the ability to disrupt the metabolic rate in an opposite way. Therefore, our study highlights the need for ecotoxicological studies to include a large variety of contaminants which can act in an antagonistic manner. Copyright © 2017 Elsevier Inc. All rights reserved.

Visual rating of medial temporal lobe metabolism in mild cognitive impairment and Alzheimer's disease using FDG-PET

International Nuclear Information System (INIS)

Mosconi, Lisa; Santi, Susan De; Li, Yi; Li, Juan; Zhan, Jiong; Boppana, Madhu; Tsui, Wai Hon; Leon, Mony J. de; Pupi, Alberto

2006-01-01

This study was designed to examine the utility of visual inspection of medial temporal lobe (MTL) metabolism in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) using FDG-PET scans. Seventy-five subjects [27 normal controls (NL), 26 MCI, and 22 AD] with FDG-PET and MRI scans were included in this study. We developed a four-point visual rating scale to evaluate the presence and severity of MTL hypometabolism on FDG-PET scans. The visual MTL ratings were compared with quantitative glucose metabolic rate (MR glc ) data extracted using regions of interest (ROIs) from the MRI-coregistered PET scans of all subjects. A standard rating evaluation of neocortical hypometabolism was also completed. Logistic regressions were used to determine and compare the diagnostic accuracy of the MTL and cortical ratings. For both MTL and cortical ratings, high intra- and inter-rater reliabilities were found (p values glc measures (p values <0.001). The combination of MTL and cortical ratings significantly improved the diagnostic accuracy over the cortical rating alone, with 100% of AD, 77% of MCI, and 85% of NL cases being correctly identified. This study shows that the visual rating of MTL hypometabolism on PET is reliable, yields a diagnostic accuracy equal to the quantitative ROI measures, and is clinically useful and more sensitive than cortical ratings for patients with MCI. We suggest this method be further evaluated for its potential in the early diagnosis of AD. (orig.)

Increased susceptibility of dystrophin-deficient brain to mild hypoxia

International Nuclear Information System (INIS)

Wallis, T.; Rae, C.; Bubb, W.A.; Head, S.I.

2002-01-01

Full text: Duchenne muscular dystrophy is an X-linked disorder resulting from total absence of the 427 kDa protein dystrophin. Dystrophin is normally expressed in the brain mainly in a neuronal subpopulation: cortical pyramidal cells, hippocampal CA1 neurons and cerebellar Purkinje cells. One suggested role for dystrophin is in colocalising mitochondrial creatine kinase with ADP translocase and ATP synthase in mitochondria. Brain tissue slices in the murine model of Duchenne dystrophy, the mdx mouse, have been shown to be more sensitive to hypoxia than control. In this work, we used 13 C NMR to monitor the metabolic response of mdx cortical brain tissue slices to normoxia (95%O 2 /5% CO 2 ) and mild hypoxia (95%air/5% CO 2 ). Under normoxic conditions, mdx cortical slices displayed increased net flux through the Krebs cycle and glutamate/glutamine cycle, consistent with the proposed GABA A lesion which results in decreased inhibitory input. By contrast, mild hypoxia resulted in a significant increase in the total pool size of lactate and decreased net flux of 13 C from [3- 13 C]pyruvate into glutamate C4, GABA C2 and Ala C2, as well as decreased anaplerotic activity as measured by the ratio of Asp C2: Asp C3 label. Mild hypoxia has a significantly greater effect on brain oxidative metabolism in mdx mice, than in control

The frequency and severity of metabolic acidosis related to topiramate.

Science.gov (United States)

Türe, Hatice; Keskin, Özgül; Çakır, Ülkem; Aykut Bingöl, Canan; Türe, Uğur

2016-12-01

Objective We planned a cross-sectional analysis to determine the frequency and severity of metabolic acidosis in patients taking topiramate while awaiting craniotomy. Methods Eighty patients (18 - 65 years) taking topiramate to control seizures while awaiting elective craniotomy were enrolled. Any signs of metabolic acidosis or topiramate-related side effects were investigated. Blood chemistry levels and arterial blood gases, including lactate, were obtained. The severity of metabolic acidosis was defined according to base excess levels as mild or moderate. Results Blood gas analysis showed that 71% ( n = 57) of patients had metabolic acidosis. The frequency of moderate metabolic acidosis was 56% ( n = 45), while that of mild metabolic acidosis was 15% ( n = 12). A high respiratory rate was reported in only 10% of moderately acidotic patients. Conclusions In patients receiving topiramate, baseline blood gas analysis should be performed preoperatively to determine the presence and severity of metabolic acidosis.

[Perspective of peer helpers regarding their experience animating a self-treatment program for panic disorders].

Science.gov (United States)

Perreault, Michel; Bouchard, Stéphane; Lapalme, Micheline; Laverdure, Anick; Audet, Denis; Cusson, Jean-Claude; Zacchia, Camillo; Milton, Diana; Sam Tion, Michaël; Chartier-Otis, Mariko; Marchand, André; Bélanger, Claude

2015-01-01

Support groups can help to reach individuals with anxiety disorders who are not or are only partly obtaining health services. The present study is based on a program that involves peer helpers as animators of a self-treatment group (Zéro-ATAQ). Their perspective has been documented in order to identify the aspects of the program which can be improved. Eleven peer helpers led the 12 sessions of the program, which was dispensed in four regions of Quebec for 32 persons having panic disorders with agoraphobia. The perspectives of ten peer animators were documented based on a semi-structured interview that took place at the end of the program, and a focus group that was held over six months later with peer animators from each of the groups. Their comments were transcribed and a thematic content analysis was conducted. All of the peer helper animators reported that they enjoyed participating in the program, that they appreciated being able to help others having an anxiety disorder, and that the program helped them in their role as animators of these types of activities. Nearly all of the peer helpers emphasized the importance of being able to count on the supervision of a professional when needed. This study revealed (1) the feasibility of implementing a program of this kind in partnership with peers, (2) the qualifications necessary to lead this type of program, (3) the requirements in terms of training and available material, and (4) the importance of supervision.

T Helper 17 Cells Interplay with CD4+CD25highFoxp3+ Tregs in Regulation of Inflammations and Autoimmune Diseases

Science.gov (United States)

Mai, Jietang; Wang, Hong; Yang#, Xiao-Feng

2010-01-01

Interleukin-17 (IL-17)-secreting T helper 17 cells (Th17) are a recently identified CD4+ T helper subset that has been implicated in various inflammatory and autoimmune diseases. Th17, along with CD4+CD25high Foxp3+ regulatory T cells (Tregs) and other newly emergent T helper subsets, Th9 and Tfh, have expanded the Th1-Th2 paradigm. Although this newly proposed six-subset paradigm significantly improved our understanding on the differentiation of CD4+ T helper cell subsets and the regulation of T helper cells in inflammation and autoimmunity, many questions remain to be answered. In this overview, we will briefly review the following issues: a) Old Th1-Th2 paradigm versus new multi-subset paradigm; b) Structural features of IL-17 family cytokines; c) Th17 cells; d) Effects of IL-17 on various cell types and tissues; e) IL-17 receptor and signaling pathways; f) Th17-mediated inflammations; and g) Protective mechanisms of IL-17 in infections. Lastly, we will look into the interaction of Th17 and Treg in autoimmune diseases and inflammation: Th17 cells interplay with Tregs. Regulation of autoimmunity and inflammation lies in the interplays of the different T helper subsets, therefore, better understanding of these subsets’ interactions with one another would greatly improve our approaches in developing therapy to combat inflammatory and autoimmune diseases. PMID:20515737

Preschoolers' social and moral judgments of third-party helpers and hinderers align with infants' social evaluations.

Science.gov (United States)

Van de Vondervoort, Julia W; Hamlin, J Kiley

2017-12-01

Two experiments explored preschoolers' social preferences and moral judgments of prosocial and antisocial others. In Experiment 1, 3- to 5-year-olds (N=74) observed helping and hindering scenarios previously used to explore sociomoral evaluation in preverbal infants. Whereas 3-year-olds in Experiment 1 did not reliably distinguish between the helper and hinderer when reporting social preferences or moral judgments, both 4- and 5-year-olds preferred the helper, judged the helper to be "nicer" than the hinderer, selectively allocated punishment to the hinderer, and were able to justify their punishment allocations. A simplified procedure and the addition of comprehension questions in Experiment 2 (N=24) improved 3-year-olds' performance, suggestive that their performance in Experiment 1 was likely due to processing or memory difficulties rather than an inability to engage in explicit social and moral evaluation. These studies reveal that young children readily interpret helping and hindering scenarios as socially and morally relevant. Copyright © 2017 Elsevier Inc. All rights reserved.

Model-based investigation of intracellular processes determining antibody Fc-glycosylation under mild hypothermia.

Science.gov (United States)

Sou, Si Nga; Jedrzejewski, Philip M; Lee, Ken; Sellick, Christopher; Polizzi, Karen M; Kontoravdi, Cleo

2017-07-01

Despite the positive effects of mild hypothermic conditions on monoclonal antibody (mAb) productivity (q mAb ) during mammalian cell culture, the impact of reduced culture temperature on mAb Fc-glycosylation and the mechanism behind changes in the glycan composition are not fully established. The lack of knowledge about the regulation of dynamic intracellular processes under mild hypothermia restricts bioprocess optimization. To address this issue, a mathematical model that quantitatively describes Chinese hamster ovary (CHO) cell behavior and metabolism, mAb synthesis and mAb N-linked glycosylation profile before and after the induction of mild hypothermia is constructed. Results from this study show that the model is capable of representing experimental results well in all of the aspects mentioned above, including the N-linked glycosylation profile of mAb produced under mild hypothermia. Most importantly, comparison between model simulation results for different culture temperatures suggests the reduced rates of nucleotide sugar donor production and galactosyltransferase (GalT) expression to be critical contributing factors that determine the variation in Fc-glycan profiles between physiological and mild hypothermic conditions in stable CHO transfectants. This is then confirmed using experimental measurements of GalT expression levels, thereby closing the loop between the experimental and the computational system. The identification of bottlenecks within CHO cell metabolism under mild hypothermic conditions will aid bioprocess optimization, for example, by tailoring feeding strategies to improve NSD production, or manipulating the expression of specific glycosyltransferases through cell line engineering. Biotechnol. Bioeng. 2017;114: 1570-1582. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals Inc. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals Inc.

Epidermal filaggrin deficiency mediates increased systemic T-helper 17 immune response

DEFF Research Database (Denmark)

Bonefeld, C. M.; Petersen, T. H.; Bandier, J.

2016-01-01

Background: Cellular T-helper (Th)17 infiltrates dominate skin inflammation in filaggrin-deficient flaky tail (ft/ft) mice, and Th17 cells are found in both the skin and blood of patients with acute atopic dermatitis. However, the potential role of loss-of-function mutations in the filaggrin gene...

T-helper cytokine patterns and related antibodies in patients with gestational diabetes mellitus

Directory of Open Access Journals (Sweden)

Etaati Z

2012-04-01

Conclusion: The changes in T-helper 1 and 2 associated antibodies and cytokines are not associated with gestational diabetes mellitus and could not be considered as a predictor for gestational diabetes mellitus.

Single-Cell RNA Sequencing Reveals T Helper Cells Synthesizing Steroids De Novo to Contribute to Immune Homeostasis

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Bidesh Mahata

2014-05-01

Full Text Available T helper 2 (Th2 cells regulate helminth infections, allergic disorders, tumor immunity, and pregnancy by secreting various cytokines. It is likely that there are undiscovered Th2 signaling molecules. Although steroids are known to be immunoregulators, de novo steroid production from immune cells has not been previously characterized. Here, we demonstrate production of the steroid pregnenolone by Th2 cells in vitro and in vivo in a helminth infection model. Single-cell RNA sequencing and quantitative PCR analysis suggest that pregnenolone synthesis in Th2 cells is related to immunosuppression. In support of this, we show that pregnenolone inhibits Th cell proliferation and B cell immunoglobulin class switching. We also show that steroidogenic Th2 cells inhibit Th cell proliferation in a Cyp11a1 enzyme-dependent manner. We propose pregnenolone as a “lymphosteroid,” a steroid produced by lymphocytes. We speculate that this de novo steroid production may be an intrinsic phenomenon of Th2-mediated immune responses to actively restore immune homeostasis.

[Development of Patient Transfer Techniques based on Postural-stability Principles for the Care Helpers in Nursing Homes and Evaluation of Effectiveness].

Science.gov (United States)

Ma, Ryewon; Jung, Dukyoo

2016-02-01

This study was done to develop a postural-stability patient transfer technique for care helpers in nursing homes and to evaluate its effectiveness. Four types of patient transfer techniques (Lifting towards the head board of the bed, turning to the lateral position, sitting upright on the bed, transferring from wheel chair to bed) were practiced in accordance with the following three methods; Care helpers habitually used transfer methods (Method 1), patient transfer methods according to care helper standard textbooks (Method 2), and a method developed by the author ensuring postural-stability (Method 3). The care helpers' muscle activity and four joint angles were measured. The collected data were analyzed using the program SPSS Statistic 21.0. To differentiate the muscle activity and joint angle, the Friedman test was executed and the post-hoc analysis was conducted using the Wilcoxon Signed Rank test. Muscle activity was significantly lower during Method 3 compared to Methods 1 and 2. In addition, the joint angle was significantly lower for the knee and shoulder joint angle while performing Method 3 compared to Methods 1 and 2. Findings indicate that using postural-stability patient transfer techniques can contribute to the prevention of musculoskeletal disease which care helpers suffer from due to physically demanding patient care in nursing homes.

[Chronic mild inflammation links obesity, metabolic syndrome, atherosclerosis and diabetes].

Science.gov (United States)

Andel, M; Polák, J; Kraml, P; Dlouhý, P; Stich, V

2009-01-01

Chronic low grade inflammation is relatively new concept in metabolic medicine. This concept describes the relations between the inflammation and adipose tissue, insulin resistence, atherosclerosis and type 2 diabetes mellitus. Macrophages and lymphocytes deposed in adipose tissue produce proinflammatory cytokines which directly or through the CRP liver secretion are targeting endothelial cells, hepatocytes and beta cells of Langerhans islets of pancreas. The dysfunction of these cells follows often further disturbances and in case of beta cells - the cell death. The connection between the adipose tissue insulin resistence, atherosclerosis and type 2 diabetes was earlier described with endocrine and metabolic descriptors. The concept of chronic low grade inflammation creates also another description of multilateral connections in metabolic syndome. The salicylates and the drugs related to them seem to have some glucose lowering properties. The recent development in the field ofchronic low grade inflammation represents also certain therapeutic hope for antiinflammatory intervention in type 2 diabetes.

Going “old school”: From bedside manner to deskside manner

Directory of Open Access Journals (Sweden)

David Fleischman

2015-08-01

Full Text Available Interaction between tertiary educators and students, we contend, improves trust and betters student responses to emotional distress while at university. Therefore, we introduce the “Deskside Manner Framework” as an emerging practice in the tertiary teaching and learning context to aid student transition success. Based on concepts and practice that originated primarily in the medical profession and later in other high credence professional contexts, the deskside manner framework includes: show respect, critical listening, the four Bs and follow up. Deskside manner is transferrable and we aim to facilitate it through workshops and by developing a digital repository of educator-student interaction stories.  

Rat eosinophils stimulate the expansion of Cryptococcus neoformans-specific CD4+ and CD8+ T cells with a T-helper 1 profile

Science.gov (United States)

Garro, Ana P; Chiapello, Laura S; Baronetti, José L; Masih, Diana T

2011-01-01

Experimental Cryptococcus neoformans infection in rats has been shown to have similarities with human cryptococcosis, revealing a strong granulomatous response and a low susceptibility to dissemination. Moreover, it has been shown that eosinophils are components of the inflammatory response to C. neoformans infections. In this in vitro study, we demonstrated that rat peritoneal eosinophils phagocytose opsonized live yeasts of C. neoformans, and that the phenomenon involves the engagement of FcγRII and CD18. Moreover, our results showed that the phagocytosis of opsonized C. neoformans triggers eosinophil activation, as indicated by (i) the up-regulation of major histocompatibility complex (MHC) class I, MHC class II and costimulatory molecules, and (ii) an increase in interleukin (IL)-12, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production. However, nitric oxide (NO) and hydrogen peroxide (H2O2) synthesis by eosinophils was down-regulated after interaction with C. neoformans. Furthermore, this work demonstrated that CD4+ and CD8+ T lymphocytes isolated from spleens of infected rats and cultured with C. neoformans-pulsed eosinophils proliferate in an MHC class II- and class I-dependent manner, respectively, and produce important amounts of T-helper 1 (Th1) type cytokines, such as TNF-α and IFN-γ, in the absence of T-helper 2 (Th2) cytokine synthesis. In summary, the present study demonstrates that eosinophils act as fungal antigen-presenting cells and suggests that C. neoformans-loaded eosinophils might participate in the adaptive immune response. PMID:21039463

Error checking and near matching in helper data systems for biometric authentication

NARCIS (Netherlands)

Papatsimpa, Charikleia; Linnartz, Jean-Paul; de Groot, Joep; Skoric, B.; Ignatenko, T.

2014-01-01

Helper data systems mitigate the risk that biometric templates are stolen from a biometric data base. Yet, current systems face the drawback that strong Error Correction is needed in order to mitigate variations in the measured biometric during verification. Error correction codes are not always

T-Helper Subsets Cytokine Production in Kidney Transplant Recipients: Diverting Influences and Impact on Graft Outcome

Directory of Open Access Journals (Sweden)

Hassan A

2000-01-01

Full Text Available A large body of evidence suggests the existence of functionally polarized human T-helper responses based on their profile of cytokine secretion. Human T-helper cell clones can be divided into two mutually exclusive subsets, T-helper cell 1 (Th1 and T-helper cell 2 (Th2. Substantial work in several animal models has demonstrated that allograft rejection is associated with enhanced Th1 activity and tolerance with enhanced Th2. Some studies have not been consistent with this association. In this study, gamma interferon (INF-y and interleukin 4 (IL-4 levels (as indicators of Th1 and Th2 activity, respectively were assayed in supernatant of cultured peripheral lymphocytes. The levels of these cytokines were compared between a study group of 26 stable kidney transplant recipients immunosuppressed with cyclosporine A, corticosteroids and azathioprine or mycophenolate mofetil, and a control group of 10 healthy blood donors. The mean INF-γ and IL-4 levels in the control group were considered as the cutoff levels for comparison. Our results showed that 25/26 of the study patients (96% had low levels of INF-γ compared to 4/10 of the control subjects (40%, (P< 0.05. However, the IL-4 level was high in 10/26 of the study patients (38% and 3/10 of the control subjects (30%, not a statistically significant difference, (P>0.05. In conclusion: These results suggest that well-established graft tolerance may be mediated via depressed Th1 activity rather than enhanced Th2 activity.

Morphine Suppresses T helper Lymphocyte Differentiation to Th1 Type Through PI3K/AKT Pathway.

Science.gov (United States)

Mao, Mao; Qian, Yanning; Sun, Jie

2016-04-01

To investigate the effect of morphine on T helper lymphocyte differentiation and PI3K/AKT pathway mechanism, CD4+ lymphocytes were treated by phorbol-myristate-acetate (25 ng/ml) (PMA) plus ionomycin (1 μg/ml) in the presence of various concentrations of morphine (25, 50, 100, 200 ng/ml) for 4 h. Th1 and Th2 subsets, supernatant cytokines, and PI3K, AKT, and protein kinase C-theta (PKC-θ) levels were detected. The Th1 cell percentage, Th1-derived cytokines, and ratio of Th1/Th2 decreased in the presence of morphine in a concentration-dependent manner. However, Th2 cell percentage kept stable after morphine treatment. The phosphorylation of PI3K and AKT decreased, but the phosphorylation of PKC-θ did not change in the presence of morphine. The decreased percentage of Th1 cells and ratio of Th1/Th2 was recovered by naloxone concentration-dependently. Morphine can inhibit the differentiation of Th1 lymphocytes and decrease the ratio of Th1/Th2 via the pathway of PI3K/AKT. The effect can be inhibited by naloxone.

Chronic Mild Cold Conditioning Modulates the Expression of Hypothalamic Neuropeptide and Intermediary Metabolic-Related Genes and Improves Growth Performances in Young Chicks.

Directory of Open Access Journals (Sweden)

Phuong Nguyen

Full Text Available Low environmental temperatures are among the most challenging stressors in poultry industries. Although landmark studies using acute severe cold exposure have been conducted, still the molecular mechanisms underlying cold-stress responses in birds are not completely defined. In the present study we determine the effect of chronic mild cold conditioning (CMCC on growth performances and on the expression of key metabolic-related genes in three metabolically important tissues: brain (main site for feed intake control, liver (main site for lipogenesis and muscle (main site for thermogenesis.80 one-day old male broiler chicks were divided into two weight-matched groups and maintained in two different temperature floor pen rooms (40 birds/room. The temperature of control room was 32°C, while the cold room temperature started at 26.7°C and gradually reduced every day (1°C/day to reach 19.7°C at the seventh day of the experiment. At day 7, growth performances were recorded (from all birds and blood samples and tissues were collected (n = 10. The rest of birds were maintained at the same standard environmental condition for two more weeks and growth performances were measured.Although feed intake remained unchanged, body weight gain was significantly increased in CMCC compared to the control chicks resulting in a significant low feed conversion ratio (FCR. Circulating cholesterol and creatine kinase levels were higher in CMCC chicks compared to the control group (P<0.05. CMCC significantly decreased the expression of both the hypothalamic orexigenic neuropeptide Y (NPY and anorexigenic cocaine and amphetamine regulated transcript (CART in chick brain which may explain the similar feed intake between the two groups. Compared to the control condition, CMCC increased the mRNA abundance of AMPKα1/α2 and decreased mTOR gene expression (P<0.05, the master energy and nutrient sensors, respectively. It also significantly decreased the expression of fatty

The Microbiota and Epigenetic Regulation of T Helper 17/Regulatory T Cells

DEFF Research Database (Denmark)

Luo, Annie; Leach, Steven T; Barres, Romain

2017-01-01

Immune cells not only affect tissue homeostasis at the site of inflammation but also exert systemic effects contributing to multiple chronic conditions. Recent evidence clearly supports an altered T helper 17/regulatory T cell (Th17/Treg) balance leading to the development and progression of infl...

VICTORIA PARK: A DEMOCTRATIC PUBLIC OPEN SPACE FOR INDONESIA DOMESTIC HELPERS (TKW

Directory of Open Access Journals (Sweden)

Parmonangan Manurung

2016-01-01

Full Text Available Victoria Park is the largest city park in Hong Kong. This city park is not only known in Hong Kong, but also very well known in Indonesia as a gathering place for Indonesia domestic helpers (TKW in Hong Kong. This research tried to find out some determinant factors that have been affected the public open spac of Victoria Park to be a gathering place for thousands of TKW in Sunday and holidays as their day off. In order to get the results of research, some methodological research had been conducted such as: observation (survey, mapping, interviews and literature studies. The results showed that Victoria Park has a number of factors capable of meeting the needs of domestic help-ers in Hong Kong, these factors consist of internal factors and external factors. Internally, the character and functions held Victoria Park became a very influential factor, while externally, the accessibility and support functions around Victoria Park also has a considerable influence.

Chemical constraints governing the origin of metabolism: the thermodynamic landscape of carbon group transformations under mild aqueous conditions

Science.gov (United States)

Weber, Arthur L.

2002-01-01

The thermodynamics of organic chemistry under mild aqueous conditions was examined in order to begin to understand its influence on the structure and operation of metabolism and its antecedents. Free energies (deltaG) were estimated for four types of reactions of biochemical importance carbon-carbon bond cleavage and synthesis, hydrogen transfer between carbon groups, dehydration of alcohol groups, and aldo-keto isomerization. The energies were calculated for mainly aliphatic groups composed of carbon, hydrogen, and oxygen. The energy values showed (1) that generally when carbon-carbon bond cleavage involves groups from different functional group classes (i.e., carboxylic acids, carbonyl groups, alcohols, and hydrocarbons), the transfer of the shared electron-pair to the more reduced carbon group is energetically favored over transfer to the more oxidized carbon group, and (2) that the energy of carbon-carbon bond transformation is primarily determined by the functional group class of the group that changes oxidation state in the reaction (i.e., the functional group class of the group that donates the shared electron-pair during cleavage, or that accepts the incipient shared electron-pair during synthesis). In contrast, the energy of hydrogen transfer between carbon groups is determined by the functional group class of both the hydrogen-donor group and the hydrogen-acceptor group. From these and other observations we concluded that the chemistry involved in the origin of metabolism (and to a lesser degree modern metabolism) was strongly constrained by (1) the limited redox-based transformation energy of organic substrates that is readily dissipated in a few energetically favorable irreversible reactions; (2) the energy dominance of a few transformation half-reactions that determines whether carbon-carbon bond transformation (cleavage or synthesis) is energetically favorable (deltaG +3.5 kcal/mol); and (3) the dependence of carbon group transformation energy on the

SU-E-T-218: The IHE-RO Helper Tool: Demonstrating the Connectivity Issues Solved by IHE-RO.

Science.gov (United States)

Kapoor, Rishabh; Yeung, Daniel; Kumar, Sabari Ajay; Alex, Daley; Kapur, Priyanka; Palta, Jatinder

2012-06-01

To develop a Web-based application (IHE-RO Helper) to allow comprehensive review of the interconnectivity and interoperability of various radiotherapy devices established through testing sanctioned by the Integrating Healthcare Enterprise-Radiation Oncology (IHE-RO). IHE-RO is an initiative sponsored by ASTRO to improve the way computer based systems in radiation oncology share information using well-defined data exchange standards (DICOM / HL7). At the IHE-RO Connectathon events over the last 4 years, 11 vendors with 14 different products have successfully tested and identified solutions to connectivity problems in treatment planning, simulation and delivery. Because the test results are highly technical, the interconnectivity issues amongst the RT devices may get overlooked by the end users. The IHE-RO helper tool is designed to operate in simple clinical terms with queries and presentations organized based on treatment techniques and clinical features that are familiar to the practitioners. For example, if you are planning to purchase a treatment planning system capable of generating plans (e.g. Stereotactic treatments) and are concerned whether the TPS can successfully transfer such data to your treatment management system (TMS) and subsequently to your treatment delivery system (TDS), the IHE-RO Helper can identify the connectivity requirements and list vendors that have successfully passed an IHE-RO Connectathon and validated their solution to the specific requirements. The IHE-RO helper tool provides a graphical and textual user interface to effectively demonstrate the solved interconnectivity problems between TPS, TMS and TDS. A report is also provided that explains the interconnectivity problems and its solutions. The IHE-RO helper is an effective tool to clearly identify vendor products that are IHE-RO compliant, thereby encourages vendor participation in testing and validation. Such a tool will be invaluable in procurement of new equipment to ensure a

Examining Live-In Foreign Domestic Helpers as a Coping Resource for Family Caregivers of People With Dementia in Singapore.

Science.gov (United States)

Basnyat, Iccha; Chang, Leanne

2017-09-01

In Singapore, the responsibility of caring for persons with dementia falls on family members who cope with a long-term caregiver burden, depending on available support resources. Hiring foreign domestic workers to alleviate caregiver burden becomes a prevalent coping strategy that caregivers adopt. This strategy allows caregivers to provide home care as part of fulfilling family obligations while managing the caregiver burden. This study aimed to investigate primary caregivers' relationship with hired support and its impact on coping with caregiver burden. Twenty in-depth interviews were conducted with primary caregivers who hired live-in domestic helpers to take care of their family members with dementia. The findings revealed that caregivers perceived the normative obligations to provide home care to family members with dementia. They sought support from domestic helpers to cope with physical and mental burnout, disruption of normal routines, and avoidance of financial strain. A mutual-support relationship was built between caregivers and domestic helpers through trust and interdependence. The presence of domestic helpers as a coping resource reveals the positive outcomes of problem-, emotional-, and diversion-focused coping. This study illustrates that coping strategies are employed in different ways depending on the needs of caregivers, access to infrastructure, cultural expectations, and available resources.

A randomized controlled trial to examine the effectiveness of case management model for community dwelling older persons with mild dementia in Hong Kong.

Science.gov (United States)

Lam, Linda C W; Lee, Jenny S W; Chung, Jenny C C; Lau, Anna; Woo, Jean; Kwok, Timothy C Y

2010-04-01

To evaluate a case management (CM) model for people with mild dementia, whereby resources within the family and in the community were mobilized and optimally used. Community dwelling psychiatric and geriatrics outpatients with mild dementia were randomized to receive CM by a trained occupational therapist for 4 months (CM group, N = 59) or usual care only (control group, N = 43). Primary outcome indicators included the Zarit Burden Scale (ZBI), General Health Questionnaire (GHQ), and Personal Well-Being Index for Adult (PWI-A) of the family caregivers. Secondary outcome indicators included the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Cornell Scale for Depression in Dementia (CSDD), and Personal Well-Being Index for Intellectually Disabled (PWI-ID) of the demented subjects as measured at fourth and twelfth months. CSDDis reduced in the CM group at fourth month, but not at twelfth month. The changes in outcome variables of persons with dementia did not differ between the groups (Mann-Whitney U-test, p > 0.05). At follow-up, CM group used more day care and domestic helpers than control group (chi (2), p > 0.05). Case management for Chinese persons with mild dementia outpatients did not show significant effects in reducing caregiver burden, but encouraged family caregivers to seek external support.

Dose assessment of the patient and the helper in emergency head computed tomography

International Nuclear Information System (INIS)

Chang, Rong-Chou; Yu, Cheng-Ching; Hsu, Fang-Yuh; Chen, Tou-Rong; Hsu, Shih-Ming; Tyan, Yeu-Sheng

2011-01-01

Computed Tomography (CT) becomes more and more important and is frequently used in modern diagnostic techniques. CT offers an effective diagnosis on lesion and pathology; however, it also delivers a radiation dose to patients. Besides, in some special emergency cases, the patient may require someone to help him in the examination room to perform the head CT, due to the patient lost intellectual and operational capacity. This study evaluated the delivered radiation dose and the risk of radiation-induced cancer for the patient and for the helper after carrying out the emergent head CT examination. A Rando phantom with thermoluminescent dosimeter (TLD) chips inside relevant organs was used to simulate the patient during head CT examination. An effective dose of 2.06 ± 0.16 mSv and 1.46 ± 0.07 mSv without and with wearing the lead apron were found respectively, considering ICRP 60 recommendation. ICRP 103 recommendations the readings would have been 1.29 ± 0.15 mSv and 0.71 ± 0.04 mSv. The effective dose determined from the dose-length product (DLP) method (2.19 mSv) was similar to the value (2.06 ± 0.16 mSv) estimated by TLD method considering the ICRP 60 recommendation (without lead apron). Assuming a 5% total risk for fatal cancer per Sv in the general population, risk of radiation-induced cancer for patients were 1.03 × 10 −2 % (without lead apron) and 7.80 × 10 −3 % (with lead apron) for ICRP 60, and were 6.45 × 10 −3 % (without lead apron) and 3.55 × 10 −3 % (with lead apron) for ICRP 103. The dose received by the helper was assessed by wearing a personal badge. The helper during emergent head CT examination may receive a personal dose equivalent (H p (10)) of 19.36 ± 5.89 μSv and 138.81 ± 101.28 μSv with and without lead apron, respectively, at distance of 0.3–1 m from the center of CT scanner. Based on the observed dose reduction of a factor of 7.17 we recommend that helpers wear lead apron in the CT examination room.

Security of helper data Schemes for SRAM-PUF in multiple enrollment scenarios

NARCIS (Netherlands)

Kusters, C.J.; Ignatenko, T.; Maes, R.; van der Sluis, E.; Selimis, G.; Willems, F.M.J.

2017-01-01

Fuzzy commitment and syndrome-based schemes are two well-known helper data schemes used to bind and generate, respectively, a secret key to/from SRAM-PUF observations. To allow the decoder to reconstruct this secret key from a new (verification) observation of an SRAM-PUF, an encoder has to generate

Role of Medium Chain Triglycerides (Axona®) in the Treatment of Mild to Moderate Alzheimer's Disease.

Science.gov (United States)

Sharma, Alok; Bemis, Marc; Desilets, Alicia R

2014-08-01

Treatment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists provides symptomatic relief but do not prevent its progression. Thus, additional approaches aimed at slowing the progression of the disease have been investigated. Reports detailing reduced brain glucose metabolism in the early stages of AD led to the hypothesis that alternate energy sources aimed at increasing neuronal metabolism may protect neurons and thus benefit patients with AD. Medium-chain triglycerides (MCTs) are metabolized to ketone bodies that serve as an alternative source of energy for neurons. Data from clinical trials suggest that MCTs improve cognition in patients with mild to moderate AD in apolipoprotein E4-negative patients. Adverse events observed were mild and included minor gastrointestinal problems such as diarrhea, dyspepsia, and flatulence. However, since genomic profiles are not routinely conducted in patients with AD in a clinical setting, the role of MCTs in clinical practice seems to be minimal. © The Author(s) 2014.

Comparison of the diagnostic performance of FDG-PET and VBM-MRI in very mild Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Kawachi, Takashi [Division of Neuroimaging Research, HIABCD, Himeji, Hyogo (Japan); Kobe University Graduate School of Medicine, Department of Psychiatry, Kobe, Hyogo (Japan); Ishii, Kazunari; Mori, Tetsuya [Division of Neuroimaging Research, HIABCD, Himeji, Hyogo (Japan); Hyogo Brain and Heart Center, Department of Radiology and Nuclear Medicine, Himeji, Hyogo (Japan); Sakamoto, Setsu; Sasaki, Masahiro [Division of Neuroimaging Research, HIABCD, Himeji, Hyogo (Japan); Yamashita, Fumio; Matsuda, Hiroshi [National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry, Department of Radiology, Kodaira, Tokyo (Japan); Mori, Etsuro [Institute for Aging Brain and Cognitive Disorders, Hyogo Brain and Heart Center, Himeji, Hyogo (Japan)

2006-07-15

The aim of this study was to compare the diagnostic performance of{sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and voxel-based morphometry (VBM) on magnetic resonance imaging (MRI) in the same group of patients with very mild Alzheimer's disease (AD). Thirty patients with very mild AD (age 67.0{+-}5.8 years; MMSE score 25.5{+-}1.2, range 24-28), 32 patients with mild AD (age 67.0{+-}4.5 years, MMSE score 22.1{+-}0.8, range 21-23) and 60 age- and sex-matched normal volunteers underwent both FDG-PET and three-dimensional spoiled gradient echo MRI. Statistical parametric mapping was used to conduct voxel by voxel analysis and Z score mapping. First, the region of interest (ROI) maps of significant reductions in glucose metabolism and grey matter density in the mild AD patients were defined. Secondly, analysis of receiver operating characteristic (ROC) curves for Z scores in the ROI maps discriminating very mild AD patients and normal controls was performed. In mild AD patients, FDG-PET indicated significant reductions in glucose metabolism in the bilateral posterior cingulate gyri and the right parietotemporal area, while VBM analysis showed a significant decrease in grey matter volume density in the bilateral amygdala/hippocampus complex, compared with the normal control group. ROC analysis showed that in very mild AD patients the accuracy of FDG-PET diagnosis was 89% and that of VBM-MRI diagnosis was 83%. The accuracy of the combination of FDG-PET and VBM-MRI diagnosis was 94%. In very mild AD, both FDG-PET and VBM-MRI had high accuracy for diagnosis, but FDG-PET showed slightly higher accuracy than VBM-MRI. Combination of the two techniques will yield a higher diagnostic accuracy in very mild AD by making full use of functional and morphological images. (orig.)

Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

Directory of Open Access Journals (Sweden)

Bart eEverts

2014-05-01

Full Text Available Dendritic cells (DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

The Role of Protein Modifications of T-Bet in Cytokine Production and Differentiation of T Helper Cells

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Sera Oh

2014-01-01

Full Text Available T-Bet (T-box protein expressed in T cells, also called as TBX21 was originally cloned as a key transcription factor involved in the commitment of T helper (Th cells to the Th1 lineage. T-Bet directly activates IFN-γ gene transcription and enhances development of Th1 cells. T-Bet simultaneously modulates IL-2 and Th2 cytokines in an IFN-γ-independent manner, resulting in an attenuation of Th2 cell development. Numerous studies have demonstrated that T-bet plays multiple roles in many subtypes of immune cells, including B cell, dendritic cells, natural killer (NK cells, NK T cells, and innate lymphoid cells. Therefore, T-bet is crucial for the development and coordination of both innate and adaptive immune responses. To fulfill these multiple roles, T-bet undergoes several posttranslational protein modifications, such as phosphorylation at tyrosine, serine, and threonine residues, and ubiquitination at lysine residues, which affect lineage commitment during Th cell differentiation. This review presents a current overview of the progress made in understanding the roles of various types of T-bet protein modifications in the regulation of cytokine production during Th cell differentiation.

Genetic Variant in Flavin-Containing Monooxygenase 3 Alters Lipid Metabolism in Laying Hens in a Diet-Specific Manner

OpenAIRE

Wang, Jing; Long, Cheng; Zhang, Haijun; Zhang, Yanan; Wang, Hao; Yue, Hongyuan; Wang, Xiaocui; Wu, Shugeng; Qi, Guanghai

2016-01-01

Genetic variant T329S in flavin-containing monooxygenase 3 (FMO3) impairs trimethylamine (TMA) metabolism in birds. The TMA metabolism that under complex genetic and dietary regulation, closely linked to cardiovascular disease risk. We determined whether the genetic defects in TMA metabolism may change other metabolic traits in birds, determined whether the genetic effects depend on diets, and to identify genes or gene pathways that underlie the metabolic alteration induced by genetic and die...

Pregnancies After the Diagnosis of Mild Gestational Diabetes Mellitus and Risk of Cardiometabolic Disorders.

Science.gov (United States)

Varner, Michael W; Rice, Madeline Murguia; Landon, Mark B; Casey, Brian M; Reddy, Uma M; Wapner, Ronald J; Rouse, Dwight J; Tita, Alan T N; Thorp, John M; Chien, Edward K; Saade, George R; Peaceman, Alan M; Blackwell, Sean C; Vandorsten, J Peter

2017-02-01

To assess the association of subsequent pregnancy with subsequent metabolic syndrome and type II diabetes mellitus after a pregnancy complicated by mild gestational diabetes mellitus (GDM). We conducted a prospective observational follow-up study of women with mild GDM randomized from 2002 to 2007 to usual care or dietary intervention and glucose self-monitoring. Women were evaluated 5-10 years after the parent study. Participants were grouped according to the number of subsequent pregnancies (group A, none [reference]; group B, one; group C, two or greater). Serum triglycerides, glucose tolerance, high-density lipoprotein cholesterol, blood pressure, and waist circumference were assessed. Metabolic syndrome was diagnosed by American Heart Association and National Heart Lung and Blood Institute criteria. Multivariable regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). Of 905 eligible women from the original trial, 483 agreed to participate, 426 of whom were included in this analysis. Groups A, B, and C consisted of 212, 143, and 71 women, respectively. Of women with subsequent pregnancies, 32% (69/214) had another pregnancy complicated with GDM. No difference between groups was observed for metabolic syndrome (group A, 34%; group B, 33%; group C, 30%). Subsequent pregnancies were associated with diabetes mellitus outside of pregnancy (group A, 5.2%; group B, 10.5%, RR 2.62, 95% CI 1.16-5.91; group C, 11.3%, RR 2.83, 95% CI 1.06-7.59), and if complicated with GDM (no subsequent GDM pregnancy, RR 1.99, 95% CI 0.82-4.84; subsequent GDM pregnancy, RR 3.75, 95% CI 1.60-8.82). In women with prior mild GDM, subsequent pregnancies did not increase the frequency of metabolic syndrome, but subsequent pregnancies with GDM increased the risk of diabetes mellitus outside of pregnancy.

Correlation Between Metabolic Syndrome, Periodontitis and Reactive Oxygen Species Production. A Pilot Study

OpenAIRE

Patini, Romeo; Gallenzi, Patrizia; Spagnuolo, Gianrico; Cordaro, Massimo; Cantiani, Monica; Amalfitano, Adriana; Arcovito, Alessandro; Callà, Cinzia; Mingrone, Gertrude; Nocca, Giuseppina

2017-01-01

Background and Objective: Metabolic syndrome (MetS) is associated with an increased risk of periodontitis even if the mechanism is unknown. Since both MetS and periodontitis are characterized by an alteration of inflammation status, the aim of this pilot study was to determine if differences in ROS metabolism of phagocytes isolated from (A) patients with MetS, (B) patients with both MetS and mild periodontitis, (C) healthy subjects and (D) normal weight subjects with mild periodontitis, were ...

Bacterial CpG-DNA activates dendritic cells in vivo: T helper cell-independent cytotoxic T cell responses to soluble proteins.

Science.gov (United States)

Sparwasser, T; Vabulas, R M; Villmow, B; Lipford, G B; Wagner, H

2000-12-01

Receptors for conserved molecular patterns associated with microbial pathogens induce synthesis of co-stimulatory molecules and cytokines in immature dendritic cells (DC), as do antigen-reactive CD4 T helper cells via CD40 signaling. Once activated, antigen-presenting DC may activate CD8 T cell responses in a T helper cell-independent fashion. Using immunostimulatory CpG-oligonucleotides (ODN) mimicking bacterial CpG-DNA, we tested whether CpG-DNA bypasses the need for T helper cells in CTL responses towards proteins by directly activating antigen-presenting DC to transit into professional APC. We describe that immature DC in situ constitutively process soluble proteins and generate CD8 T cell determinants yet CD8 T cell responses remain abortive. Induction of primary antigen-specific CD8 cytotoxic T lymphocyte (CTL)-mediated responses becomes initiated in wild-type as well as T helper cell-deficient mice, provided soluble protein and CpG-ODN are draining into the same lymph node. Specifically we show that CpG-ODN trigger antigen-presenting immature DC within the draining lymph node to acutely up-regulate co-stimulatory molecules and produce IL-12. These results provide new insights for generating in vivo efficient CTL responses to soluble proteins which may influence vaccination strategies.

NFIL3 Orchestrates the Emergence of Common Helper Innate Lymphoid Cell Precursors

Directory of Open Access Journals (Sweden)

Wei Xu

2015-03-01

Full Text Available Innate lymphoid cells (ILCs are a family of effectors that originate from a common innate lymphoid cell progenitor. However, the transcriptional program that sets the identity of the ILC lineage remains elusive. Here, we show that NFIL3 is a critical regulator of the common helper-like innate lymphoid cell progenitor (CHILP. Cell-intrinsic Nfil3 ablation led to variably impaired development of fetal and adult ILC subsets. Conditional gene targeting demonstrated that NFIL3 exerted its function prior to ILC subset commitment. Accordingly, NFIL3 ablation resulted in loss of ID2+ CHILP and PLZF+ ILC progenitors. Nfil3 expression in lymphoid progenitors was under the control of the mesenchyme-derived hematopoietin IL-7, and NFIL3 exerted its function via direct Id2 regulation in the CHILP. Moreover, ectopic Id2 expression in Nfil3-null precursors rescued defective ILC lineage development in vivo. Our data establish NFIL3 as a key regulator of common helper-like ILC progenitors as they emerge during early lymphopoiesis.

Analysis of the frequency of mutant T-helpers as a parameter for biological dosimetry

International Nuclear Information System (INIS)

Mel'nov, S.B.; Minenko, V.F.; Demidchik, E.P.

1998-01-01

It was made the attempt of quantitatively estimation of radiation damage by the frequency of mutant T-helpers, i.e. CD4+cells, depleted of T-cell receptor (TCR). The object of the study was lymphocytes of peripheral blood of children exposed to iodine radioisotopes therapy on medical indications. The examined group consisted of 36 patients 10 -21 years old, which were injected from 0,3 to 27,6 GBq of iodine 131. The time between exposition to iodine 131 and the investigation varied from 2 months to 3 years. The results gave evidence about the existence of direct relation between the frequency of mutant T-helpers and integrated dose. The character of the relation was described on the basis of mathematical processing. It was concluded that TCR-test can be used for restoration of the biological radiation dose

Attitudes of Future Human Service Professionals: The Effects of Victim and Helper Qualities.

Science.gov (United States)

Liebkind, Karmela; Eranen, Liisa

2001-01-01

Investigates the attitudes of future members in human service professions toward victims, based on the qualities effected by trauma victims and their helpers. Reports that the high-trauma and poorly adapted victims elicited more negative attitudes than did the low-trauma and well-adapted victims. (CMK)

Early secreted antigen ESAT-6 of Mycobacterium tuberculosis promotes protective T helper 17 cell responses in a toll-like receptor-2-dependent manner.

Directory of Open Access Journals (Sweden)

Samit Chatterjee

2011-11-01

Full Text Available Despite its relatively poor efficacy, Bacillus Calmette-Guérin (BCG has been used as a tuberculosis (TB vaccine since its development in 1921. BCG induces robust T helper 1 (Th1 immune responses but, for many individuals, this is not sufficient for host resistance against Mycobacterium tuberculosis (M. tb infection. Here we provide evidence that early secreted antigenic target protein 6 (ESAT-6, expressed by the virulent M. tb strain H37Rv but not by BCG, promotes vaccine-enhancing Th17 cell responses. These activities of ESAT-6 were dependent on TLR-2/MyD88 signalling and involved IL-6 and TGF-β production by dendritic cells. Thus, animals that were previously infected with H37Rv or recombinant BCG containing the RD1 region (BCG::RD1 exhibited improved protection upon re-challenge with virulent H37Rv compared with mice previously infected with BCG or RD1-deficient H37Rv (H37RvΔRD1. However, TLR-2 knockout (TLR-2⁻/⁻ animals neither showed Th17 responses nor exhibited improved protection in response to immunization with H37Rv. Furthermore, H37Rv and BCG::RD1 infection had little effect on the expression of the anti-inflammatory microRNA-146a (miR146a in dendritic cells (DCs, whereas BCG and H37RvΔRD1 profoundly induced its expression in DCs. Consistent with these findings, ESAT-6 had no effect on miR146a expression in uninfected DCs, but dramatically inhibited its upregulation in BCG-infected or LPS-treated DCs. Collectively, our findings indicate that, in addition to Th1 immunity induced by BCG, RD1/ESAT-6-induced Th17 immune responses are essential for optimal vaccine efficacy.

Generation and characterization of peptide-specific, MHC-restricted cytotoxic T lymphocyte (CTL) and helper T cell lines from unprimed T cells under microculture conditions.

Science.gov (United States)

Sambhara, S R; Upadhya, A G; Miller, R G

1990-06-12

We describe a microculture system for the generation of CTL and T helper cells against peptides. Tryptic digest and cyanogen bromide fragments of chicken ovalbumin and synthetic peptides of ovalbumin (323-339) and influenza virus (NP 365-380) were used to generate CTL and T helper lines from unprimed T cells. These lines were both peptide-specific and MHC-restricted. The relative ease of generating peptide-specific, MHC-restricted CTL and helper T cell lines with as few as 10(6) unprimed lymphocytes can be an efficient method of detecting potential immunogenic determinants of an antigen.

Sex, Attribution, and Severity Influence Intervention Decisions of Informal Helpers in Domestic Violence

Science.gov (United States)

Chabot, Heather Frasier; Tracy, Tracy L.; Manning, Christine A.; Poisson, Chelsea A.

2009-01-01

Most domestic violence (DV) researchers examine professional intervention (e.g., police and nurses), but informal helpers (e.g., friends and bystanders) are critical. The authors measure undergraduates' intervention likelihood, type of involvement (i.e., contact with abuser), and the influence of attribution decisions in DV situations where the…

Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study

Energy Technology Data Exchange (ETDEWEB)

Drzezga, Alexander; Willoch, Frode; Schwaiger, Markus [Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675, Muenchen (Germany); Lautenschlager, Nicola; Riemenschneider, Matthias; Kurz, Alexander [Department of Psychiatry and Psychotherapy, Technische Universitaet Muenchen, Muenchen (Germany); Siebner, Hartwig [Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London (United Kingdom); Minoshima, Satoshi [Department of Radiology, University of Washington, Seattle, WA (United States)

2003-08-01

A high percentage of patients with mild cognitive impairment (MCI) develop clinical dementia of the Alzheimer type (AD) within 1 year. The aim of this longitudinal study was to identify characteristic patterns of cerebral metabolism at baseline in patients converting from MCI to AD, and to evaluate the changes in these patterns over time. Baseline and follow-up examinations after 1 year were performed in 22 MCI patients (12 males, 10 females, aged 69.8{+-}5.8 years); these examinations included neuropsychological testing, structural cranial magnetic resonance imaging and fluorine-18 fluorodeoxyglucose positron emission tomography (PET) evaluation of relative cerebral glucose metabolic rate (rCMRglc). Individual PET scans were stereotactically normalised with NEUROSTAT software (Univ. of Michigan, Ann Arbor, USA). Subsequently, statistical comparison of PET data with an age-matched healthy control population and between patient subgroups was performed using SPM 99 (Wellcome Dept. of Neuroimaging Sciences, London, UK). After 1 year, eight patients (36%) had developed probable AD (referred to as MCI{sub AD}), whereas 12 (55%) were still classified as having stable MCI (referred to as MCI{sub MCI}). Compared with the healthy control group, a reduced rCMRglc in AD-typical regions, including the temporoparietal and posterior cingulate cortex, was detected at baseline in patients with MCI{sub AD}. Abnormalities in the posterior cingulate cortex reached significance even in comparison with the MCI{sub MCI} group. After 1 year, MCI{sub AD} patients demonstrated an additional bilateral reduction of rCMRglc in prefrontal areas, along with a further progression of the abnormalities in the parietal and posterior cingulate cortex. No such changes were observed in the MCI{sub MCI} group. In patients with MCI, characteristic cerebral metabolic differences can be delineated at the time of initial presentation, which helps to define prognostic subgroups. A newly emerging reduction

Biophysical characterization data of the artificial protein Octarellin V.1 and binding test with its X-ray helpers

Directory of Open Access Journals (Sweden)

Maximiliano Figueroa

2016-09-01

Full Text Available The artificial protein Octarellin V.1 (http://dx.doi.org/10.1016/j.jsb.2016.05.004 [1] was obtained through a direct evolution process over the de novo designed Octarellin V (http://dx.doi.org/10.1016/S0022-2836(0201206-8 [2]. The protein has been characterized by circular dichroism and fluorescence techniques, in order to obtain data related to its thermo and chemical stability. Moreover, the data for the secondary structure content studied by circular dichroism and infra red techniques is reported for the Octarellin V and V.1. Two crystallization helpers, nanobodies (http://dx.doi.org/10.1038/nprot.2014.039 [3] and αRep (http://dx.doi.org/10.1016/j.jmb.2010.09.048 [4], have been used to create stable complexes. Here we present the data obtained of the binding characterization of the Octarellin V.1 with the crystallization helpers by isothermal titration calorimetry. Keywords: Artificial proteins, Circular dichroism, Crystallization helpers, Infra red spectroscopy, Protein design, Isothermal Titration Calorimetry

T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

Science.gov (United States)

van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

2018-05-01

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4

Specificity in the association of tomato black ring virus satellite RNA with helper virus.

Science.gov (United States)

Oncino, C; Hemmer, O; Fritsch, C

1995-10-20

The satellite RNAs (sat-RNAs) associated with some isolates of tomato black ring virus (TBRV) consist of single-stranded molecules of about 1375 nucleotides, encoding a nonstructural protein of 48K which has been shown to be involved in the replication of the sat-RNA. The TBRV sat-RNAs are also dependent for their replication and for their encapsidation on the helper virus. To characterize the nature of the association between sat-RNA and helper virus, transcripts of sat-RNA from TBRV isolates C and L (respectively, of serotypes G and S) have been prepared and inoculated onto Chenopodium quinoa leaves or protoplasts. Transcript of the TBRV sat-RNA C is efficiently multiplied when coinoculated with the genomic RNAs of TBRV isolate G (used instead of TBRV isolate C, because isolate G was depleted of sat-RNA), but does not multiply with TBRV isolate L. On the other hand, transcript of the sat-RNA L is able to multiply with the cognate helper virus and, less efficiently, with grapevine chrome mosaic virus (another nepovirus, 80% similar to TBRV), but does not multiply with TBRV G. The specificity of the association resides at the level of sat-RNA replication. Analysis of the multiplication of chimeric sat-RNAs, obtained by exchanging different regions between the two sat-RNAs C and L, showed that the 5' and the 3' noncoding regions of the sat-RNA, although important for replication, are not implicated in specificity. The results suggest that the determinants of the specificity are contained in the 48K sat-RNA-encoded protein.

Electrolyte engineering toward efficient water splitting at mild pH

KAUST Repository

Shinagawa, Tatsuya; Ng, Marcus Tze-Kiat; Takanabe, Kazuhiro

2017-01-01

The development of processes for the conversion of H2O/CO2 driven by electricity generated in renewable manners is essential to achieve sustainable energy and chemical cycles, in which the electrocatalytic oxygen evolution reaction (OER) is one of the bottlenecks. In this contribution, the influences of the electrolyte molarity and identity on OER at alkaline to neutral pH were investigated at an appreciable current density of ~10 mA cm-2, revealing (1) the clear boundary of reactant switching between H2O/OH- due to the diffusion limitation of OH- and (2) the substantial contribution of the mass transport of the buffered species in buffered mild pH conditions. These findings propose a strategy of electrolyte engineering: tuning the electrolyte properties to maximize the mass-transport flux. The concept was successfully demonstrated for OER as well as overall water electrolysis in buffered mild pH conditions, shedding light on the development of practical solar fuel production systems.

Electrolyte engineering toward efficient water splitting at mild pH

KAUST Repository

Shinagawa, Tatsuya

2017-08-28

The development of processes for the conversion of H2O/CO2 driven by electricity generated in renewable manners is essential to achieve sustainable energy and chemical cycles, in which the electrocatalytic oxygen evolution reaction (OER) is one of the bottlenecks. In this contribution, the influences of the electrolyte molarity and identity on OER at alkaline to neutral pH were investigated at an appreciable current density of ~10 mA cm-2, revealing (1) the clear boundary of reactant switching between H2O/OH- due to the diffusion limitation of OH- and (2) the substantial contribution of the mass transport of the buffered species in buffered mild pH conditions. These findings propose a strategy of electrolyte engineering: tuning the electrolyte properties to maximize the mass-transport flux. The concept was successfully demonstrated for OER as well as overall water electrolysis in buffered mild pH conditions, shedding light on the development of practical solar fuel production systems.

Essential competencies for the education of nursing assistants and care helpers in elderly care

NARCIS (Netherlands)

Oeseburg, Barth; Hilberts, Rudi; Roodbol, Petrie F

2015-01-01

BACKGROUND: The Dutch health care system faces huge challenges with regard to the demand on elderly care and the competencies of professionals required to meet this demand. However, a recent study showed that the curricula in vocational education for nursing assistants and care helpers remains

[11C]PIB, [18F]FDG and MR imaging in patients with mild cognitive impairment

DEFF Research Database (Denmark)

Brück, A; Virta, J R; Koivunen, J

2013-01-01

Cortical glucose metabolism, brain amyloid β accumulation and hippocampal atrophy imaging have all been suggested as potential biomarkers in predicting which patients with mild cognitive impairment (MCI) will convert to Alzheimer's disease (AD). The aim of this study was to compare the prognostic...

Demonstration of decreased posterior cingulate perfusion in mild Alzheimer's disease by means of H215O positron emission tomography

International Nuclear Information System (INIS)

Ishii, Kazunari; Sasaki, Masahiro; Yamaji, Shigeru; Sakamoto, Setsu; Kitagaki, Hajime; Mori, Etsuro

1997-01-01

Although decreased posterior cingulate metabolism in Alzheimer's disease (AD) has been previously reported, there have been no reports on posterior cingulate perfusion. In this study we evaluated posterior cingulate perfusion as a relative value using statistical parametric maps (SPMs) and as an absolute value using conventional region of interest (ROI) settings. Twenty-eight subjects, including 14 patients with mild AD (mean age: 66.4±12.1 years) and 14 normal controls (65.9±7.3 years) were studied. Regional cerebral blood flow (CBF) was measured with H 2 15 O and positron emission tomography (PET). In the SPM analysis, the left posterior cingulate and left parietotemporal CBFs were significantly decreased in the patients with mild AD (P<0.001). At a lower statistical threshold (P<0.05), the right posterior cingulate and right parietotemporal CBFs were also significantly decreased in the AD patients. In the ROI studies, the left parietal and posterior cingulate CBFs in the patients with mild AD were significantly lower than those of the normal controls by analysis of variance and post-hoc Scheffe's test (P<0.001). We conclude that posterior cingulate perfusion is decreased in mild AD, reflecting the pathological changes and metabolic reduction in the posterior cingulate gyrus that have previously been reported to occur in mild AD. (orig.). With 1 fig., 2 tabs

From idealistic helper to enterprising learner: critical reflections on personal development through experiences from Afghanistan.

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Wickford, Jenny; Rosberg, Susanne

2012-05-01

There is little written about the cultural, social, and ethical challenges encountered by physiotherapists engaging in development work. This article takes a critical perspective on what it means to engage in development work as an expatriate physiotherapist, through a self-critical reflection on experiences from Afghanistan. The field notes from an ethnographic study of a development project conducted in Afghanistan were analysed to explore the transformative process of personal and professional development of the development worker. The critical reflective process entailed a change in meaning perspective, described as a shift from the position of an Idealistic Helper to an Enterprising Learner. Of importance in this process were "disorienting dilemmas" that challenged personal perceptions. Critical reflection over such dilemmas led to deeper understanding facilitating the process of change. The essential lesson learned is that the baseline for understanding others is an understanding of one's own meaning perspectives and manner of participation in relation to others and their context. The insights gained have implications for physiotherapists working in development contexts, for other development workers, and for physiotherapists working with patients in clinical practice in a nondevelopment context. Exploring how to collaborate in development contexts could be done using reflective groups with expatriate and local physiotherapists and/or patients. This could lead to greater understanding of oneself, each other, and the local context.

Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4+ T helper responses.

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Fiorentini, Simona; Marconi, Peggy; Avolio, Manuela; Marini, Elena; Garrafa, Emirena; Caracciolo, Sonia; Rossi, Daniele; Bozac, Alexandra; Becker, Pablo D; Gentili, Francesca; Facchetti, Fabio; Guzman, Carlos A; Manservigi, Roberto; Caruso, Arnaldo

2007-07-01

Both neutralizing antibodies and cytotoxic T-cells are necessary to control a viral infection. However, vigorous T helper responses are essential for their elicitation and maintenance. Here we show that a recombinant replication-deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in the mouse dermis generated a strong p17-specific CD4+ T helper response preceding both p17-specific humoral and effector T cell responses. Moreover, we show that T0-p17 infection did not interfere with the endogenous processing of the transgene encoded antigen, since infected APCs were able to evoke a strong recall response in vitro. Our results demonstrate that replication-deficient HSV vectors can be appealing candidates for the development of vaccines able to trigger T helper responses.

Detection of tmRNA molecules on microarrays at low temperatures using helper oligonucleotides

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Palta Priit

2010-04-01

Full Text Available Abstract Background The hybridization of synthetic Streptococcus pneumoniae tmRNA on a detection microarray is slow at 34°C resulting in low signal intensities. Results We demonstrate that adding specific DNA helper oligonucleotides (chaperones to the hybridization buffer increases the signal strength at a given temperature and thus makes the specific detection of Streptococcus pneumoniae tmRNA more sensitive. No loss of specificity was observed at low temperatures compared to hybridization at 46°C. The effect of the chaperones can be explained by disruption of the strong secondary and tertiary structure of the target RNA by the selective hybridization of helper molecules. The amplification of the hybridization signal strength by chaperones is not necessarily local; we observed increased signal intensities in both local and distant regions of the target molecule. Conclusions The sensitivity of the detection of tmRNA at low temperature can be increased by chaperone oligonucleotides. Due to the complexity of RNA secondary and tertiary structures the effect of any individual chaperone is currently not predictable.

Visual rating of medial temporal lobe metabolism in mild cognitive impairment and Alzheimer's disease using FDG-PET

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Mosconi, Lisa [New York University School of Medicine, Department of Psychiatry, New York, NY (United States); University of Florence, Department of Clinical Pathophysiology, Nuclear Medicine Unit, Florence (Italy); New York University School of Medicine, Center for Brain Health, New York, NY (United States); Santi, Susan De; Li, Yi; Li, Juan; Zhan, Jiong; Boppana, Madhu [New York University School of Medicine, Department of Psychiatry, New York, NY (United States); Tsui, Wai Hon; Leon, Mony J. de [New York University School of Medicine, Department of Psychiatry, New York, NY (United States); Nathan Kline Institute, Orangeburg, NY (United States); Pupi, Alberto [University of Florence, Department of Clinical Pathophysiology, Nuclear Medicine Unit, Florence (Italy)

2006-02-01

This study was designed to examine the utility of visual inspection of medial temporal lobe (MTL) metabolism in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) using FDG-PET scans. Seventy-five subjects [27 normal controls (NL), 26 MCI, and 22 AD] with FDG-PET and MRI scans were included in this study. We developed a four-point visual rating scale to evaluate the presence and severity of MTL hypometabolism on FDG-PET scans. The visual MTL ratings were compared with quantitative glucose metabolic rate (MR{sub glc}) data extracted using regions of interest (ROIs) from the MRI-coregistered PET scans of all subjects. A standard rating evaluation of neocortical hypometabolism was also completed. Logistic regressions were used to determine and compare the diagnostic accuracy of the MTL and cortical ratings. For both MTL and cortical ratings, high intra- and inter-rater reliabilities were found (p values <0.001). The MTL rating was highly correlated with and yielded a diagnostic accuracy equivalent to the ROI MR{sub glc} measures (p values <0.001). The combination of MTL and cortical ratings significantly improved the diagnostic accuracy over the cortical rating alone, with 100% of AD, 77% of MCI, and 85% of NL cases being correctly identified. This study shows that the visual rating of MTL hypometabolism on PET is reliable, yields a diagnostic accuracy equal to the quantitative ROI measures, and is clinically useful and more sensitive than cortical ratings for patients with MCI. We suggest this method be further evaluated for its potential in the early diagnosis of AD. (orig.)

Impact of Weight Regain on Metabolic Disease Risk: A Review of Human Trials

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Cynthia M. Kroeger

2014-01-01

Full Text Available Dietary restriction interventions are effective for weight loss and reduction of chronic disease risk. Unfortunately, most people tend to regain much of this lost weight within one year after intervention. While some studies suggest that minor degrees of weight regain have no effect on metabolic disease risk parameters, other studies demonstrate a complete reversal in metabolic benefits. In light of these conflicting findings, it is of interest to determine how complete weight maintenance versus mild weight regain affects key risk parameters. These findings would have important clinical implications, as they could help identify a weight regain threshold that could preserve the metabolic benefits of weight loss. Accordingly, this review examined the impact of no weight regain versus mild regain on various metabolic disease risk parameters, including plasma lipids, blood pressure, glucose, and insulin concentrations, in adult subjects.

Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer's disease

International Nuclear Information System (INIS)

Mosconi, Lisa; Rusinek, Henry; De Santi, Susan; Li, Yi; Tsui, Wai H.; De Leon, Mony J.; Wang, Gene-Jack; Fowler, Joanna; Pupi, Alberto

2007-01-01

To examine CMRglc measures and corresponding glucose transport (K 1 and k 2 ) and phosphorylation (k 3 ) rates in the medial temporal lobe (MTL, comprising the hippocampus and amygdala) and posterior cingulate cortex (PCC) in mild Alzheimer's disease (AD). Dynamic FDG PET with arterial blood sampling was performed in seven mild AD patients (age 68 ± 8 years, four females, median MMSE 23) and six normal (NL) elderly (age 69 ± 9 years, three females, median MMSE 30). Absolute CMRglc (μmol/100 g/min) was calculated from MRI-defined regions of interest using multiparametric analysis with individually fitted kinetic rate constants, Gjedde-Patlak plot, and Sokoloff's autoradiographic method with population-based rate constants. Relative ROI/pons CMRglc (unitless) was also examined. With all methods, AD patients showed significant CMRglc reductions in the hippocampus and PCC, and a trend towards reduced parietotemporal CMRglc, as compared with NL. Significant k 3 reductions were found in the hippocampus, PCC and amygdala. K 1 reductions were restricted to the hippocampus. Relative CMRglc had the largest effect sizes in separating AD from NL. However, the magnitude of CMRglc reductions was 1.2- to 1.9-fold greater with absolute than with relative measures. CMRglc reductions are most prominent in the MTL and PCC in mild AD, as detected with both absolute and relative CMRglc measures. Results are discussed in terms of clinical and pharmaceutical applicability. (orig.)

Examining the impact of grape consumption on brain metabolism and cognitive function in patients with mild decline in cognition: A double-blinded placebo controlled pilot study.

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Lee, Jooyeon; Torosyan, Nare; Silverman, Daniel H

2017-01-01

Natural compounds in grapes such as resveratrol are known for their antioxidant and anti-inflammatory properties. Some studies have shown a potential role for grapes or wine in slowing cognitive decline and other effects of aging. However, well-controlled experimental data obtained in human subjects are still in need of further development. Here we aimed to systematically assess effects of grapes on regional cerebral metabolism. Ten subjects with mild decline in cognition (mean, 72.2±4.7years; 50% female) were included in this analysis. Participants were randomized into an active grape formulation arm or a placebo arm which consumed a formulation free of polyphenols for six months. Cognitive performance was measured through neuropsychological assessments performed at baseline and 6months after initiation of therapy. Changes in brain metabolism occurring with each therapy regimen were assessed by brain PET scans with the radiotracer [F-18] fluorodeoxyglucose (FDG), obtained during initial evaluation and 6months later. Standardized volumes of interest (sVOI) and statistical parametric mapping (SPM) methods were applied to FDG-PET scans to identify significant regional cerebral metabolic changes. In contrast to participants taking the active grape formulation, who displayed no significant decline in metabolism, the placebo arm underwent significant metabolic decline in sVOI's of the right posterior cingulate cortex (p=0.01), and left superior posterolateral temporal cortex (p=0.04). SPM analyses also found significant declines in the placebo group, particularly in left prefrontal, cingulate, and left superior posterolateral temporal cortex (pbrain metabolism in the active formulation arm. No significant differences were seen in scores on the neuropsychological battery of tests between the two groups. However, metabolism in right superior parietal cortex and left inferior anterior temporal cortex was correlated with improvements in attention/working memory, as

Forensic applications of cerebral single photon emission computed tomography in mild traumatic brain injury.

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Wortzel, Hal S; Filley, Christopher M; Anderson, C Alan; Oster, Timothy; Arciniegas, David B

2008-01-01

Traumatic brain injury (TBI) is a substantial source of mortality and morbidity world wide. Although most such injuries are relatively mild, accurate diagnosis and prognostication after mild TBI are challenging. These problems are complicated further when considered in medicolegal contexts, particularly civil litigation. Cerebral single photon emission computed tomography (SPECT) may contribute to the evaluation and treatment of persons with mild TBI. Cerebral SPECT is relatively sensitive to the metabolic changes produced by TBI. However, such changes are not specific to this condition, and their presence on cerebral SPECT imaging does not confirm a diagnosis of mild TBI. Conversely, the absence of abnormalities on cerebral SPECT imaging does not exclude a diagnosis of mild TBI, although such findings may be of prognostic value. The literature does not demonstrate consistent relationships between SPECT images and neuropsychological testing or neuropsychiatric symptoms. Using the rules of evidence shaped by Daubert v. Merrell Dow Pharmaceuticals, Inc., and its progeny to analyze the suitability of SPECT for forensic purposes, we suggest that expert testimony regarding SPECT findings should be admissible only as evidence to support clinical history, neuropsychological test results, and structural brain imaging findings and not as stand-alone diagnostic data.

Do children with obesity have worse table manners? Associations between child table manners, weight status and weight gain.

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Briones, Naomi F; Cesaro, Robert J; Appugliese, Danielle P; Miller, Alison L; Rosenblum, Katherine L; Pesch, Megan H

2018-06-01

Children with obesity experience stigma stemming from stereotypes, one such stereotype is that people with obesity are "sloppy" or have poor manners. Teaching children "proper table manners" has been proposed as an obesity prevention strategy. Little is known about the association between children's weight status and table manners. To examine correlates of child table manners and to examine the association of child table manners with child obese weight status and prospective change in child body mass index z-score (BMIz). Mother-child dyads (N = 228) participated in a videotaped laboratory eating task with cupcakes. Coding schemes to capture child table manners (making crumbs, chewing with mouth open, getting food on face, shoving food in mouth, slouching, and getting out of seat), and maternal attentiveness to child table manners, were reliably applied. Anthropometrics were measured at baseline and at follow-up two years later. Regression analyses examined the association of participant characteristics with child table manners, as well as the associations of child table manners with child obese weight status, and prospective change in BMIz/year. Predictors of poorer child table manners were younger child age, greater cupcake consumption, and greater maternal attentiveness to child table manners. Poorer child table manners were not associated with child obese (vs. not) weight status, but were associated with a prospective decrease in BMIz/year in children with overweight/obesity. Obesity interventions to improve table manners may be perpetuating unfavorable stereotypes and stigma. Future work investigating these associations is warranted to inform childhood obesity guidelines around table manners. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular Mechanisms of Mild and Severe Pneumonia: Insights from RNA Sequencing.

Science.gov (United States)

Huang, Sai; Feng, Cong; Chen, Li; Huang, Zhi; Zhou, Xuan; Li, Bei; Wang, Li-Li; Chen, Wei; Lv, Fa-Qin; Li, Tan-Shi

2017-04-06

BACKGROUND This study aimed to uncover the molecular mechanisms underlying mild and severe pneumonia by use of mRNA sequencing (RNA-seq). MATERIAL AND METHODS RNA was extracted from the peripheral blood of patients with mild pneumonia, severe pneumonia, and healthy controls. Sequencing was performed on the HiSeq4000 platform. After filtering, clean reads were mapped to the human reference genome hg19. Differentially expressed genes (DEGs) were identified between the control group and the mild or severe group. A transcription factor-gene network was constructed for each group. Biological process (BP) terms enriched by DEGs in the network were analyzed and these genes were also mapped to the Connectivity map to search for small-molecule drugs. RESULTS A total of 199 and 560 DEGs were identified from the mild group and severe group, respectively. A transcription factor-gene network consisting of 215 nodes and another network consisting of 451 nodes were constructed in the mild group and severe group, respectively, and 54 DEGs (e.g., S100A9 and S100A12) were found to be common, with consistent differential expression changes in the 2 groups. Genes in the transcription factor-gene network for the mild group were mainly enriched in 13 BP terms, especially defense and inflammatory response (e.g., S100A8) and spermatogenesis, while the top BP terms enriched by genes in the severe group include response to oxidative stress (CCL5), wound healing, and regulation of cell differentiation (CCL5), and of the cellular protein metabolic process. CONCLUSIONS S100A9 and S100A12 may have a role in the pathogenesis of pneumonia: S100A9 and CXCL1 may contribute solely in mild pneumonia, and CCL5 and CXCL11 may contribute in severe pneumonia.

Th17 Polarization under Hypoxia Results in Increased IL-10 Production in a Pathogen-Independent Manner

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Roman Volchenkov

2017-06-01

Full Text Available The IL-17-producing CD4+ T helper cell (Th17 differentiation is affected by stimulation of the aryl hydrocarbon receptor (AhR pathway and by hypoxia-inducible factor 1 alpha (HIF-1α. In some cases, Th17 become non-pathogenic and produce IL-10. However, the initiating events triggering this phenotype are yet to be fully understood. Here, we show that such cells may be differentiated at low oxygen and regardless of AhR ligand treatment such as cigarette smoke extract. Hypoxia led to marked alterations of the transcriptome of IL-10-producing Th17 cells affecting genes involved in metabolic, anti-apoptotic, cell cycle, and T cell functional pathways. Moreover, we show that oxygen regulates the expression of CD52, which is a cell surface protein that has been shown to suppress the activation of other T cells upon release. Taken together, these findings suggest a novel ability for Th17 cells to regulate immune responses in vivo in an oxygen-dependent fashion.

Murine Adseverin (D5), a Novel Member of the Gelsolin Family, and Murine Adseverin Are Induced by Interleukin-9 in T-Helper Lymphocytes

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Robbens, Johan; Louahed, Jamila; De Pestel, Kathleen; Van Colen, Inge; Ampe, Christophe; Vandekerckhove, Joel; Renauld, Jean-Christophe

1998-01-01

We identified a number of upregulated genes by differential screening of interleukin-9-stimulated T-helper lymphocytes. Interestingly, two of these messengers encode proteins that are similar to proteins of the gelsolin family. The first displays a typical structure of six homologous domains and shows a high level of identity (90%) with bovine adseverin (or scinderin) and may therefore be considered the murine adseverin homolog. The second encodes a protein with only five segments. Sequence comparison shows that most of the fifth segment and a short amino-terminal part of the sixth segment (amino acids 528 to 628 of adseverin) are missing, and thus, this form may represent an alternatively spliced product derived from the same gene. The corresponding protein is called mouse adseverin (D5). We expressed both proteins in Escherichia coli and show that mouse adseverin displays the typical characteristics of all members of the gelsolin family with respect to actin binding (capping, severing, and nucleation) and its regulation by Ca2+. In contrast, mouse adseverin (D5) fails to nucleate actin polymerization, although like mouse adseverin and gelsolin, it severs and caps actin filaments in a Ca2+-dependent manner. Adseverin is present in all of the tissues and most of the cell lines tested, although at low concentrations. Mouse adseverin (D5) was found only in blood cells and in cell lines derived from T-helper lymphocytes and mast cells, where it is weakly expressed. In a gel filtration experiment, we demonstrated that mouse adseverin forms a 1:2 complex with G actin which is stable only in the presence of Ca2+, while no stable complex was observed for mouse adseverin (D5). PMID:9671468

Does human bocavirus infection depend on helper viruses? A challenging case report

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Brockmann Michael

2011-08-01

Full Text Available Abstract A case of severe diarrhoea associated with synergistic human bocavirus type 1 (HBoV and human herpes virus type 6 (HHV6 is reported. The case supports the hypotheses that HBoV infection under clinical conditions may depend on helper viruses, or that HBoV replicates by a mechanism that is atypical for parvoviruses, or that HBoV infection can be specifically treated with cidofovir.

Helper T cell epitope-mapping reveals MHC-peptide binding affinities that correlate with T helper cell responses to pneumococcal surface protein A.

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Rajesh Singh

2010-02-01

Full Text Available Understanding the requirements for protection against pneumococcal carriage and pneumonia will greatly benefit efforts in controlling these diseases. Several proteins and polysaccharide capsule have recently been implicated in the virulence of and protective immunity against Streptococcus pneumonia. Pneumococcal surface protein A (PspA is highly conserved among S. pneumonia strains, inhibits complement activation, binds lactoferrin, elicits protective systemic immunity against pneumococcal infection, and is necessary for full pneumococcal virulence. Identification of PspA peptides that optimally bind human leukocyte antigen (HLA would greatly contribute to global vaccine efforts, but this is hindered by the multitude of HLA polymorphisms. Here, we have used an experimental data set of 54 PspA peptides and in silico methods to predict peptide binding to HLA and murine major histocompatibility complex (MHC class II. We also characterized spleen- and cervical lymph node (CLN-derived helper T lymphocyte (HTL cytokine responses to these peptides after S. pneumonia strain EF3030-challenge in mice. Individual, yet overlapping peptides, 15 amino acids in length revealed residues 199 to 246 of PspA (PspA(199-246 consistently caused the greatest IFN-gamma, IL-2, IL-5 and proliferation as well as moderate IL-10 and IL-4 responses by ex vivo stimulated splenic and CLN CD4(+ T cells isolated from S. pneumonia strain EF3030-challeged F(1 (B6xBALB/c mice. IEDB, RANKPEP, SVMHC, MHCPred, and SYFPEITHI in silico analysis tools revealed peptides in PspA(199-246 also interact with a broad range of HLA-DR, -DQ, and -DP allelles. These data suggest that predicted MHC class II-peptide binding affinities do not always correlate with T helper (Th cytokine or proliferative responses to PspA peptides, but when used together with in vivo validation can be a useful tool to choose candidate pneumococcal HTL epitopes.

Fasting glucose, obesity, and metabolic syndrome as predictors of type 2 diabetes: the Cooper Center Longitudinal Study.

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DeFina, Laura F; Vega, Gloria Lena; Leonard, David; Grundy, Scott M

2012-12-01

To determine risk for type 2 diabetes in subjects with fasting glucose levels in the ranges of normoglycemia, mild hyperglycemia, and intermediate hyperglycemia and to assess the effect of obesity and metabolic syndrome on this risk. Incidence of type 2 diabetes mellitus was evaluated in 28,209 relatively healthy subjects participating in the Cooper Center Longitudinal Study. They were included in the study if they had more than 1 fasting plasma glucose measurement, anthropometry, and other parameters of interest. Three subgroups were identified: normoglycemic (obesity, and metabolic syndrome status. Incident diabetes was assessed at the earliest clinic visit at which the individual exhibited a blood glucose level of more than 7.0 mmol/L or reported a diagnosis of diabetes. Thirty-one percent of men and 15.9% of women had mild hyperglycemia and 11.9% of men and 3.6% of women had intermediate hyperglycemia. Yearly conversion rates to diabetes were low in individuals with normoglycemia and mild hyperglycemia but were strikingly higher in those with intermediate hyperglycemia. In subjects with intermediate hyperglycemia, presence of obesity and/or metabolic syndrome doubled conversion rates to diabetes. This study showed a marked difference in outcomes in subjects with mild and intermediate hyperglycemia. Moreover, obesity and metabolic syndrome were associated with strikingly elevated risk for diabetes in subjects with intermediate hyperglycemia. Thus intermediate hyperglycemia plus obesity/metabolic syndrome seemingly justifies intensive clinical intervention for prevention of both diabetes and cardiovascular disease.

The role of social environment on parental care: offspring benefit more from the presence of female than male helpers.

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Brouwer, Lyanne; van de Pol, Martijn; Cockburn, Andrew

2014-03-01

Investment in offspring depends on the costs and benefits to the carer, which can vary with sex and social status. Investment also depends on the effort of others by allowing for compensation (load-lightening), with biparental care studies showing that this depends on the state and type of the other carer. By contrast, studies on cooperative breeders have solely focussed on the effects of group size rather than its composition (i.e. social environment). Here we propose and provide the first test of the 'Social Environment' hypothesis, that is, how the characteristics (here the sex) of other helpers present in the group affect parental care and how this in turn affects offspring fitness in cooperatively breeding red-winged fairy-wrens (Malurus elegans). Breeders provisioned nestlings at a higher rate than helpers, but there was no sex difference in provisioning rate. Compensation to increasing group size varied little with sex and status, but strongly depended on social environment. All group members reduced their provisioning rates in response to an increasing number of male (load-lightening), but not female helpers (additive care). As a result, nestlings received more food and grew faster in the presence of female helpers. The increased nestling growth did convey a fitness advantage due to a higher post-fledging survival to adulthood. Our study provides the first evidence that parental care can depend on social environment. This could be an important overlooked aspect to explain variation in parental care in cooperative breeders in general and in particular the enormous variation between the sexes, which we reveal in a literature overview. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

Effects of introducing heterologous pathways on microbial metabolism with respect to metabolic optimality

DEFF Research Database (Denmark)

Kim, Hyun Uk; Kim, Byoungjin; Seung, Do Young

2014-01-01

reactions are more frequently introduced into various microbial hosts. The genome-scale metabolic simulations of Escherichia coli strains engineered to produce 1,4-butanediol, 1,3-propanediol, and amorphadiene suggest that microbial metabolism shows much different responses to the introduced heterologous...... reactions in a strain-specific manner than typical gene knockouts in terms of the energetic status (e.g., ATP and biomass generation) and chemical production capacity. The 1,4-butanediol and 1,3-propanediol producers showed greater metabolic optimality than the wild-type strains and gene knockout mutants...... for the energetic status, while the amorphadiene producer was metabolically less optimal. For the optimal chemical production capacity, additional gene knockouts were most effective for the strain producing 1,3-propanediol, but not for the one producing 1,4-butanediol. These observations suggest that strains having...

An optimization model for metabolic pathways.

Science.gov (United States)

Planes, F J; Beasley, J E

2009-10-15

Different mathematical methods have emerged in the post-genomic era to determine metabolic pathways. These methods can be divided into stoichiometric methods and path finding methods. In this paper we detail a novel optimization model, based upon integer linear programming, to determine metabolic pathways. Our model links reaction stoichiometry with path finding in a single approach. We test the ability of our model to determine 40 annotated Escherichia coli metabolic pathways. We show that our model is able to determine 36 of these 40 pathways in a computationally effective manner.

Social evaluation of intentional, truly accidental, and negligently accidental helpers and harmers by 10-month-old infants.

Science.gov (United States)

Woo, Brandon M; Steckler, Conor M; Le, Doan T; Hamlin, J Kiley

2017-11-01

Whereas adults largely base their evaluations of others' actions on others' intentions, a host of research in developmental psychology suggests that younger children privilege outcome over intention, leading them to condemn accidental harm. To date, this question has been examined only with children capable of language production. In the current studies, we utilized a non-linguistic puppet show paradigm to examine the evaluation of intentional and accidental acts of helping or harming in 10-month-old infants. In Experiment 1 (n=64), infants preferred intentional over accidental helpers but accidental over intentional harmers, suggestive that by this age infants incorporate information about others' intentions into their social evaluations. In Experiment 2 (n=64), infants did not distinguish "negligently" accidental from intentional helpers or harmers, suggestive that infants may find negligent accidents somewhat intentional. In Experiment 3 (n=64), we found that infants preferred truly accidental over negligently accidental harmers, but did not reliably distinguish negligently accidental from truly accidental helpers, consistent with past work with adults and children suggestive that humans are particularly sensitive to negligently accidental harm. Together, these results imply that infants engage in intention-based social evaluation of those who help and harm accidentally, so long as those accidents do not stem from negligence. Copyright © 2017 Elsevier B.V. All rights reserved.

Homology Requirements for Efficient, Footprintless Gene Editing at the CFTR Locus in Human iPSCs with Helper-dependent Adenoviral Vectors

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Donna J Palmer

2016-01-01

Full Text Available Helper-dependent adenoviral vectors mediate high efficiency gene editing in induced pluripotent stem cells without needing a designer nuclease thereby avoiding off-target cleavage. Because of their large cloning capacity of 37 kb, helper-dependent adenoviral vectors with long homology arms are used for gene editing. However, this makes vector construction and recombinant analysis difficult. Conversely, insufficient homology may compromise targeting efficiency. Thus, we investigated the effect of homology length on helper-dependent adenoviral vector targeting efficiency at the cystic fibrosis transmembrane conductance regulator locus in induced pluripotent stem cells and found a positive correlation. With 23.8 and 21.4 kb of homology, the frequencies of targeted recombinants were 50–64.6% after positive selection for vector integration, and 97.4–100% after negative selection against random integrations. With 14.8 kb, the frequencies were 26.9–57.1% after positive selection and 87.5–100% after negative selection. With 9.6 kb, the frequencies were 21.4 and 75% after positive and negative selection, respectively. With only 5.6 kb, the frequencies were 5.6–16.7% after positive selection and 50% after negative selection, but these were more than high enough for efficient identification and isolation of targeted clones. Furthermore, we demonstrate helper-dependent adenoviral vector-mediated footprintless correction of cystic fibrosis transmembrane conductance regulator mutations through piggyBac excision of the selectable marker. However, low frequencies (≤ 1 × 10−3 necessitated negative selection for piggyBac-excision product isolation.

Analysis of recombinant mycobacteria as T helper type 1 vanccines in an allergy challange model

NARCIS (Netherlands)

Janssen, R.; Kruisselbrink, A.; Hoogteyling, L.; Lamb, J.R.; Young, D.B.; Thole, J.E.R.

2001-01-01

The potential for development of mycobacteria as T helper type 1 (Th1) vaccines capable of induction of Th1 responses to recombinant antigens was explored in a model system based on an immunodominant peptide from house dust mite. Different recombinant mycobacterial preparations were compared for

Hypoglycemia in pregnant women with type 1 diabetes - Predictors and role of metabolic control

DEFF Research Database (Denmark)

Nielsen, L.R.; Johansen, M.; Pedersen-Bjergaard, U.

2008-01-01

OBJECTIVE- In pregnancy with type 1 diabetes, we evaluated occurrence of mild and severe hypoglycemia and analyzed the influence of strict metabolic control, nausea, Vomiting, and other potential predictors of occurrence of severe hypoglycemia. RESEARCH DESIGN AND METHODS- A prospective...... awareness or unawareness (3.2 [1.2-8.2]) as independent predictors for severe hypoglycemia. CONCLUSIONS - In pregnancy with type 1 diabetes, the incidence of mild and severe hypoglycemia was highest in early pregnancy, although metabolic control was tighter in the last part of pregnancy. Predictors...... observational study of 108 consecutive pregnant women with type 1 diabetes was conducted. At 8, 14, 21, 27, and 33 weeks of gestation, patients performed self-monitored plasma glucose (SMPG) (eight/day) for 3 days and completed a questionnaire on nausea, vomiting, hypoglycemia awareness, and history of mild...

Speech Mannerisms: Games Clients Play

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Morgan, Lewis B.

1978-01-01

This article focuses on speech mannerisms often employed by clients in a helping relationship. Eight mannerisms are presented and discussed, as well as possible interpretations. Suggestions are given to help counselors respond to them. (Author)

[Effects of T helper 1 cells and T helper 17 cells secreting cytokines on rat models of experimental periodontitis].

Science.gov (United States)

Wang, Z X; Yang, L; Tan, J Y; Chen, L L

2017-12-09

Objectvie: To investigate the effects of secreting cytokines interferon-gamma (IFN-γ) and interleukin-17 (IL-17) of T helper 1 cells (Th1) and T helper 17 cells (Th17) on the peripheral blood and alveolar bone destruction, so as to provide a new explanation for cellular immunity-mediated alveolar bone destruction. Methods: Eighteen eight-week-old male Sprague-Dawley rats were divided, randomly and equally, into 3 groups: lipopolysaccharide (LPS) group, ligation group and normal control group. In the LPS group, Escherichia coli LPS was injected into the alveolar mucosa on the buccalmedian site of the left upper first molar, while the right upper first molar was injected with equal volume of physiological saline as self-controls. The injections were performed every other day for four times totally. In the ligation group, the left upper first molars were ligatured with 0.2 mm orthodontic cords, while the right upper first molars were left untreated as self-controls, and supplemented with high-sugar diet to promote the periodontitis status. The rats in normal control group were fed normally. The concentrations of IFN-γ and IL-17 in peripheral blood were measured using enzyme linked immunosorbent assay (ELISA) method at the fourth week after the start of injection and at the eighth week after ligation. The histological of periodontal tissues were observed after hematoxylin-eosin (HE) staining and osteoclast count was performed under light microscope. The histological of osteoclasts were observed after tartrate-resistant acid phosphatase (TRAP) staining. Expression of IFN-γ and IL-17 were detected by immunohistochemical assay. Results: The concentrations of IFN-γ in peripheral blood of LPS group [(185.0±50.7) ng/L] and ligation group [(202.9±60.4) ng/L] were significantly higher than that of normal control group [(106.3±17.2) ng/L]( Pperiodontitis and alveolar bone resorption could be successfully established by means of ligationand LPS injection, respectively

Physiological Requirements to Perform the Glittre Activities of Daily Living Test by Subjects With Mild-to-Severe COPD.

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Souza, Gérson F; Moreira, Graciane L; Tufanin, Andréa; Gazzotti, Mariana R; Castro, Antonio A; Jardim, José R; Nascimento, Oliver A

2017-08-01

The Glittre activities of daily living (ADL) test is supposed to evaluate the functional capacity of COPD patients. The physiological requirements of the test and the time taken to perform it by COPD patients in different disease stages are not well known. The objective of this work was to compare the metabolic, ventilatory, and cardiac requirements and the time taken to carry out the Glittre ADL test by COPD subjects with mild, moderate, and severe disease. Spirometry, Medical Research Council questionnaire, cardiopulmonary exercise test, and 2 Glittre ADL tests were evaluated in 62 COPD subjects. Oxygen uptake (V̇ O 2 ), carbon dioxide production, pulmonary ventilation, breathing frequency, heart rate, S pO 2 , and dyspnea were analyzed before and at the end of the tests. Maximum voluntary ventilation, Glittre peak V̇ O 2 /cardiopulmonary exercise test (CPET) peak V̇ O 2 , Glittre V̇ E /maximum voluntary ventilation, and Glittre peak heart rate/CPET peak heart rate ratios were calculated to analyze their reserves. Subjects carried out the Glittre ADL test with similar absolute metabolic, ventilatory, and cardiac requirements. Ventilatory reserve decreased progressively from mild to severe COPD subjects ( P reserve than the mild and moderate subjects ( P = .006 and P = .043, respectively) and significantly lower Glittre peak heart rate/CPET peak heart rate than mild subjects ( P = .01). Time taken to carry out the Glittre ADL test was similar among the groups ( P = .82 for GOLD 1 vs GOLD 2, P = .19 for GOLD 1 vs GOLD 3, and P = .45 for GOLD 2 vs GOLD 3). As the degree of air-flow obstruction progresses, the COPD subjects present significant lower ventilatory reserve to perform the Glittre ADL test. In addition, metabolic and cardiac reserves may differentiate the severe subjects. These variables may be better measures to differentiate functional performance than Glittre ADL time. Copyright © 2017 by Daedalus Enterprises.

CHEMOKINE RECEPTORS AT DISTINCT DIFFERENTIATION STAGES OF T-HELPERS FROM PERIPHERAL BLOOD

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I. V. Kudryavtsev

2016-01-01

Full Text Available Expression of chemokine receptors (CCR4, CCR6, CXCR3 and CXCR5 on T-helper (Th cells at various levels of differentiation in a group of healthy volunteers (n = 52 was assessed on the basis of CD45RA and CD62L expression, using the eight-color flow cytometry. It was found that the “naive” T helper cells (N with CD45RA+CD62L+ phenotype express CXCR3 (4.94±0.39%, and CXCR5 (3.63±0.25%. About 50% of central memory T helpers (CD45RA–CD62L+, CM were CXCR3 positive, and 43.72±1.27% of CM cells expressed CCR6, whereas CXCR5 and CCR4 levels were about 30%. Furthermore, CXCR3 was expressed by 76.76±0.75% of the CD3+CD4+CD45RA–CD62L– (EM population, and similar values were obtained for CCR6, while the relative abundance of CXCR5+ cells decreased to 13.68±0.50%, and CCR4 levels did not change and accounted for 33.26±1.13% positive cells. Likewise, co-expression of the chemokine receptors was studied for the abovementioned subpopulations of T helper cells. Among the CXCR5– Th, Th1 cells were identified as CXCR3+CCR6–CCR4– (this subset also contained Th9, and CXCR3+CCR6+CCR4– subsets, referred to as Th1/Th17. Th2 were detected on the basis of CCR4 expression in absence of all other chemokine receptors. In addition to the mentioned Th1/Th17 populations, Th 17 cells were found in the subsets of Th17 CXCR3–CCR6+CCR4– and CXCR3–CR6+CCR4+. The latter also contained a Th22 population. Follicular Th cell populations (CXCR5+ consisted of, at least, six different subsets: CXCR3–CCR6–CCR4– (Tfh/Tfh2, CXCR3–CCR6–CCR4+ (Tfh2, CXCR3-CCR6+CCR4–(Tfh17, CXCR3–CCR6+CCR4+ (Tfh17, CXCR3+CCR6–CCR4– (Tfh1 and CXCR3+CCR6+CCR4–(Tfh1/Tfh17. The cells with Th1/Th9 and Th1/Th17 phenotypes dominated among CM (about 13%, whereas their relative abundance within EM increased to 22.37±1.69% and 31.69±1.52%, respectively. The amounts of Th2 were 8.15±0.46% within CM, and only 1.72±0.15% for EM population. For the cells

Prolonged peritoneal gene expression using a helper-dependent adenovirus.

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Liu, Limin; Shi, Chang-Xin; Ghayur, Ayesha; Zhang, Claire; Su, Je Yen; Hoff, Catherine M; Margetts, Peter J

2009-01-01

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis. The causes of EPS are not well defined and are likely multifactorial. A suitable animal model would facilitate research into the pathophysiology and treatment of EPS. We developed a helper-dependent adenovirus that expresses both green fluorescent protein (GFP) and active transforming growth factor-beta (TGF-beta1; HDAdTGF-beta1). Mice were administered HDAdTGF-beta1 via intraperitoneal injection and the response was compared with mice administered either first-generation adenovirus expressing TGF-beta1 (AdTGF-beta1) or control adenovirus (AdGFP). HDAdTGF-beta1-treated mice continued to express the GFP reporter transgene to day 74, the end of the observation period. Transgene expression lasted less than 28 days in the animals treated with first-generation adenoviruses. Animals treated with first-generation AdTGF-beta1 demonstrated submesothelial thickening and angiogenesis at day 7, with almost complete resolution by day 28. The HDAdTGF-beta1-treated mice demonstrated progressive peritoneal fibrosis with adhesion formation and encapsulation of bowels. Weight gain was significantly reduced in animals treated with HDAdTGF-beta1 compared to both the control-treated animals and the AdTGF-beta1-treated animals. Inflammation was not a major component of the fibroproliferative response. Peritoneal administration of a first-generation AdTGF-beta1 leads to transient gene expression, resulting in a resolving fibrotic response and histology similar to that seen in simple peritoneal sclerosis. Prolonged TGF-beta1 expression induced by the helper-dependent HDAdTGF-beta1 led to changes in peritoneal morphology resembling EPS. This suggests that TGF-beta1 may be a contributing factor in both simple peritoneal sclerosis and EPS. This model will be useful for elucidation of the mechanism of EPS and evaluation of potential treatment.

Buried Messages, Hidden Meanings: Speech Mannerisms Revisited.

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Morgan, Lewis B.

1988-01-01

Introduces counselors to 10 commonly used mannerisms of speech and the part that each mannerism plays in the communication process, especially in the counseling context. Offers suggestions on how to respond to these speech mannerisms in a straightforward and effective manner. (Author)

Human Rights and International Labour Law issues concerning Migrant Women Working as Domestic Helpers in China

NARCIS (Netherlands)

Peng, Q.|info:eu-repo/dai/nl/375803998

2017-01-01

This book addresses the human rights and international labour law issues concerning rural migrant women workers as domestic helpers in China and offers several legislative suggestions to the Chinese government. By describing the current de facto and de jure condition of rural migrant women working

Mild cold effects on hunger, food intake, satiety and skin temperature in humans

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M Langeveld

2016-04-01

Full Text Available Background Mild cold exposure increases energy expenditure and can influence energy balance, but at the same time it does not increase appetite and energy intake. Objective To quantify dermal insulative cold response, we assessed thermal comfort and skin temperatures changes by infrared thermography. Methods We exposed healthy volunteers to either a single episode of environmental mild cold or thermoneutrality. We measured hunger sensation and actual free food intake. After a thermoneutral overnight stay, five males and five females were exposed to either 18°C (mild cold or 24°C (thermoneutrality for 2.5 h. Metabolic rate, vital signs, skin temperature, blood biochemistry, cold and hunger scores were measured at baseline and for every 30 min during the temperature intervention. This was followed by an ad libitum meal to obtain the actual desired energy intake after cold exposure. Results We could replicate the cold-induced increase in REE. But no differences were detected in hunger, food intake, or satiety after mild cold exposure compared with thermoneutrality. After long-term cold exposure, high cold sensation scores were reported, which were negatively correlated with thermogenesis. Skin temperature in the sternal area was tightly correlated with the increase in energy expenditure. Conclusions It is concluded that short-term mild cold exposure increases energy expenditure without changes in food intake. Mild cold exposure resulted in significant thermal discomfort, which was negatively correlated with the increase in energy expenditure. Moreover, there is a great between-subject variability in cold response. These data provide further insights on cold exposure as an anti-obesity measure.

Diffusion MRI and MR spectroscopy reveal microstructural and metabolic brain alterations in chronic mild stress exposed rats: A CMS recovery study.

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Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove; Kroenke, Christopher D; Jespersen, Sune Nørhøj

2018-02-15

Chronic mild stress (CMS) induced depression elicits several debilitating symptoms and causes a significant economic burden on society. High variability in the symptomatology of depression poses substantial impediment to accurate diagnosis and therapy outcome. CMS exposure induces significant metabolic and microstructural alterations in the hippocampus (HP), prefrontal cortex (PFC), caudate-putamen (CP) and amygdala (AM), however, recovery from these maladaptive changes are limited and this may provide negative effects on the therapeutic treatment and management of depression. The present study utilized anhedonic rats from the unpredictable CMS model of depression to study metabolic recovery in the ventral hippocampus (vHP) and microstructural recovery in the HP, AM, CP, and PFC. The study employed 1 H MR spectroscopy ( 1 H MRS) and in-vivo diffusion MRI (d-MRI) at the age of week 18 (week 1 post CMS exposure) week 20 (week 3 post CMS) and week 25 (week 8 post CMS exposure) in the anhedonic group, and at the age of week 18 and week 22 in the control group. The d-MRI data have provided an array of diffusion tensor metrics (FA, MD, AD, and RD), and fast kurtosis metrics (MKT, W L and W T ). CMS exposure induced a significant metabolic alteration in vHP, and significant microstructural alterations were observed in the HP, AM, and PFC in comparison to the age match control and within the anhedonic group. A significantly high level of N-acetylaspartate (NAA) was observed in vHP at the age of week 18 in comparison to age match control and week 20 and week 25 of the anhedonic group. HP and AM showed significant microstructural alterations up to the age of week 22 in the anhedonic group. PFC showed significant microstructural alterations only at the age of week 18, however, most of the metrics showed significantly higher value at the age of week 20 in the anhedonic group. The significantly increased NAA concentration may indicate impaired catabolism due to astrogliosis or

Cerebral glucose metabolism in Wernicke's, Broca's, and conduction aphasia

International Nuclear Information System (INIS)

Metter, E.J.; Kempler, D.; Jackson, C.; Hanson, W.R.; Mazziotta, J.C.; Phelps, M.E.

1989-01-01

Cerebral glucose metabolism was evaluated in patients with either Wernicke's (N = 7), Broca's (N = 11), or conduction (N = 10) aphasia using 18 F-2-fluoro-2-deoxy-D-glucose with positron emission tomography. The three aphasic syndromes differed in the degree of left-to-right frontal metabolic asymmetry, with Broca's aphasia showing severe asymmetry and Wernicke's aphasia mild-to-moderate metabolic asymmetry, while patients with conduction aphasia were metabolically symmetric. On the other hand, the three syndromes showed the same degree of metabolic decline in the left temporal region. The parietal region appeared to separate conduction aphasia from both Broca's and Wernicke's aphasias. Common aphasic features in the three syndromes appear to be due to common changes in the temporal region, while unique features were associated with frontal and parietal metabolic differences

Tracking by flow cytometry antigen-specific follicular helper T cells in wild-type animals after protein vaccination.

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Chakarov, Svetoslav; Fazilleau, Nicolas

2015-01-01

Flow cytometry is a valuable technology used in immunology to characterize and enumerate the different cell subpopulations specific for a nonself-antigen in the context of an ongoing immune response. Among them, follicular helper T cells are the cognate regulators of B cells in secondary lymphoid tissues. Thus, tracking them is of high interest especially in the context of protein vaccination. For this purpose, transgenic antigen-receptor mouse models have been largely used. It is now clear that transgenic models are not always the best means to study the dynamics of the immune response since they can modify the response. In this chapter, we describe how to track endogenous antigen-specific follicular helper T cells by flow cytometry after protein vaccination in nonmodified wild-type animals, which ultimately provides a comprehensive way to enumerate, characterize, and isolate these particular cells in vivo.

CD4 T-helper cell cytokine phenotypes and antibody response following tetanus toxoid booster immunization

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Routine methods for enumerating antigen-specific T-helper cells may not identify low-frequency phenotypes such as Th2 cells. We compared methods of evaluating such responses to identify tetanus toxoid- (TT) specific Th1, Th2, Th17 and IL10+ cells. Eight healthy subjects were given a TT booster vacci...

Morphological divergence of breeders and helpers in wild Damaraland mole-rat societies.

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Young, Andrew J; Bennett, Nigel C

2010-11-01

The specialization of body shape to an individual's role within society represents a pinnacle of social evolution. Although commonplace among social insects, divergence in the body shapes of breeders and helpers has to date been documented in just one social vertebrate, the naked mole-rat, Heterocephalus glaber; an extraordinary species in which large colony size and frequent inbreeding may have favored the evolution of such specialization. Here, we present new evidence of morphological divergence between breeders and helpers in the Damaraland mole-rat, Fukomys damarensis; a much less socially extreme species that reflects an independent evolutionary origin of sociality. Using longitudinal data from wild populations, we show that dominant female Damaraland mole-rats, like many social insect queens, have a significantly more elongate body shape than subordinates. This difference arises not from a pre-existing difference in the body shapes of subordinates that do, and those that do not, become dominant, but from a modification to the growth trajectory of subordinates on dominance acquisition. Our findings reveal a wider role for morphological divergence within vertebrate societies and, as Damaraland mole-rats neither live in unusually large groups nor inbreed, suggest that circumstances favoring the evolution of such specializations may be more widespread among vertebrates than previously supposed. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

Variation of Neisseria gonorrhoeae lipooligosaccharide directs dendritic cell-induced T helper responses.

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Sandra J van Vliet

2009-10-01

Full Text Available Gonorrhea is one of the most prevalent sexually transmitted diseases in the world. A naturally occurring variation of the terminal carbohydrates on the lipooligosaccharide (LOS molecule correlates with altered disease states. Here, we investigated the interaction of different stable gonoccocal LOS phenotypes with human dendritic cells and demonstrate that each variant targets a different set of receptors on the dendritic cell, including the C-type lectins MGL and DC-SIGN. Neisseria gonorrhoeae LOS phenotype C constitutes the first bacterial ligand to be described for the human C-type lectin receptor MGL. Both MGL and DC-SIGN are locally expressed at the male and female genital area, the primary site of N. gonorrhoeae infection. We show that targeting of different C-type lectins with the N. gonorrhoeae LOS variants results in alterations in dendritic cell cytokine secretion profiles and the induction of distinct adaptive CD4(+ T helper responses. Whereas N. gonorrhoeae variant A with a terminal N-acetylglucosamine on its LOS was recognized by DC-SIGN and induced significantly more IL-10 production, phenotype C, carrying a terminal N-acetylgalactosamine, primarily interacted with MGL and skewed immunity towards the T helper 2 lineage. Together, our results indicate that N. gonorrhoeae LOS variation allows for selective manipulation of dendritic cell function, thereby shifting subsequent immune responses in favor of bacterial survival.

The Factor Inhibiting HIF Asparaginyl Hydroxylase Regulates Oxidative Metabolism and Accelerates Metabolic Adaptation to Hypoxia.

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Sim, Jingwei; Cowburn, Andrew S; Palazon, Asis; Madhu, Basetti; Tyrakis, Petros A; Macías, David; Bargiela, David M; Pietsch, Sandra; Gralla, Michael; Evans, Colin E; Kittipassorn, Thaksaon; Chey, Yu C J; Branco, Cristina M; Rundqvist, Helene; Peet, Daniel J; Johnson, Randall S

2018-04-03

Animals require an immediate response to oxygen availability to allow rapid shifts between oxidative and glycolytic metabolism. These metabolic shifts are highly regulated by the HIF transcription factor. The factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that controls HIF transcriptional activity in an oxygen-dependent manner. We show here that FIH loss increases oxidative metabolism, while also increasing glycolytic capacity, and that this gives rise to an increase in oxygen consumption. We further show that the loss of FIH acts to accelerate the cellular metabolic response to hypoxia. Skeletal muscle expresses 50-fold higher levels of FIH than other tissues: we analyzed skeletal muscle FIH mutants and found a decreased metabolic efficiency, correlated with an increased oxidative rate and an increased rate of hypoxic response. We find that FIH, through its regulation of oxidation, acts in concert with the PHD/vHL pathway to accelerate HIF-mediated metabolic responses to hypoxia. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Mild gestational diabetes mellitus and long-term child health.

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Landon, Mark B; Rice, Madeline Murguia; Varner, Michael W; Casey, Brian M; Reddy, Uma M; Wapner, Ronald J; Rouse, Dwight J; Biggio, Joseph R; Thorp, John M; Chien, Edward K; Saade, George; Peaceman, Alan M; Blackwell, Sean C; VanDorsten, J Peter

2015-03-01

To evaluate whether treatment of mild gestational diabetes mellitus (GDM) confers sustained offspring health benefits, including a lower frequency of obesity. Follow-up study of children (ages 5-10) of women enrolled in a multicenter trial of treatment versus no treatment of mild GDM. Height, weight, blood pressure, waist circumference, fasting glucose, fasting insulin, triglycerides, and HDL cholesterol were measured. Five hundred of 905 eligible offspring (55%) were enrolled. Maternal baseline characteristics were similar between the follow-up treated and untreated groups. The frequencies of BMI ≥95th (20.8% and 22.9%) and 85th (32.6% and 38.6%) percentiles were not significantly different in treated versus untreated offspring (P = 0.69 and P = 0.26). No associations were observed for BMI z score, log waist circumference, log triglycerides, HDL cholesterol, blood pressure, or log HOMA-estimated insulin resistance (HOMA-IR). The effect of treatment was different by sex for fasting glucose and log HOMA-IR (P for interaction = 0.002 and 0.02, respectively) but not by age-group (5-6 and 7-10 years) for any outcomes. Female offspring of treated women had significantly lower fasting glucose levels. Although treatment for mild GDM has been associated with neonatal benefits, no reduction in childhood obesity or metabolic dysfunction in the offspring of treated women was found. However, only female offspring of women treated for mild GDM had lower fasting glucose. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The lupus susceptibility gene Pbx1 regulates the balance between follicular helper T cell and regulatory T cell differentiation

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Choi, Seung-Chul; Hutchinson, Tarun E.; Titov, Anton A.; Seay, Howard R.; Li, Shiwu; Brusko, Todd M.; Croker, Byron P.; Salek-Ardakani, Shahram; Morel, Laurence

2016-01-01

Pbx1 controls chromatin accessibility to a large number of genes and is entirely conserved between mice and humans. The Pbx1-d dominant negative isoform is more frequent in the CD4+ T cells from lupus patients than from healthy controls. Pbx1-d is associated with the production of autoreactive T cells in mice carrying the Sle1a1 lupus susceptibility locus. Transgenic expression of Pbx1-d in CD4+ T cells reproduced the phenotypes of Sle1a1 mice, with increased inflammatory functions of CD4+ T cells and impaired regulatory T cell homeostasis. Pbx1-d Tg also expanded the number of follicular helper T cells in a cell-intrinsic and antigen-specific manner that was enhanced in recall responses, and resulted in TH1-biased antibodies. Moreover, Pbx1-d Tg CD4+ T cells upregulated the expression of miR-10a, miR-21 and miR-155, which have been implicated in Treg and TFH cell homeostasis. Our results suggest that Pbx1-d impacts lupus development by regulating effector T cell differentiation and promoting TFH cells at the expense of Treg cells. In addition, our results identify Pbx1 as a novel regulator of CD4+ T cell effector function. PMID:27296664

Brain metabolic impairment of OSAS: evidence from MRS

International Nuclear Information System (INIS)

Shen Jie; Long Miaomiao; Shen Wen; Qi Ji

2011-01-01

Objective: To evaluate the impact of obstructive sleep apnea syndrome (OSAS) on human cerebral metabolism by using magnetic resonance spectroscopy (MRS). Materials and methods: Twenty-one severe OSAS patients, 14 mild-moderate OSAS patients, and 15 healthy control subjects were included. All subjects underwent MRS using the point-resolved echo spin spectroscopy (PRESS). Proton volumes of interest were placed in the bilateral frontal lobes and left temporal -parietal-occipital cortex, and left hippocampus. Results: 1. Compared to the controls, the NAA/Cr ratio was significantly decreased in the left frontal lobe in the severe OSAS group (P=0.004), and in the right frontal lobe in the severe (P=0.002) and mild-moderate (P=0.007) OSAS patients. The NAA/Cr ratio trended to be decreased in the left hippocampus in the OSAS patients compared to controls. 2. A significant increase in the ml/Cr ratio was detected in the right frontal regions in the severe (P=0.008) and mild-moderate (P<0.001) OSAS groups. 3. Clx/Cr ratio values were significantly smaller than controls in the left (P=0.006) and right (P=0.027) frontal regions. Conclusion: Bilateral frontal lobes are the vulnerable location in patients with OSAS. MRS can be used to screen the brain metabolic impairment. (authors)

Serum metabonomics study of anti-depressive effect of Xiao-Chai-Hu-Tang on rat model of chronic unpredictable mild stress.

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Xiong, Zhili; Yang, Jie; Huang, Yue; Zhang, Kuo; Bo, Yunhai; Lu, Xiumei; Su, Guangyue; Ma, Jie; Yang, Jingyu; Zhao, Longshan; Wu, Chunfu

2016-09-01

Xiao-Chai-Hu-Tang (XCHT) has been proven to be effective for the clinical treatment of depression. However, the mechanisms of definite antidepressant-like effects and detailed metabolic biomarkers were still unclear in this prior study. Here, we have investigated the metabolic profiles and potential biomarkers in a chronic unpredictable mild stress model after treatment with XCHT. Metabonomics based on ultra-high performance liquid chromatography coupled with mass spectrometry was used to profile the metabolic fingerprints of serum obtained from a rat model with chronic unpredictable mild stress with and without XCHT treatment. The model rats showed a significant decrease in sucrose preference and food consumption, and these depression-like symptoms were significantly improved by XCHT. Through principal component analysis (PCA), nine potential biomarkers of tryptophan, uric acid, phenylalanine, cholic acid and lysophosphatidylcholine (C18:0 LPC, C16:0 LPC, C16:1 LPC, C18:1 LPC, C20:4 LPC) were characterized as potential biomarkers involved the pathogenesis of depression. The therapeutic effect of XCHT on depression may involve in amino acid metabolism, lipid metabolism, oxidative stress and inflammation response. The present investigation highlights that metabonomics is a valuable tool for studying the essence of depression as well as evaluating the efficacy of the corresponding drug treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation.

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Sinclair, Charles; Bommakanti, Gayathri; Gardinassi, Luiz; Loebbermann, Jens; Johnson, Matthew Joseph; Hakimpour, Paul; Hagan, Thomas; Benitez, Lydia; Todor, Andrei; Machiah, Deepa; Oriss, Timothy; Ray, Anuradha; Bosinger, Steven; Ravindran, Rajesh; Li, Shuzhao; Pulendran, Bali

2017-09-08

Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103 + DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b + DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (T H 2) to neutrophilic T H 17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Metabolism of murine TH 17 cells: Impact on cell fate and function.

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Wang, Ran; Solt, Laura A

2016-04-01

An effective adaptive immune response relies on the ability of lymphocytes to rapidly act upon a variety of insults. In T lymphocytes, this response includes cell growth, clonal expansion, differentiation, and cytokine production, all of which place a significant energy burden on the cell. Recent evidence shows that T-cell metabolic reprogramming is an essential component of the adaptive immune response and specific metabolic pathways dictate T-cell fate decisions, including the development of TH 17 versus T regulatory (Treg) cells. TH 17 cells have garnered significant attention due to their roles in the pathology of immune-mediated inflammatory diseases. Attempts to characterize TH 17 cells have demonstrated that they are highly dynamic, adjusting their function to environmental cues, which dictate their metabolic program. In this review, we highlight recent data demonstrating the impact of cellular metabolism on the TH 17/Treg balance and present factors that mediate TH 17-cell metabolism. Some examples of these include the differential impact of the mTOR signaling complexes on T-helper-cell differentiation, hypoxia inducible factor 1 alpha (HIF1α) promotion of glycolysis to favor TH 17-cell development, and ACC1-dependent de novo fatty acid synthesis favoring TH 17-cell development over Treg cells. Finally, we discuss the potential therapeutic options and the implications of modulating TH 17-cell metabolism for the treatment of TH 17-mediated diseases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nuclear receptors and metabolism: from feast to famine.

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Hong, Suk-Hyun; Ahmadian, Maryam; Yu, Ruth T; Atkins, Annette R; Downes, Michael; Evans, Ronald M

2014-05-01

The ability to adapt to cycles of feast and famine is critical for survival. Communication between multiple metabolic organs must be integrated to properly metabolise nutrients. By controlling networks of genes in major metabolic organs, nuclear hormone receptors (NHRs) play central roles in regulating metabolism in a tissue-specific manner. NHRs also establish daily rhythmicity by controlling the expression of core clock genes both centrally and peripherally. Recent findings show that many of the metabolic effects of NHRs are mediated through certain members of the fibroblast growth factor (FGF) family. This review focuses on the roles of NHRs in critical metabolic organs, including adipose tissue, liver and muscle, during the fed and fasted states, as well as their roles in circadian metabolism and downstream regulation of FGFs.

Splenic T helper cell type 1 cytokine profile and extramedullary haematopoiesis in severe combined immunodeficient (scid) mice with inflammatory bowel disease (IBD)

DEFF Research Database (Denmark)

Bregenholt, S; Claesson, Mogens Helweg

1998-01-01

Scid mice develop a severe, chronic, and lethal IBD 3-6 months after engraftment of gut wall from immunocompetent congenic donors, induced by donor-derived CD4+ T cells migrating from the graft. We have investigated intracellular T-helper type 1 (Th1) cytokines in the spleens of gut wall-transpla......Scid mice develop a severe, chronic, and lethal IBD 3-6 months after engraftment of gut wall from immunocompetent congenic donors, induced by donor-derived CD4+ T cells migrating from the graft. We have investigated intracellular T-helper type 1 (Th1) cytokines in the spleens of gut wall...

Mycorrhization between Cistus ladanifer L. and Boletus edulis Bull is enhanced by the mycorrhiza helper bacteria Pseudomonas fluorescens Migula.

Science.gov (United States)

Mediavilla, Olaya; Olaizola, Jaime; Santos-del-Blanco, Luis; Oria-de-Rueda, Juan Andrés; Martín-Pinto, Pablo

2016-02-01

Boletus edulis Bull. is one of the most economically and gastronomically valuable fungi worldwide. Sporocarp production normally occurs when symbiotically associated with a number of tree species in stands over 40 years old, but it has also been reported in 3-year-old Cistus ladanifer L. shrubs. Efforts toward the domestication of B. edulis have thus focused on successfully generating C. ladanifer seedlings associated with B. edulis under controlled conditions. Microorganisms have an important role mediating mycorrhizal symbiosis, such as some bacteria species which enhance mycorrhiza formation (mycorrhiza helper bacteria). Thus, in this study, we explored the effect that mycorrhiza helper bacteria have on the efficiency and intensity of the ectomycorrhizal symbiosis between C. ladanifer and B. edulis. The aim of this work was to optimize an in vitro protocol for the mycorrhizal synthesis of B. edulis with C. ladanifer by testing the effects of fungal culture time and coinoculation with the helper bacteria Pseudomonas fluorescens Migula. The results confirmed successful mycorrhizal synthesis between C. ladanifer and B. edulis. Coinoculation of B. edulis with P. fluorescens doubled within-plant mycorrhization levels although it did not result in an increased number of seedlings colonized with B. edulis mycorrhizae. B. edulis mycelium culture time also increased mycorrhization levels but not the presence of mycorrhizae. These findings bring us closer to controlled B. edulis sporocarp production in plantations.

Kant, Xunzi and the Artificiality of Manners

Directory of Open Access Journals (Sweden)

Anja BERNINGER

2017-01-01

Full Text Available Both Chinese and Western philosophers have argued for the ethical importance of manners. Their approaches are sometimes criticized on the grounds that manners are artificial. I compare Xunzi’s and Kant’s responses to this claim, and discuss the relevance of both positions for the development of a theory of manners. I show that there is no single artificiality claim, but rather four different claims: the claim that polite behavior lacks spontaneity, the claim that it is insincere, the claim that it goes against human nature, and the claim that it is arbitrary. While Kant is mainly concerned with the insincerity claim, Xunzi focusses on the claim that manners are arbitrary rules. Because of their different understandings of the function of manners both authors only provide a partial answer to the artificiality claim. To arrive at a full account of manners both perspectives must be combined.

The positive bystander effect: passive bystanders increase helping in situations with high expected negative consequences for the helper.

Science.gov (United States)

Fischer, Peter; Greitemeyer, Tobias

2013-01-01

The present field study investigated the interplay between the presence of a passive bystander (not present versus present) in a simulated bike theft and expected negative consequences (low versus high) in predicting intervention behavior when no physical victim is present. It was found that an additional bystander increases individual intervention in situations where the expected negative consequences for the helper in case of intervention were high (i.e., when the bike thief looks fierce) compared to situations where the expected negative consequences for the helper were low (i.e., when the bike thief does not look fierce). In contrast, no such effect for high vs. low expected negative consequences was observed when no additional bystander observed the critical situation. The results are discussed in light of previous laboratory findings on expected negative consequences and bystander intervention.

Relationship between obesity, metabolic syndrome, and nonalcoholic fatty liver disease in the elderly agricultural and fishing population of Taiwan.

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Shen, Hsi-Che; Zhao, Zi-Hao; Hu, Yi-Chun; Chen, Yu-Fen; Tung, Tao-Hsin

2014-01-01

The purpose of this study was to explore the relationship between obesity, the metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) in the elderly agricultural and fishing population of Taipei, Taiwan. The study participants comprised 6,511 (3,971 male and 2,540 female) healthy elderly subjects voluntarily attending a teaching hospital for a physical check-up in 2010. Blood samples and real-time ultrasound-proven fatty liver sonography results were collected. The prevalence of NAFLD in this elderly population was 27.2%, including mild NAFLD (16.0%), moderate NAFLD (10.3%), and severe NAFLD (0.9%). The prevalence of moderate or severe NAFLD for metabolic syndrome proved to be substantially greater (P<0.0001, χ(2) test) for one or two metabolic factors. Using multinomial logistic regression analysis, age, sex, metabolic syndrome, and higher body mass index had a statistically significant association with mild NAFLD. Age, sex, metabolic syndrome, higher body mass index, and higher alanine aminotransferase were significantly related to moderate NAFLD. In addition, higher body mass index, higher uric acid, and higher alanine aminotransferase levels were significantly related to severe NAFLD. The sensitivity and specificity of body mass index and waist circumference as markers of NAFLD were estimated to be 81% and 84%, respectively, and 77% and 69%, respectively. The prevalence of mild or moderate NAFLD was related to obesity and metabolic syndrome. Higher body mass index was also related to severe NAFLD but not to metabolic syndrome. Targeting this population for control of obesity and improved metabolic function is important.

Recent developments in basophil research : do basophils initiate and perpetuate type 2 T-helper cell responses?

NARCIS (Netherlands)

Beek, van A.A.; Knol, E.F.; Vos, de P.; Smelt, M.J.; Savelkoul, H.F.J.; Neerven, van R.J.J.

2013-01-01

Basophils account for only 0.1–1% of all peripheral blood leukocytes. They were considered to be a redundant cell type for a long time. However, several findings show a non-redundant role for basophils in type 2 T-helper cell (Th2) immune responses in helminth infections, allergy and autoimmunity.

Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer's disease

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Mosconi, Lisa; Rusinek, Henry; De Santi, Susan; Li, Yi [New York University School of Medicine, Center for Brain Health, MHL 400, Department of Psychiatry, New York, NY (United States); Tsui, Wai H.; De Leon, Mony J. [New York University School of Medicine, Center for Brain Health, MHL 400, Department of Psychiatry, New York, NY (United States); Nathan Kline Institute, Orangeburg, NY (United States); Wang, Gene-Jack; Fowler, Joanna [Brookhaven National Laboratory, Upton, NY (United States); Pupi, Alberto [University of Florence, Department of Clinical Pathophysiology, Nuclear Medicine Unit, Florence (Italy)

2007-09-15

To examine CMRglc measures and corresponding glucose transport (K{sub 1} and k{sub 2}) and phosphorylation (k{sub 3}) rates in the medial temporal lobe (MTL, comprising the hippocampus and amygdala) and posterior cingulate cortex (PCC) in mild Alzheimer's disease (AD). Dynamic FDG PET with arterial blood sampling was performed in seven mild AD patients (age 68 {+-} 8 years, four females, median MMSE 23) and six normal (NL) elderly (age 69 {+-} 9 years, three females, median MMSE 30). Absolute CMRglc ({mu}mol/100 g/min) was calculated from MRI-defined regions of interest using multiparametric analysis with individually fitted kinetic rate constants, Gjedde-Patlak plot, and Sokoloff's autoradiographic method with population-based rate constants. Relative ROI/pons CMRglc (unitless) was also examined. With all methods, AD patients showed significant CMRglc reductions in the hippocampus and PCC, and a trend towards reduced parietotemporal CMRglc, as compared with NL. Significant k{sub 3} reductions were found in the hippocampus, PCC and amygdala. K{sub 1} reductions were restricted to the hippocampus. Relative CMRglc had the largest effect sizes in separating AD from NL. However, the magnitude of CMRglc reductions was 1.2- to 1.9-fold greater with absolute than with relative measures. CMRglc reductions are most prominent in the MTL and PCC in mild AD, as detected with both absolute and relative CMRglc measures. Results are discussed in terms of clinical and pharmaceutical applicability. (orig.)

Association between metabolic syndrome and mild cognitive impairment and its age difference in a Chinese community elderly population.

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Liu, Miao; He, Yao; Jiang, Bin; Wu, Lei; Wang, Jianghua; Yang, Shanshan; Wang, Yiyan

2015-06-01

To examine associations between metabolic syndrome (MetS) and its individual components with risk of mild cognitive impairment (MCI) among community elderly and explore the age difference. Cross-sectional study. About 2,102 aged 60 and older community residents in Beijing metropolitan area, China. Cognitive function was assessed by Mini-Mental State Examination (MMSE). MetS was defined by the 2009 harmonizing definition. Overnight-fasting blood samples were obtained to measure biochemistry indicators. The prevalence of MetS and MCI was 59·1% and 15·9%, respectively. After adjusting age, gender, other demographic factors, lifestyle variables and medication use, participants with MetS or its individual components are at significantly elevated risk for MCI. In terms of MMSE score, as the continuous dependent variable, the β (95% CI) of MetS was -0·68(-0·99, -0·37). For prevalence of MCI, as the dichotomy dependent variable, the odds ratio (OR) of Mets is 1·52 compared to control group (or baseline) with 95% confidence interval (CI) of 1·16 to 1·95. The multivariate association only showed significant results among participants aged less than 80 years old. MetS is associated with worse cognitive function among younger elderly. Managing MetS, as well as its components, may contribute to control cognitive decline and reduce related disease and social burden. © 2015 John Wiley & Sons Ltd.

Targeting CD4(+) T-Helper Cells Improves the Induction of Antitumor Responses in Dendritic Cell-Based Vaccination

NARCIS (Netherlands)

Aarntzen, Erik H. J. G.; de Vries, I. Jolanda M.; Lesterhuis, W. Joost; Schuurhuis, Danita; Jacobs, Joannes F. M.; Bol, Kalijn; Schreibelt, Gerty; Mus, Roel; de Wilt, Johannes H. W.; Haanen, John B. A. G.; Schadendorf, Dirk; Croockewit, Alexandra; Blokx, Willeke A. M.; van Rossum, Michelle M.; Kwok, William W.; Adema, Gosse J.; Punt, Cornelis J. A.; Figdor, Carl G.

2013-01-01

To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)-restricted epitopes alone or both MHC

Retrospective case studies of the efficacy of caprylic triglyceride in mild-to-moderate Alzheimer's disease

Directory of Open Access Journals (Sweden)

Maynard SD

2013-10-01

Full Text Available Steven Douglas Maynard,1,2 Jeff Gelblum31Union Associated Physicians Clinic, 2Indiana University School of Medicine, Terre Haute, IN, 3Mt Sinai Medical Center of Miami, Aventura Hospital, Aventura, FL, USAAbstract: Under normal conditions, the adult human brain is fueled primarily by glucose. A prominent feature of Alzheimer's disease (AD is region-specific decreases in cerebral glucose metabolism. Ketone bodies are a group of compounds produced from fat stores during periods of low glucose availability that can provide an alternative to glucose for brain metabolism. Consumption of sufficient quantities of caprylic triglyceride (CT increases plasma concentrations of ketone bodies and may be beneficial in conditions of compromised glucose metabolism, such as AD. The present study describes the use of CT in mild-to-moderate AD in routine clinical practice. Case records from eight patients with extensive monitoring of cognitive function using the Mini-Mental State Examination (MMSE and who had received CT for ≥6 months were reviewed. All were outpatients aged ≥50 years, cared for in standard practice, had a diagnosis of probable AD of mild-to-moderate severity (MMSE 14–24, and had received CT for at least 6 months in addition to other approved pharmacotherapy for AD. Response to CT administration as measured by MMSE scores varied by patient. However, the rate of decline in MMSE scores appeared slower than previously published reports for patients treated with pharmacotherapy alone. Profiling of individual patients may provide insight regarding those most likely to benefit from addition of CT to currently approved AD pharmacotherapy.Keywords: ketosis, cognition, Alzheimer's disease, metabolism, glucose

Mind Your Manners

Energy Technology Data Exchange (ETDEWEB)

Wiley, H. S.

2010-01-01

There has been a lot of talk in the media about the loss of courtesy in modern society. By many criteria, it seems that people in general have lost a degree of politeness. Reading some of the online comments after several recent articles in The Scientist would seem to indicate that biologists have also lost their manners. This lack of basic manners alarms me not only because of the obvious danger to our sense of community, but also because this type of behavior could damage society’s positive perception of scientists. Every time scientists (or anonymous bloggers posing as scientists) rant about the idiocy of someone who disagrees with them, our collective credibility erodes. Yes, there are a number of issues that we as scientists should be passionate about, but our objectives are best served by retaining an objective demeanor and respecting those to whom we happen to disagree.

Mental status of the elderly receiving home health services and the associated stress of home helpers.

Science.gov (United States)

Nagatomo, I; Takigawa, M

1998-01-01

One hundred and ninety elderly people receiving home health service were investigated. The intellectual levels, depressive state evaluated by the Cornell scale for depression in dementia (CSDD) scale, abnormal behaviors evaluated by the dementia behavior disturbance (DBD) scale, and activities of daily living (ADL) were examined. These assessments were performed by 72 skilled home helpers who also assessed the severity of their own level of stress using the Burnout scale. The intellectual level and mood-related signs, based on the CSDD scale, of the elderly living with families or with a spouse were diminished significantly as compared to the elderly living alone. The elderly living with families also performed worse on all ADL categories except for visual acuity as compared to the elderly living with a spouse or living alone. There was no significant correlation between the Burnout scale score and age or frequency of working as a home helper. These results suggest that elderly people living with families as compared to the elderly living with a spouse or living alone have greater mental health needs as well as more profound physical limitations.

Adapting a natural (lay) helpers model of change for worksite health promotion for women.

Science.gov (United States)

Tessaro, I A; Taylor, S; Belton, L; Campbell, M K; Benedict, S; Kelsey, K; DeVellis, B

2000-10-01

Social network interventions that utilize informal systems of helping can be an important strategy for health promotion change. This article describes the development, implementation and evaluation of a natural (lay) helping intervention for health promotion change, specifically designed for women in small rural blue-collar worksites. One hundred and four women in four intervention worksites were recruited as natural helpers, and received health and skill-building education over an 18-month period. Qualitative evaluation showed: (1) two patterns of natural helping for women, i.e. participation due to a specific health concern with either themselves or others in their personal networks, and participation due to a larger sense of the importance of health and prevention; (2) over time natural helpers expanded the diffusion of health promotion information from close network members to co-workers and were more likely to be approached by their co-workers for information; (3) group activities at the worksite, particularly around physical activity, increased over time; and (4) because of time constraints at the workplace, written materials were a major way of spreading information to co-workers. This study shows that women can be recruited and trained to diffuse health promotion information and provide support to co-workers for health behavior change.

Constraint based modeling of metabolism allows finding metabolic cancer hallmarks and identifying personalized therapeutic windows.

Science.gov (United States)

Bordel, Sergio

2018-04-13

In order to choose optimal personalized anticancer treatments, transcriptomic data should be analyzed within the frame of biological networks. The best known human biological network (in terms of the interactions between its different components) is metabolism. Cancer cells have been known to have specific metabolic features for a long time and currently there is a growing interest in characterizing new cancer specific metabolic hallmarks. In this article it is presented a method to find personalized therapeutic windows using RNA-seq data and Genome Scale Metabolic Models. This method is implemented in the python library, pyTARG. Our predictions showed that the most anticancer selective (affecting 27 out of 34 considered cancer cell lines and only 1 out of 6 healthy mesenchymal stem cell lines) single metabolic reactions are those involved in cholesterol biosynthesis. Excluding cholesterol biosynthesis, all the considered cell lines can be selectively affected by targeting different combinations (from 1 to 5 reactions) of only 18 metabolic reactions, which suggests that a small subset of drugs or siRNAs combined in patient specific manners could be at the core of metabolism based personalized treatments.

Chronic mild stress influences nerve growth factor through a matrix metalloproteinase-dependent mechanism.

Science.gov (United States)

Kucharczyk, Mateusz; Kurek, Anna; Detka, Jan; Slusarczyk, Joanna; Papp, Mariusz; Tota, Katarzyna; Basta-Kaim, Agnieszka; Kubera, Marta; Lason, Wladyslaw; Budziszewska, Bogusława

2016-04-01

Stress is generally a beneficial experience that motivates an organism to action to overcome the stressful challenge. In particular situations, when stress becomes chronic might be harmful and devastating. The hypothalamus is a critical coordinator of stress and the metabolic response; therefore, disruptions in this structure may be a significant cause of the hormonal and metabolic disturbances observed in depression. Chronic stress induces adverse changes in the morphology of neural cells that are often associated with a deficiency of neurotrophic factors (NTFs); additionally, many studies indicate that insufficient NTF synthesis may participate in the pathogenesis of depression. The aim of the present study was to determine the expression of the nerve growth factor (NGF) in the hypothalamus of male rats subjected to chronic mild stress (CMS) or to prenatal stress (PS) and to PS in combination with an acute stress event (AS). It has been found that chronic mild stress, but not prenatal stress, acute stress or a combination of PS with AS, decreased the concentration of the mature form of NGF (m-NGF) in the rat hypothalamus. A discrepancy between an increase in the Ngf mRNA and a decrease in the m-NGF levels suggested that chronic mild stress inhibited NGF maturation or enhanced the degradation of this factor. We have shown that NGF degradation in the hypothalamus of rats subjected to chronic mild stress is matrix metalloproteinase-dependent and related to an increase in the active forms of some metalloproteinases (MMP), including MMP2, MMP3, MMP9 and MMP13, while the NGF maturation process does not seem to be changed. We suggested that activated MMP2 and MMP9 potently cleave the mature but not the pro- form of NGF into biologically inactive products, which is the reason for m-NGF decomposition. In turn, the enhanced expression of Ngf in the hypothalamus of these rats is an attempt to overcome the reduced levels of m-NGF. Additionally, the decreased level of m

The sustainability of Egan’s Skilled Helper Model in students’ social work practice

OpenAIRE

Riggall, Sally

2016-01-01

This paper investigates the nature of students’ learning of the Egan Skilled Helper model in enabling them to develop collaborative communication skills which place service-users at the centre of decision making. The paper is a follow-up to an earlier paper which found that the Egan model was helpful to students as a communication and problem management tool and that they had transferred their learning into practice. The current study involves seven students from the first study and examines ...

Antigen-specific T8+ human clone of cells with a nonspecific augmenting function on the T4 cell-B cell helper interaction

International Nuclear Information System (INIS)

Brines, R.D.; Sia, D.Y.; Lehner, T.

1987-01-01

The authors isolated a T8 + T3 + Ia + clone of cells from the peripheral blood mononuclear cells of a healthy subject. The clone was expanded and maintained with autologous feed cells, interleukin 2, and a streptococcal antigen. The T8 + clone of cells responded specifically to the streptococcal antigen, in the absence of accessory cells,and released a soluble factor. Both the cloned cells and the corresponding soluble factor expressed augmenting helper but not suppressor activity. The augmenting helper activity for B cell antibody synthesis was demonstrable only in the presence of autologous T 4 cells. Radioimmunoassay was used to measure antibodies. Although stimulation of the T8 + cloned cells was antigen-specific, the resulting soluble factor elicited nonspecific antibody synthesis in the presence of T4 and B cells. The T8 + cloned cell-derived factor was adsorbed by B cells but not by T4 cells. Preliminary studies suggest that the factor has the properties of a B cell growth factor. They suggest that the T8 + population consists of functionally heterogeneous cell subsets, some that have suppressor function and others that augment the T4 + helper-inducer activity in B cell antibody synthesis

Efficient Gene Delivery to Pig Airway Epithelia and Submucosal Glands Using Helper-Dependent Adenoviral Vectors

Directory of Open Access Journals (Sweden)

Huibi Cao

2013-01-01

Full Text Available Airway gene delivery is a promising strategy to treat patients with life-threatening lung diseases such as cystic fibrosis (CF. However, this strategy has to be evaluated in large animal preclinical studies in order to translate it to human applications. Because of anatomic and physiological similarities between the human and pig lungs, we utilized pig as a large animal model to examine the safety and efficiency of airway gene delivery with helper-dependent adenoviral vectors. Helper-dependent vectors carrying human CFTR or reporter gene LacZ were aerosolized intratracheally into pigs under bronchoscopic guidance. We found that the LacZ reporter and hCFTR transgene products were efficiently expressed in lung airway epithelial cells. The transgene vectors with this delivery can also reach to submucosal glands. Moreover, the hCFTR transgene protein localized to the apical membrane of both ciliated and nonciliated epithelial cells, mirroring the location of wild-type CF transmembrane conductance regulator (CFTR. Aerosol delivery procedure was well tolerated by pigs without showing systemic toxicity based on the limited number of pigs tested. These results provide important insights into developing clinical strategies for human CF lung gene therapy.

Cytolytic T lymphocyte responses to metabolically inactivated stimulator cells. I. Metabolic inactivation impairs both CD and LD antigen signals

International Nuclear Information System (INIS)

Kelso, A.; Boyle, W.

1982-01-01

The effects of metabolic inactivation of spleen cells on antigen presentation to precursors of alloreactive cytolytic T lymphocytes (T/sub c/) were examined. By serological methods, populations inactivated by ultraviolet irradiation, glutaraldehyde fixation or plasma membrane isolation were found to retain normal levels of H-2K/D and Ia antigens. However, comparison of the antigen doses required to stimulate secondary T/sub c/ responses in mixed leukocyte culture showed that the inactivated preparations were approximately 10-fold less immunogenic than X-irradiated spleen cells. Their total inability to stimulate primary cytolytic responses pointed to at least a 100-fold impairment of immunogenicity for unprimed T/sub c/ precursors in the case of uv-irradiated and glutaraldehyde-treated stimulator cells, and at least a 10-fold impairment for membrane fragments. Experiments showing that the capacity of cell monolayers to absorb precursor T/sub c/ from unprimed spleen populations was reduced following uv-irradiation or glutaraldehyde treatment provided direct evidence that this loss of immunogenicity was due in part to suboptimal antigen presentation to precursor T/sub c/. It is concluded that, in addition to the traditional view that these treatments damage the ''LD'' signal to helper T lymphocytes, metabolic inactivation also impairs recognition of ''CD'' determinants by precursor T/sub c/

Differential TCR signals for T helper cell programming.

Science.gov (United States)

Morel, Penelope A

2018-05-02

Upon encounter with their cognate antigen naïve CD4 T cells become activated and are induced to differentiate into several possible T helper (Th) cell subsets. This differentiation depends on a number of factors including antigen presenting cells, cytokines and costimulatory molecules. The strength of the T cell receptor (TCR) signal, related to the affinity of TCR for antigen and antigen dose, has emerged as a dominant factor in determining Th cell fate. Recent studies have revealed that TCR signals of high or low strength do not simply induce quantitatively different signals in the T cells, but rather qualitatively distinct pathways can be induced based on TCR signal strength. This review examines the recent literature in this area and highlights important new developments in our understanding of Th cell differentiation and TCR signal strength. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Mild traumatic brain injury results in depressed cerebral glucose uptake: An (18)FDG PET study.

Science.gov (United States)

Selwyn, Reed; Hockenbury, Nicole; Jaiswal, Shalini; Mathur, Sanjeev; Armstrong, Regina C; Byrnes, Kimberly R

2013-12-01

Moderate to severe traumatic brain injury (TBI) in humans and rats induces measurable metabolic changes, including a sustained depression in cerebral glucose uptake. However, the effect of a mild TBI on brain glucose uptake is unclear, particularly in rodent models. This study aimed to determine the glucose uptake pattern in the brain after a mild lateral fluid percussion (LFP) TBI. Briefly, adult male rats were subjected to a mild LFP and positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)FDG), which was performed prior to injury and at 3 and 24 h and 5, 9, and 16 days post-injury. Locomotor function was assessed prior to injury and at 1, 3, 7, 14, and 21 days after injury using modified beam walk tasks to confirm injury severity. Histology was performed at either 10 or 21 days post-injury. Analysis of function revealed a transient impairment in locomotor ability, which corresponds to a mild TBI. Using reference region normalization, PET imaging revealed that mild LFP-induced TBI depresses glucose uptake in both the ipsilateral and contralateral hemispheres in comparison with sham-injured and naïve controls from 3 h to 5 days post-injury. Further, areas of depressed glucose uptake were associated with regions of glial activation and axonal damage, but no measurable change in neuronal loss or gross tissue damage was observed. In conclusion, we show that mild TBI, which is characterized by transient impairments in function, axonal damage, and glial activation, results in an observable depression in overall brain glucose uptake using (18)FDG-PET.

Metabolic enzymes: key modulators of functionality in cancer stem-like cells.

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Dong, Bo-Wen; Qin, Guang-Ming; Luo, Yan; Mao, Jian-Shan

2017-02-21

Cancer Stem-like Cells (CSCs) are a subpopulation of cancer cells with self-renewal capacity and are important for the initiation, progression and recurrence of cancer diseases. The metabolic profile of CSCs is consistent with their stem-like properties. Studies have indicated that enzymes, the main regulators of cellular metabolism, dictate functionalities of CSCs in both catalysis-dependent and catalysis-independent manners. This paper reviews diverse studies of metabolic enzymes, and describes the effects of these enzymes on metabolic adaptation, gene transcription and signal transduction, in CSCs.

Helper T lymphocyte precursor frequency analysis in alloreactivity detection

International Nuclear Information System (INIS)

Cukrova, V.; Dolezalova, L.; Loudova, M.; Vitek, A.

1998-01-01

The utility of IL-2 secreting helper T lymphocyte precursors (HTLp) frequency testing has been evaluated for detecting alloreactivity. The frequency of HTLp was approached by limiting dilution assay. High HTLp frequency was detected in 20 out of 30 HLA matched unrelated pairs (67%). The comparison of HTLp and CTLp (cytotoxic T lymphocyte precursors) frequencies in HLA matched unrelated pairs showed that the two examinations are not fully alternative in detecting alloreactivity. This could suggest the utility of combined testing of both HTLp and CTLp frequencies for alloreactivity assessment. In contrast, five positive HTLp values were only found among 28 HLA genotypic identical siblings (18%). Previous CTLp limiting dilution studies showed very low or undetectable CTLp frequency results in that group. For that, HTLp assay remains to be the only cellular in vitro technique detecting alloreactivity in these combinations. (authors)

Brain metabolic correlates of decision making in amnestic mild cognitive impairment.

Science.gov (United States)

Griffith, H Randall; Okonkwo, Ozioma C; den Hollander, Jan A; Belue, Katherine; Copeland, Jacqueline; Harrell, Lindy E; Brockington, John C; Clark, David G; Marson, Daniel C

2010-01-01

Persons with amnestic mild cognitive impairment (MCI) have subtle impairments in medical decision-making capacity (MDC). We examined the relationship between proton magnetic resonance spectroscopy (MRS) and MDC in MCI. Twenty-nine MCI patients and 42 controls underwent MRS to obtain ratios of N-acetylaspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, and myo-Inositol (mI)/Cr of the posterior cingulate. They also completed the Capacity to Consent to Treatment Instrument (CCTI), a vignette-based instrument measuring decisional standards of expressing choice, appreciating consequences of choice, providing rational reasons for choice, and understanding treatment choices. Patients showed abnormal MRS ratios of mI/Cr and Cho/Cr compared to controls, and impairments on the CCTI understanding and reasoning Standards. Performance on the reasoning standard of the CCTI was correlated with NAA/Cr (r = .46, p decision-making suggests a role for posterior cortical neuronal functioning in performance of complex IADLs in MCI.

Impact of Hypoglycemia on Brain Metabolism During Diabetes.

Science.gov (United States)

Rehni, Ashish K; Dave, Kunjan R

2018-04-10

Diabetes is a metabolic disease afflicting millions of people worldwide. A substantial fraction of world's total healthcare expenditure is spent on treating diabetes. Hypoglycemia is a serious consequence of anti-diabetic drug therapy, because it induces metabolic alterations in the brain. Metabolic alterations are one of the central mechanisms mediating hypoglycemia-related functional changes in the brain. Acute, chronic, and/or recurrent hypoglycemia modulate multiple metabolic pathways, and exposure to hypoglycemia increases consumption of alternate respiratory substrates such as ketone bodies, glycogen, and monocarboxylates in the brain. The aim of this review is to discuss hypoglycemia-induced metabolic alterations in the brain in glucose counterregulation, uptake, utilization and metabolism, cellular respiration, amino acid and lipid metabolism, and the significance of other sources of energy. The present review summarizes information on hypoglycemia-induced metabolic changes in the brain of diabetic and non-diabetic subjects and the manner in which they may affect brain function.

Mild Cognitive Impairment (MCI)

Science.gov (United States)

Mild cognitive impairment (MCI) Overview Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It ...

Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

Energy Technology Data Exchange (ETDEWEB)

Picco, Agnese; Ferrara, Michela; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio [University of Genoa and IRCCS San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Largo P. Daneo, 3, 16132, Genoa (Italy); Polidori, M.C. [University of Cologne, Institute of Geriatrics, Cologne (Germany); Cecchetti, Roberta; Baglioni, Mauro; Bastiani, Patrizia; Mecocci, Patrizia [University of Perugia, Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, Perugia (Italy); Morbelli, Silvia; Bossert, Irene [University of Genoa and IRCCS San Martino-IST, Nuclear Medicine, Department of Health Science (DISSAL), Genoa (Italy); Fiorucci, Giuliana; Dottorini, Massimo Eugenio [Nuclear Medicine, S. M. della Misericordia Hospital, Perugia (Italy)

2014-04-15

The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain{sup 18}F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

International Nuclear Information System (INIS)

Picco, Agnese; Ferrara, Michela; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio; Polidori, M.C.; Cecchetti, Roberta; Baglioni, Mauro; Bastiani, Patrizia; Mecocci, Patrizia; Morbelli, Silvia; Bossert, Irene; Fiorucci, Giuliana; Dottorini, Massimo Eugenio

2014-01-01

The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain 18 F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

New paradigms for metabolic modeling of human cells

DEFF Research Database (Denmark)

Mardinoglu, Adil; Nielsen, Jens

2015-01-01

review recent work on reconstruction of GEMs for human cell/tissue types and cancer, and the use of GEMs for identification of metabolic changes occurring in response to disease development. We further discuss how GEMs can be used for the development of efficient therapeutic strategies. Finally......, challenges in integration of cell/tissue models for simulation of whole body functions as well as integration of GEMs with other biological networks for generating complete cell/tissue models are presented.......Abnormalities in cellular functions are associated with the progression of human diseases, often resulting in metabolic reprogramming. GEnome-scale metabolic Models (GEMs) have enabled studying global metabolic reprogramming in connection with disease development in a systematic manner. Here we...

Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.

Science.gov (United States)

Unzu, C; Melero, I; Hervás-Stubbs, S; Sampedro, A; Mancheño, U; Morales-Kastresana, A; Serrano-Mendioroz, I; de Salamanca, R E; Benito, A; Fontanellas, A

2015-11-01

Helper-dependent adenoviral (HDA) vectors constitute excellent gene therapy tools for metabolic liver diseases. We have previously shown that an HDA vector encoding human porphobilinogen deaminase (PBGD) corrects acute intermittent porphyria mice. Now, six non-human primates were injected in the left hepatic lobe with the PBGD-encoding HDA vector to study levels and persistence of transgene expression. Intrahepatic administration of 5 × 10(12) viral particles kg(-1) (10(10) infective units kg(-1)) of HDA only resulted in transient (≈14 weeks) transgene expression in one out of three individuals. In contrast, a more prolonged 90-day immunosuppressive regimen (tacrolimus, mycophenolate, rituximab and steroids) extended meaningful transgene expression for over 76 weeks in two out of two cases. Transgene expression under immunosuppression (IS) reached maximum levels 6 weeks after HDA administration and gradually declined reaching a stable plateau within the therapeutic range for acute porphyria. The non-injected liver lobes also expressed the transgene because of vector circulation. IS controlled anticapsid T-cell responses and decreased the induction of neutralizing antibodies. Re-administration of HDA-hPBGD at week +78 achieved therapeutically meaningful transgene expression only in those animals receiving IS again at the time of this second vector exposure. Overall, immunity against adenoviral capsids poses serious hurdles for long-term HDA-mediated liver transduction, which can be partially circumvented by pharmacological IS.

Topological analysis of metabolic control.

Science.gov (United States)

Sen, A K

1990-12-01

A topological approach is presented for the analysis of control and regulation in metabolic pathways. In this approach, the control structure of a metabolic pathway is represented by a weighted directed graph. From an inspection of the topology of the graph, the control coefficients of the enzymes are evaluated in a heuristic manner in terms of the enzyme elasticities. The major advantage of the topological approach is that it provides a visual framework for (1) calculating the control coefficients of the enzymes, (2) analyzing the cause-effect relationships of the individual enzymes, (3) assessing the relative importance of the enzymes in metabolic regulation, and (4) simplifying the structure of a given pathway, from a regulatory viewpoint. Results are obtained for (a) an unbranched pathway in the absence of feedback the feedforward regulation and (b) an unbranched pathway with feedback inhibition. Our formulation is based on the metabolic control theory of Kacser and Burns (1973) and Heinrich and Rapoport (1974).

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

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Laura ePaixão

2015-10-01

Full Text Available Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonised by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonisation to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc on this response at the transcriptional, physiological and metabolic levels. Galactose (Gal, N-acetylglucosamine (GlcNAc and mannose (Man affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s was readily consumed and elicited a metabolic shift towards a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome. In central carbon metabolism (most represented category, Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism.

Science.gov (United States)

Paixão, Laura; Caldas, José; Kloosterman, Tomas G; Kuipers, Oscar P; Vinga, Susana; Neves, Ana R

2015-01-01

Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo (13)C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

Effects of high-intensity interval versus mild-intensity endurance training on metabolic phenotype and corticosterone response in rats fed a high-fat or control diet.

Science.gov (United States)

Shen, Youqing; Huang, Guoyuan; McCormick, Bryan P; Song, Tao; Xu, Xiangfeng

2017-01-01

The aim of the present study was to compare the effects of high-intensity interval training (HI) to mild-intensity endurance training (ME), combined with a high-fat diet (HFD) or control diet (CD) on metabolic phenotype and corticosterone levels in rats. Fifty-three rats were randomized to 6 groups according to diet and training regimen as follows: CD and sedentary (CS, n = 11), CD and ME (CME, n = 8), CD and HI (CHI, n = 8), HFD and sedentary (HS, n = 10), HFD and ME (HME, n = 8), and HFD and HI (HHI, n = 8). All exercise groups were trained for 10 weeks and had matched running distances. Dietary intake, body composition, blood metabolites, and corticosterone levels were measured. Histological lipid droplets were observed in the livers. The HFD led to hyperglycemia, hyperlipidemia and higher body fat (all, P 0.06), as well as higher corticosterone levels (P training improved fat weight, glucose, and lipid profiles, and reduced corticosterone levels (P body and fat weight, serum glucose and triglycerides, lipid content in the liver, and corticosterone levels (P training compared to ME training. Reductions in HFD-induced body weight gain, blood glucose and lipid profiles, and corticosterone levels, as well as improvements in QUICKI were better with HHI compared to HME. Correlation analyses revealed that corticosterone levels were significantly associated with phenotype variables (P training, HI training contributes to greater improvements in metabolic and corticosterone responses, leading to a greater reduction in susceptibility to HFD-induced disorders.

They need to be recognized as a person in everyday life: Teachers' and helpers' experiences of teacher-student relationships in upper secondary school.

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Krane, Vibeke; Karlsson, Bengt; Ness, Ottar; Binder, Per-Einar

2016-01-01

The aim of this study was to explore how teachers and helpers experience that teacher-student relationship (TSR) is developed and promoted in upper secondary school.We also explored their experiences of qualities of TSR with students with mental health problems or at risk of dropping out. The study used a qualitative and participative approach; key stakeholders were included as co-researchers. Focus group interviews were held with 27 teachers and helpers. A thematic analysis was conducted. The participants' descriptions of important experiential dimensions of TSR were clustered around four themes: (1) to be recognized as a person with strengths and challenges in everyday life, (2) collaborative relationships between students and teachers, (3) flexible boundaries in the relationship between teachers and students and (4) organization of classes and procedures set the stage for TSR. Collaborative, emotional and contextual qualities were found important to the development of TSR in upper secondary school. Experiences of negative qualities of TSR can contribute to push students out of school. Teachers and helpers experience that TSR may have the potential to play a role in promoting mental health in students' everyday life.

Follicular helper T cells poise immune responses to the development of autoimmune pathology.

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Gómez-Martín, Diana; Díaz-Zamudio, Mariana; Romo-Tena, Jorge; Ibarra-Sánchez, María J; Alcocer-Varela, Jorge

2011-04-01

Follicular helper T cells (T(FH)) have been implicated as a lineage that provides sufficient help to B cells in order to become professional antibody producers. This T helper subset is characterized by a distinctive cell-surface phenotype (CD4(+)CD57(+)CXCR5(+)) and cytokine profile (IL-21, IL-6, and IL-27) as well as transcriptional program (BCL-6, ICOS, and PD-1). Evidence supports the concept that T(FH) subset development, as well as for other lineages, is dependent on microenvironment cues that modulate a particular transcriptional program, susceptible to plasticity. Recently, it has been shown that BCL-6 and IL-21 act as master regulators for the development and function of T(FH) cells. Moreover, costimulation via ICOS, as well as signaling proteins such as SAP constitute required elements of the regulatory network that modulates T(FH) functions. T(FH) dysregulation has been implicated in the development of autoimmune pathology, such as SLE. Indeed, the Sanroque mice associated to the mutation of Roquin, a ubiquitin ligase, essential for the regulation of ICOS and germinal center responses, constitutes a model that shares features with human SLE. Recently, the expansion of "circulating T(FH) cells" (CD4(+)CXCR5(+)ICOS(high)PD1(high)) has been described for a subset of SLE patients that share T(FH) dependent features of disease with Sanroque mice, such as glomerulonephritis and cytopenias. Copyright © 2010 Elsevier B.V. All rights reserved.

Dysfunction of irradiated thymus for the development of helper T cells

International Nuclear Information System (INIS)

Amagai, T.; Kina, T.; Hirokawa, K.; Nishikawa, S.; Imanishi, J.; Katsura, Y.

1987-01-01

The development of cytotoxic T cells and helper T cells in an intact or irradiated thymus was investigated. C57BL/6 (H-2b, Thy-1.2) mice were whole body-irradiated, or were irradiated with shielding over either the thymus or right leg and tail, and were transferred with 1.5 X 10(7) bone marrow cells from B10.Thy-1.1 mice (H-2b, Thy-1.1). At various days after reconstitution, thymus cells from the recipient mice were harvested and a peanut agglutinin low-binding population was isolated. This population was further treated with anti-Thy-1.2 plus complement to remove host-derived cells and was assayed for the frequency of cytotoxic T cell precursors (CTLp) and for the activity of helper T cells (Th). In the thymus of thymus-shielded and irradiated mice, Th activity reached normal control level by day 25, whereas CTLp frequency remained at a very low level during these days. In the thymus of whole body-irradiated mice, generation of CTLp was highly accelerated while that of Th was retarded, the period required for reconstitution being 25 days and more than 42 days for CTLp and Th, respectively. Preferential development of CTLp was also seen in right leg- and tail-shielded (L-T-shielded) and irradiated recipients. Histological observation indicated that Ia+ nonlymphoid cells were well preserved in the thymus of thymus-shielded and irradiated recipients, whereas in L-T-shielded and irradiated recipients, such cells in the medulla were markedly reduced in number. These results suggest strongly that the generation of Th but not CTLp is dependent on radiosensitive thymic component(s), and that such components may represent Ia+ cells themselves in the medulla or some microenvironment related to Ia+ cells

Neuron-astrocyte interaction enhance GABAergic synaptic transmission in a manner dependent on key metabolic enzymes.

OpenAIRE

Przemysław eKaczor; Dariusz eRakus; Jerzy Władysław Mozrzymas; Jerzy Władysław Mozrzymas

2015-01-01

GABA is the major inhibitory neurotransmitter in the adult brain and mechanisms of GABAergic inhibition have been intensely investigated in the past decades. Recent studies provided evidence for an important role of astrocytes in shaping GABAergic currents. One of the most obvious, but yet poorly understood, mechanisms of the cross-talk between GABAergic currents and astrocytes is metabolism including neurotransmitter homeostasis. In particular, how modulation of GABAergic currents by astrocy...

Structural and Nonstructural Viral Proteins Are Targets of T-Helper Immune Response against Human Respiratory Syncytial Virus.

Science.gov (United States)

Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Mir, Carmen; Gebe, John A; Admon, Arie; López, Daniel

2016-06-01

Proper antiviral humoral and cellular immune responses require previous recognition of viral antigenic peptides that are bound to HLA class II molecules, which are exposed on the surface of antigen-presenting cells. The helper immune response is critical for the control and the clearance of human respiratory syncytial virus (HRSV) infection, a virus with severe health risk in infected pediatric, immunocompromised, and elderly populations. In this study, using a mass spectrometry analysis of complex HLA class II-bound peptide pools that were isolated from large amounts of HRSV-infected cells, 19 naturally processed HLA-DR ligands, most of them included in a complex nested set of peptides, were identified. Both the immunoprevalence and the immunodominance of the HLA class II response to HRSV were focused on one nonstructural (NS1) and two structural (matrix and mainly fusion) proteins of the infective virus. These findings have clear implications for analysis of the helper immune response as well as for antiviral vaccine design. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization.

Science.gov (United States)

Mohamadzadeh, Mansour; Olson, Scott; Kalina, Warren V; Ruthel, Gordon; Demmin, Gretchen L; Warfield, Kelly L; Bavari, Sina; Klaenhammer, Todd R

2005-02-22

Professional antigen-presenting dendritic cells (DCs) are critical in regulating T cell immune responses at both systemic and mucosal sites. Many Lactobacillus species are normal members of the human gut microflora and most are regarded as safe when administered as probiotics. Because DCs can naturally or therapeutically encounter lactobacilli, we investigated the effects of several well defined strains, representing three species of Lactobacillus on human myeloid DCs (MDCs) and found that they modulated the phenotype and functions of human MDCs. Lactobacillus-exposed MDCs up-regulated HLA-DR, CD83, CD40, CD80, and CD86 and secreted high levels of IL-12 and IL-18, but not IL-10. IL-12 was sustained in MDCs exposed to all three Lactobacillus species in the presence of LPS from Escherichia coli, whereas LPS-induced IL-10 was greatly inhibited. MDCs activated with lactobacilli clearly skewed CD4(+) and CD8(+) T cells to T helper 1 and Tc1 polarization, as evidenced by secretion of IFN-gamma, but not IL-4 or IL-13. These results emphasize a potentially important role for lactobacilli in modulating immunological functions of DCs and suggest that certain strains could be particularly advantageous as vaccine adjuvants, by promoting DCs to regulate T cell responses toward T helper 1 and Tc1 pathways.

Arachidonic Acid Metabolism Pathway Is Not Only Dominant in Metabolic Modulation but Associated With Phenotypic Variation After Acute Hypoxia Exposure

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Chang Liu

2018-03-01

Full Text Available Background: The modulation of arachidonic acid (AA metabolism pathway is identified in metabolic alterations after hypoxia exposure, but its biological function is controversial. We aimed at integrating plasma metabolomic and transcriptomic approaches to systematically explore the roles of the AA metabolism pathway in response to acute hypoxia using an acute mountain sickness (AMS model.Methods: Blood samples were obtained from 53 enrolled subjects before and after exposure to high altitude. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and RNA sequencing were separately performed for metabolomic and transcriptomic profiling, respectively. Influential modules comprising essential metabolites and genes were identified by weighted gene co-expression network analysis (WGCNA after integrating metabolic information with phenotypic and transcriptomic datasets, respectively.Results: Enrolled subjects exhibited diverse response manners to hypoxia. Combined with obviously altered heart rate, oxygen saturation, hemoglobin, and Lake Louise Score (LLS, metabolomic profiling detected that 36 metabolites were highly related to clinical features in hypoxia responses, out of which 27 were upregulated and nine were downregulated, and could be mapped to AA metabolism pathway significantly. Integrated analysis of metabolomic and transcriptomic data revealed that these dominant molecules showed remarkable association with genes in gas transport incapacitation and disorders of hemoglobin metabolism pathways, such as ALAS2, HEMGN. After detailed description of AA metabolism pathway, we found that the molecules of 15-d-PGJ2, PGA2, PGE2, 12-O-3-OH-LTB4, LTD4, LTE4 were significantly up-regulated after hypoxia stimuli, and increased in those with poor response manner to hypoxia particularly. Further analysis in another cohort showed that genes in AA metabolism pathway such as PTGES, PTGS1, GGT1, TBAS1 et al. were excessively

Intermittent Hypoxia Disrupts Glucose Homeostasis in Liver Cells in an Insulin-Dependent and Independent Manner

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Chen Juan Gu

2018-05-01

Full Text Available Background/Aims: Obstructive sleep apnea is associated with diabetes and insulin resistance, but the underlying mechanisms remain unclear. The purpose of the current study was to determine the molecular effects of intermittent hypoxia (IH on hepatic insulin signaling and glucose homeostasis, and whether c-Jun NH2-terminal-kinase (JNK contributed to metabolic responses to IH in liver cells. Methods: The human HepG2 cells and rat FAO cells were exposed to 10, 30, 120, 240 or 360 cycles of IH (1% O2 for 60 s followed by 21% O2 for 60s, 7.5 cycles per hour or normoxia as a control. In a subgroup, we exposed cells to 360 cycles of IH with the JNK inhibitor SP600125. After IH exposure, cell glycogen content and glucose output were measured using colorimetric assay kits. Canonical insulin signaling and gluconeogenic genes were measured by western blot and quantitative polymerase chain reaction. Results: IH decreased insulin-stimulated protein kinase B (AKT/glycogen synthase kinase-3β (GSK-3β phosphorylation in a time-dependent manner, while inhibiting forkhead box protein O1 (FOXO1 expression and phosphoenolpyruvate carboxykinase (PEPCK transcription independent of insulin signaling. JNK inhibitor SP600125 partially restored AKT/ GSK-3β phosphorylation and glycogen synthesis, but did not affect other IH-induced glucose metabolic changes. Conclusion: IH in vitro impaired insulin signal transduction in liver cells as assessed by inhibited AKT/GSK-3β phosphorylation via JNK activation. IH inhibited FOXO1 and gluconeogenesis in an insulin-independent manner.

Type II membrane protein CD69 regulates the formation of resting T-helper memory.

OpenAIRE

Shinoda, K.; Tokoyoda, K.; Hanazawa, A.; Hayashizaki, K.; Zehentmeier, S.; Hosokawa, H.; Iwamura, C.; Koseki, H.; Tumes, D. J.; Radbruch, A.; Nakayama, T.

2012-01-01

Memory T-helper (Th) lymphocytes are crucial for the maintenance of acquired immunity to eliminate infectious pathogens. We have previously demonstrated that most memory Th lymphocytes reside and rest on stromal niches of the bone marrow (BM). Little is known, however, regarding the molecular basis for the generation and maintenance of BM memory Th lymphocytes. Here we show that CD69-deficient effector CD4 T lymphocytes fail to relocate into and persist in the BM and therefore to differentiat...

Obesity-related metabolic dysfunction in dogs: a comparison with human metabolic syndrome.

Science.gov (United States)

Tvarijonaviciute, Asta; Ceron, Jose J; Holden, Shelley L; Cuthbertson, Daniel J; Biourge, Vincent; Morris, Penelope J; German, Alexander J

2012-08-28

Recently, metabolic syndrome (MS) has gained attention in human metabolic medicine given its associations with development of type 2 diabetes mellitus and cardiovascular disease. Canine obesity is associated with the development of insulin resistance, dyslipidaemia, and mild hypertension, but the authors are not aware of any existing studies examining the existence or prevalence of MS in obese dogs.Thirty-five obese dogs were assessed before and after weight loss (median percentage loss 29%, range 10-44%). The diagnostic criteria of the International Diabetes Federation were modified in order to define canine obesity-related metabolic dysfunction (ORMD), which included a measure of adiposity (using a 9-point body condition score [BCS]), systolic blood pressure, fasting plasma cholesterol, plasma triglyceride, and fasting plasma glucose. By way of comparison, total body fat mass was measured by dual-energy X-ray absorptiometry, whilst total adiponectin, fasting insulin, and high-sensitivity C-reactive protein (hsCRP) were measured using validated assays. Systolic blood pressure (P = 0.008), cholesterol (P = 0.003), triglyceride (P = 0.018), and fasting insulin (P disease associations and outcomes of weight loss.

Transcription factor interplay in T helper cell differentiation

Science.gov (United States)

Evans, Catherine M.

2013-01-01

The differentiation of CD4 helper T cells into specialized effector lineages has provided a powerful model for understanding immune cell differentiation. Distinct lineages have been defined by differential expression of signature cytokines and the lineage-specifying transcription factors necessary and sufficient for their production. The traditional paradigm of differentiation towards Th1 and Th2 subtypes driven by T-bet and GATA3, respectively, has been extended to incorporate additional T cell lineages and transcriptional regulators. Technological advances have expanded our view of these lineage-specifying transcription factors to the whole genome and revealed unexpected interplay between them. From these data, it is becoming clear that lineage specification is more complex and plastic than previous models might have suggested. Here, we present an overview of the different forms of transcription factor interplay that have been identified and how T cell phenotypes arise as a product of this interplay within complex regulatory networks. We also suggest experimental strategies that will provide further insight into the mechanisms that underlie T cell lineage specification and plasticity. PMID:23878131

Transcription factor interplay in T helper cell differentiation.

Science.gov (United States)

Evans, Catherine M; Jenner, Richard G

2013-11-01

The differentiation of CD4 helper T cells into specialized effector lineages has provided a powerful model for understanding immune cell differentiation. Distinct lineages have been defined by differential expression of signature cytokines and the lineage-specifying transcription factors necessary and sufficient for their production. The traditional paradigm of differentiation towards Th1 and Th2 subtypes driven by T-bet and GATA3, respectively, has been extended to incorporate additional T cell lineages and transcriptional regulators. Technological advances have expanded our view of these lineage-specifying transcription factors to the whole genome and revealed unexpected interplay between them. From these data, it is becoming clear that lineage specification is more complex and plastic than previous models might have suggested. Here, we present an overview of the different forms of transcription factor interplay that have been identified and how T cell phenotypes arise as a product of this interplay within complex regulatory networks. We also suggest experimental strategies that will provide further insight into the mechanisms that underlie T cell lineage specification and plasticity.

Analysis of Aspergillus nidulans metabolism at the genome-scale

DEFF Research Database (Denmark)

David, Helga; Ozcelik, İlknur Ş; Hofmann, Gerald

2008-01-01

of relevant secondary metabolites, was reconstructed based on detailed metabolic reconstructions available for A. niger and Saccharomyces cerevisiae, and information on the genetics, biochemistry and physiology of A. nidulans. Thereby, it was possible to identify metabolic functions without a gene associated...... a function. Results: In this work, we have manually assigned functions to 472 orphan genes in the metabolism of A. nidulans, by using a pathway-driven approach and by employing comparative genomics tools based on sequence similarity. The central metabolism of A. nidulans, as well as biosynthetic pathways......, in an objective and systematic manner. The functional assignments served as a basis to develop a mathematical model, linking 666 genes (both previously and newly annotated) to metabolic roles. The model was used to simulate metabolic behavior and additionally to integrate, analyze and interpret large-scale gene...

Akt signaling-associated metabolic effects of dietary gold nanoparticles in Drosophila

Science.gov (United States)

Wang, Bin; Chen, Nan; Wei, Yingliang; Li, Jiang; Sun, Li; Wu, Jiarui; Huang, Qing; Liu, Chang; Fan, Chunhai; Song, Haiyun

2012-08-01

Gold nanoparticles (AuNPs) are often used as vehicles to deliver drugs or biomolecules, due to their mild effect on cell survival and proliferation. However, little is known about their effect on cellular metabolism. Here we examine the in vivo effect of AuNPs on metabolism using Drosophila as a model. Drosophila and vertebrates possess similar basic metabolic functions, and a highly conserved PI3K/Akt/mTOR signaling pathway plays a central role in the regulation of energy metabolism in both organisms. We show that dietary AuNPs enter the fat body, a key metabolic tissue in Drosophila larvae. Significantly, larvae fed with AuNP show increased lipid levels without triggering stress responses. In addition, activities of the PI3K/Akt/mTOR signaling pathway and fatty acids synthesis are increased in these larvae. This study thus reveals a novel function of AuNPs in influencing animal metabolism and suggests its potential therapeutic applications for metabolic disorders.

Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells.

Science.gov (United States)

Sadtler, Kaitlyn; Estrellas, Kenneth; Allen, Brian W; Wolf, Matthew T; Fan, Hongni; Tam, Ada J; Patel, Chirag H; Luber, Brandon S; Wang, Hao; Wagner, Kathryn R; Powell, Jonathan D; Housseau, Franck; Pardoll, Drew M; Elisseeff, Jennifer H

2016-04-15

Immune-mediated tissue regeneration driven by a biomaterial scaffold is emerging as an innovative regenerative strategy to repair damaged tissues. We investigated how biomaterial scaffolds shape the immune microenvironment in traumatic muscle wounds to improve tissue regeneration. The scaffolds induced a pro-regenerative response, characterized by an mTOR/Rictor-dependent T helper 2 pathway that guides interleukin-4-dependent macrophage polarization, which is critical for functional muscle recovery. Manipulating the adaptive immune system using biomaterials engineering may support the development of therapies that promote both systemic and local pro-regenerative immune responses, ultimately stimulating tissue repair. Copyright © 2016, American Association for the Advancement of Science.

Understanding mild persistent asthma in children

DEFF Research Database (Denmark)

Bisgaard, Hans; Szefler, Stanley J

2005-01-01

Limitations in asthma prevalence studies and difficulties in diagnosing pediatric asthma lead to uncertainty over the full extent of mild persistent asthma in children and adolescents. Although recent surveys have reported that the majority of pediatric patients with asthma in the United States...... and Europe have symptoms consistent with mild disease, these surveys have limitations in design. Thus, the true prevalence of mild asthma remains unknown. It is unclear whether children with mild persistent asthma progress to more severe asthma, but the risk of severe asthma exacerbations seems...... to be unrelated to the symptom severity. Clinical studies restricted to pediatric patients with mild asthma are limited, but available data do suggest substantial morbidity of mild persistent asthma in this population and support inhaled corticosteroid intervention. There is a need for further investigation...

Metabolic disorders of the vestibular system.

Science.gov (United States)

Rybak, L P

1995-01-01

This article reviews the impact of metabolic disorders on vestibular function. Diabetes mellitus is a disorder of glucose metabolism that can be associated with vestibular dysfunction. Vertigo can be alleviated by diet management in many cases. Elevated levels of blood lipids have been implicated in cochleovestibular disorders. Treatment with a lipid-lowering drug has resulted in improved auditory and vestibular function in a placebo-controlled trial. Hypothyroidism may affect different parts of the vestibular system depending on the severity and duration of thyroid deficiency. Severe congenital hypothyroidism can cause central vestibular disorders affecting the cerebellum, whereas mild hypothyroidism may result in peripheral vestibulopathy. Endogenous alterations in concentrations of estrogen and progesterone in the premenstrual syndrome or with the use of exogenous hormones such as oral contraceptives may trigger vertigo. Metabolic evaluations for unexplained vertigo should include a lipoprotein profile, with cholesterol and triglyceride levels, glucose tolerance test, and thyroid hormone measurements. Nutritional and drug therapy may be useful to reverse the vestibular dysfunction.

Apolipoprotein A-IV constrains HPA and behavioral stress responsivity in a strain-dependent manner.

Science.gov (United States)

Packard, Amy E B; Zhang, Jintao; Myers, Brent; Ko, Chih-Wei; Wang, Fei; Tso, Patrick; Ulrich-Lai, Yvonne M

2017-12-01

There is a critical gap in our knowledge of the mechanisms that govern interactions between daily life experiences (e.g., stress) and metabolic diseases, despite evidence that stress can have profound effects on cardiometabolic health. Apolipoprotein A-IV (apoA-IV) is a protein found in chylomicrons (lipoprotein particles that transport lipids throughout the body) where it participates in lipid handling and the regulation of peripheral metabolism. Moreover, apoA-IV is expressed in brain regions that regulate energy balance including the arcuate nucleus. Given that both peripheral and central metabolic processes are important modulators of hypothalamic-pituitary-adrenocortical (HPA) axis activity, the present work tests the hypothesis that apoA-IV activity affects stress responses. As emerging data suggests that apoA-IV actions can vary with background strain, we also explore the strain-dependence of apoA-IV stress regulation. These studies assess HPA axis, metabolic (hyperglycemia), and anxiety-related behavioral responses to psychogenic stress in control (wildtype) and apoA-IV-deficient (KO) mice on either the C57Bl/6J (C57) or 129×1/SvJ (129) background strain. The results indicate that apoA-IV KO increases post-stress corticosterone and anxiety-related behavior specifically in the 129 strain, and increases stress-induced hyperglycemia exclusively in the C57 strain. These data support the hypothesis that apoA-IV is a novel factor that limits stress reactivity in a manner that depends on genetic background. An improved understanding of the complex relationship among lipid homeostasis, stress sensitivity, and genetics is needed to optimize the development of personalized treatments for stress- and metabolism-related diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aplikasi Pembelajaran Table Manners Berbasis Multimedia

OpenAIRE

Yosanny, Agustinna; Pradipta, Albert; Viles, Dody; Pensen, Pensen

2011-01-01

Table manners adalah aturan-aturan pokok yang berlaku di meja makan. Aturan ini biasanya diterapkan padajamuan makan resmi. Penelitian ini bertujuan untuk merancang dan mengembangkan suatu aplikasipembelajaran tentang table manners untuk memudahkan dalam mempelajari aturan-aturan yang perlu diketahuidalam jamuan makan resmi, meliputi etika sebelum dan saat proses menyantap makanan, serta penggunaanalat-alat makan. Metode penelitian yang digunakan adalah metode Interactive Multimedia System De...

High-Mobility Group Box 1 Disrupts Metabolic Function with Cigarette Smoke Exposure in a Ceramide-Dependent Manner

Directory of Open Access Journals (Sweden)

Oliver J. Taylor

2017-05-01

Full Text Available We have previously found that cigarette smoke disrupts metabolic function, in part, by increasing muscle ceramide accrual. To further our understanding of this, we sought to determine the role of the cytokine high-mobility group box 1 (HMGB1, which is increased with smoke exposure, in smoke-induced muscle metabolic perturbations. To test this theory, we determined HMGB1 from lungs of human smokers, as well as from lung cells from mice exposed to cigarette smoke. We also treated cells and mice directly with HMGB1, in the presence or absence of myriocin, an inhibitor of serine palmitoyltransferase, the rate-limiting enzyme in ceramide biosynthesis. Outcomes included assessments of insulin resistance and muscle mitochondrial function. HMGB1 was significantly increased in both human lungs and rodent alveolar macrophages. Further testing revealed that HMGB1 treatment elicited a widespread increase in ceramide species and reduction in myotube mitochondrial respiration, an increase in reactive oxygen species, and reduced insulin-stimulated Akt phosphorylation. Inhibition of ceramide biosynthesis with myriocin was protective. In mice, by comparing treatments of HMGB1 injections with or without myriocin, we found that HMGB1 injections resulted in increased muscle ceramides, especially C16 and C24, which were necessary for reduced muscle mitochondrial respiration and compromised insulin and glucose tolerance. In conclusion, HMGB1 may be a necessary intermediate in the ceramide-dependent metabolic consequences of cigarette smoke exposure.

Effects of high-intensity interval versus mild-intensity endurance training on metabolic phenotype and corticosterone response in rats fed a high-fat or control diet.

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Youqing Shen

Full Text Available The aim of the present study was to compare the effects of high-intensity interval training (HI to mild-intensity endurance training (ME, combined with a high-fat diet (HFD or control diet (CD on metabolic phenotype and corticosterone levels in rats. Fifty-three rats were randomized to 6 groups according to diet and training regimen as follows: CD and sedentary (CS, n = 11, CD and ME (CME, n = 8, CD and HI (CHI, n = 8, HFD and sedentary (HS, n = 10, HFD and ME (HME, n = 8, and HFD and HI (HHI, n = 8. All exercise groups were trained for 10 weeks and had matched running distances. Dietary intake, body composition, blood metabolites, and corticosterone levels were measured. Histological lipid droplets were observed in the livers. The HFD led to hyperglycemia, hyperlipidemia and higher body fat (all, P 0.06, as well as higher corticosterone levels (P < 0.01, η2 = 0.09 compared with the CD groups. Exercise training improved fat weight, glucose, and lipid profiles, and reduced corticosterone levels (P < 0.01, η2 = 0.123. Furthermore, body and fat weight, serum glucose and triglycerides, lipid content in the liver, and corticosterone levels (P < 0.05 were lower with HI training compared to ME training. Reductions in HFD-induced body weight gain, blood glucose and lipid profiles, and corticosterone levels, as well as improvements in QUICKI were better with HHI compared to HME. Correlation analyses revealed that corticosterone levels were significantly associated with phenotype variables (P < 0.01. Corticosterone level was inversely correlated with QUICKI (r = -0.38, P < 0.01. Altogether, these results indicate that HFD may elicit an exacerbated basal serum corticosterone level and thus producing a metabolic imbalance. Compared with ME training, HI training contributes to greater improvements in metabolic and corticosterone responses, leading to a greater reduction in susceptibility to HFD-induced disorders.

Induction of non-responsiveness in human allergen-specific type 2 T helper cells.

Science.gov (United States)

Yssel, H; Fasler, S; Lamb, J; de Vries, J E

1994-12-01

Activation of allergen-reactive human T helper (Th)2 cells in the absence of professional antigen-presenting cells, induces non-responsiveness or anergy in these cells in vitro. This induction of anergy is accompanied by phenotypic modulation and altered cytokine production. Furthermore, peptide-treated Th2 cells fail to provide B-cell help for IgE synthesis. Recent studies indicate that impaired signal transduction via the T-cell receptor may account for the lack of responsiveness to antigenic stimulation. Here, we review present knowledge on the cell biology of non-responsive or anergic Th2 cells.

T helper cell 2 immune skewing in pregnancy/early life

DEFF Research Database (Denmark)

McFadden, J P; Thyssen, J P; Basketter, D A

2015-01-01

During the last 50 years there has been a significant increase in Western societies of atopic disease and associated allergy. The balance between functional subpopulations of T helper cells (Th) determines the quality of the immune response provoked by antigen. One such subpopulation - Th2 cells...... that in Westernized societies reduced exposure during early childhood to pathogenic microorganisms favours the development of atopic allergy. Pregnancy is normally associated with Th2 skewing, which persists for some months in the neonate before Th1/Th2 realignment occurs. In this review, we consider...... the immunophysiology of Th2 immune skewing during pregnancy. In particular, we explore the possibility that altered and increased patterns of exposure to certain chemicals have served to accentuate this normal Th2 skewing and therefore further promote the persistence of a Th2 bias in neonates. Furthermore, we propose...

A rapid Q-PCR titration protocol for adenovirus and helper-dependent adenovirus vectors that produces biologically relevant results

Science.gov (United States)

Gallaher, Sean D.; Berk, Arnold J.

2013-01-01

Adenoviruses are employed in the study of cellular processes and as expression vectors used in gene therapy. The success and reproducibility of these studies is dependent in part on having accurate and meaningful titers of replication competent and helper-dependent adenovirus stocks, which is problematic due to the use of varied and divergent titration protocols. Physical titration methods, which quantify the total number of viral particles, are used by many, but are poor at estimating activity. Biological titration methods, such as plaque assays, are more biologically relevant, but are time consuming and not applicable to helper-dependent gene therapy vectors. To address this, a protocol was developed called “infectious genome titration” in which viral DNA is isolated from the nuclei of cells ~3 h post-infection, and then quantified by Q-PCR. This approach ensures that only biologically active virions are counted as part of the titer determination. This approach is rapid, robust, sensitive, reproducible, and applicable to all forms of adenovirus. Unlike other Q-PCR-based methods, titers determined by this protocol are well correlated with biological activity. PMID:23624118

Nuclear receptors of the NR4a family are not required for the development and function of follicular T helper cells.

Science.gov (United States)

Ma, Weiwei; Zhao, Ruozhu; Yang, Runqing; Liu, Bo; Chen, Xin; Wu, Longyan; Qi, Hai

2015-10-01

Follicular T helper (Tfh) cells promote germinal center (GC) reaction and high-affinity antibody production. The molecular mechanisms that regulate development and function of Tfh cells are not fully understood. Here we report that ligand-independent nuclear receptors of the Nr4a family are highly expressed in Tfh cells. In a well-established adoptive transfer model, enforced expression of Nr4a receptors reduces helper T cell expansion but apparently increased the T cell capacity to promote the GC response. On the other hand, deletion of all Nr4a receptors in T cells did not significantly affect expansion or differentiation of Tfh cells or the development of GC reaction. These findings suggest that Nr4a receptors may promote but are not necessary for Tfh development or function in vivo. Copyright © 2015 Elsevier B.V. All rights reserved.

T helper cell subsets specific for Pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis.

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Hannah K Bayes

Full Text Available We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis.Peripheral blood human memory CD4(+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines.Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4(+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6(+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood.Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions.

Comparing Cognitive Profiles of Licensed Drivers with Mild Alzheimer’s Disease and Mild Dementia with Lewy Bodies

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Stephanie Yamin

2016-01-01

Full Text Available Purpose. Alzheimer’s disease (AD and dementia with Lewy Bodies (DLB constitute two of the most common forms of dementia in North America. Driving is a primary means of mobility among older adults and the risk of dementia increases with advanced age. The purpose of this paper is to describe the cognitive profile of licensed drivers with mild AD and mild DLB. Method. Licensed drivers with mild AD, mild DLB, and healthy controls completed neuropsychological tests measuring general cognition, attention, visuospatial/perception, language, and cognitive fluctuations. Results. The results showed differences between healthy controls and demented participants on almost all neuropsychological measures. Participants with early DLB were found to perform significantly worse on some measures of attention and visuospatial functioning in comparison with early AD. Discussion. Future research should examine the relationship between neuropsychological measures and driving outcomes among individuals with mild AD and mild DLB.

A randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention).

Science.gov (United States)

Bandak, Mikkel; Jørgensen, Niels; Juul, Anders; Lauritsen, Jakob; Kreiberg, Michael; Oturai, Peter Sandor; Helge, Jørn Wulff; Daugaard, Gedske

2017-07-03

Elevated serum levels of luteinizing hormone and slightly decreased serum levels of testosterone (mild Leydig cell insufficiency) is a common hormonal disturbance in testicular cancer (TC) survivors. A number of studies have shown that low serum levels of testosterone is associated with low grade inflammation and increased risk of metabolic syndrome. However, so far, no studies have evaluated whether testosterone substitution improves metabolic dysfunction in TC survivors with mild Leydig cell insufficiency. This is a single-center, randomized, double-blind, placebo-controlled study, designed to evaluate the effect of testosterone replacement therapy in TC survivors with mild Leydig cell insufficiency. Seventy subjects will be randomized to receive either testosterone replacement therapy or placebo. The subjects will be invited for an information meeting where informed consent will be obtained. Afterwards, a 52-weeks treatment period begins in which study participants will receive a daily dose of transdermal testosterone or placebo. Dose adjustment will be made three times during the initial 8 weeks of the study to a maximal daily dose of 40 mg of testosterone in the intervention arm. Evaluation of primary and secondary endpoints will be performed at baseline, 26 weeks post-randomization, at the end of treatment (52 weeks) and 3 months after completion of treatment (week 64). This study is the first to investigate the effect of testosterone substitution in testicular cancer survivors with mild Leydig cell insufficiency. If positive, it may change the clinical handling of testicular cancer survivors with borderline low levels of testosterone. ClinicalTrials.gov : NCT02991209 (November 25, 2016).

Correlations between cerebral glucose metabolism and neuropsychological test performance in nonalcoholic cirrhotics.

Science.gov (United States)

Lockwood, Alan H; Weissenborn, Karin; Bokemeyer, Martin; Tietge, U; Burchert, Wolfgang

2002-03-01

Many cirrhotics have abnormal neuropsychological test scores. To define the anatomical-physiological basis for encephalopathy in nonalcoholic cirrhotics, we performed resting-state fluorodeoxyglucose positron emission tomographic scans and administered a neuropsychological test battery to 18 patients and 10 controls. Statistical parametric mapping correlated changes in regional glucose metabolism with performance on the individual tests and a composite battery score. In patients without overt encephalopathy, poor performance correlated with reductions in metabolism in the anterior cingulate. In all patients, poor performance on the battery was positively correlated (p glucose metabolism in bifrontal and biparietal regions of the cerebral cortex and negatively correlated with metabolism in hippocampal, lingual, and fusiform gyri and the posterior putamen. Similar patterns of abnormal metabolism were found when comparing the patients to 10 controls. Metabolic abnormalities in the anterior attention system and association cortices mediating executive and integrative function form the pathophysiological basis for mild hepatic encephalopathy.

Consumer preferences for mild cheddar cheese flavors.

Science.gov (United States)

Drake, S L; Gerard, P D; Drake, M A

2008-11-01

Flavor is an important factor in consumer selection of cheeses. Mild Cheddar cheese is the classification used to describe Cheddar cheese that is not aged extensively and has a "mild" flavor. However, there is no legal definition or age limit for Cheddar cheese to be labeled mild, medium, or sharp, nor are the flavor profiles or flavor expectations of these cheeses specifically defined. The objectives of this study were to document the distinct flavor profiles among commercially labeled mild Cheddar cheeses, and to characterize if consumer preferences existed for specific mild Cheddar cheese flavors or flavor profiles. Flavor descriptive sensory profiles of a representative array of commercial Cheddar cheeses labeled as mild (n= 22) were determined using a trained sensory panel and an established cheese flavor sensory language. Nine representative Cheddar cheeses were selected for consumer testing. Consumers (n= 215) assessed the cheeses for overall liking and other consumer liking attributes. Internal preference mapping, cluster analysis, and discriminant analysis were conducted. Mild Cheddar cheeses were diverse in flavor with many displaying flavors typically associated with more age. Four distinct consumer clusters were identified. The key drivers of liking for mild Cheddar cheese were: color, cooked/milky, whey and brothy flavors, and sour taste. Consumers have distinct flavor and color preferences for mild Cheddar cheese. These results can help manufacturers understand consumer preferences for mild Cheddar cheese.

Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection

OpenAIRE

Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

2015-01-01

Background Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. Methods The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules inc...

29 CFR 1905.21 - Manner of service.

Science.gov (United States)

2010-07-01

...-STEIGER OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Hearings § 1905.21 Manner of service. Service of any... 29 Labor 5 2010-07-01 2010-07-01 false Manner of service. 1905.21 Section 1905.21 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...

Ensemble Kinetic Modeling of Metabolic Networks from Dynamic Metabolic Profiles

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Gengjie Jia

2012-11-01

Full Text Available Kinetic modeling of metabolic pathways has important applications in metabolic engineering, but significant challenges still remain. The difficulties faced vary from finding best-fit parameters in a highly multidimensional search space to incomplete parameter identifiability. To meet some of these challenges, an ensemble modeling method is developed for characterizing a subset of kinetic parameters that give statistically equivalent goodness-of-fit to time series concentration data. The method is based on the incremental identification approach, where the parameter estimation is done in a step-wise manner. Numerical efficacy is achieved by reducing the dimensionality of parameter space and using efficient random parameter exploration algorithms. The shift toward using model ensembles, instead of the traditional “best-fit” models, is necessary to directly account for model uncertainty during the application of such models. The performance of the ensemble modeling approach has been demonstrated in the modeling of a generic branched pathway and the trehalose pathway in Saccharomyces cerevisiae using generalized mass action (GMA kinetics.

Effects of Refined Xiaoyaosan on Depressive-Like Behaviors in Rats with Chronic Unpredictable Mild Stress through Neurosteroids, Their Synthesis and Metabolic Enzymes

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Xiaoling Guo

2017-08-01

Full Text Available Abstract: To observe the effects of refined Xiaoyaosan (XYS on the depressive-like behaviors in rats with chronic unpredictable mild stress (CUMS, and to explore the relationship between the changes of neurosteroids and mRNA expressions of their synthesis and metabolic enzymes, and the mechanism of XYS in the treatment of depression. Methods: Eighty-four healthy male Sprague-Dawley rats were randomly divided into normal group, model group, XYS group and fluoxetine group. The latter three groups were subjected to 21 days of CUMS to prepare the stress depression model. Rats in the XYS group, and fluoxetine group were given intragastric administration with refined XYS and fluoxetine, respectively. The behavioral changes of the rats were observed after 21 days. The contents of pregnenolone (PREG, progesterone (PROG and alloprognanolone (ALLO in the plasma of rats were measured by ELISA. The levels of PREG, PROG and ALLO in the hippocampus and amygdala tissues were measured by LC-MS/MS. The mRNA expressions of 3α-hydroxysteroid dehydrogenase (3α-HSD, 3β-hydroxysteroid dehydrogenase (3β-HSD, cholesterol side-chain cleavage enzyme (P450scc and 5α-reductase (5a-R in the hippocampus and amygdala were detected by RT-qPCR methods. Results: There were changes in the model rats. The contents of PREG, PROG and ALLO changed similarly, which reflected in the decrease of PROG and ALLO, and the increase of PREG. The mRNA expression of P450scc was increased, and the mRNA expressions of 3α-HSD, 3β-HSD and 5a-R were decreased. Refined XYS could improve the behaviors of rats and the biological indicators. Conclusions: There is a neurosteroid dysfunction in the brain region of depression rat model animals, and the mechanism of refined XYS depression treatment may be related to the regulation of the control of mRNA expression of related synthesis and metabolic enzymes in the hippocampus and amygdala, further affecting the contents of neurosteroids.

Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease.

Science.gov (United States)

Hayashi, Atsuko; Nomura, Hiroshi; Mochizuki, Ruriko; Ohnuma, Ayumu; Kimpara, Teiko; Suzuki, Kyoko; Mori, Etsuro

2015-01-01

We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients.

Leucine metabolism in patients with Hepatic Encephalopathy

International Nuclear Information System (INIS)

McGhee, A.S.; Kassouny, M.E.; Matthews, D.E.; Millikan, W.

1986-01-01

A primed continuous infusion of [ 15 N, 1- 13 C]leucine was used to determine whether increased oxidation and/or protein synthesis of leucine occurs in patients with cirrhosis. Five controls and patients were equilibrated on a metabolic balance diet [0.6 g protein per kg ideal body weight (IBW)]. An additional four patients were equilibrated in the same manner with the same type of diet with a protein level of 0.75 g per kg IBW. Plasma leucine and breath CO 2 enrichments were measured by mass spectrometry. Protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW. Results indicate that systemic derangements of leucine metabolism are not the cause of Hepatic Encephalopathy

Bad Influence?--An Investigation into the Purported Negative Influence of Foreign Domestic Helpers on Children's Second Language English Acquisition

Science.gov (United States)

Leung, Alex Ho-Cheong

2012-01-01

This paper explores the purported negative influence of foreign domestic helpers (FDHs) on child second language acquisition (SLA) by studying Hong Kong Cantonese children's listening ability in second language (L2) English. 31 kindergarten third graders aged 4;6 to 6, and 29 first year secondary students aged 11-14 who have had a Filipino…

Role of ethylene metabolism in Amaranthus retroflexus

International Nuclear Information System (INIS)

Raskin, I.; Beyer, E. Jr.

1989-01-01

14 C-Ethylene was metabolized by etiolated pigweed seedlings (Amaranthus retroflexus L.) in the manner similar to that observed in other plants. The hormone was oxidized to 14 CO 2 and incorporated into 14 -tissue components. Selected cyclic olefins with differing abilities to block ethylene action were used to determine if ethylene metabolism in pigweed is necessary for ethylene action. 2,5-Norbornadiene and 1,3-cyclohexadiene were effective inhibitors of ethylene action at 800 and 6400 μ1/1, respectively, in the gas phase, while 1,4-cyclohexadiene and cyclohexene were not. However, all four cyclic olefins inhibited the incorporation and conversion of 14 C-ethylene to 14 CO 2 by 95% with I 50 values below 100 μ1/1. The results indicate that total ethylene metabolism does not directly correlate with changes in ethylene action. Additionally, the fact that inhibition of ethylene metabolism by the cyclic olefins did not result in a corresponding increase in ethylene evolution, indicates that ethylene metabolism does not serve to significantly reduce endogenous ethylene levels

MicroRNAs regulate T-cell production of interleukin-9 and identify hypoxia-inducible factor-2α as an important regulator of T helper 9 and regulatory T-cell differentiation.

Science.gov (United States)

Singh, Yogesh; Garden, Oliver A; Lang, Florian; Cobb, Bradley S

2016-09-01

MicroRNAs (miRNAs) regulate many aspects of helper T cell (Th) development and function. Here we found that they are required for the suppression of interleukin-9 (IL-9) expression in Th9 cells and other Th subsets. Two highly related miRNAs (miR-15b and miR-16) that we previously found to play an important role in regulatory T (Treg) cell differentiation were capable of suppressing IL-9 expression when they were over-expressed in Th9 cells. We used these miRNAs as tools to identify novel regulators of IL-9 expression and found that they could regulate the expression of Epas1, which encodes hypoxia-inducible factor (HIF)-2α. HIF proteins regulate metabolic pathway usage that is important in determining appropriate Th differentiation. The related protein, HIF-1α enhances Th17 differentiation and inhibits Treg cell differentiation. Here we found that HIF-2α was required for IL-9 expression in Th9 cells, but its expression was not sufficient in other Th subsets. Furthermore, HIF-2α suppressed Treg cell differentiation like HIF-1α, demonstrating both similar and distinct roles of the HIF proteins in Th differentiation and adding a further dimension to their function. Ironically, even though miR-15b and miR-16 suppressed HIF-2α expression in Treg cells, inhibiting their function in Treg cells did not lead to an increase in IL-9 expression. Therefore, the physiologically relevant miRNAs that regulate IL-9 expression in Treg cells and other subsets remain unknown. Nevertheless, the analysis of miR-15b and miR-16 function led to the discovery of the importance of HIF-2α so this work demonstrated the utility of studying miRNA function to identify novel regulatory pathways in helper T-cell development. © 2016 John Wiley & Sons Ltd.

Serum Metabonomics of Mild Acute Pancreatitis.

Science.gov (United States)

Xu, Hongmin; Zhang, Lei; Kang, Huan; Zhang, Jiandong; Liu, Jie; Liu, Shuye

2016-11-01

Mild acute pancreatitis (MAP) is a common acute abdominal disease, and exhibits rising incidence in recent decades. As an important component of systemic biology, metabonomics is a new discipline developed following genomics and proteomics. In this study, the objective was to analyze the serum metabonomics of patients with MAP, aiming to screen metabolic markers with potential diagnostic values. An analysis platform with ultra performance liquid chromatography-high-resolution mass spectrometry was used to screen the difference metabolites related to MAP diagnosis and disease course monitoring. A total of 432 endogenous metabolites were screened out from 122 serum samples, and 49 difference metabolites were verified, among which 12 difference metabolites were identified by nonparametric test. After material identification, eight metabolites exhibited reliable results, and their levels in MAP serum were higher than those in healthy serum. Four metabolites exhibited gradual downward trend with treatment process going on, and the differences were statistically significant (P Metabonomic analysis has revealed eight metabolites with potential diagnostic values toward MAP, among which four metabolites can be used to monitor the disease course. © 2016 Wiley Periodicals, Inc.

Chronic obstructive pulmonary disease may be one of the terminal end points of metabolic syndrome

International Nuclear Information System (INIS)

Helvaci, M.R.; Aydin, L.Y.; Aydin, Y.

2012-01-01

Objective: We tried to understand presence of any effect of excess weight on respiratory system by means of excessive adipose tissue functioning as an endocrine organ and causing a Methodology: Mild (stage 1), moderate (stage 2), and severe (stage 3 and 4) chronic obstructive pulmonary disease (COPD) patients were detected, and compared according to the metabolic parameters in between. Results: There were 145, 56, and 34 patients in the mild, moderate, and severe COPD groups, respectively. The mean age increased gradually (52.4, 56.4, and 60.0 years) from the mild towards the severe COPD groups, respectively (p<0.05 nearly in all steps). Similarly, the mean direction (p<0.05 nearly in all steps). Parallel to them, the mean body mass index increased Conclusion: The metabolic syndrome includes some reversible indicators such as overweight, hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia, impaired fasting glucose, impaired glucose tolerance, and white coat hypertension for the development of terminal diseases including obesity, hypertension, diabetes mellitus, peripheral artery disease, coronary heart disease, and stroke. In our opinion, COPD may be one of the terminal end points of the syndrome. (author)

Chronic obstructive pulmonary disease may be one of the terminal end points of metabolic syndrome

Energy Technology Data Exchange (ETDEWEB)

Helvaci, M R; Aydin, L Y; Aydin, Y

2012-04-15

Objective: We tried to understand presence of any effect of excess weight on respiratory system by means of excessive adipose tissue functioning as an endocrine organ and causing a Methodology: Mild (stage 1), moderate (stage 2), and severe (stage 3 and 4) chronic obstructive pulmonary disease (COPD) patients were detected, and compared according to the metabolic parameters in between. Results: There were 145, 56, and 34 patients in the mild, moderate, and severe COPD groups, respectively. The mean age increased gradually (52.4, 56.4, and 60.0 years) from the mild towards the severe COPD groups, respectively (p<0.05 nearly in all steps). Similarly, the mean direction (p<0.05 nearly in all steps). Parallel to them, the mean body mass index increased Conclusion: The metabolic syndrome includes some reversible indicators such as overweight, hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia, impaired fasting glucose, impaired glucose tolerance, and white coat hypertension for the development of terminal diseases including obesity, hypertension, diabetes mellitus, peripheral artery disease, coronary heart disease, and stroke. In our opinion, COPD may be one of the terminal end points of the syndrome. (author)

Cerebral glucose metabolism in Wernicke's, Broca's, and conduction aphasia

Energy Technology Data Exchange (ETDEWEB)

Metter, E.J.; Kempler, D.; Jackson, C.; Hanson, W.R.; Mazziotta, J.C.; Phelps, M.E.

1989-01-01

Cerebral glucose metabolism was evaluated in patients with either Wernicke's (N = 7), Broca's (N = 11), or conduction (N = 10) aphasia using /sup 18/F-2-fluoro-2-deoxy-D-glucose with positron emission tomography. The three aphasic syndromes differed in the degree of left-to-right frontal metabolic asymmetry, with Broca's aphasia showing severe asymmetry and Wernicke's aphasia mild-to-moderate metabolic asymmetry, while patients with conduction aphasia were metabolically symmetric. On the other hand, the three syndromes showed the same degree of metabolic decline in the left temporal region. The parietal region appeared to separate conduction aphasia from both Broca's and Wernicke's aphasias. Common aphasic features in the three syndromes appear to be due to common changes in the temporal region, while unique features were associated with frontal and parietal metabolic differences.

Do patients with mild to moderate psoriasis really have a sedentary lifestyle?

Science.gov (United States)

Demirel, Reha; Genc, Abdurrahman; Ucok, Kagan; Kacar, Seval Dogruk; Ozuguz, Pinar; Toktas, Muhsin; Sener, Umit; Karabacak, Hatice; Karaca, Semsettin

2013-09-01

The aim of this study was to compare aerobic exercise capacity, daily physical activity, pulmonary functions, resting metabolic rate, and body composition parameters in patients with psoriasis and healthy controls. A total of 60 participants (30 [15 men, 15 women] patients with psoriasis, and 30 [15 men, 15 women] healthy controls) ranging in age from 22-57 were included in the study. Maximal aerobic capacity was determined by Astrand exercise protocol. Daily physical activity was measured with an accelerometer. Resting metabolic rate was determined with an indirect calorimeter. Pulmonary function tests were performed with a portable spirometer. Body composition was established with a bioelectric impedance analysis system. Skinfold thicknesses and body circumference measurements were carried out. Short Form 36 quality of life questionnaire was applied to all participants. In both genders, daily physical activity parameters were found to be higher in the psoriasis group compared to the control. Maximal aerobic capacity, resting metabolic rate, pulmonary function tests, body fatness, body fat distributions, and quality of life were not statistically different between patients with psoriasis and controls in males and females. We suggest that patients with psoriasis who do not have psoriatic arthritis or severe psoriasis are well in performing daily physical activities. In addition, we suggest that this lifestyle helped to prevent impairments of body fatness, body fat distributions, resting metabolic rate, pulmonary functions, and quality of life in patients with mild to moderate psoriasis. © 2013 The International Society of Dermatology.

Construction of adeno-associated virus packaging plasmids and cells that directly select for AAV helper functions.

Science.gov (United States)

Whiteway, Alistair; Deru, Wale; Prentice, H Grant; Anderson, Robert

2003-12-01

Recombinant adeno-associated virus type 2 (rAAV) has promise for use as a gene therapy vector. Potential problems in the production of rAAV stocks are both the limited amount of recombinant virus that is produced by traditional methods and the possibility of wild-type replication competent adeno-associated virus (wtAAV) contamination. The presence of these contaminants is largely dependent upon the helper plasmid used. Whilst wtAAV is not a pathogen, the presence of these contaminants is undesirable as they may affect experiments concerning the biology of rAAV. Additionally as protocols using rAAV with altered tropism are becoming more prevalent, it is important that no recombination be permitted that may cause the creation of a replication competent AAV with modified (targeting) capsids. Many experimental protocols require the generation of large amounts of high titre rAAV stocks. We describe the production of several AAV helper plasmids and cell lines designed to achieve this goal. These plasmids possess split AAV rep and cap genes to eliminate the production of wtAAV and they possess a selection mechanism which is operatively linked to expression from the AAV cap gene. This allows positive selection of those cells expressing the highest level of the structural capsid proteins and therefore those cells which yield the highest amount of rAAV.

Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease

Directory of Open Access Journals (Sweden)

Atsuko Hayashi

2015-09-01

Full Text Available Background/Aims: We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI and mild Alzheimer's disease (AD. To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji. Methods: A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. Results: For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. Conclusions: The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients.

User manual for SPLASH (Single Panel Lamp and Shroud Helper).

Energy Technology Data Exchange (ETDEWEB)

Larsen, Marvin Elwood

2006-02-01

The radiant heat test facility develops test sets providing well-characterized thermal environments, often representing fires. Many of the components and procedures have become standardized to such an extent that the development of a specialized design tool to determine optimal configurations for radiant heat experiments was appropriate. SPLASH (Single Panel Lamp and Shroud Helper) is that tool. SPLASH is implemented as a user-friendly, Windows-based program that allows a designer to describe a test setup in terms of parameters such as number of lamps, power, position, and separation distance. This document is a user manual for that software. Any incidental descriptions of theory are only for the purpose of defining the model inputs. The theory for the underlying model is described in SAND2005-2947 (Ref. [1]). SPLASH provides a graphical user interface to define lamp panel and shroud designs parametrically, solves the resulting radiation enclosure problem for up to 2500 surfaces, and provides post-processing to facilitate understanding and documentation of analyzed designs.

Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Retardation and Down Syndrome.

Science.gov (United States)

Haier, Richard J.; And Others

1995-01-01

Brain size and cerebral glucose metabolic rate were determined for 10 individuals with mild mental retardation (MR), 7 individuals with Down syndrome (DS), and 10 matched controls. MR and DS groups both had brain volumes of about 80% compared to controls, with variance greatest within the MR group. (SLD)

Mannerisms of the Elderly and Approaches to Rapport.

Science.gov (United States)

French, Warren A.; And Others

1980-01-01

Many older adults react to old age with empirically identified distinguishable mannerisms. Using these mannerisms, or behavior patterns, as a basis for rapport, gerontologists can: (1) uncover causes of adjustment problems; (2) assess seriousness of problems; and (3) implement counseling suggestions. (Author/JAC)

NARRATIVE PERSPECTIVE MEDIATED BY MANNER OF MOTION VERBS

Directory of Open Access Journals (Sweden)

Olesea BODEAN-VOZIAN

2016-12-01

Full Text Available There is typological variation in the way languages encode manner as an element of a motion event. Languages like English view it as relevant, and the lexicalization of the variety of ways to move results in a rich class of motion verbs, contrary to other types of languages, like Romanian, which leave the manner element to be encoded by verbids or adverbs (for these reasons some linguists refer to the first type as manner-rich and second type as manner-poor languages. Still, several studies contrasting typologically different languages showed that languages of the latter type are not so poor in manner-of-motion verbs. The question then might rather be: which manner components are more likely to be lexicalized?For research purposes, we distinguish manner in terms of objective elements (medium, speed or intensity and subjective elements (attitude, intention. The aim of the study is to focus on the manner-of-motion verbs that embed an evaluative or qualitative dimension of motion and to examine the way these verbs encode somebody’s perspective in a narrative. The first question in such a case is whose evaluation or point of view is being represented. The second one is how the subjective point of view (narrative perspective mediated through manner-of-motion verbs in an English narrative (The Lord of the Rings, by J.R.R. Tolkien is translated into Romanian, supposedly a manner-poor or low-manner language.PERSPECTIVA NARATIVĂ MEDIATĂ DE VERBELE DE MIŞCARE DE MODExistă o variaţie tipologică în felul în care limbile codifică modul ca element al unui eveniment de mişcare. Limbile precum engleza îl percep drept unul relevant, iar lexicalizarea gamei de mijloace de redare a mişcării a dat naştere unei clase bogate de verbe de mişcare, contrar altor tipuri de limbi, aşa ca româna, în care elementul ce redă modul este codificat de gerunziu sau adverbe. Din aceasta cauză, unii lingvişti numesc primul tip limbi bogate în verbe de mod (�

Hepatic folate metabolism in the chronic alcoholic monkey

International Nuclear Information System (INIS)

Tamura, T.; Romero, J.J.; Watson, J.E.; Gong, E.J.; Halsted, C.H.

1981-01-01

To assess the role of altered hepatic folate metabolism in the pathogenesis of the folate deficiency of chronic alcoholism, the hepatic metabolism of a tracer dose of 3 H-PteGlu was compared in monkeys given 50% of energy as ethanol for 2 years and in control monkeys. Long-term ethanol feeding resulted in mild hepatic injury, with a significant decrease in hepatic folate levels. Chromatographic studies of liver biopsies obtained after the tracer dose indicated that the processes of reduction, methylation, and formylation of reduced folate and the synthesis of polyglutamyl folates were not affected by long-term ethanol feeding. Hepatic tritium levels were significantly decreased in the ethanol-fed group. These studies suggest that the decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decreased ability to retain folates in the liver, whereas reduction and further metabolism of folates is not affected

Subpopulation of human helper and suppressor T lymphocytes

International Nuclear Information System (INIS)

Venkataraman, M.; Levin, R.D.; Westerman, M.P.

1983-01-01

Mitogen driven differentiation of normal human mononuclear cells is a well-established model for the study of antibody synthesis in man. In certain rare individuals who are clinically normal, unfractionated mononuclear cells or a mixture of purified B plus T lymphocytes differentiate into immunoglobulin producing cells in response to purified protein derivative of tuberculin (PPD) but not in response to pokeweed mitogen (PWM). To evaluate this observation we have irradiated T cells from such individuals to eliminate naturally occurring suppressor T cell activity and then added the irradiated T cells back to autologous B cells before culture. The B cells then responded to PWM. The original PPD responses of cells from these individuals were now significantly reduced. Although, there was no difference between PWM nonresponders and responders in the number of OKT-8 positive cells, elimination of OKT-8 positive cells in the PWM nonresponders with OKT-8 monoclonal antibody and complement resulted in a significantly increased response to PWM. This study indicates that there are suppressor T cells which specifically inhibit B cell response to PWM without affecting the PPD response. These results also show that the helper T cells involved in the PWM response are radioresistant and those involved in the PPD response are radiosensitive

Cerebral blood flow and oxygen metabolism after subarachnoid hemorrhage

International Nuclear Information System (INIS)

Ito, Hidemichi; Sakurai, Takashi; Hayashi, Tatsuo; Hashimoto, Takuo

2004-01-01

The mechanism of reduction of cerebral circulation in the early phase of aneurysmal subarachnoid hemorrhage (SAH) has not yet been clarified. Previous studies have variously indicated that cerebral blood flow (CBF) reduction may be due to cerebral vasospasm, an elevation in intracranial pressure (ICP), constriction of intraparenchymal arterioles, or metabolic reduction. The aim of this study is to investigate the relationship between cerebral circulation and oxygen metabolism. In 36 patients with aneurysmal SAH, the values of mean cerebral blood flow (mCBF), cerebral metabolic rate of oxygen (GMRO 2 ) and oxygen extraction fraction (OEF) were measured by using single photon emission computed tomography (SPECT) with arterial blood drawing and oxygen saturation of internal jugular bulb blood (SjO 2 ) in the acute stage (1-3 days after onset) and the spasm stage (7-10 days after onset). The patients in our study were selected by using the following criteria: no history of cerebrovascular or cardiopulmonary diseases; under the age of 70; the ruptured aneurysm was treated by clipping or coil embolization within 72 hours after onset; no symptoms of cerebral vasospasm; no signs of cerebral ischemic change on CT scans. These patients were divided into 2 groups according to the World Federation of Neurological Surgeons (WFNS) grading classification; the mild group (Grades I and II) consisted of 27 cases and the severe group (Grade IV) consisted of 9 cases. We studied differences in mCBF CMRO 2 , and OEF between the mild group and severe group. In the mild group, mCBF, CMRO 2 , and OEF were significantly higher than in the severe group during both the acute and the spasm stage. Also mCBF showed a direct correlation with CMRO 2 . All the patients were kept under the following conditions: the bed was positioned so that the upper body was raised at an angle at 30 deg; blood pressure was maintained at 130-150 mmHg and PaCO 2 of arterial blood was maintained at 35-40 mmHg; ICP

Metabolic engineering of biosynthetic pathway for production of renewable biofuels.

Science.gov (United States)

Singh, Vijai; Mani, Indra; Chaudhary, Dharmendra Kumar; Dhar, Pawan Kumar

2014-02-01

Metabolic engineering is an important area of research that involves editing genetic networks to overproduce a certain substance by the cells. Using a combination of genetic, metabolic, and modeling methods, useful substances have been synthesized in the past at industrial scale and in a cost-effective manner. Currently, metabolic engineering is being used to produce sufficient, economical, and eco-friendly biofuels. In the recent past, a number of efforts have been made towards engineering biosynthetic pathways for large scale and efficient production of biofuels from biomass. Given the adoption of metabolic engineering approaches by the biofuel industry, this paper reviews various approaches towards the production and enhancement of renewable biofuels such as ethanol, butanol, isopropanol, hydrogen, and biodiesel. We have also identified specific areas where more work needs to be done in the future.

Being Both Helpers and Victims: Health Professionals' Experiences of Working During a Natural Disaster.

Science.gov (United States)

Hugelius, Karin; Adolfsson, Annsofie; Örtenwall, Per; Gifford, Mervyn

2017-04-01

In November 2013, the Haiyan typhoon hit parts of the Philippines. The typhoon caused severe damage to the medical facilities and many injuries and deaths. Health professionals have a crucial role in the immediate disaster response system, but knowledge of their experiences of working during and in the immediate aftermath of a natural disaster is limited. Aim The aim of this study was to explore health professionals' experiences of working during and in the immediate aftermath of a natural disaster. Eight health professionals were interviewed five months after the disaster. The interviews were analyzed using phenomenological hermeneutic methods. The main theme, being professional and survivor, described both positive and negative emotions and experiences from being both a helper, as part of the responding organization, and a victim, as part of the surviving but severely affected community. Sub-themes described feelings of strength and confidence, feelings of adjustment and acceptance, feelings of satisfaction, feelings of powerless and fear, feelings of guilt and shame, and feelings of loneliness. Being a health professional during a natural disaster was a multi-faceted, powerful, and ambiguous experience of being part of the response system at the same time as being a survivor of the disaster. Personal values and altruistic motives as well as social aspects and stress-coping strategies to reach a balance between acceptance and control were important elements of the experience. Based on these findings, implications for disaster training and response strategies are suggested. Hugelius K , Adolfsson A , Örtenwall P , Gifford M . Being both helpers and victims: health professionals' experiences of working during a natural disaster. Prehosp Disaster Med. 2017;32(2):117-123.

Metabolism as an Integral Cog in the Mammalian Circadian Clockwork

Science.gov (United States)

Gamble, Karen L.; Young, Martin E.

2013-01-01

Circadian rhythms are an integral part of life. These rhythms are apparent in virtually all biological processes studies to date, ranging from the individual cell (e.g., DNA synthesis) to the whole organism (e.g., behaviors such as physical activity). Oscillations in metabolism have been characterized extensively in various organisms, including mammals. These metabolic rhythms often parallel behaviors such as sleep/wake and fasting/feeding cycles that occur on a daily basis. What has become increasingly clear over the past several decades is that many metabolic oscillations are driven by cell autonomous circadian clocks, which orchestrate metabolic processes in a temporally appropriate manner. During the process of identifying the mechanisms by which clocks influence metabolism, molecular-based studies have revealed that metabolism should be considered an integral circadian clock component. The implications of such an interrelationship include the establishment of a vicious cycle during cardiometabolic disease states, wherein metabolism-induced perturbations in the circadian clock exacerbate metabolic dysfunction. The purpose of this review is therefore to highlight recent insights gained regarding links between cell autonomous circadian clocks and metabolism, and the implications of clock dysfunction in the pathogenesis of cardiometabolic diseases. PMID:23594144

The medical food Souvenaid affects brain phospholipid metabolism in mild Alzheimer's disease: results from a randomized controlled trial

NARCIS (Netherlands)

Rijpma, A.; Graaf, M. van der; Lansbergen, M.M.; Meulenbroek, O.V.; Cetinyurek-Yavuz, A.; Sijben, J.W.; Heerschap, A.; Olde Rikkert, M.G.M.

2017-01-01

BACKGROUND: Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients

Dehalogenation of vicinal dihalo compounds by 1,1'-bis(trimethylsilyl)-1H,1'H-4,4'-bipyridinylidene for giving alkenes and alkynes in a salt-free manner.

Science.gov (United States)

Rej, Supriya; Pramanik, Suman; Tsurugi, Hayato; Mashima, Kazushi

2017-12-07

We report a transition metal-free dehalogenation of vicinal dihalo compounds by 1,1'-bis(trimethylsilyl)-1H,1'H-4,4'-bipyridinylidene (1) under mild conditions, in which trimethylsilyl halide and 4,4'-bipyridine were generated as byproducts. The synthetic protocol for this dehalogenation reaction was effective for a wide scope of dibromo compounds as substrates while keeping the various functional groups intact. Furthermore, the reduction of vicinal dichloro alkanes and vicinal dibromo alkenes also proceeded in a salt-free manner to afford the corresponding alkenes and alkynes.

MHC class II expression through a hitherto unknown pathway supports T helper cell-dependent immune responses: implications for MHC class II deficiency

NARCIS (Netherlands)

Buch, Thorsten; Polic, Bojan; Clausen, Björn E.; Weiss, Susanne; Akilli-Ozturk, Ozlem; Chang, Cheong-Hee; Flavell, Richard; Schulz, Ansgar; Jonjic, Stipan; Waisman, Ari; Förster, Irmgard

2006-01-01

MHC class II (MHCII) deficiency or bare lymphocyte syndrome (BLS) is a severe immunodeficiency characterized by deficient T helper (Th)-cell-dependent immunity. The disease is caused by defects of the MHCII promoter complex resulting in low or absent MHCII expression. We demonstrate in a murine

Metabolic Effects of the Very-Low-Carbohydrate Diets: Misunderstood "Villains" of Human Metabolism

Directory of Open Access Journals (Sweden)

Manninen Anssi H

2004-12-01

Full Text Available Abstract During very low carbohydrate intake, the regulated and controlled production of ketone bodies causes a harmless physiological state known as dietary ketosis. Ketone bodies flow from the liver to extra-hepatic tissues (e.g., brain for use as a fuel; this spares glucose metabolism via a mechanism similar to the sparing of glucose by oxidation of fatty acids as an alternative fuel. In comparison with glucose, the ketone bodies are actually a very good respiratory fuel. Indeed, there is no clear requirement for dietary carbohydrates for human adults. Interestingly, the effects of ketone body metabolism suggest that mild ketosis may offer therapeutic potential in a variety of different common and rare disease states. Also, the recent landmark study showed that a very-low-carbohydrate diet resulted in a significant reduction in fat mass and a concomitant increase in lean body mass in normal-weight men. Contrary to popular belief, insulin is not needed for glucose uptake and utilization in man. Finally, both muscle fat and carbohydrate burn in an amino acid flame.

Hierarchical multivariate covariance analysis of metabolic connectivity.

Science.gov (United States)

Carbonell, Felix; Charil, Arnaud; Zijdenbos, Alex P; Evans, Alan C; Bedell, Barry J

2014-12-01

Conventional brain connectivity analysis is typically based on the assessment of interregional correlations. Given that correlation coefficients are derived from both covariance and variance, group differences in covariance may be obscured by differences in the variance terms. To facilitate a comprehensive assessment of connectivity, we propose a unified statistical framework that interrogates the individual terms of the correlation coefficient. We have evaluated the utility of this method for metabolic connectivity analysis using [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. As an illustrative example of the utility of this approach, we examined metabolic connectivity in angular gyrus and precuneus seed regions of mild cognitive impairment (MCI) subjects with low and high β-amyloid burdens. This new multivariate method allowed us to identify alterations in the metabolic connectome, which would not have been detected using classic seed-based correlation analysis. Ultimately, this novel approach should be extensible to brain network analysis and broadly applicable to other imaging modalities, such as functional magnetic resonance imaging (MRI).

Migration of allosensitized helper but not cytolytic T-lymphocyte clones is inhibited by prostaglandin E2

International Nuclear Information System (INIS)

Jordan, M.L.; Hoffman, R.A.; Simmons, R.L.

1986-01-01

The authors have previously reported that random migration of one clone of C57BL/6 anti DBA/2 helper lymphocytes is significantly inhibited by physiologic concentrations of prostaglandin E 2 (PGE 2 ). The present studies were designed to determine if lymphocyte locomotor responses to PGE 2 are dictated by (1) clone effector function and/or (2) the presence of specific cell surface binding sites for PGE 2 . Random locomotion of eight different lymphocyte clones (all C57BL/6 anti DBA/2) was studied in a modified Boyden chamber assay. Clone function was characterized as helper (H, n = 3), cytolytic (C, n = 4) or cytolytic only in the presence of lectin (L, n = 1). Random migration of all H clones was consistently inhibited by PGE 2 . However, none of the clones possessing a lytic mechanism (C or L) were inhibited by even the highest (1000 ng/ml) concentration of PGE 2 tested. Incubation of clones with 3 H-PGE 2 in the presence of excess unlabelled PGE 2 did not demonstrate specific binding of PGE 2 to either H or C clones. The authors conclude that (1) the effects of PGE 2 on lymphocyte random migration are effector function specific and (2) these responses do not appear to be mediated by specialized cell surface receptors for PGE 2 . Subset specific locomotor responses to PGE 2 may constitute a mechanism whereby lymphocytes with distinct effector functions may differentially accumulate at sites of inflammation

JAK inhibition induces silencing of T Helper cytokine secretion and a profound reduction in T regulatory cells.

Science.gov (United States)

Keohane, Clodagh; Kordasti, Shahram; Seidl, Thomas; Perez Abellan, Pilar; Thomas, Nicholas S B; Harrison, Claire N; McLornan, Donal P; Mufti, Ghulam J

2015-10-01

CD4(+) T cells maintain cancer surveillance and immune tolerance. Chronic inflammation has been proposed as a driver of clonal evolution in myeloproliferative neoplasms (MPN), suggesting that T cells play an important role in their pathogenesis. Treatment with JAK inhibitors (JAKi) results in improvements in MPN-associated constitutional symptoms as well as reductions in splenomegaly. However, effects of JAKi on T cells in MPN are not well established and the baseline immune signature remains unclear. We investigated the frequency and function of CD4(+) T cell subsets in 50 MPN patients at baseline as well as during treatment with either ruxolitinib or fedratinib in a subset. We show that CD4(+)  CD127(low)  CD25(high)  FOXP3(+) T regulatory cells are reduced in MPN patients compared to healthy controls and that this decrease is even more pronounced following JAKi therapy. Moreover, we show that after 6 months of treatment the number of T helper (Th)-17 cells increased. We also describe a functional 'silencing' of T helper cells both in vivo and in vitro and a blockade of pro-inflammatory cytokines from these cells. This profound effect of JAKi on T cell function may underlay augmented rates of atypical infections that have been reported with use of these drugs. © 2015 John Wiley & Sons Ltd.

48 CFR 1371.101 - Inspection and manner of doing work.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Inspection and manner of... DEPARTMENT SUPPLEMENTAL REGULATIONS ACQUISITIONS INVOLVING SHIP CONSTRUCTION AND SHIP REPAIR Provisions and Clauses 1371.101 Inspection and manner of doing work. Insert clause 1352.271-70, Inspection and Manner of...

Reevaluating Metabolism in Alzheimer's Disease from the Perspective of the Astrocyte-Neuron Lactate Shuttle Model

OpenAIRE

Newington, Jordan T.; Harris, Richard A.; Cumming, Robert C.

2013-01-01

The conventional view of central nervous system (CNS) metabolism is based on the assumption that glucose is the main fuel source for active neurons and is processed in an oxidative manner. However, since the early 1990s research has challenged the idea that the energy needs of nerve cells are met exclusively by glucose and oxidative metabolism. This alternative view of glucose utilization contends that astrocytes metabolize glucose to lactate, which is then released and taken up by nearby neu...

Gene Therapy of T Helper Cells in HIV Infection. Mathematical Model of the Criteria for Clinical Effect

DEFF Research Database (Denmark)

Lund, Ole; Lund, Ole søgaard; Gram, Gregers

1997-01-01

The paper presents a mathematical model of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. Our main results are that the therapy should be designed to give the transduced cells a significant but not necessarily total protection against HIV-induced cell...... deaths, and to avoid the production of viral mutants that are insensitive to gene therapy. The transduced cells will not survive if the gene therapy only blocks the spread of virus....

Differentiation of human B lymphocyte subpopulations induced by an alloreactive helper T-cell clone

International Nuclear Information System (INIS)

Anderson, S.J.; Hummell, D.S.; Lawton, A.R.

1988-01-01

We have used cloned alloreactive helper T cells to determine if direct T cell-B cell interaction can induce differentiation of human peripheral blood B cells which do not respond to pokeweed mitogen (PWM). T-cell clone 2F8 was derived from a one-way mixed lymphocyte reaction. 2F8 cells are T3+T4+T8-IL-2R+ and proliferate in response to irradiated stimulator cells, but not autologous cells, in the absence of exogenous interleukin-2. 2F8 cells provide allospecific help for polyclonal proliferation and differentiation of B cells in the absence of any other stimulus. The magnitude of this response is comparable to that of the response of the same B cells to PWM and fresh autologous T cells. 2F8 cells could also provide nonspecific help for unrelated donor B cells in the presence of PWM, with no requirement for costimulation by irradiated stimulator cells. Allospecific stimulation of B cells was completely inhibited by antibodies to class II major histocompatibility complex (MHC) framework determinants and was abrogated by 1000-rad irradiation. Cloned 2F8 T cells stimulated differentiation of both small, high-density B cells and larger B cells, generating up to 30% plasma cells with either fraction. B cells forming rosettes with mouse erythrocytes were also induced to differentiate by the helper T cell clone. As found previously, neither small, high-density B cells nor mouse rosette+ B cells responded well to PWM. Direct interaction with allospecific T cells induces differentiation of a broader spectrum of B cells than soluble growth and differentiation factors in conjunction with polyclonal activators such as PWM and protein A containing staphylococci

Gene Therapy with Helper-Dependent Adenoviral Vectors: Current Advances and Future Perspectives

Directory of Open Access Journals (Sweden)

Philip Ng

2010-09-01

Full Text Available Recombinant Adenoviral vectors represent one of the best gene transfer platforms due to their ability to efficiently transduce a wide range of quiescent and proliferating cell types from various tissues and species. The activation of an adaptive immune response against the transduced cells is one of the major drawbacks of first generation Adenovirus vectors and has been overcome by the latest generation of recombinant Adenovirus, the Helper-Dependent Adenoviral (HDAd vectors. HDAds have innovative features including the complete absence of viral coding sequences and the ability to mediate high level transgene expression with negligible chronic toxicity. This review summarizes the many aspects of HDAd biology and structure with a major focus on in vivo gene therapy application and with an emphasis on the unsolved issues that these vectors still presents toward clinical application.

Mild induced hypothermia

DEFF Research Database (Denmark)

Johansen, Maria E; Jensen, Jens-Ulrik; Bestle, Morten H

2014-01-01

INTRODUCTION: Coagulopathy associates with poor outcome in sepsis. Mild induced hypothermia has been proposed as treatment in sepsis but it is not known whether this intervention worsens functional coagulopathy. MATERIALS AND METHODS: Interim analysis data from an ongoing randomized controlled...... trial; The Cooling And Surviving Septic shock (CASS) study. Patients suffering severe sepsis/septic shock are allocated to either mild induced hypothermia (cooling to 32-34°C for 24hours) or control (uncontrolled temperature). TRIAL REGISTRATION: NCT01455116. Thrombelastography (TEG) is performed three....... At enrollment, 3%, 38%, and 59% had a hypocoagulable, normocoagulable, and hypercoagulable TEG clot strength (MA), respectively. In the hypothermia group, functional coagulopathy improved during the hypothermia phase, measured by R and MA, in patients with hypercoagulation as well as in patients...

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

Directory of Open Access Journals (Sweden)

JoĂŤl Pestel

2008-06-01

Full Text Available Mycobacterium bovis bacillus Calmette-GuĂŠrin (BCG is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

Science.gov (United States)

Kowalewicz-Kulbat, Magdalena; Kaźmierczak, Dominik; Donevski, Stefan; Biet, Franck; Pestel, Joël; Rudnicka, Wiesława

2008-01-01

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs) are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

Chronic Caloric Restriction and Exercise Improve Metabolic Conditions of Dietary-Induced Obese Mice in Autophagy Correlated Manner without Involving AMPK

Directory of Open Access Journals (Sweden)

Mingxia Cui

2013-01-01

Full Text Available Aim. To investigate the role of AMPK activation and autophagy in mediating the beneficial effects of exercise and caloric restriction in obesity. Methods. Dietary-induced obesity mice were made and divided into 5 groups; one additional group of normal mice serves as control. Mice in each group received different combinations of interventions including low fat diet, caloric restriction, and exercise. Then their metabolic conditions were assessed by measuring serum glucose and insulin, serum lipids, and liver function. AMPK phosphorylation and autophagy activity were detected by western blotting. Results. Obese mice models were successfully induced by high fat diet. Caloric restriction consistently improved the metabolic conditions of the obese mice, and the effects are more prominent than the mice that received only exercise. Also, caloric restriction, exercise, and low fat diet showed a synergistic effect in the improvement of metabolic conditions. Western blotting results showed that this improvement was not related with the activation of AMPK in liver, skeletal muscle, or heart but correlates well with the autophagy activity. Conclusion. Caloric restriction has more prominent beneficial effects than exercise in dietary-induced obese mice. These effects are correlated with the autophagy activity and may be independent of AMPK activation.

CCR3, CCR5, CCR8 and CXCR3 expression in memory T helper cells from allergic rhinitis patients, asymptomatically sensitized and healthy individuals

DEFF Research Database (Denmark)

Holse, Mille; Assing, Kristian; Poulsen, Lars K.

2006-01-01

Chemokine receptors have been suggested to be preferentially expressed on CD4+ T cells with CCR3 and CCR8 linked to the T helper (Th) 2 subset and CCR5 and CXCR3 to the Th1 subset, however this remains controversial....

MILD CHOLESTEROL DEPLETION REDUCES AMYLOID-β PRODUCTION BY IMPAIRING APP TRAFFICKING TO THE CELL SURFACE

Science.gov (United States)

Guardia-Laguarta, Cristina; Coma, Mireia; Pera, Marta; Clarimón, Jordi; Sereno, Lidia; Agulló, José M.; Molina-Porcel, Laura; Gallardo, Eduard; Deng, Amy; Berezovska, Oksana; Hyman, Bradley T.; Blesa, Rafael; Gómez-Isla, Teresa; Lleó, Alberto

2009-01-01

It has been suggested that cellular cholesterol levels can modulate the metabolism of the amyloid precursor protein (APP) but the underlying mechanism remains controversial. In the current study, we investigate in detail the relationship between cholesterol reduction, APP processing and γ-secretase function in cell culture studies. We found that mild membrane cholesterol reduction led to a decrease in Aβ40 and Aβ42 in different cell types. We did not detect changes in APP intracellular domain or Notch intracellular domain generation. Western blot analyses showed a cholesterol-dependent decrease in the APP C-terminal fragments and cell surface APP. Finally, we applied a fluorescence resonance energy transfer (FRET)-based technique to study APP-Presenilin 1 (PS1) interactions and lipid rafts in intact cells. Our data indicate that cholesterol depletion reduces association of APP into lipid rafts and disrupts APP-PS1 interaction. Taken together, our results suggest that mild membrane cholesterol reduction impacts the cleavage of APP upstream of γ-secretase and appears to be mediated by changes in APP trafficking and partitioning into lipid rafts. PMID:19457132

Assessing the Metabolic Effects of Aromatherapy in Human Volunteers

Directory of Open Access Journals (Sweden)

Yinan Zhang

2013-01-01

Full Text Available Aromatherapy, a form of complementary and alternative medicine (CAM that uses essential oils through inhalation, is believed to enhance physical and spiritual conditions. Although clinical studies suggest that the use of essential oils may have therapeutic potential, evidence for the efficacy of aromatherapy in treating medical conditions remains poor, with a particular lack of studies employing rigorous analytical methods that capture its identifiable impact on human biology. Here, we report a comprehensive metabolomics study that reveals metabolic changes in people after exposed to aroma inhalation for 10 continuous days. In this study, the metabolic alterations in urine of 31 females with mild anxiety symptoms exposed to aerial diffusion of aromas were measured by GC-TOF-MS and UPLC-Q-TOF-MS analyses. A significant alteration of metabolic profile in subjects responsive to essential oil was found, which is characterized by the increased levels of arginine, homocysteine, and betaine, as well as decreased levels of alcohols, carbohydrates, and organic acids in urine. Notably, the metabolites from tricarboxylic acid (TCA cycle and gut microbial metabolism were significantly altered. This study demonstrates that the metabolomics approach can capture the subtle metabolic changes resulting from exposure to essential oils, which may lead to an improved mechanistic understanding of aromatherapy.

Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response.

Science.gov (United States)

Ueda, Norihiro; Uemura, Yasushi; Zhang, Rong; Kitayama, Shuichi; Iriguchi, Shoichi; Kawai, Yohei; Yasui, Yutaka; Tatsumi, Minako; Ueda, Tatsuki; Liu, Tian-Yi; Mizoro, Yasutaka; Okada, Chihiro; Watanabe, Akira; Nakanishi, Mahito; Senju, Satoru; Nishimura, Yasuharu; Kuzushima, Kiyotaka; Kiyoi, Hitoshi; Naoe, Tomoki; Kaneko, Shin

2018-06-05

CD4 + T helper (Th) cell activation is essential for inducing cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into original TCR-expressing T-lineage cells (iPS-T cells) with gene expression patterns resembling those of group 1 innate lymphoid cells. CD4 gene transduction into iPS-T cells enhanced b3a2 peptide-specific responses via b3a2 peptide-specific TCR. iPS-T cells upregulated CD40 ligand (CD40L) expression in response to interleukin-2 and interleukin-15. In the presence of Wilms tumor 1 (WT1) peptide, antigen-specific dendritic cells (DCs) conditioned by CD4-modified CD40L high iPS-T cells stimulated WT1-specific CTL priming, which eliminated WT1 peptide-expressing CML cells in vitro and in vivo. Thus, CD4 modification of CD40L high iPS-T cells generates innate lymphoid helper-like cells inducing bcr-abl-specific TCR signaling that mediates effectiveanti-leukemic CTL responses via DC maturation, showing potential for adjuvant immunotherapy against leukemia. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Captopril increases the intensity of monocyte infection by Trypanosoma cruzi and induces human T helper type 17 cells.

Science.gov (United States)

Coelho dos Santos, J S; Menezes, C A S; Villani, F N A; Magalhães, L M D; Scharfstein, J; Gollob, K J; Dutra, W O

2010-12-01

The anti-hypertensive drug captopril is used commonly to reduce blood pressure of patients with severe forms of Chagas disease, a cardiomyopathy caused by chronic infection with the intracellular protozoan Trypanosoma cruzi. Captopril acts by inhibiting angiotensin-converting enzyme (ACE), the vasopressor metallopeptidase that generates angiotensin II and promotes the degradation of bradykinin (BK). Recent studies in mice models of Chagas disease indicated that captopril can potentiate the T helper type 1 (Th1)-directing natural adjuvant property of BK. Equipped with kinin-releasing cysteine proteases, T. cruzi trypomastigotes were shown previously to invade non-professional phagocytic cells, such as human endothelial cells and murine cardiomyocytes, through the signalling of G protein-coupled bradykinin receptors (B(2) KR). Monocytes are also parasitized by T. cruzi and these cells are known to be important for the host immune response during infection. Here we showed that captopril increases the intensity of T. cruzi infection of human monocytes in vitro. The increased parasitism was accompanied by up-regulated expression of ACE in human monocytes. While T. cruzi infection increased the expression of interleukin (IL)-10 by monocytes significantly, compared to uninfected cells, T. cruzi infection in association with captopril down-modulated IL-10 expression by the monocytes. Surprisingly, studies with peripheral blood mononuclear cells revealed that addition of the ACE inhibitor in association with T. cruzi increased expression of IL-17 by CD4(+) T cells in a B(2) KR-dependent manner. Collectively, our results suggest that captopril might interfere with host-parasite equilibrium by enhancing infection of monocytes, decreasing the expression of the modulatory cytokine IL-10, while guiding development of the proinflammatory Th17 subset. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

Determinants of job satisfaction in foreign domestic helpers caring for people with dementia in Hong Kong.

Science.gov (United States)

Bai, Xue; Kwok, Timothy C Y; Chan, Natalie Y T; Ho, Florence K Y

2013-09-01

The job satisfaction of live-in foreign domestic helpers (FDHs) may influence their caring motivation and the quality of care they provide, which may in turn affect the health status of care recipients. This study identifies the factors affecting job satisfaction of FDHs caring for people with dementia in Hong Kong, focusing especially on the role of FDHs' adaptation status, job self-efficacy and care recipients' situation. A total of 152 FDHs taking care of people with dementia were recruited from 6 day care centres for elderly people in Hong Kong when they attended with their care recipients. Data were collected from February to August 2011 and the response rate was 95%. Participants completed questionnaires which included measures of care recipients' dementia severity and disruptive behaviours, FDHs' demographic factors, personal adaptation status, caregiving self-efficacy and job satisfaction. Hierarchical regression analysis was conducted to analyse the data. The results showed that longer stay in Hong Kong, better fluency in Cantonese (local dialect), greater satisfaction in living conditions, higher caregiving self-efficacy and less disruptive behaviour of care recipients were independently associated with stronger job satisfaction in FDHs looking after people with dementia. On the basis of these findings, we would suggest that employers should consider helpers who have been in Hong Kong for a longer period of time and speak fluent Cantonese, and have previous experience of taking care of people with dementia. In addition, FDHs caring for people with dementia may benefit from carer training which improves their self-efficacy in dementia care. © 2013 Blackwell Publishing Ltd.

Loss of circulating CD4 T cells with B cell helper function during chronic HIV infection.

Directory of Open Access Journals (Sweden)

Kristin L Boswell

2014-01-01

Full Text Available The interaction between follicular T helper cells (TFH and B cells in the lymph nodes and spleen has a major impact on the development of antigen-specific B cell responses during infection or vaccination. Recent studies described a functional equivalent of these cells among circulating CD4 T cells, referred to as peripheral TFH cells. Here, we characterize the phenotype and in vitro B cell helper activity of peripheral TFH populations, as well as the effect of HIV infection on these populations. In co-culture experiments we confirmed CXCR5+ cells from HIV-uninfected donors provide help to B cells and more specifically, we identified a CCR7(highCXCR5(highCCR6(highPD-1(high CD4 T cell population that secretes IL-21 and enhances isotype-switched immunoglobulin production. This population is significantly decreased in treatment-naïve, HIV-infected individuals and can be recovered after anti-retroviral therapy. We found impaired immunoglobulin production in co-cultures from HIV-infected individuals and found no correlation between the frequency of peripheral TFH cells and memory B cells, or with neutralization activity in untreated HIV infection in our cohort. Furthermore, we found that within the peripheral TFH population, the expression level of TFH-associated genes more closely resembles a memory, non-TFH population, as opposed to a TFH population. Overall, our data identify a heterogeneous population of circulating CD4 T cells that provides in vitro help to B cells, and challenges the origin of these cells as memory TFH cells.

Regional analysis of the magnetization transfer ratio of the brain in mild Alzheimer disease and amnestic mild cognitive impairment.

Science.gov (United States)

Mascalchi, M; Ginestroni, A; Bessi, V; Toschi, N; Padiglioni, S; Ciulli, S; Tessa, C; Giannelli, M; Bracco, L; Diciotti, S

2013-01-01

Manually drawn VOI-based analysis shows a decrease in magnetization transfer ratio in the hippocampus of patients with Alzheimer disease. We investigated with whole-brain voxelwise analysis the regional changes of the magnetization transfer ratio in patients with mild Alzheimer disease and patients with amnestic mild cognitive impairment. Twenty patients with mild Alzheimer disease, 27 patients with amnestic mild cognitive impairment, and 30 healthy elderly control subjects were examined with high-resolution T1WI and 3-mm-thick magnetization transfer images. Whole-brain voxelwise analysis of magnetization transfer ratio maps was performed by use of Statistical Parametric Mapping 8 software and was supplemented by the analysis of the magnetization transfer ratio in FreeSurfer parcellation-derived VOIs. Voxelwise analysis showed 2 clusters of significantly decreased magnetization transfer ratio in the left hippocampus and amygdala and in the left posterior mesial temporal cortex (fusiform gyrus) of patients with Alzheimer disease as compared with control subjects but no difference between patients with amnestic mild cognitive impairment and either patients with Alzheimer disease or control subjects. VOI analysis showed that the magnetization transfer ratio in the hippocampus and amygdala was significantly lower (bilaterally) in patients with Alzheimer disease when compared with control subjects (ANOVA with Bonferroni correction, at P ratio values in the hippocampus and amygdala in patients with amnestic mild cognitive impairment were between those of healthy control subjects and those of patients with mild Alzheimer disease. Support vector machine-based classification demonstrated improved classification performance after inclusion of magnetization transfer ratio-related features, especially between patients with Alzheimer disease versus healthy subjects. Bilateral but asymmetric decrease of magnetization transfer ratio reflecting microstructural changes of the

Impact of leptin on memory function and hippocampal structure in mild cognitive impairment.

Science.gov (United States)

Witte, A Veronica; Köbe, Theresa; Graunke, Anders; Schuchardt, Jan Philipp; Hahn, Andreas; Tesky, Valentina A; Pantel, Johannes; Flöel, Agnes

2016-12-01

Metabolic changes have been suggested to contribute to dementia and its precursor mild cognitive impairment (MCI), yet previous results particularly for the "satiety hormone" leptin are mixed. Therefore, we aimed to determine if MCI patients show systematic differences in leptin, independent of sex, adipose mass, age, and glucose and lipid metabolism, and whether leptin levels correlated with memory performance and hippocampal integrity. Forty MCI patients (20 females, aged 67 years ± 7 SD) were compared to 40 healthy controls (HC) that were pair-wise matched for sex, age, and body fat. Memory performance was assessed using the auditory verbal learning test. Volume and microstructure of the hippocampus were determined using 3T-neuroimaging. Fasting serum markers of leptin, glucose and lipid metabolism, and other confounding factors were assayed. MCI patients, compared with HC, showed lower serum leptin, independent of sex, age, and body fat (P memory and lower volume and microstructural integrity within hippocampal subfields. While leptin and memory were not significantly correlated, mediation analyses indicated that lower leptin contributed to poorer memory through its negative effect on right hippocampus volume and left hippocampus microstructure. We demonstrated that MCI is associated with lower serum leptin independent of sex, age, body fat, glucose, and lipid metabolism. Our data further suggest that inefficient leptin signaling could partly contribute to decreases in memory performance through changes in hippocampus structure, a hypothesis that should now be verified in longitudinal studies. Hum Brain Mapp 37:4539-4549, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Intestinal IgA responses to Giardia muris in mice depleted of helper T lymphocytes and in immunocompetent mice.

Science.gov (United States)

Heyworth, M F

1989-04-01

Immunocompetent mice infected with Giardia muris generate an intestinal antibody response to this parasite and clear G. muris infection. Previous work has shown that G. muris infection is prolonged in mice that have been depleted of helper (CD4+) T lymphocytes by treatment with a monoclonal antibody (mAb) directed against the murine CD4 antigen. The aim of the present study was to compare the intestinal anti-Giardia antibody response in immunocompetent mice and in mice depleted of helper T (Th) lymphocytes by treatment with anti-CD4 mAb. Immunocompetent mice generated an IgA response to G. muris, as judged by the presence of IgA on Giardia trophozoites harvested from the intestine of these animals more than 10 days after the start of the infection. The anti-Giardia IgA response was impaired in mice depleted of Th lymphocytes, as judged by virtual absence of immunofluorescent staining of trophozoites from these animals for surface-bound IgA. Clearance of G. muris infection was impaired by treatment of mice with anti-CD4 mAb. The results suggest that Th (CD4+) lymphocytes are important for the generation of a local IgA response against G. muris trophozoites in the mouse intestine and that IgA anti-trophozoite antibody may contribute to the clearance of G. muris from the intestine of immunocompetent mice.

Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

Directory of Open Access Journals (Sweden)

Wen Liang

adaptations in expression of gene clusters that control lipid metabolism and inflammatory processes in an orchestrated and interrelated manner.

Mimoza: web-based semantic zooming and navigation in metabolic networks.

Science.gov (United States)

Zhukova, Anna; Sherman, David J

2015-02-26

The complexity of genome-scale metabolic models makes them quite difficult for human users to read, since they contain thousands of reactions that must be included for accurate computer simulation. Interestingly, hidden similarities between groups of reactions can be discovered, and generalized to reveal higher-level patterns. The web-based navigation system Mimoza allows a human expert to explore metabolic network models in a semantically zoomable manner: The most general view represents the compartments of the model; the next view shows the generalized versions of reactions and metabolites in each compartment; and the most detailed view represents the initial network with the generalization-based layout (where similar metabolites and reactions are placed next to each other). It allows a human expert to grasp the general structure of the network and analyze it in a top-down manner Mimoza can be installed standalone, or used on-line at http://mimoza.bordeaux.inria.fr/ , or installed in a Galaxy server for use in workflows. Mimoza views can be embedded in web pages, or downloaded as COMBINE archives.

A Newly Emergent Turkey Arthritis Reovirus Shows Dominant Enteric Tropism and Induces Significantly Elevated Innate Antiviral and T Helper-1 Cytokine Responses.

Directory of Open Access Journals (Sweden)

Tamer A Sharafeldin

Full Text Available Newly emergent turkey arthritis reoviruses (TARV were isolated from tendons of lame 15-week-old tom turkeys that occasionally had ruptured leg tendons. Experimentally, these TARVs induced remarkable tenosynovitis in gastrocnemius tendons of turkey poults. The current study aimed to characterize the location and the extent of virus replication as well as the cytokine response induced by TARV during the first two weeks of infection. One-week-old male turkeys were inoculated orally with TARV (O'Neil strain. Copy numbers of viral genes were estimated in intestines, internal organs and tendons at ½, 1, 2, 3, 4, 7, 14 days Post inoculation (dpi. Cytokine profile was measured in intestines, spleen and leg tendons at 0, 4, 7 and 14 dpi. Viral copy number peaked in jejunum, cecum and bursa of Fabricius at 4 dpi. Copy numbers increased dramatically in leg tendons at 7 and 14 dpi while minimal copies were detected in internal organs and blood during the same period. Virus was detected in cloacal swabs at 1-2 dpi, and peaked at 14 dpi indicating enterotropism of the virus and its early shedding in feces. Elevation of IFN-α and IFN-β was observed in intestines at 7 dpi as well as a prominent T helper-1 response (IFN-γ at 7 and 14 dpi. IFN-γ and IL-6 were elevated in gastrocnemius tendons at 14 dpi. Elevation of antiviral cytokines in intestines occurred at 7dpi when a significant decline of viral replication in intestines was observed. T helper-1 response in intestines and leg tendons was the dominant T-helper response. These results suggest the possible correlation between viral replication and cytokine response in early infection of TARV in turkeys. Our findings provide novel insights which help elucidate viral pathogenesis in turkey tendons infected with TARV.

Innate scavenger receptor-A regulates adaptive T helper cell responses to pathogen infection

Science.gov (United States)

Xu, Zhipeng; Xu, Lei; Li, Wei; Jin, Xin; Song, Xian; Chen, Xiaojun; Zhu, Jifeng; Zhou, Sha; Li, Yong; Zhang, Weiwei; Dong, Xiaoxiao; Yang, Xiaowei; Liu, Feng; Bai, Hui; Chen, Qi; Su, Chuan

2017-01-01

The pattern recognition receptor (PRR) scavenger receptor class A (SR-A) has an important function in the pathogenesis of non-infectious diseases and in innate immune responses to pathogen infections. However, little is known about the role of SR-A in the host adaptive immune responses to pathogen infection. Here we show with mouse models of helminth Schistosoma japonicum infection and heat-inactivated Mycobacterium tuberculosis stimulation that SR-A is regulated by pathogens and suppresses IRF5 nuclear translocation by direct interaction. Reduced abundance of nuclear IRF5 shifts macrophage polarization from M1 towards M2, which subsequently switches T-helper responses from type 1 to type 2. Our study identifies a role for SR-A as an innate PRR in regulating adaptive immune responses. PMID:28695899

System-level perturbations of cell metabolism using CRISPR/Cas9

Energy Technology Data Exchange (ETDEWEB)

Jakočiūnas, Tadas [Technical Univ. of Denmark, Lyngby (Denmark); Jensen, Michael K. [Technical Univ. of Denmark, Lyngby (Denmark); Keasling, Jay D. [Technical Univ. of Denmark, Lyngby (Denmark); Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)

2017-03-30

CRISPR/Cas9 (clustered regularly interspaced palindromic repeats and the associated protein Cas9) techniques have made genome engineering and transcriptional reprogramming studies much more advanced and cost-effective. For metabolic engineering purposes, the CRISPR-based tools have been applied to single and multiplex pathway modifications and transcriptional regulations. The effectiveness of these tools allows researchers to implement genome-wide perturbations, test model-guided genome editing strategies, and perform transcriptional reprogramming perturbations in a more advanced manner than previously possible. In this mini-review we highlight recent studies adopting CRISPR/Cas9 for systems-level perturbations and model-guided metabolic engineering.

Traumatic brain injury alters methionine metabolism: implications for pathophysiology

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Pramod K Dash

2016-04-01

Full Text Available Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S-adenosylmethionine (SAM that serves as the principal methyl (-CH3 donor for DNA and histone methyltransferases to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling.. Under conditions of oxidative stress, homocysteine (which is derived from SAM enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (n = 20 and patients with mild TBI (GCS > 12; n = 20 or severe TBI (GCS < 8; n = 20 within the first 24 hours of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS. Severe TBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to healthy volunteers, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline. Mild TBI also decreased the levels of methionine, α-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser

The Generating Mechanism of the Perlocutionary Effects of Train Manner Posters

OpenAIRE

水田, 洋子

2013-01-01

Manner posters, which are used for the purpose of improving people’s manners in public spaces, attempt to be effective without being impositional. How do they meet the challenge? Manner posters can be considered to perform speech acts with written words and visual devices. The current work investigates the generating mechanism of their perlocutionary effects such as persuasion. It provides a case study of Japanese train manner posters by Tokyo Metro in 2008-2010. The analysis is conducted wit...

Comparison of the quick mild cognitive impairment (Qmci) screen and the SMMSE in screening for mild cognitive impairment.

LENUS (Irish Health Repository)

O'Caoimh, Rónán

2012-09-01

differentiating mild cognitive impairment (MCI) from normal cognition (NC) is difficult. The AB Cognitive Screen (ABCS) 135, sensitive in differentiating MCI from dementia, was modified to improve sensitivity and specificity, producing the quick mild cognitive impairment (Qmci) screen.

inhibition performance of mild ste thiophene ac rmance of mild steel

African Journals Online (AJOL)

userpc

d Industrial Chemistry, Faculty of Physical Science, Bayero University, Kan. P. M. B. 3011 ..... chemical studies on the inhibition potentials of some ... Efficiency of Thiophene Derivatives on. Mild Steel : A QSAR Model. International. Journal.

Mild Primary Hyperparathyroidism: A Literature Review

Science.gov (United States)

Applewhite, Megan K.

2014-01-01

The biochemical profile of classic primary hyperparathyroidism (pHPT) consists of both elevated calcium and parathyroid hormone levels. The standard of care is parathyroidectomy unless prohibited by medical comorbidities. Because more patients are undergoing routine bone density evaluation and neck imaging studies for other purposes, there is a subset of people identified with a biochemically mild form of the pHPT that expresses itself as either elevated calcium or parathyroid hormone levels. These patients often do not fall into the criteria for operation based on the National Institutes of Health consensus guidelines, and they can present a challenge of diagnosis and management. The purpose of this paper is to review the available literature on mild pHPT in an effort to better characterize this patient population and to determine whether patients benefit from parathyroidectomy. Evidence suggests that there are patients with mild pHPT who have overt symptoms that are found to improve after parathyroidectomy. There is also a group of patients with biochemically mild pHPT who are found to progress to classic pHPT over time; however, it is not predictable which group of patients this will be. Early intervention for this group with mild pHPT may prevent progression of bone, psychiatric, and renal complications, and parathyroidectomy has proven safe in appropriately selected patients at high volume centers. PMID:25063228

Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

Directory of Open Access Journals (Sweden)

Bell Jimmy D

2009-04-01

Full Text Available Abstract The metabolic syndrome may have its origins in thriftiness, insulin resistance and one of the most ancient of all signalling systems, redox. Thriftiness results from an evolutionarily-driven propensity to minimise energy expenditure. This has to be balanced with the need to resist the oxidative stress from cellular signalling and pathogen resistance, giving rise to something we call 'redox-thriftiness'. This is based on the notion that mitochondria may be able to both amplify membrane-derived redox growth signals as well as negatively regulate them, resulting in an increased ATP/ROS ratio. We suggest that 'redox-thriftiness' leads to insulin resistance, which has the effect of both protecting the individual cell from excessive growth/inflammatory stress, while ensuring energy is channelled to the brain, the immune system, and for storage. We also suggest that fine tuning of redox-thriftiness is achieved by hormetic (mild stress signals that stimulate mitochondrial biogenesis and resistance to oxidative stress, which improves metabolic flexibility. However, in a non-hormetic environment with excessive calories, the protective nature of this system may lead to escalating insulin resistance and rising oxidative stress due to metabolic inflexibility and mitochondrial overload. Thus, the mitochondrially-associated resistance to oxidative stress (and metabolic flexibility may determine insulin resistance. Genetically and environmentally determined mitochondrial function may define a 'tipping point' where protective insulin resistance tips over to inflammatory insulin resistance. Many hormetic factors may induce mild mitochondrial stress and biogenesis, including exercise, fasting, temperature extremes, unsaturated fats, polyphenols, alcohol, and even metformin and statins. Without hormesis, a proposed redox-thriftiness tipping point might lead to a feed forward insulin resistance cycle in the presence of excess calories. We therefore suggest

26 CFR 1.9005-4 - Manner of exercising election.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Manner of exercising election. 1.9005-4 Section 1.9005-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9005-4 Manner of exercising election. (a...

26 CFR 1.9004-4 - Manner of exercising election.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Manner of exercising election. 1.9004-4 Section 1.9004-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9004-4 Manner of exercising election. (a...

26 CFR 1.9002-8 - Manner of exercising elections.

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2010-04-01

... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Manner of exercising elections. 1.9002-8 Section 1.9002-8 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9002-8 Manner of exercising elections...

26 CFR 1.9003-4 - Manner of exercising election.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Manner of exercising election. 1.9003-4 Section 1.9003-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9003-4 Manner of exercising election. (a...

Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats

Science.gov (United States)

Figueroa-García, María del Consuelo; Espinosa-García, María Teresa; Martinez-Montes, Federico; Palomar-Morales, Martín; Mejía-Zepeda, Ricardo

2015-01-01

It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6–7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction. PMID:26630275

Impact of CD1d deficiency on metabolism.

Directory of Open Access Journals (Sweden)

Maya E Kotas

Full Text Available Invariant natural killer T cells (iNKTs are innate-like T cells that are highly concentrated in the liver and recognize lipids presented on the MHC-like molecule CD1d. Although capable of a myriad of responses, few essential functions have been described for iNKTs. Among the many cell types of the immune system implicated in metabolic control and disease, iNKTs seem ideally poised for such a role, yet little has been done to elucidate such a possible function. We hypothesized that lipid presentation by CD1d could report on metabolic status and engage iNKTs to regulate cellular lipid content through their various effector mechanisms. To test this hypothesis, we examined CD1d deficient mice in a variety of metabolically stressed paradigms including high fat feeding, choline-deficient feeding, fasting, and acute inflammation. CD1d deficiency led to a mild exacerbation of steatosis during high fat or choline-deficient feeding, accompanied by impaired hepatic glucose tolerance. Surprisingly, however, this phenotype was not observed in Jα18⁻/⁻ mice, which are deficient in iNKTs but express CD1d. Thus, CD1d appears to modulate some metabolic functions through an iNKT-independent mechanism.

Neuronal Progenitor Maintenance Requires Lactate Metabolism and PEPCK-M-Directed Cataplerosis.

Science.gov (United States)

Álvarez, Zaida; Hyroššová, Petra; Perales, José Carlos; Alcántara, Soledad

2016-03-01

This study investigated the metabolic requirements for neuronal progenitor maintenance in vitro and in vivo by examining the metabolic adaptations that support neuronal progenitors and neural stem cells (NSCs) in their undifferentiated state. We demonstrate that neuronal progenitors are strictly dependent on lactate metabolism, while glucose induces their neuronal differentiation. Lactate signaling is not by itself capable of maintaining the progenitor phenotype. The consequences of lactate metabolism include increased mitochondrial and oxidative metabolism, with a strict reliance on cataplerosis through the mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) pathway to support anabolic functions, such as the production of extracellular matrix. In vivo, lactate maintains/induces populations of postnatal neuronal progenitors/NSCs in a PEPCK-M-dependent manner. Taken together, our data demonstrate that, lactate alone or together with other physical/biochemical cues maintain NSCs/progenitors with a metabolic signature that is classically found in tissues with high anabolic capacity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Neurochemical metabolites in prefrontal cortex in patients with mild/moderate levels in first-episode depression

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Sozeri-Varma G

2013-08-01

Full Text Available Gülfizar Sözeri-Varma,1 Nalan Kalkan-Oğuzhanoglu,1 Muharrem Efe,1 Yilmaz Kiroglu,2 Taçlan Duman11Department of Psychiatry, 2Department of Radiology, Faculty of Medicine, Pamukkale University, Denizli, TurkeyBackground: Previous studies have determined the neurochemical metabolite abnormalities in major depressive disorder (MDD. The results of studies are inconsistent. Severity of depression may relate to neurochemical metabolic changes. The aim of this study is to investigate neurochemical metabolite levels in the prefrontal cortex (PFC of patients with mild/moderate MDD.Methods: Twenty-one patients with mild MDD, 18 patients with moderate MDD, and 16 matched control subjects participated in the study. Patients had had their first episode. They had not taken treatment. The severity of depression was assessed by the Hamilton Rating Scale for Depression (HAM-D. Levels of N-acetyl aspartate (NAA, choline-containing compounds (Cho, and creatine-containing compounds (Cr were measured using proton magnetic resonance spectroscopy (1H-MRS at 1.5 T, with an 8-cm3 single voxel placed in the right PFC.Results: The moderate MDD patients had lower NAA/Cr levels than the control group. No differences were found in neurochemical metabolite levels between the mild MDD and control groups. No correlation was found between the patients’ neurochemical metabolite levels and HAM-D scores.Conclusion: Our findings suggest that NAA/Cr levels are low in moderate-level MDD in the PFC. Neurochemical metabolite levels did not change in mild depressive disorder. Our results suggest that the severity of depression may affect neuronal function and viability. Studies are needed to confirm this finding, including studies on severely depressive patients.Keywords: major depressive disorder, magnetic resonance spectroscopy, N-acetyl aspartate, creatine, choline

26 CFR 1.853-4 - Manner of making election.

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2010-04-01

... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Manner of making election. 1.853-4 Section 1.853-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Regulated Investment Companies and Real Estate Investment Trusts § 1.853-4 Manner of...

MILD COGNITIVE IMPAIRMENT: STRUCTURAL, METABOLICAL AND NEUROPHYSIOLOGICAL EVIDENCE OF A NOVEL EEG BIOMARKER

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Davide Vito Moretti

2015-07-01

Full Text Available Background: recent studies demonstrate that the alpha 3/alpha 2 power ratio correlates with cortical atrophy, regional hypoperfusion and memory impairment in subjects with mild cognitive impairment (MCI.Methods: evidences were reviewed in subjects with MCI who underwent EEG recording, Magnetic Resonance Imaging (MRI scans and memory evaluation. Alpha3/alpha2 power ratio (alpha2 8.9–10.9 Hz range; alpha3 10.9–12.9 Hz range, cortical thickness, linear EEG coherence and memory impairment have been evaluated in a large group of 74 patients. A subset of 27 subjects within the same group underwent also Single Photon Emission Computed Tomography (SPECT evaluation. Results: in MCI subjects with higher EEG upper/low alpha power ratio a greater temporo-parietal and hippocampal atrophy was found as well as a decrease in regional blood perfusion and memory impairment. In this group, an increase of theta oscillations is associated with a greater interhemispheric coupling between temporal areas. Conclusion: the increase of alpha3/alpha2 power ratio is a promising novel biomarker in identifying MCI subjects at risk for Alzheimer’s disease

Dual-task as a predictor of falls in older people with mild cognitive impairment and mild Alzheimer's disease: a prospective cohort study.

Science.gov (United States)

Gonçalves, Jessica; Ansai, Juliana Hotta; Masse, Fernando Arturo Arriagada; Vale, Francisco Assis Carvalho; Takahashi, Anielle Cristhine de Medeiros; Andrade, Larissa Pires de

2018-04-04

A dual-task tool with a challenging and daily secondary task, which involves executive functions, could facilitate the screening for risk of falls in older people with mild cognitive impairment or mild Alzheimer's disease. To verify if a motor-cognitive dual-task test could predict falls in older people with mild cognitive impairment or mild Alzheimer's disease, and to establish cutoff scores for the tool for both groups. A prospective study was conducted with community-dwelling older adults, including 40 with mild cognitive impairment and 38 with mild Alzheimer's disease. The dual-task test consisted of the Timed up and Go Test associated with a motor-cognitive task using a phone to call. Falls were recorded during six months by calendar and monthly telephone calls and the participants were categorized as fallers or non-fallers. In the Mild cognitive impairment Group, fallers presented higher values in time (35.2s), number of steps (33.7 steps) and motor task cost (116%) on dual-task compared to non-fallers. Time, number of steps and motor task cost were significantly associated with falls in people with mild cognitive impairment. Multivariate analysis identified higher number of steps spent on the test to be independently associated with falls. A time greater than 23.88s (sensitivity=80%; specificity=61%) and a number of steps over 29.50 (sensitivity=65%; specificity=83%) indicated prediction of risk of falls in the Mild cognitive impairment Group. Among people with Alzheimer's disease, no differences in dual-task between fallers and non-fallers were found and no variable of the tool was able to predict falls. The dual-task predicts falls only in older people with mild cognitive impairment. Copyright © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Do we over treat mild hypertension?

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Zanchetti, Alberto

2015-06-01

The important question whether 'mild' hypertension should or should not be treated by drugs is difficult to answer, because the only randomized controlled trials (RCTs) investigating this question were conducted when the definition of 'mild' hypertension was based on diastolic blood pressure only, whereas the present definition of grade 1 hypertension includes both systolic and diastolic values (SBP/DBP), and the concept of 'mild' hypertension also includes that of low-moderate cardiovascular risk (hypertension only on the basis of expert opinion. However, recent meta-analyses have provided some support to drug treatment intervention in low-moderate risk grade 1 hypertensives and have shown that, when treatment is deferred until organ damage or cardiovascular disease occur, absolute residual risk (events occurring despite treatment) markedly increases. Although evidence favoring therapeutic intervention in mild hypertension is nowadays stronger than expert opinion, meta-analyses are not substitutes for specific RCTs, and the wide BP spans defining grade 1 hypertension as well as the span defining low-moderate risk leave a wide space for individualized or personalized decisions.

Radithor and the era of mild radium therapy

International Nuclear Information System (INIS)

Macklis, R.M.

1990-01-01

Soon after the discovery of radium, a school of practitioners arose who were interested primarily in the physiological rather than the tumoricidal powers of this new radioactive element. This treatment philosophy was called mild radium therapy and involved the oral or parenteral administration of microgram quantities of radium and its daughter isotopes, often as cures for rheumatic diseases, hypertension, and metabolic disorders. Manufacturers of patent medicines responded to this market by producing a variety of over-the-counter radioactive preparations including pills, elixirs, and salves. One such nostrum was Radithor, a popular and expensive mixture of radium 226 and radium 228 in distilled water. Radithor was advertised as an effective treatment for over 150 endocrinologic diseases, especially lassitude and sexual impotence. Over 400,000 bottles, each containing over 2 muCi (74 kBq) of radium, were apparently marketed and sold worldwide between 1925 and 1930. The death of the Pittsburgh millionaire sportsman Eben M. Byers, who was an avid Radithor user, by radium poisoning in 1932 brought an end to this era and prompted the development of regulatory controls for all radiopharmaceuticals

Effect of physical activity on memory function in older adults with mild Alzheimer's disease and mild cognitive impairment.

Science.gov (United States)

Tanigawa, Takanori; Takechi, Hajime; Arai, Hidenori; Yamada, Minoru; Nishiguchi, Shu; Aoyama, Tomoki

2014-10-01

It is very important to maintain cognitive function in patients with mild cognitive disorder. The aim of the present study was to determine whether the amount of physical activity is associated with memory function in older adults with mild cognitive disorder. A total of 47 older adults with mild cognitive disorder were studied; 30 were diagnosed with mild Alzheimer's disease and 17 with mild cognitive impairment. The global cognitive function, memory function, physical performance and amount of physical activity were measured in these patients. We divided these patients according to their walking speed (1 m/s). A total of 26 elderly patients were classified as the slow walking group, whereas 21 were classified as the normal walking group. The normal walking group was younger and had significantly better scores than the slow walking group in physical performance. Stepwise multiple linear regression analysis showed that only the daily step counts were associated with the Scenery Picture Memory Test in patients of the slow walking group (β=0.471, P=0.031), but not other variables. No variable was significantly associated with the Scenery Picture Memory Test in the normal walking group. Memory function was strongly associated with the amount of physical activity in patients with mild cognitive disorder who showed slow walking speed. The results show that lower physical activities could be a risk factor for cognitive decline, and that cognitive function in the elderly whose motor function and cognitive function are declining can be improved by increasing the amount of physical activity. © 2014 Japan Geriatrics Society.

Computational Modeling of Lipid Metabolism in Yeast

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Vera Schützhold

2016-09-01

Full Text Available Lipid metabolism is essential for all major cell functions and has recently gained increasing attention in research and health studies. However, mathematical modeling by means of classical approaches such as stoichiometric networks and ordinary differential equation systems has not yet provided satisfactory insights, due to the complexity of lipid metabolism characterized by many different species with only slight differences and by promiscuous multifunctional enzymes.Here, we present a object-oriented stochastic model approach as a way to cope with the complex lipid metabolic network. While all lipid species are treated objects in the model, they can be modified by the respective converting reactions based on reaction rules, a hybrid method that integrates benefits of agent-based and classical stochastic simulation. This approach allows to follow the dynamics of all lipid species with different fatty acids, different degrees of saturation and different headgroups over time and to analyze the effect of parameter changes, potential mutations in the catalyzing enzymes or provision of different precursors. Applied to yeast metabolism during one cell cycle period, we could analyze the distribution of all lipids to the various membranes in time-dependent manner.The presented approach allows to efficiently treat the complexity of cellular lipid metabolism and to derive conclusions on the time- and location-dependent distributions of lipid species and their properties such as saturation. It is widely applicable, easily extendable and will provide further insights in healthy and diseased states of cell metabolism.

Light at night acutely impairs glucose tolerance in a time-, intensity- and wavelength-dependent manner in rats.

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Opperhuizen, Anne-Loes; Stenvers, Dirk J; Jansen, Remi D; Foppen, Ewout; Fliers, Eric; Kalsbeek, Andries

2017-07-01

Exposure to light at night (LAN) has increased dramatically in recent decades. Animal studies have shown that chronic dim LAN induced obesity and glucose intolerance. Furthermore, several studies in humans have demonstrated that chronic exposure to artificial LAN may have adverse health effects with an increased risk of metabolic disorders, including type 2 diabetes. It is well-known that acute exposure to LAN affects biological clock function, hormone secretion and the activity of the autonomic nervous system, but data on the effects of LAN on glucose homeostasis are lacking. This study aimed to investigate the acute effects of LAN on glucose metabolism. Male Wistar rats were subjected to i.v. glucose or insulin tolerance tests while exposed to 2 h of LAN in the early or late dark phase. In subsequent experiments, different light intensities and wavelengths were used. LAN exposure early in the dark phase at ZT15 caused increased glucose responses during the first 20 min after glucose infusion (p light of 50 and 150 lx induced greater glucose responses than 5 and 20 lx, whereas all intensities other than 5 lx reduced locomotor activity. Green light induced glucose intolerance, but red and blue light did not, suggesting the involvement of a specific retina-brain pathway. Together, these data show that exposure to LAN has acute adverse effects on glucose metabolism in a time-, intensity- and wavelength-dependent manner.

Wechsler Memory Scale-III Faces test performance in patients with mild cognitive impairment and mild Alzheimer's disease.

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Seelye, Adriana M; Howieson, Diane B; Wild, Katherine V; Moore, Mindy Milar; Kaye, Jeffrey A

2009-08-01

Little is known about the sensitivity of the Wechsler Memory Scale-Third Edition (WMS-III) Faces subtest to memory impairment associated with mild cognitive impairment (MCI). In this study, Faces performance was examined in 24 MCI patients, 46 mild Alzheimer's disease (AD) patients, and 98 elderly controls. We hypothesized that participants with diagnoses of MCI or AD would be impaired relative to controls on Faces. Analyses showed that AD participants performed significantly worse than MCI and intact participants, although there were no significant differences between MCI and intact participants. Data suggest that brain areas specialized for face recognition memory may be less affected by MCI and mild AD than regions specialized for verbal memory.

Mild obstructive sleep apnoea: clinical relevance and approaches to management.

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McNicholas, Walter T; Bonsignore, Maria R; Lévy, Patrick; Ryan, Silke

2016-10-01

Obstructive sleep apnoea is highly prevalent in the general population worldwide, especially in its mild form. Clinical manifestations correlate poorly with disease severity measured by the apnoea-hypopnoea index (AHI), which complicates diagnosis. Full polysomnography might be more appropriate to assess suspected mild cases because limited ambulatory diagnostic systems are least accurate in mild disease. Treatment options in mild obstructive sleep apnoea include continuous positive airway pressure (CPAP) and oral appliance therapy, in addition to positional therapy and weight reduction when appropriate. The superior efficacy of CPAP in reducing AHI is offset by greater tolerance of oral appliances, especially in mild disease. Although severe obstructive sleep apnoea is associated with adverse health consequences, including cardiometabolic comorbidities, the association with mild disease is unclear, and reports differ regarding the clinical relevance of mild obstructive sleep apnoea. Improved diagnostic techniques and evidence-based approaches to management in mild obstructive sleep apnoea require further research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells

DEFF Research Database (Denmark)

Kirkin, Alexei F.; Dzhandzhugazyan, Karine N.; Guldberg, Per

2018-01-01

In cancer cells, cancer/testis (CT) antigens become epigenetically derepressed through DNA demethylation and constitute attractive targets for cancer immunotherapy. Here we report that activated CD4+ T helper cells treated with a DNA-demethylating agent express a broad repertoire of endogenous CT...... antigens and can be used as antigen-presenting cells to generate autologous cytotoxic T lymphocytes (CTLs) and natural killer cells. In vitro, activated CTLs induce HLA-restricted lysis of tumor cells of different histological types, as well as cells expressing single CT antigens. In a phase 1 trial of 25...... patients with recurrent glioblastoma multiforme, cytotoxic lymphocytes homed to the tumor, with tumor regression ongoing in three patients for 14, 22, and 27 months, respectively. No treatment-related adverse effects were observed. This proof-of-principle study shows that tumor-reactive effector cells can...

[Definition and clinical characteristics of mild hypertension].

Science.gov (United States)

Saruta, Takao

2008-08-01

Mild hypertension is defined as blood pressure level of 140-159 mmHg systolic and/or 90-99 mmHg diastolic. The patients with blood pressure level of mild hypertension occupy about 60% of total hypertensive patients in Japan, and most of them are free of subjective symptoms except elevated blood pressure. However, some of the patients with mild hypertension develop cardiovascular events, since thay have occasionally cardiovascular damages on this level of blood pressure and several risk factors of cardiovascular diseases such as diabetes mellitus and hyperlipidemia.

Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism

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Nadia eUcciferri

2014-12-01

Full Text Available Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step towards building an integrated picture of systemic metabolism and signalling in physiological or pathological conditions. However the rational design of in vitro models of cell-cell or cell-tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here we analyse the physiologic relationship between cells, cell metabolism and exchange in the human body using allometric rules, downscaling them to an organ-on-a plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (Cell Number Scaling Model, CNSM, and Metabolic and Surface Scaling model, MSSM are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions which can be extrapolated to the in vivo

Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism

International Nuclear Information System (INIS)

Ucciferri, Nadia; Sbrana, Tommaso; Ahluwalia, Arti

2014-01-01

Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell–cell or cell–tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism

Energy Technology Data Exchange (ETDEWEB)

Ucciferri, Nadia [CNR Institute of Clinical Physiology, Pisa (Italy); Interdepartmental Research Center “E. Piaggio”, University of Pisa, Pisa (Italy); Sbrana, Tommaso [Interdepartmental Research Center “E. Piaggio”, University of Pisa, Pisa (Italy); Ahluwalia, Arti, E-mail: arti.ahluwalia@unipi.it [CNR Institute of Clinical Physiology, Pisa (Italy); Interdepartmental Research Center “E. Piaggio”, University of Pisa, Pisa (Italy)

2014-12-17

Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell–cell or cell–tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism.

Science.gov (United States)

Ucciferri, Nadia; Sbrana, Tommaso; Ahluwalia, Arti

2014-01-01

Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell-cell or cell-tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

Toxicity of Xanthene Food Dyes by Inhibition of Human Drug-Metabolizing Enzymes in a Noncompetitive Manner

International Nuclear Information System (INIS)

Mizutani, T.

2010-01-01

The synthetic food dyes studied were rose bengal (RB), phroxine (PL), amaranth, erythrosine B (ET), allura red, new coccine, acid red (AR), tartrazine, sunset yellow FCF, brilliant blue FCF, and indigo carmine. First, data confirmed that these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. ET inhibited UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone). We showed the inhibitory effect of xanthene dye on human UGT1A6 activity. Basic ET, PL, and RB in those food dyes strongly inhibited UGT1A6 activity, with IC50 values = 0.05, 0.04, and 0.015 mM, respectively. Meanwhile, AR of an acidic xanthene food dye showed no inhibition. Next, we studied the inhibition of CYP3A4 of a major phase I drug-metabolizing enzyme and P-glycoprotein of a major transporter by synthetic food dyes. Human CYP3A4 and P-glycoprotein were also inhibited by basic xanthene food dyes. The IC50 values of these dyes to inhibit CYP3A4 and P-glycoprotein were the same as the inhibition level of UGT1A6 by three halogenated xanthene food dyes (ET, PL, and RB) described above, except AR, like the results with UGT1A6 and UGT2B7. We also confirmed the non inhibition of CYP3A4 and P-gp by other synthetic food dyes. Part of this inhibition depended upon the reaction of O 12 originating on xanthene dyes by light irradiation, because inhibition was prevented by O 12 quenchers. We studied the influence of superoxide dismutase and catalase on this inhibition by dyes and we found prevention of inhibition by superoxide dismutase but not catalase. This result suggests that superoxide anions, originating on dyes by light irradiation, must attack drug-metabolizing enzymes. It is possible that red cosmetics containing phloxine, erythrosine, or rose bengal react with proteins on skin under lighting and may lead to rough skin.

Toxicity of xanthene food dyes by inhibition of human drug-metabolizing enzymes in a noncompetitive manner.

Science.gov (United States)

Mizutani, Takaharu

2009-01-01

The synthetic food dyes studied were rose bengal (RB), phroxine (PL), amaranth, erythrosine B (ET), allura red, new coccine, acid red (AR), tartrazine, sunset yellow FCF, brilliant blue FCF, and indigo carmine. First, data confirmed that these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. ET inhibited UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone). We showed the inhibitory effect of xanthene dye on human UGT1A6 activity. Basic ET, PL, and RB in those food dyes strongly inhibited UGT1A6 activity, with IC(50) values = 0.05, 0.04, and 0.015 mM, respectively. Meanwhile, AR of an acidic xanthene food dye showed no inhibition. Next, we studied the inhibition of CYP3A4 of a major phase I drug-metabolizing enzyme and P-glycoprotein of a major transporter by synthetic food dyes. Human CYP3A4 and P-glycoprotein were also inhibited by basic xanthene food dyes. The IC(50) values of these dyes to inhibit CYP3A4 and P-glycoprotein were the same as the inhibition level of UGT1A6 by three halogenated xanthene food dyes (ET, PL, and RB) described above, except AR, like the results with UGT1A6 and UGT2B7. We also confirmed the noninhibition of CYP3A4 and P-gp by other synthetic food dyes. Part of this inhibition depended upon the reaction of (1)O(2) originating on xanthene dyes by light irradiation, because inhibition was prevented by (1)O(2) quenchers. We studied the influence of superoxide dismutase and catalase on this inhibition by dyes and we found prevention of inhibition by superoxide dismutase but not catalase. This result suggests that superoxide anions, originating on dyes by light irradiation, must attack drug-metabolizing enzymes. It is possible that red cosmetics containing phloxine, erythrosine, or rose bengal react with proteins on skin under lighting and may lead to rough skin.

Mild Cognitive Impairment

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... more: Key Types of Dementia , What Is Alzheimer's? , Alzheimer's Risk Factors Symptoms back to top Experts classify Mild cognitive ... in Chronic Traumatic Encephalopathy 2014 Thor Stein Genetic Risk Factors Underlying Chronic Trauma and Alzheimer's Disease Pathology 2014 Kun Ping Lu Validation of ...

Unraveling the involvement of ABA in the water deficit-induced modulation of nitrogen metabolism in Medicago truncatula seedlings.

Science.gov (United States)

Planchet, Elisabeth; Rannou, Olivier; Ricoult, Claudie; Limami, Anis M

2011-07-01

Effects of water deficit and/or abscisic acid (ABA) were investigated on early seedling growth of Medicago truncatula, and on glutamate metabolism under dark conditions. Water deficit (simulated by polyethylene glycol, PEG), ABA and their combination resulted in a reduction in growth rate of the embryo axis, and also in a synergistic increase of free amino acid (AA) content. However, the inhibition of water uptake retention induced by water deficit seemed to occur in an ABA-independent manner. Expression of several genes involved in glutamate metabolism was induced during water deficit, whereas ABA, in combination or not with PEG, repressed them. The only exception came from a gene encoding 1-pyrroline-5-carboxylate synthetase (P5CS) which appeared to be induced in an ABA-dependent manner under water deficit. Our results demonstrate clearly the involvement of an ABA-dependent and an ABA-independent regulatory system, governing growth and glutamate metabolism under water deficit.

Correlation Between Metabolic Syndrome, Periodontitis and Reactive Oxygen Species Production. A Pilot Study.

Science.gov (United States)

Patini, Romeo; Gallenzi, Patrizia; Spagnuolo, Gianrico; Cordaro, Massimo; Cantiani, Monica; Amalfitano, Adriana; Arcovito, Alessandro; Callà, Cinzia; Mingrone, Gertrude; Nocca, Giuseppina

2017-01-01

Metabolic syndrome (MetS) is associated with an increased risk of periodontitis even if the mechanism is unknown. Since both MetS and periodontitis are characterized by an alteration of inflammation status, the aim of this pilot study was to determine if differences in ROS metabolism of phagocytes isolated from (A) patients with MetS, (B) patients with both MetS and mild periodontitis, (C) healthy subjects and (D) normal weight subjects with mild periodontitis, were present. ROS metabolism was studied by a Chemiluminescence (CL) technique: the system was made up of luminol (100 nmol/L) and cells (1 × 10 5 ) in the presence or absence of stimulus constituted by opsonized zymosan (0.5 mg). The final volume (1.0 mL) was obtained using modified KRP buffer. ROS production was measured at 25°C for 2 h, using an LB 953 luminometer (Berthold, EG & G Co, Germany). All the experiments were performed in triplicate. All results are mean ± standard deviation (SD). The group of means was compared by the analysis of variance "(ANOVA)". A value of p < 0.05 was considered significant. Results showed that basal ROS production (both from PMNs and from PBMs) of groups A, B and D was increased with respect to that obtained from group C ( p <0.05). These results are congruent with literature data, although the actual clinical relevance of the phenomenon remains to be evaluated.

Fat body glycogen serves as a metabolic safeguard for the maintenance of sugar levels in Drosophila.

Science.gov (United States)

Yamada, Takayuki; Habara, Okiko; Kubo, Hitomi; Nishimura, Takashi

2018-03-14

Adapting to changes in food availability is a central challenge for survival. Glucose is an important resource for energy production, and therefore many organisms synthesize and retain sugar storage molecules. In insects, glucose is stored in two different forms: the disaccharide trehalose and the branched polymer glycogen. Glycogen is synthesized and stored in several tissues, including in muscle and the fat body. Despite the major role of the fat body as a center for energy metabolism, the importance of its glycogen content remains unclear. Here, we show that glycogen metabolism is regulated in a tissue-specific manner under starvation conditions in the fruit fly Drosophila The mobilization of fat body glycogen in larvae is independent of Adipokinetic hormone (Akh, the glucagon homolog) but is regulated by sugar availability in a tissue-autonomous manner. Fat body glycogen plays a crucial role in the maintenance of circulating sugars, including trehalose, under fasting conditions. These results demonstrate the importance of fat body glycogen as a metabolic safeguard in Drosophila . © 2018. Published by The Company of Biologists Ltd.

dSir2 in the Adult Fat Body, but Not in Muscles, Regulates Life Span in a Diet-Dependent Manner

Directory of Open Access Journals (Sweden)

Kushal Kr. Banerjee

2012-12-01

Full Text Available Sir2, an evolutionarily conserved NAD+-dependent deacetylase, has been implicated as a key factor in mediating organismal life span. However, recent contradictory findings have brought into question the role of Sir2 and its orthologs in regulating organismal longevity. In this study, we report that Drosophila Sir2 (dSir2 in the adult fat body regulates longevity in a diet-dependent manner. We used inducible Gal4 drivers to knock down and overexpress dSir2 in a tissue-specific manner. A diet-dependent life span phenotype of dSir2 perturbations (both knockdown and overexpression in the fat body, but not muscles, negates the effects of background genetic mutations. In addition to providing clarity to the field, our study contrasts the ability of dSir2 in two metabolic tissues to affect longevity. We also show that dSir2 knockdown abrogates fat-body dFOXO-dependent life span extension. This report highlights the importance of the interplay between genetic factors and dietary inputs in determining organismal life spans.

29 CFR 1614.703 - Manner and format of data.

Science.gov (United States)

2010-07-01

... § 1614.704(a) through (m). (3) When posting data pursuant to § 1614.704(d) and (j), bases of... 29 Labor 4 2010-07-01 2010-07-01 false Manner and format of data. 1614.703 Section 1614.703 Labor... Retaliation Act of 2002 (No FEAR Act) § 1614.703 Manner and format of data. (a) Agencies shall post their...

Knockdown of the fat mass and obesity gene disrupts cellular energy balance in a cell-type specific manner.

Directory of Open Access Journals (Sweden)

Ryan T Pitman

Full Text Available Recent studies suggest that FTO variants strongly correlate with obesity and mainly influence energy intake with little effect on the basal metabolic rate. We suggest that FTO influences eating behavior by modulating intracellular energy levels and downstream signaling mechanisms which control energy intake and metabolism. Since FTO plays a particularly important role in adipocytes and in hypothalamic neurons, SH-SY5Y neuronal cells and 3T3-L1 adipocytes were used to understand how siRNA mediated knockdown of FTO expression alters cellular energy homeostasis. Cellular energy status was evaluated by measuring ATP levels using a luminescence assay and uptake of fluorescent glucose. FTO siRNA in SH-SY5Y cells mediated mRNA knockdown (-82%, increased ATP concentrations by up to 46% (P = 0.013 compared to controls, and decreased phosphorylation of AMPk and Akt in SH-SY5Y by -52% and -46% respectively as seen by immunoblotting. In contrast, FTO siRNA in 3T3-L1 cells decreased ATP concentration by -93% (p<0.0005, and increased AMPk and Akt phosphorylation by 204% and 70%, respectively suggesting that FTO mediates control of energy levels in a cell-type specific manner. Furthermore, glucose uptake was decreased in both SH-SY5Y (-51% p = 0.015 and 3T3-L1 cells (-30%, p = 0.0002. We also show that FTO knockdown decreases NPY mRNA expression in SH-SY5Y cells (-21% through upregulation of pSTAT3 (118%. These results provide important evidence that FTO-variant linked obesity may be associated with altered metabolic functions through activation of downstream metabolic mediators including AMPk.

Mild Traumatic Brain Injury

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... mild Traumatic Brain Injury Resilience Families with Kids Depression Families & Friendships Tobacco Life Stress Spirituality Anger Physical Injury Stigma Health & Wellness Work Adjustment Community Peer-2-Peer Forum ...

Recent neuroimaging techniques in mild traumatic brain injury.

Science.gov (United States)

Belanger, Heather G; Vanderploeg, Rodney D; Curtiss, Glenn; Warden, Deborah L

2007-01-01

Mild traumatic brain injury (TBI) is characterized by acute physiological changes that result in at least some acute cognitive difficulties and typically resolve by 3 months postinjury. Because the majority of mild TBI patients have normal structural magnetic resonance imaging (MRI)/computed tomography (CT) scans, there is increasing attention directed at finding objective physiological correlates of persistent cognitive and neuropsychiatric symptoms through experimental neuroimaging techniques. The authors review studies utilizing these techniques in patients with mild TBI; these techniques may provide more sensitive assessment of structural and functional abnormalities following mild TBI. Particular promise is evident with fMRI, PET, and SPECT scanning, as demonstrated by associations between brain activation and clinical outcomes.

Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression

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Zhao, Jing; Jung, Yang-Hee; Jang, Choon-Gon; Chun, Kwang-Hoon; Kwon, Sung Won; Lee, Jeongmi

2015-03-01

Metabolomics was applied to a C57BL/6N mouse model of chronic unpredictable mild stress (CMS). Such mice were treated with two antidepressants from different categories: fluoxetine and imipramine. Metabolic profiling of the hippocampus was performed using gas chromatography-mass spectrometry analysis on samples prepared under optimized conditions, followed by principal component analysis, partial least squares-discriminant analysis, and pair-wise orthogonal projections to latent structures discriminant analyses. Body weight measurement and behavior tests including an open field test and the forced swimming test were completed with the mice as a measure of the phenotypes of depression and antidepressive effects. As a result, 23 metabolites that had been differentially expressed among the control, CMS, and antidepressant-treated groups demonstrated that amino acid metabolism, energy metabolism, adenosine receptors, and neurotransmitters are commonly perturbed by drug treatment. Potential predictive markers for treatment effect were identified: myo-inositol for fluoxetine and lysine and oleic acid for imipramine. Collectively, the current study provides insights into the molecular mechanisms of the antidepressant effects of two widely used medications.

Cryopreservation of Precision-cut Tissue Slices for Application in Drug Metabolism Research

NARCIS (Netherlands)

Graaf, Inge Anne Maria de

2002-01-01

The research described in this thesis had two important aims. The first was to determine whether tissue slices could be used as an in vitro tool to predict the in vivo metabolism of new drugs. The second aim was to find a manner to store tissue slices for longer time periods by cryopreservation.

Mild cognitive dysfunction does not affect diabetes mellitus control in minority elderly adults.

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Palta, Priya; Golden, Sherita H; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S; Shea, Steven; Manly, Jennifer J; Luchsinger, Jose A

2014-12-01

To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. Prospective cohort study. A minority cohort in New York City previously recruited for a trial of telemedicine. Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Metabolic alterations in experimental models of depression

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Maria G. Puiu

2016-10-01

Full Text Available Introduction: Major depressive disorder is one of the most prevalent psychiatric disorders and is associated with a severe impact on the personal functioning, thus with incurring significant direct and indirect costs. The presence of depression in patients with medical comorbidities increases the risks of myocardial infarction and decreases diabetes control, and adherence to treatment. The mechanism through which these effects are produced is still uncertain. Objectives of this study were to evaluate the metabolic alterations in female Wistar rats with induced depression, with and without administration of Agomelatine. The methods included two experiments. All data were analyzed by comparison with group I (control, and with each other. In the first experiment we induced depression by: exposure to chronic mild stress-group II; olfactory bulbectomy-group III; and exposure to chronic mild stress and hyperlipidic/ hyper caloric dietgroup IV. The second experiment was similar with the first but the rats received Agomelatine (0.16mg/ animal: group V (depression induced through exposure to chronic mild stress, VI (depression induced through olfactory bulbectomy and VII (depression induced through exposure to chronic mild stressing hyperlipidic/ hypercaloric diet. Weight, cholesterol, triglycerides and glycaemia were measured at day 0 and 28, and leptin value was measured at day 28. The results in the 1st experiment revealed significant differences (p<0.01 for weight and cholesterol in Group IV, for triglycerides in groups III and IV (p<0.001, and for glycaemia in group II. The 2nd experiment revealed significant differences (p<0.001 in group VII for weight and triglycerides, and in groups V and VI for triglycerides (p<0.01. In conclusion, significant correlations were found between high level of triglycerides and depression induced by chronic stress and olfactory bulbectomy. Agomelatine groups had a lower increase of triglycerides levels.

Linseed oil increases HDL3 cholesterol and decreases blood pressure in patients diagnosed with mild hypercholesterolemia.

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Skoczyńska, Anna H; Gluza, Ewa; Wojakowska, Anna; Turczyn, Barbara; Skoczyńska, Marta

2018-04-24

Linseed oil has cardio-protective effects. However, its antihypertensive action has not yet been well characterized. The primary purpose of the study was to evaluate the effect of short-term dietary supplementation with linseed oil on blood pressure (BP) and lipid metabolism in patients with mild hypercholesterolemia. The secondary aim was to evaluate the effect of linseed oil on nitric oxide pathway and selected serum trace metals. 150 volunteers: 43 men (49.9±11.5 years) and 107 women (53.2±10.3 years), diagnosed with mild hypercholesterolemia, were assessed prospectively for BP and lipids' levels, before and after lipid-lowering diet plus linseed oil supplementation at a dose of 15 ml daily for 4 weeks (study groups) or 4-weekly lipid-lowering diet (control group). The multivariate logistic regression analysis model was used to determine the effect of linseed oil on BP after adjustment for age, gender, height, body weight, BMI, smoking and alcohol consumption. The supplementation with linseed oil significantly decreased LDL- and non-HDL cholesterol, and increased HDL- and HDL₃- cholesterol levels. Additionally, linseed oil decreased diastolic BP in men (CI:-6.0;-1.1, poil reduced (poil consumption was associated with a decrease in mean BP (aOR 3.85, 95%CI 1.32-11.33). Our findings confirm the benefit of short-term linseed oil use in mild hypercholesterolemia, in particular in patients with increased blood pressure.

Metabolic profiles of cow's blood; a review.

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Puppel, Kamila; Kuczyńska, Beata

2016-10-01

The term 'metabolic profile' refers to the analysis of blood biochemical parameters that are useful to assess and prevent metabolic and nutritional disorders in dairy herds. In the higher standards of milk production, the priority in modern breeding is keeping dairy cows in high lactation and healthy. The proper analysis, as well as control. of their feeding and metabolic status is immensely important for the health condition of the herd. The disproportion between the genetically determined ability for milk production and the limitations in improving the energy value of the ration may be the cause of metabolic disorders. Negative energy balance has a major impact on the body's hormonal balance and organ functions and mostly appears during transition periods: from 3 to 2 weeks prepartum until 2-3 weeks postpartum. The term 'transition' is used to underscore the important physiological, metabolic and nutritional changes occurring in this time. The manner in which these changes occur and how they are diagnosed and detected are extremely important, as they are closely related to clinical and subclinical postpartum diseases, lactation and reproductive performance - factors that significantly shape the profitability of production. Therefore the priority for intensive milk production is prevention of metabolic diseases and other disorders. It is the intent of this review to synthesize and summarize the information currently available on metabolic status and physiological changes in the cow's body that occur during lactation, as well as to discuss the interpretation of the results, which will be a useful diagnostic tool in nutritional evaluations of the dairy herd. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Broad-spectrum health improvements with one year of soccer training in inactive mildly hypertensive middle-aged women.

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Krustrup, P; Skoradal, M-B; Randers, M B; Weihe, P; Uth, J; Mortensen, J; Mohr, M

2017-12-01

The study tested the hypothesis that long-term soccer training has positive impact on cardiovascular profile, body composition, bone health, and physical capacity in inactive, pre-menopausal women with mild hypertension. The study applied a randomized controlled design in which physically inactive middle-aged women were separated into a soccer training group (n=19; SOC) and a control group (n=12; CON). SOC performed 128±29 (±SD) one-h small-sided soccer training sessions over one year. Blood pressure, body composition, blood lipid profile, and fitness level were determined pre- and post-intervention. Over one year, mean arterial pressure decreased more in SOC than in CON (-5±7 vs +4±5 mmHg; Pendurance level 1 (122±105 vs 2±21%) and 20-m sprint performance (6±6 vs -1±2%) increased more (Ptraining resulted in broad-spectrum improvements in the health profile of untrained, pre-menopausal women with mild hypertension, including cardiovascular, metabolic, and musculo-skeletal benefits. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

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Lucio Della Guardia

2018-05-01

Full Text Available Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and metabolic status considerably flaws available findings, and the lack of solid data on the background physiopathology contributes to the questionability of results. Furthermore, evidence from interventional studies is very limited and the trials carried out report no beneficial results following alkali supplementation. Available literature suggests that poor acid load control may contribute to impaired insulin sensitivity and glucose homeostasis, but it is not sufficiently supportive to fully elucidate the issue and additional well-designed studies are clearly needed.

Dynamic metabolic modeling of heterotrophic and mixotrophic microalgal growth on fermentative wastes.

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Caroline Baroukh

2017-06-01

Full Text Available Microalgae are promising microorganisms for the production of numerous molecules of interest, such as pigments, proteins or triglycerides that can be turned into biofuels. Heterotrophic or mixotrophic growth on fermentative wastes represents an interesting approach to achieving higher biomass concentrations, while reducing cost and improving the environmental footprint. Fermentative wastes generally consist of a blend of diverse molecules and it is thus crucial to understand microalgal metabolism in such conditions, where switching between substrates might occur. Metabolic modeling has proven to be an efficient tool for understanding metabolism and guiding the optimization of biomass or target molecule production. Here, we focused on the metabolism of Chlorella sorokiniana growing heterotrophically and mixotrophically on acetate and butyrate. The metabolism was represented by 172 metabolic reactions. The DRUM modeling framework with a mildly relaxed quasi-steady-state assumption was used to account for the switching between substrates and the presence of light. Nine experiments were used to calibrate the model and nine experiments for the validation. The model efficiently predicted the experimental data, including the transient behavior during heterotrophic, autotrophic, mixotrophic and diauxic growth. It shows that an accurate model of metabolism can now be constructed, even in dynamic conditions, with the presence of several carbon substrates. It also opens new perspectives for the heterotrophic and mixotrophic use of microalgae, especially for biofuel production from wastes.

Collagen-derived markers of bone metabolism in osteogenesis imperfecta

DEFF Research Database (Denmark)

Lund, A M; Hansen, M; Kollerup, Gina Birgitte

1998-01-01

)] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low....... The in vivo findings correlated with in vitro results of collagen I SDS-PAGE. Bone turnover is reduced in OI children and mildly affected OI adults, whereas bone resorption is elevated in severely affected adults. These findings may prove helpful for diagnosis and decision-making regarding therapy in OI....

Reduced Sympathetic Response to Head-Up Tilt in Subjects with Mild Cognitive Impairment or Mild Alzheimer's Dementia

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Marte Rognstad Mellingsæter

2015-03-01

Full Text Available Background: Hemodynamic control was compared in patients with mild cognitive impairment (MCI or mild Alzheimer's dementia (AD as well as in healthy elderly subjects. Methods: Noninvasive, continuous hemodynamic recordings were obtained from 14 patients and 48 controls during supine rest (tilt of 30 and 70°. Cardiac output, end-diastolic volume, total peripheral resistance, heart rate variability (HRV, systolic blood pressure variability (SBPV, and baroreceptor sensitivity were calculated. Results: At 70° tilt, the HRV indices differed significantly, with higher high-frequency (HF variability as well as lower low-frequency (LF variability and LF/HF ratios in the patients. The patients had significantly lower SBPV in the LF range at 30° tilt. Conclusions: The results indicate a poorer sympathetic response to orthostatic stress in MCI and mild AD.

Toxicity of Xanthene Food Dyes by Inhibition of Human Drug-Metabolizing Enzymes in a Noncompetitive Manner

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Mizutani, Takaharu

2009-01-01

The synthetic food dyes studied were rose bengal (RB), phroxine (PL), amaranth, erythrosine B (ET), allura red, new coccine, acid red (AR), tartrazine, sunset yellow FCF, brilliant blue FCF, and indigo carmine. First, data confirmed that these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. ET inhibited UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone). We showed the inhibitory effect of xanthene dye on human UGT1A6 activity. Basic ET, PL, and RB in those food dyes strongly inhibited UGT1A6 activity, with IC50 values = 0.05, 0.04, and 0.015 mM, respectively. Meanwhile, AR of an acidic xanthene food dye showed no inhibition. Next, we studied the inhibition of CYP3A4 of a major phase I drug-metabolizing enzyme and P-glycoprotein of a major transporter by synthetic food dyes. Human CYP3A4 and P-glycoprotein were also inhibited by basic xanthene food dyes. The IC50 values of these dyes to inhibit CYP3A4 and P-glycoprotein were the same as the inhibition level of UGT1A6 by three halogenated xanthene food dyes (ET, PL, and RB) described above, except AR, like the results with UGT1A6 and UGT2B7. We also confirmed the noninhibition of CYP3A4 and P-gp by other synthetic food dyes. Part of this inhibition depended upon the reaction of 1O2 originating on xanthene dyes by light irradiation, because inhibition was prevented by 1O2 quenchers. We studied the influence of superoxide dismutase and catalase on this inhibition by dyes and we found prevention of inhibition by superoxide dismutase but not catalase. This result suggests that superoxide anions, originating on dyes by light irradiation, must attack drug-metabolizing enzymes. It is possible that red cosmetics containing phloxine, erythrosine, or rose bengal react with proteins on skin under lighting and may lead to rough skin. PMID:20041016

Mild heat treatments induce long-term changes in metabolites associated with energy metabolism in Drosophila melanogaster

DEFF Research Database (Denmark)

Sarup, Pernille; Petersen, Simon Metz Mariendal; Nielsen, Niels Christian

2016-01-01

treatments on the metabolome of male Drosophila melanogaster. 10 days after the heat treatment, metabolic aging appears to be slowed down, and a treatment response with 40 % higher levels of alanine and lactate and lower levels of aspartate and glutamate were measured. All treatment effects had disappeared...

Definition of herpes simplex virus type 1 helper activities for adeno-associated virus early replication events.

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Nathalie Alazard-Dany

2009-03-01

Full Text Available The human parvovirus Adeno-Associated Virus (AAV type 2 can only replicate in cells co-infected with a helper virus, such as Adenovirus or Herpes Simplex Virus type 1 (HSV-1; whereas, in the absence of a helper virus, it establishes a latent infection. Previous studies demonstrated that the ternary HSV-1 helicase/primase (HP complex (UL5/8/52 and the single-stranded DNA-Binding Protein (ICP8 were sufficient to induce AAV-2 replication in transfected cells. We independently showed that, in the context of a latent AAV-2 infection, the HSV-1 ICP0 protein was able to activate rep gene expression. The present study was conducted to integrate these observations and to further explore the requirement of other HSV-1 proteins during early AAV replication steps, i.e. rep gene expression and AAV DNA replication. Using a cellular model that mimics AAV latency and composite constructs coding for various sets of HSV-1 genes, we first confirmed the role of ICP0 for rep gene expression and demonstrated a synergistic effect of ICP4 and, to a lesser extent, ICP22. Conversely, ICP27 displayed an inhibitory effect. Second, our analyses showed that the effect of ICP0, ICP4, and ICP22 on rep gene expression was essential for the onset of AAV DNA replication in conjunction with the HP complex and ICP8. Third, and most importantly, we demonstrated that the HSV-1 DNA polymerase complex (UL30/UL42 was critical to enhance AAV DNA replication to a significant level in transfected cells and that its catalytic activity was involved in this process. Altogether, this work represents the first comprehensive study recapitulating the series of early events taking place during HSV-1-induced AAV replication.

Visualizing Hyperactivation in Neurodegeneration Based on Prefrontal Oxygenation: A Comparative Study of Mild Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls

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Kah Hui Yap

2017-09-01

Full Text Available Background: Cognitive performance is relatively well preserved during early cognitive impairment owing to compensatory mechanisms.Methods: We explored functional near-infrared spectroscopy (fNIRS alongside a semantic verbal fluency task (SVFT to investigate any compensation exhibited by the prefrontal cortex (PFC in Mild Cognitive Impairment (MCI and mild Alzheimer's disease (AD. In addition, a group of healthy controls (HC was studied. A total of 61 volunteers (31 HC, 12 patients with MCI and 18 patients with mild AD took part in the present study.Results: Although not statistically significant, MCI exhibited a greater mean activation of both the right and left PFC, followed by HC and mild AD. Analysis showed that in the left PFC, the time taken for HC to achieve the activation level was shorter than MCI and mild AD (p = 0.0047 and 0.0498, respectively; in the right PFC, mild AD took a longer time to achieve the activation level than HC and MCI (p = 0.0469 and 0.0335, respectively; in the right PFC, HC, and MCI demonstrated a steeper slope compared to mild AD (p = 0.0432 and 0. 0107, respectively. The results were, however, not significant when corrected by the Bonferroni-Holm method. There was also found to be a moderately positive correlation (R = 0.5886 between the oxygenation levels in the left PFC and a clinical measure [Mini-Mental State Examination (MMSE score] in MCI subjects uniquely.Discussion: The hyperactivation in MCI coupled with a better SVFT performance may suggest neural compensation, although it is not known to what degree hyperactivation manifests as a potential indicator of compensatory mechanisms. However, hypoactivation plus a poorer SVFT performance in mild AD might indicate an inability to compensate due to the degree of structural impairment.Conclusion: Consistent with the scaffolding theory of aging and cognition, the task-elicited hyperactivation in MCI might reflect the presence of compensatory mechanisms and

Postmarketing study of efficacy and safety of losartan during the treatment of patients with mild and moderate hypertension: Lothar study

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Vasiljević Zorana

2013-01-01

Full Text Available Introduction. Losartan, the angiotensin type 1 receptor blocker (ARB exercises its main antihypertensive effect by vasodilatation of peripheral arteries. Objective. The aim of this study was to evaluate the antihypertensive effect and safety of losartan in patients with mild and moderate arterial hypertension (AH. Methods. This was an open post-marketing study with losartan as monotherapy in previously treated or untreated patients with AH. Primary efficacy parameter was the percentage of patients that achieved target blood pressure after 8-week treatment with a single daily dose of losartan of 50-100 mg. Safety parameters were assessed according to the percentage of adverse events and metabolic effects of therapy. Results. The study included 550 patients with AH (59% female and 41% male, mean age 56.8±11.4 years, BMI=27±4 kg/m2. Losartan was applied in 31% of untreated and 69% of previously treatment-resistant patients After 8 weeks target blood pressure was achieved in 67.8% (SBP and in 81.1% (DBP of patients, respectively. The mean decrease was 21.8% for SBP and 21.1% for DBP (p<0.001. Out of all, 65% of patients achieved both target SBP and DBP values. Hydrochlorothiazide was added to the therapy in 11.6% of patients. There were no significant differences in drug efficacy between the entire group and subgroups of patients with diabetes mellitus and impaired renal function (p=ns. Adverse events were rare and metabolic effect was favorable. Conclusion. Monotherapy with losartan in a dosage of 50-100 mg applied during 8 weeks resulted in achieving target values of blood pressure in 65% of patient with mild and moderate hypertension, also including the patients with diabetes mellitus and impaired renal function. Losartan is a safe and metabolically neutral medication.

Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized C-13 magnetic resonance

DEFF Research Database (Denmark)

Mishkovsky, Mor; Anderson, Brian; Karlsson, Magnus

2017-01-01

The mammalian brain relies primarily on glucose as a fuel to meet its high metabolic demand. Among the various techniques used to study cerebral metabolism, C-13 magnetic resonance spectroscopy (MRS) allows following the fate of C-13-enriched substrates through metabolic pathways. We herein...... glucose is split into 3-carbon intermediates by aldolase. This unique method allows direct detection of glycolysis in vivo in the healthy brain in a noninvasive manner....... demonstrate that it is possible to measure cerebral glucose metabolism in vivo with sub-second time resolution using hyperpolarized C-13 MRS. In particular, the dynamic C-13-labeling of pyruvate and lactate formed from C-13-glucose was observed in real time. An ad-hoc synthesis to produce [2,3,4,6,6-H-2(5), 3...

Possibility of objective diagnosis in patients with mild Alzheimer-type dementia

International Nuclear Information System (INIS)

Kodama, Naoki; Shimada, Tetsuo; Kaeriyama, Tomoharu; Kaneko, Tomoyuki; Fukumoto, Ichiro; Okamoto, Koichiro

2003-01-01

In this study, patients with mild Alzheimer-type dementia were compared with healthy elderly volunteers by means of 12 features to evaluate the possibility of objective diagnosis of mild dementia. The subjects included 9 patients with questionable dementia, 14 patients with mild dementia, and 30 healthy elderly volunteers as controls. In addition, the 23 patients with questionable or mild dementia were included in the mild Alzheimer-type dementia group. A statistically significant difference was found between the mild Alzheimer-type dementia group and the healthy volunteers in 4 of the 10 textural features. Discriminant analysis using these 4 features demonstrated a sensitivity of 87.0% and a specificity of 66.7%. These results suggest the possibility of objective diagnosis in patients with mild Alzheimer-type dementia. (author)

Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS.

Science.gov (United States)

Vieira-Marques, Claudia; Arbo, Bruno Dutra; Cozer, Aline Gonçalves; Hoefel, Ana Lúcia; Cecconello, Ana Lúcia; Zanini, Priscila; Niches, Gabriela; Kucharski, Luiz Carlos; Ribeiro, Maria Flávia M

2017-07-01

DHEA is a neuroactive steroid, due to its modulatory actions on the central nervous system (CNS). DHEA is able to regulate neurogenesis, neurotransmitter receptors and neuronal excitability, function, survival and metabolism. The levels of DHEA decrease gradually with advancing age, and this decline has been associated with age related neuronal dysfunction and degeneration, suggesting a neuroprotective effect of endogenous DHEA. There are significant sex differences in the pathophysiology, epidemiology and clinical manifestations of many neurological diseases. The aim of this study was to determine whether DHEA can alter glucose metabolism in different structures of the CNS from male and female rats, and if this effect is sex-specific. The results showed that DHEA decreased glucose uptake in some structures (cerebral cortex and olfactory bulb) in males, but did not affect glucose uptake in females. When compared, glucose uptake in males was higher than females. DHEA enhanced the glucose oxidation in both males (cerebral cortex, olfactory bulb, hippocampus and hypothalamus) and females (cerebral cortex and olfactory bulb), in a sex-dependent manner. In males, DHEA did not affect synthesis of glycogen, however, glycogen content was increased in the cerebral cortex and olfactory bulb. DHEA modulates glucose metabolism in a tissue-, dose- and sex-dependent manner to increase glucose oxidation, which could explain the previously described neuroprotective role of this hormone in some neurodegenerative diseases. Copyright © 2016. Published by Elsevier Ltd.

Retinal metabolic events in preconditioning light stress as revealed by wide-spectrum targeted metabolomics.

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de la Barca, Juan Manuel Chao; Huang, Nuan-Ting; Jiao, Haihan; Tessier, Lydie; Gadras, Cédric; Simard, Gilles; Natoli, Riccardo; Tcherkez, Guillaume; Reynier, Pascal; Valter, Krisztina

2017-01-01

Light is the primary stimulus for vision, but may also cause damage to the retina. Pre-exposing the retina to sub-lethal amount of light (or preconditioning) improves chances for retinal cells to survive acute damaging light stress. This study aims at exploring the changes in retinal metabolome after mild light stress and identifying mechanisms that may be involved in preconditioning. Retinas from 12 rats exposed to mild light stress (1000 lux × for 12 h) and 12 controls were collected one and seven days after light stress (LS). One retina was used for targeted metabolomics analysis using the Biocrates p180 kit while the fellow retina was used for histological and immunohistochemistry analysis. Immunohistochemistry confirmed that in this experiment, a mild LS with retinal immune response and minimal photoreceptor loss occurred. Compared to controls, LS induced an increased concentration in phosphatidylcholines. The concentration in some amino acids and biogenic amines, particularly those related to the nitric oxide pathway (like asymmetric dimethylarginine (ADMA), arginine and citrulline) also increased 1 day after LS. 7 days after LS, the concentration in two sphingomyelins and phenylethylamine was found to be higher. We further found that in controls, retina metabolome was different between males and females: male retinas had an increased concentration in tyrosine, acetyl-ornithine, phosphatidylcholines and (acyl)-carnitines. Besides retinal sexual metabolic dimorphism, this study shows that preconditioning is mostly associated with re-organisation of lipid metabolism and changes in amino acid composition, likely reflecting the involvement of arginine-dependent NO signalling.

Different perception of cognitive impairment, behavioral disturbances, and functional disabilities between persons with mild cognitive impairment and mild Alzheimer's disease and their caregivers.

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Onor, M L; Trevisiol, M; Negro, C; Aguglia, E

2006-01-01

Insight in dementia is a multifaceted concept and ability, which includes the persons' perception of their behavioral and cognitive symptoms and functional disability. This ability seems to deteriorate as dementia progresses. The aim of this study was to evaluate the level of insight in the cognitive, behavioral, and functional disorders in a group of persons with mild cognitive impairment (MCI) or mild AD (Alzheimer's disease) and to compare their perception of their illness with that of their caregivers. The study involved a group of 121 persons with MCI and mild AD and their caregivers. The persons with MCI and mild AD were administered the tests Mini-Mental State Examination, Instrumental Activities of Daily Living, Activities of Daily Living, Neuropsychiatric Inventory, Schedule for the Assessment of Insight, Clinical Insight Rating Scale, and a short interview. Major differences were identified between how the persons with MCI or mild AD and their caregivers perceived the persons' cognitive and behavioral disorders. The group with MCI or mild AD underestimated their deficits, which were considered serious and disabling by their caregivers.

Metabolic Bone Disease in the Bariatric Surgery Patient

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Susan E. Williams

2011-01-01

Full Text Available Bariatric surgery has proven to be a life-saving measure for some, but for others it has precipitated a plethora of metabolic complications ranging from mild to life-threatening, sometimes to the point of requiring surgical revision. Obesity was previously thought to be bone protective, but this is indeed not the case. Morbidly obese individuals are at risk for metabolic bone disease (MBD due to chronic vitamin D deficiency, inadequate calcium intake, sedentary lifestyle, chronic dieting, underlying chronic diseases, and the use of certain medications used to treat those diseases. After bariatric surgery, the risk for bone-related problems is even greater, owing to severely restricted intake, malabsorption, poor compliance with prescribed supplements, and dramatic weight loss. Patients presenting for bariatric surgery should be evaluated for MBD and receive appropriate presurgical interventions. Furthermore, every patient who has undergone bariatric surgery should receive meticulous lifetime monitoring, as the risk for developing MBD remains ever present.

Association between different levels of dysglycemia and metabolic syndrome in pregnancy

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Negrato Carlos A

2009-08-01

Full Text Available Abstract Background In this study, we sought to evaluate the prevalence of metabolic syndrome (MS in a cohort of pregnant women with a wide range of glucose tolerance, prepregnancy risk factors for MS during pregnancy, and the effects of MS in the outcomes in the mother and in the newborn. Methods One hundred and thirty six women with positive screening for gestational diabetes mellitus (GDM were classified by two diagnostic methods: glycemic profile and 100 g OGTT as normoglycemic, mild gestational hyperglycemic, GDM, and overt GDM. Markers of MS were measured between 24–28th during the screening. Results The prevalence of MS was: 0%; 20.0%; 23.5% and 36.4% in normoglycemic, mild hyperglycemic, GDM, and overt GDM groups, respectively. Previous history of GDM with or without insulin use, BMI ≥ 25, hypertension, family history of diabetes in first degree relatives, non-Caucasian ethnicity, history of prematurity and polihydramnios were statistically significant prepregnancy predictors for MS in the index pregnancy, that by its turn increased the adverse outcomes in the mother and in the newborn. Conclusion The prevalence of MS increases with the worsening of glucose tolerance; impaired glycemic profile identifies pregnancies with important metabolic abnormalities even in the presence of a normal OGTT, in patients that are not classified as having GDM.

Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis.

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Silva, Pedro Henrique Imenez; Girardi, Adriana Castello Costa; Neri, Elida Adalgisa; Rebouças, Nancy Amaral

2012-04-01

The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 ± 0.02) and severe (6.95 ± 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 ± 0.03) and severe (6.86 ± 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

Gait, dual task and history of falls in elderly with preserved cognition, mild cognitive impairment, and mild Alzheimer's disease.

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Ansai, Juliana H; Andrade, Larissa P; Rossi, Paulo G; Takahashi, Anielle C M; Vale, Francisco A C; Rebelatto, José R

Studies with functional and applicable methods and new cognitive demands involving executive function are needed to improve screening, prevention and rehabilitation of cognitive impairment and falls. to identify differences in gait, dual task performances, and history of falls between elderly people with preserved cognition, mild cognitive impairment and mild Alzheimer's disease. A cross-sectional study was conducted. The sample consisted of 40 community-dwelling older adults with preserved cognition, 40 older adults with mild cognitive impairment, and 38 older adults with mild Alzheimer's disease. The assessment consisted of anamneses, gait (measured by the 10-meter walk test), dual task (measured by the Timed Up and Go Test associated with the motor-cognitive task of calling a phone number), and history of falls in the past year. There were no differences among all groups for all variables. However, the Alzheimer's disease Group performed significantly worse in the dual task than the other groups. No item of dual task could distinguish people with preserved cognition from those with mild cognitive impairment. The groups with cognitive impairment included more fallers, and specific characteristics in history of falls between groups were identified. Dual task could distinguish Alzheimer's disease patients specifically from other cognitive profiles. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Metabolism of citral, the major constituent of lemongrass oil, in the cabbage looper, Trichoplusia ni, and effects of enzyme inhibitors on toxicity and metabolism.

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Tak, Jun-Hyung; Isman, Murray B

2016-10-01

Although screening for new and reliable sources of botanical insecticides remains important, finding ways to improve the efficacy of those already in use through better understanding of their modes-of-action or metabolic pathways, or by improving formulations, deserves greater attention as the latter may present lesser regulation hurdles. Metabolic processing of citral (a combination of the stereoisomers geranial and neral), a main constituent of lemongrass (Cymbopogon citratus) essential oil has not been previously examined in insects. To address this, we investigated insecticidal activities of lemongrass oil and citral, as well as the metabolism of citral in larvae of the cabbage looper, Trichoplusia ni, in associations with well-known enzyme inhibitors. Among the inhibitors tested, piperonyl butoxide showed the highest increase in toxicity followed by triphenyl phosphate, but no synergistic interaction between the inhibitors was observed. Topical application of citral to fifth instar larvae produced mild reductions in food consumption, and frass analysis after 24h revealed geranic acid (99.7%) and neric acid (98.8%) as major metabolites of citral. Neither citral nor any other metabolites were found following in vivo analysis of larvae after 24h, and no significant effect of enzyme inhibitors was observed on diet consumption or citral metabolism. Copyright © 2016 Elsevier B.V. All rights reserved.

Genome-scale metabolic models applied to human health and disease.

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Cook, Daniel J; Nielsen, Jens

2017-11-01

Advances in genome sequencing, high throughput measurement of gene and protein expression levels, data accessibility, and computational power have allowed genome-scale metabolic models (GEMs) to become a useful tool for understanding metabolic alterations associated with many different diseases. Despite the proven utility of GEMs, researchers confront multiple challenges in the use of GEMs, their application to human health and disease, and their construction and simulation in an organ-specific and disease-specific manner. Several approaches that researchers are taking to address these challenges include using proteomic and transcriptomic-informed methods to build GEMs for individual organs, diseases, and patients and using constraints on model behavior during simulation to match observed metabolic fluxes. We review the challenges facing researchers in the use of GEMs, review the approaches used to address these challenges, and describe advances that are on the horizon and could lead to a better understanding of human metabolism. WIREs Syst Biol Med 2017, 9:e1393. doi: 10.1002/wsbm.1393 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4+ T helper responses.

OpenAIRE

Fiorentini, Simona; Marconi, Peggy; Avolio, Manuela; Marini, Elena; Garrafa, Emirena; Caracciolo, Sonia; Rossi, Daniele; Bozac, Alexandra; Becker, Pablo D; Gentili, Francesca; Facchetti, Fabio; Guzman, Carlos A; Manservigi, Roberto; Caruso, Arnaldo

2007-01-01

Both neutralizing antibodies and cytotoxic T-cells are necessary to control a viral infection. However, vigorous T helper responses are essential for their elicitation and maintenance. Here we show that a recombinant replication-deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in the mouse dermis generate...

Expanding beyond canonical metabolism: Interfacing alternative elements, synthetic biology, and metabolic engineering

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Kevin B. Reed

2018-03-01

Full Text Available Metabolic engineering offers an exquisite capacity to produce new molecules in a renewable manner. However, most industrial applications have focused on only a small subset of elements from the periodic table, centered around carbon biochemistry. This review aims to illustrate the expanse of chemical elements that can currently (and potentially be integrated into useful products using cellular systems. Specifically, we describe recent advances in expanding the cellular scope to include the halogens, selenium and the metalloids, and a variety of metal incorporations. These examples range from small molecules, heteroatom-linked uncommon elements, and natural products to biomining and nanotechnology applications. Collectively, this review covers the promise of an expanded range of elemental incorporations and the future impacts it may have on biotechnology.

Pragmatic awareness of Suggestions: From (ImPolite Mannerism to Attitudinal Appropriateness

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Hamid Allami

2017-09-01

Full Text Available The present research seeks to determine: (a Iranian EFL learners’ application of suggestion semantic formulae ;(b their attitude of appropriateness in terms of confidence in the employment of appropriate supportive moves; (c, their (impolite mannerism with respect to the selected strategies; and (d the relationship between attitude of appropriateness and mannerism of (impoliteness. An Oxford Quick placement Test (OQPT was administered among 60 Iranian EFL learners to check their language proficiency level and to satisfy the assumption of homogeneity among the learners. These participants along with 10 American native speakers then underwent a suggestion DCT. The questionnaire included questions addressing interlocutors’ with higher, lower or equal power status and intimate or strange social distance. The DCT also involved attitudinal appropriateness scale and (impoliteness mannerism likert scale to examine the learners’ degree of confidence and mannerism. Besides similarities and differences in the application of suggestion semantic formulae between the Iranian learners and American speakers, the results revealed variations in the two groups’ performances for appropriateness and (impoliteness. The results also indicated a positive relationship between the attitude and mannerism scales.

Roquin Suppresses the PI3K-mTOR Signaling Pathway to Inhibit T Helper Cell Differentiation and Conversion of Treg to Tfr Cells.

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Essig, Katharina; Hu, Desheng; Guimaraes, Joao C; Alterauge, Dominik; Edelmann, Stephanie; Raj, Timsse; Kranich, Jan; Behrens, Gesine; Heiseke, Alexander; Floess, Stefan; Klein, Juliane; Maiser, Andreas; Marschall, Susan; Hrabĕ de Angelis, Martin; Leonhardt, Heinrich; Calkhoven, Cornelis F; Noessner, Elfriede; Brocker, Thomas; Huehn, Jochen; Krug, Anne B; Zavolan, Mihaela; Baumjohann, Dirk; Heissmeyer, Vigo

2017-12-19

Roquin proteins preclude spontaneous T cell activation and aberrant differentiation of T follicular helper (Tfh) or T helper 17 (Th17) cells. Here we showed that deletion of Roquin-encoding alleles specifically in regulatory T (Treg) cells also caused the activation of conventional T cells. Roquin-deficient Treg cells downregulated CD25, acquired a follicular Treg (Tfr) cell phenotype, and suppressed germinal center reactions but could not protect from colitis. Roquin inhibited the PI3K-mTOR signaling pathway by upregulation of Pten through interfering with miR-17∼92 binding to an overlapping cis-element in the Pten 3' UTR, and downregulated the Foxo1-specific E3 ubiquitin ligase Itch. Loss of Roquin enhanced Akt-mTOR signaling and protein synthesis, whereas inhibition of PI3K or mTOR in Roquin-deficient T cells corrected enhanced Tfh and Th17 or reduced iTreg cell differentiation. Thereby, Roquin-mediated control of PI3K-mTOR signaling prevents autoimmunity by restraining activation and differentiation of conventional T cells and specialization of Treg cells. Copyright © 2017 Elsevier Inc. All rights reserved.

26 CFR 1.669(b)-2 - Manner of exercising election.

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2010-04-01

... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Manner of exercising election. 1.669(b)-2 Section 1.669(b)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Years Beginning Before January 1, 1969 § 1.669(b)-2 Manner of exercising election. (a) By whom election...

Plasma lipoprotein(a levels are associated with mild renal impairment in type 2 diabetics independent of albuminuria.

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Jennie Lin

Full Text Available CKD, an independent risk factor for CV disease, increases mortality in T2DM. Treating modifiable CV risk factors decreases mortality in diabetics with microalbuminuria, but the role of early CV prevention in diabetics with mild CKD by GFR criteria alone remains unclear. The purpose of this study was to probe whether T2DM patients with mild GFR impairment have atherogenic lipid profiles compared to diabetic counterparts with normal renal function.In the Penn Diabetes Heart Study (PDHS, a single-center observational cohort of T2DM patients without clinical CVD, cross-sectional analyses were performed for directly measured lipid fractions in 1852 subjects with eGFR>60 mL/min/1.73 m² determined by the CKD-EPI equation (n = 1852. Unadjusted and multivariable analyses of eGFR association with log-transformed lipid parameters in incremental linear and logistic regression models (with eGFR 90 mL/min/1.73 m² as a cut-point were performed.Mild GFR impairment (eGFR 60-90 mL/min/1.73 m², median urinary ACR 5.25 mg/g was associated with higher log-transformed Lp(a values (OR 1.17, p = 0.005 and with clinically atherogenic Lp(a levels above 30 mg/dL (OR 1.35, p = 0.013 even after full adjustment for demographics, medications, metabolic parameters, and albuminuria. Logistic regression demonstrated a trend towards significance between worse kidney function and apoB (p = 0.17 as well as apoC-III (p = 0.067 in the fully adjusted model.Elevated Lp(a levels have a robust association with mild GFR impairment in type 2 diabetics independent of race, insulin resistance, and albuminuria.

iAB-RBC-283: A proteomically derived knowledge-base of erythrocyte metabolism that can be used to simulate its physiological and patho-physiological states.

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Bordbar, Aarash; Jamshidi, Neema; Palsson, Bernhard O

2011-07-12

The development of high-throughput technologies capable of whole cell measurements of genes, proteins, and metabolites has led to the emergence of systems biology. Integrated analysis of the resulting omic data sets has proved to be hard to achieve. Metabolic network reconstructions enable complex relationships amongst molecular components to be represented formally in a biologically relevant manner while respecting physical constraints. In silico models derived from such reconstructions can then be queried or interrogated through mathematical simulations. Proteomic profiling studies of the mature human erythrocyte have shown more proteins present related to metabolic function than previously thought; however the significance and the causal consequences of these findings have not been explored. Erythrocyte proteomic data was used to reconstruct the most expansive description of erythrocyte metabolism to date, following extensive manual curation, assessment of the literature, and functional testing. The reconstruction contains 281 enzymes representing functions from glycolysis to cofactor and amino acid metabolism. Such a comprehensive view of erythrocyte metabolism implicates the erythrocyte as a potential biomarker for different diseases as well as a 'cell-based' drug-screening tool. The analysis shows that 94 erythrocyte enzymes are implicated in morbid single nucleotide polymorphisms, representing 142 pathologies. In addition, over 230 FDA-approved and experimental pharmaceuticals have enzymatic targets in the erythrocyte. The advancement of proteomic technologies and increased generation of high-throughput proteomic data have created the need for a means to analyze these data in a coherent manner. Network reconstructions provide a systematic means to integrate and analyze proteomic data in a biologically meaning manner. Analysis of the red cell proteome has revealed an unexpected level of complexity in the functional capabilities of human erythrocyte metabolism.

Weight loss after bariatric surgery reverses insulin-induced increases in brain glucose metabolism of the morbidly obese.

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Tuulari, Jetro J; Karlsson, Henry K; Hirvonen, Jussi; Hannukainen, Jarna C; Bucci, Marco; Helmiö, Mika; Ovaska, Jari; Soinio, Minna; Salminen, Paulina; Savisto, Nina; Nummenmaa, Lauri; Nuutila, Pirjo

2013-08-01

Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not different between groups. However, the hyperinsulinemic clamp increased brain glucose metabolism in a widespread manner in the obese but not control subjects, and brain glucose metabolism was significantly higher during clamp in obese than in control subjects. After follow-up, 6 months postoperatively, the increase in glucose metabolism was no longer observed, and this attenuation was coupled with improved peripheral insulin sensitivity after weight loss. We conclude that obesity is associated with increased insulin-stimulated glucose metabolism in the brain and that this abnormality can be reversed by bariatric surgery.

Mechanical behaviour of Zn-Fe alloy coated mild steel

International Nuclear Information System (INIS)

Panagopoulos, C.N.; Georgiou, E.P.; Agathocleous, P.E.; Giannakopoulos, K.I.

2009-01-01

Zinc alloy coatings containing various amounts of Fe were deposited by electrodeposition technique on a mild steel substrate. The concentration of Fe in the produced alloy coatings ranged from 0 to 14 wt.%, whereas the thickness of the coatings was about 50 μm. Structural and metallurgical characterization of the produced coatings was performed with the aid of X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) techniques. This study aims in investigating the mechanical behaviour of Zn-Fe coated mild steel specimens, as no research investigation concerning the tensile behaviour of Zn alloy coated ferrous alloys has been reported in the past. The experimental results indicated that the ultimate tensile strength of the Zn-Fe coated mild steel was lower than the bare mild steel. In addition, the ductility of the Zn-Fe coated mild steel was found to decrease significantly with increasing Fe content in the coating.

Socioeconomic disparities in work performance following mild stroke.

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Brey, Joseph K; Wolf, Timothy J

2015-01-01

The purpose of this study was to investigate the relationships among the factors that influence return to work for young individuals with mild stroke from different socioeconomic backgrounds. Prospective cohort study of working adults with mild stroke (N = 21). Participants completed an assessment battery of cognitive, work environment and work performance measures at approximately 3 weeks and 7 months post mild stroke. Individuals were placed in "skilled" and "unskilled" worker categories based on the Hollingshead Index. Unskilled workers had significantly poorer scores on the majority of the cognitive assessments. Unskilled workers also perceived less social support (p = 0.017) and autonomy (p = 0.049) in work responsibilities than individuals in the skilled worker group and also reported significantly poorer work productivity due to stroke than those in the skilled group (p = 0.015). Individuals from low socioeconomic backgrounds have more difficulty returning to work following mild stroke than individuals from higher socioeconomic backgrounds. Future work is needed to identify factors that can increase long-term work success and quality of work performance following a mild stroke that specifically targets the needs of individuals who have a lower socioeconomic status.

Curcumin reverses the depressive-like behavior and insulin resistance induced by chronic mild stress.

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Shen, Ji-Duo; Wei, Yu; Li, Yu-Jie; Qiao, Jing-Yi; Li, Yu-Cheng

2017-08-01

Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity. Serum parameters were detected using commercial kits. Real-time quantitative PCR was used to examine mRNA expression. CMS rats exhibited reduced sucrose consumption, increased serum glucose, insulin, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), non-esterified fatty acid (NEFA), glucagon, leptin, and corticosterone levels, as well as impaired insulin sensitivity. Curcumin upregulated the phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (Akt) in the liver, enhanced insulin sensitivity, and reversed the metabolic abnormalities and depressive-like behaviors mentioned above. Moreover, curcumin increased the hepatic glycogen content by inhibiting glycogen synthase kinase (GSK)-3β and prevented gluconeogenesis by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). These results suggest that curcumin not only exerted antidepressant-like effects, but also reversed the insulin resistance and metabolic abnormalities induced by CMS. These data may provide evidence to support the potential use of curcumin against depression and/or metabolic disorders.

IL-7 and CD4 T Follicular Helper Cells in HIV-1 Infection

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Francesca Chiodi

2017-04-01

Full Text Available IL-7 was previously shown to upregulate the expression of molecules important for interaction of CD4+ T cells with B cells. It is poorly studied whether IL-7 has a role in the biology of T follicular helper (Tfh cells and whether IL-7 dysregulates the expression of B-cell costimulatory molecules on Tfh cells. We review the literature and provide arguments in favor of IL-7 being involved in the biology of human Tfh cells. The CD127 IL-7 receptor is expressed on circulating Tfh and non-Tfh cells, and we show that IL-7, but not IL-6 or IL-21, upregulates the expression of CD70 and PD-1 on these cells. We conclude that IL-7, a cytokine whose level is elevated during HIV-1 infection, may have a role in increased expression of B cell costimulatory molecules on Tfh cells and lead to abnormal B cell differentiation.

The Transcription Factor c-Maf Promotes the Differentiation of Follicular Helper T Cells

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Fabienne Andris

2017-04-01

Full Text Available Follicular helper T cells (Tfh have been identified as the primary cell subpopulation regulating B cell responses in germinal centers, thus supporting high-affinity antibody production. Among the transcription factors orchestrating Tfh cell differentiation and function, the role played by the proto-oncogene c-Maf remains poorly characterized. We report herein that selective loss of c-Maf expression in the T cell compartment results in defective development of Tfh cells in response to both antigen/adjuvant vaccinations and commensal intestinal bacteria. Accordingly, c-Maf expression in T cells was essential for the development and high-affinity antibody secretion in vaccinated animals. c-Maf was expressed early, concomitantly to BCL6, in Tfh cell precursors and found to regulate Tfh fate in a cell-autonomous fashion. Altogether, our findings reveal a novel, non-redundant, function for c-Maf in the differentiation of Tfh cells and the regulation of humoral immune responses to T-cell-dependent antigens.

Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection.

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Xiaojun Chen

2014-05-01

Full Text Available Following Schistosoma japonicum (S. japonicum infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.

Cell viability of mycorrhiza helper bacteria solid inoculant in different carrier material

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Asyiah, Iis Nur; Hindersah, Reginawanti; Harni, Rita

2018-02-01

Roots of food crops are colonized by nonpathogenic mycorrhizal fungi which show natural ability to control plant pathogen. Mycorrhizal establishment in plant roots is affected by rhizobacteria, known as mycorrhiza helper bacteria (MHB), which has synergetic effects on mycorrhizal associations. Laboratory experiment has been conducted to assess the best carrier material to develop well-qualified MHB of Pseudomonas diminuta and Bacillus subtilis solid inoculant. Carrier materials were 100 mesh organic matter of agricultural waste. Different spore concentration of both bacterial liquid inoculants were grown on three kinds of 100-mesh organic matter and stored at room temperature up to 90 days. Cell viability of both MHB were counted by serial dilution plate method by using specific medium. The results showed that sugar cane baggase ash was the best carrier material to maintain cell viability for both MHB. However, the population of Pseudomonas diminuta and Bacillus subtilis in sugar cane baggase ash were slightly decreased after 90 days. The use of sugarcane baggase ash for solid MHB inoculant development could be suggested.

Electrochemistry in the mimicry of oxidative drug metabolism by cytochrome P450s.

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Nouri-Nigjeh, Eslam; Bischoff, Rainer; Bruins, Andries P; Permentier, Hjalmar P

2011-05-01

Prediction of oxidative drug metabolism at the early stages of drug discovery and development requires fast and accurate analytical techniques to mimic the in vivo oxidation reactions by cytochrome P450s (CYP). Direct electrochemical oxidation combined with mass spectrometry, although limited to the oxidation reactions initiated by charge transfer, has shown promise in the mimicry of certain CYP-mediated metabolic reactions. The electrochemical approach may further be utilized in an automated manner in microfluidics devices facilitating fast screening of oxidative drug metabolism. A wide range of in vivo oxidation reactions, particularly those initiated by hydrogen atom transfer, can be imitated through the electrochemically-assisted Fenton reaction. This reaction is based on O-O bond activation in hydrogen peroxide and oxidation by hydroxyl radicals, wherein electrochemistry is used for the reduction of molecular oxygen to hydrogen peroxide, as well as the reduction of Fe(3+) to Fe(2+). Metalloporphyrins, as surrogates for the prosthetic group in CYP, utilizing metallo-oxo reactive species, can also be used in combination with electrochemistry. Electrochemical reduction of metalloporphyrins in solution or immobilized on the electrode surface activates molecular oxygen in a manner analogous to the catalytical cycle of CYP and different metalloporphyrins can mimic selective oxidation reactions. Chemoselective, stereoselective, and regioselective oxidation reactions may be mimicked using electrodes that have been modified with immobilized enzymes, especially CYP itself. This review summarizes the recent attempts in utilizing electrochemistry as a versatile analytical and preparative technique in the mimicry of oxidative drug metabolism by CYP. © 2011 Bentham Science Publishers Ltd.

Mild cold induced thermogenesis: are BAT and skeletal muscle synergistic partners?

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Bal, Naresh C; Maurya, Santosh K; Pani, Sunil; Sethy, Chinmayee; Banerjee, Ananya; Das, Sarita; Patnaik, Srinivas; Kundu, Chanakya N

2017-10-31

There are two well-described thermogenic sites; brown adipose tissue (BAT) and skeletal muscle, which utilize distinct mechanisms of heat production. In BAT, mitochondrial metabolism is the molecular basis of heat generation, while it serves only a secondary role in supplying energy for thermogenesis in muscle. Here, we wanted to document changes in mitochondrial ultrastructure in these two tissue types based upon adaptation to mild (16°C) and severe (4°C) cold in mice. When reared at thermoneutrality (29°C), mitochondria in both tissues were loosely packed with irregular cristae. Interestingly, adaptation to even mild cold initiated ultrastructural remodeling of mitochondria including acquisition of more elaborate cristae structure in both thermogenic sites. The shape of mitochondria in the BAT remained mostly circular, whereas the intermyofibrilar mitochondria in the skeletal muscle became more elongated and tubular. The most dramatic remodeling of mitochondrial architecture was observed upon adaptation to severe cold. In addition, we report cold-induced alteration in levels of humoral factors: fibroblast growth factor 21 (FGF21), IL1α, peptide YY (PYY), tumor necrosis factor α (TNFα), and interleukin 6 (IL6) were all induced whereas both insulin and leptin were down-regulated. In summary, adaptation to cold leads to enhanced cristae formation in mitochondria in skeletal muscle as well as the BAT. Further, the present study indicates that circulating cytokines might play an important role in the synergistic recruitment of the thermogenic program including cross-talk between muscle and BAT. © 2017 The Author(s).

The Metabolic Effects of Low-Carbohydrate Diets and Incorporation into a Biochemistry Course

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Pogozelski, Wendy; Arpaia, Nicholas; Priore, Salvatore

2005-01-01

One of the challenges in teaching biochemistry is facilitating students' interest in and mastery of metabolism. The many pathways and modes of regulation can be overwhelming for students to learn and difficult for professors to teach in an engaging manner. We have found it useful to take advantage of prevailing interest in popular yet…

Cognitive Profile of Elderly Patients with Mild Stroke

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Arne Gramstad

2011-11-01

Full Text Available Background: A pattern characterizing cognitive deficits in mild stroke could help in differential diagnosis and rehabilitation planning. Methods: Fifty patients with mild stroke (modified Rankin scale ≤2 at discharge aged >60 years were given the Mini Mental State Examination (MMSE, the Hopkins Verbal Learning Test-Revised (HVLT-R and the Stroop test. Results: On HVLT-R, significant impairments were found in learning and recall, but not in delayed recall. The Stroop test revealed significant impairments in reading speed, but not in color-word interference. Using the MMSE, significant deficits were only found in the youngest age group. Conclusion: Elderly patients with mild stroke show deficits in verbal learning/recall and in reading speed, but not in the MMSE, delayed recall or color-word interference. The deficits are consistent with a mild-to-moderate brain dysfunction, with relative sparing of medial brain structures.

What on "irf" is this gene 4? Irf4 transcription-factor-dependent dendritic cells are required for T helper 2 cell responses in murine skin.

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Flutter, Barry; Nestle, Frank O

2013-10-17

Interferon regulatory factors play an important role in the transcriptional regulation of immunity. In this issue of Immunity, Kumamoto et al. (2013) and Gao et al. (2013) identify an Irf4-dependent migratory dendritic cell subset required for T helper 2 cell polarization following cutaneous challenge. Copyright © 2013 Elsevier Inc. All rights reserved.

SVD identifies transcript length distribution functions from DNA microarray data and reveals evolutionary forces globally affecting GBM metabolism.

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Nicolas M Bertagnolli

Full Text Available To search for evolutionary forces that might act upon transcript length, we use the singular value decomposition (SVD to identify the length distribution functions of sets and subsets of human and yeast transcripts from profiles of mRNA abundance levels across gel electrophoresis migration distances that were previously measured by DNA microarrays. We show that the SVD identifies the transcript length distribution functions as "asymmetric generalized coherent states" from the DNA microarray data and with no a-priori assumptions. Comparing subsets of human and yeast transcripts of the same gene ontology annotations, we find that in both disparate eukaryotes, transcripts involved in protein synthesis or mitochondrial metabolism are significantly shorter than typical, and in particular, significantly shorter than those involved in glucose metabolism. Comparing the subsets of human transcripts that are overexpressed in glioblastoma multiforme (GBM or normal brain tissue samples from The Cancer Genome Atlas, we find that GBM maintains normal brain overexpression of significantly short transcripts, enriched in transcripts that are involved in protein synthesis or mitochondrial metabolism, but suppresses normal overexpression of significantly longer transcripts, enriched in transcripts that are involved in glucose metabolism and brain activity. These global relations among transcript length, cellular metabolism and tumor development suggest a previously unrecognized physical mode for tumor and normal cells to differentially regulate metabolism in a transcript length-dependent manner. The identified distribution functions support a previous hypothesis from mathematical modeling of evolutionary forces that act upon transcript length in the manner of the restoring force of the harmonic oscillator.

Fluctuating selection on basal metabolic rate.

Science.gov (United States)

Nilsson, Johan F; Nilsson, Jan-Åke

2016-02-01

BMR (Basal metabolic rate) is an important trait in animal life history as it represents a significant part of animal energy budgets. BMR has also been shown to be positively related to sustainable work rate and maximal thermoregulatory capacity. To this date, most of the studies have focused on the causes of interspecific and intraspecific variation in BMR, and fairly little is known about the fitness consequences of different metabolic strategies. In this study, we show that winter BMR affects local survival in a population of wild blue tits (Cyanistes caeruleus), but that the selection direction differs between years. We argue that this fluctuating selection is probably a consequence of varying winter climate with a positive relation between survival and BMR during cold and harsh conditions, but a negative relation during mild winters. This fluctuating selection can not only explain the pronounced variation in BMR in wild populations, but will also give us new insights into how energy turnover rates can shape the life-history strategies of animals. Furthermore, the study shows that the process of global warming may cause directional selection for a general reduction in BMR, affecting the general life-history strategy on the population level.

Effect of air preheat temperature on the MILD combustion of syngas

International Nuclear Information System (INIS)

Huang, Mingming; Zhang, Zhedian; Shao, Weiwei; Xiong, Yan; Liu, Yan; Lei, Fulin; Xiao, Yunhan

2014-01-01

Highlights: • MILD combustion is achieved with reaction zone covering the entire combustion chamber. • Critical equivalence ratio for the occurrence of MILD combustion is identified. • MILD regime can be established for syngas fuel under air preheating conditions. - Abstract: The effect of air preheat temperature on MILD (Moderate or Intense Low-oxygen Dilution) combustion of coal-derived syngas was examined in parallel jet forward flow combustor. The results were presented on flow field using numerical simulations and on global flame signatures, OH ∗ radicals distribution and exhaust emissions using experiments. The discrete and high speed air/fuel injections into the combustor is necessary for the establishment of MILD conditions, because they cause strong gas recirculation and form large mixing region between the air and fuel jets. The critical equivalence ratio above which MILD combustion occurred was identified. The MILD regime was established for syngas fuel under air preheating conditions with lean operational limit and suppressed NO x and CO emissions. In the MILD combustion regime, the air preheating resulted in higher NO x but lower CO emissions, while the increase of equivalence ratio led to the increase of NO x and the decrease of CO emissions

Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging.

Science.gov (United States)

Sato, Shogo; Solanas, Guiomar; Peixoto, Francisca Oliveira; Bee, Leonardo; Symeonidi, Aikaterini; Schmidt, Mark S; Brenner, Charles; Masri, Selma; Benitah, Salvador Aznar; Sassone-Corsi, Paolo

2017-08-10

The process of aging and circadian rhythms are intimately intertwined, but how peripheral clocks involved in metabolic homeostasis contribute to aging remains unknown. Importantly, caloric restriction (CR) extends lifespan in several organisms and rewires circadian metabolism. Using young versus old mice, fed ad libitum or under CR, we reveal reprogramming of the circadian transcriptome in the liver. These age-dependent changes occur in a highly tissue-specific manner, as demonstrated by comparing circadian gene expression in the liver versus epidermal and skeletal muscle stem cells. Moreover, de novo oscillating genes under CR show an enrichment in SIRT1 targets in the liver. This is accompanied by distinct circadian hepatic signatures in NAD + -related metabolites and cyclic global protein acetylation. Strikingly, this oscillation in acetylation is absent in old mice while CR robustly rescues global protein acetylation. Our findings indicate that the clock operates at the crossroad between protein acetylation, liver metabolism, and aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of bilirubin metabolism and transport in the neonate.

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Gartner, L M

1977-01-01

Comprehensive physiologic study of the developmental processes of bilirubin metabolism and transport reveal a complex interaction of various steps. Phase I Physiologic Jaundice results from the simultaneous increase in bilirubin load presented to the liver and decrease in bilirubin conjugating capacity. Phase II appears to result from a mild decrease in hepatic uptake capacity, coupled with the continuing increase in bilirubin load. Since these results are based upon studies of newborn rhesus monkeys, confirmatory studies in human neonates are required. Perhaps the most challenging aspect of these observations relates to the concept of a developmentally determined delicate imbalance between two functions. It is unlikely that pharmacologic agents could radically alter a single function. Therefore, it is perhaps more realistic to think that drug treatments which only slightly alter two functions simultaneously but in the appropriate directions could more effectively reduce the risk of toxicity. Thus, a mild increase in bilirubin conjugation coupled with a small but significant decrease in bilirubin load could markedly alleviate the severity of physiologic jaundice.

Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice

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Liu, Xiao-Long; Luo, Liu; Mu, Rong-Hao; Liu, Bin-Bin; Geng, Di; Liu, Qing; Yi, Li-Tao

2015-01-01

Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway has an important role in ketamine-induced, rapid antidepressant effects despite the acute administration of fluoxetine not affecting mTOR phosphorylation in the brain. However, the effects of long-term fluoxetine treatment on mTOR modulation have not been assessed to date. In the present study, we examined whether fluoxetine, a type of commonly used antidepressant agent, alters mTOR signaling following chronic administration in different brain regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We also investigated whether fluoxetine enhanced synaptic protein levels in these regions via the activation of the mTOR signaling pathway and its downstream regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR phosphorylation reduction in the hippocampus and amygdala of mice but not in the frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and synapsin I levels were reversed by fluoxetine, and these effects were blocked by rapamycin only in the hippocampus. In conclusion, our findings suggest that chronic treatment with fluoxetine can induce synaptic protein expression by activating the mTOR signaling pathway in a region-dependent manner and mainly in the hippocampus. PMID:26522512

Exercise, Obesity and CNS Control of Metabolic Homeostasis: A Review

OpenAIRE

John K. Smith

2018-01-01

This review details the manner in which the central nervous system regulates metabolic homeostasis in normal weight and obese rodents and humans. It includes a review of the homeostatic contributions of neurons located in the hypothalamus, the midbrain and limbic structures, the pons and the medullary area postrema, nucleus tractus solitarius, and vagus nucleus, and details how these brain regions respond to circulating levels of orexigenic hormones, such as ghrelin, and anorexigenic hormones...

Obesity-related metabolic dysfunction in dogs: a comparison with human metabolic syndrome

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Tvarijonaviciute Asta

2012-08-01

Full Text Available Abstract Background Recently, metabolic syndrome (MS has gained attention in human metabolic medicine given its associations with development of type 2 diabetes mellitus and cardiovascular disease. Canine obesity is associated with the development of insulin resistance, dyslipidaemia, and mild hypertension, but the authors are not aware of any existing studies examining the existence or prevalence of MS in obese dogs. Thirty-five obese dogs were assessed before and after weight loss (median percentage loss 29%, range 10-44%. The diagnostic criteria of the International Diabetes Federation were modified in order to define canine obesity-related metabolic dysfunction (ORMD, which included a measure of adiposity (using a 9-point body condition score [BCS], systolic blood pressure, fasting plasma cholesterol, plasma triglyceride, and fasting plasma glucose. By way of comparison, total body fat mass was measured by dual-energy X-ray absorptiometry, whilst total adiponectin, fasting insulin, and high-sensitivity C-reactive protein (hsCRP were measured using validated assays. Results Systolic blood pressure (P = 0.008, cholesterol (P = 0.003, triglyceride (P = 0.018, and fasting insulin (P P = 0.001. However, hsCRP did not change with weight loss. Prior to weight loss, 7 dogs were defined as having ORMD, and there was no difference in total fat mass between these dogs and those who did not meet the criteria for ORMD. However, plasma adiponectin concentration was less (P = 0.031, and plasma insulin concentration was greater (P = 0.030 in ORMD dogs. Conclusions In this study, approximately 20% of obese dogs suffer from ORMD, and this is characterized by hypoadiponectinaemia and hyperinsulinaemia. These studies can form the basis of further investigations to determine path genetic mechanisms and the health significance for dogs, in terms of disease associations and outcomes of weight loss.

A Role for Timp3 in Microbiota-Driven Hepatic Steatosis and Metabolic Dysfunction

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Maria Mavilio

2016-07-01

Full Text Available The effect of gut microbiota on obesity and insulin resistance is now recognized, but the underlying host-dependent mechanisms remain poorly undefined. We find that tissue inhibitor of metalloproteinase 3 knockout (Timp3−/− mice fed a high-fat diet exhibit gut microbiota dysbiosis, an increase in branched chain and aromatic (BCAA metabolites, liver steatosis, and an increase in circulating soluble IL-6 receptors (sIL6Rs. sIL6Rs can then activate inflammatory cells, such as CD11c+ cells, which drive metabolic inflammation. Depleting the microbiota through antibiotic treatment significantly improves glucose tolerance, hepatic steatosis, and systemic inflammation, and neutralizing sIL6R signaling reduces inflammation, but only mildly impacts glucose tolerance. Collectively, our results suggest that gut microbiota is the primary driver of the observed metabolic dysfunction, which is mediated, in part, through IL-6 signaling. Our findings also identify an important role for Timp3 in mediating the effect of the microbiota in metabolic diseases.

Systematic Sensitivity Analysis of Metabolic Controllers During Reductions in Skeletal Muscle Blood Flow

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Radhakrishnan, Krishnan; Cabrera, Marco

2000-01-01

An acute reduction in oxygen delivery to skeletal muscle is generally associated with profound derangements in substrate metabolism. Given the complexity of the human bioenergetic system and its components, it is difficult to quantify the interaction of cellular metabolic processes to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in oxygen availability affect the pathways of ATP synthesis and their regulation. In this study, we apply a previously developed mathematical model of human bioenergetics to study effects of ischemia during periods of increased ATP turnover (e.g., exercise). By using systematic sensitivity analysis the oxidative phosphorylation rate was found to be the most important rate parameter affecting lactate production during ischemia under resting conditions. Here we examine whether mild exercise under ischemic conditions alters the relative importance of pathways and parameters previously obtained.

Memory complaints in subjective cognitive impairment, amnestic mild cognitive impairment and mild Alzheimer's disease.

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Ryu, Seon Young; Lee, Sang Bong; Kim, Tae Woo; Lee, Taek Jun

2016-12-01

Memory complaints are a frequent phenomenon in elderly individuals and can lead to opportunistic help-seeking behavior. The aim of this study was to compare different aspects of memory complaints (i.e., prospective versus retrospective complaints) in individuals with subjective cognitive impairment (SCI), amnestic mild cognitive impairment (aMCI), and mild Alzheimer's disease (AD). The study included a total of 115 participants (mean age: 68.82 ± 8.83 years) with SCI (n = 34), aMCI (n = 46), and mild AD (n = 35). Memory complaints were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), which consists of 16 items that describe everyday memory failure of both prospective memory (PM) and retrospective memory (RM). For aMCI and AD subjects, informants also completed an informant-rating of the PRMQ. All participants completed detailed neuropsychological tests. Results show that PM complaints were equivalent among the three groups. However, RM complaints differed. Specifically, RM complaints in aMCI were higher than SCI, but similar to AD. Informant-reported memory complaints were higher for AD than aMCI. Our study suggests that RM complaints of memory complaints may be helpful in discriminating between SCI and aMCI, but both PM and RM complaints are of limited value in differentiating aMCI from AD.

Nitrogen metabolism correlates with the acclimation of photosynthesis to short-term water stress in rice (Oryza sativa L.).

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Zhong, Chu; Cao, Xiaochuang; Bai, Zhigang; Zhang, Junhua; Zhu, Lianfeng; Huang, Jianliang; Jin, Qianyu

2018-04-01

Nitrogen metabolism is as sensitive to water stress as photosynthesis, but its role in plant under soil drying is not well understood. We hypothesized that the alterations in N metabolism could be related to the acclimation of photosynthesis to water stress. The features of photosynthesis and N metabolism in a japonica rice 'Jiayou 5' and an indica rice 'Zhongzheyou 1' were investigated under mild and moderate soil drying with a pot experiment. Soil drying increased non-photochemical quenching (NPQ) and reduced photon quantum efficiency of PSII and CO 2 fixation in 'Zhongzheyou 1', whereas the effect was much slighter in 'Jiayou 5'. Nevertheless, the photosynthetic rate of the two cultivars showed no significant difference between control and water stress. Soil drying increased nitrate reducing in leaves of 'Zhongzheyou 1', characterized by enhanced nitrate reductase (NR) activity and lowered nitrate content; whereas glutamate dehydrogenase (GDH), glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) were relative slightly affected. 'Jiayou 5' plants increased the accumulation of nitrate under soil drying, although its NR activity was increased. In addition, the activities of GDH, GOT and GPT were typically increased under soil drying. Besides, amino acids and soluble sugar were significantly increased under mild and moderate soil drying, respectively. The accumulation of nitrate, amino acid and sugar could serve as osmotica in 'Jiayou 5'. The results reveal that N metabolism plays diverse roles in the photosynthetic acclimation of rice plants to soil drying. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Does the combination of the MMSE and clock drawing test (mini-clock) improve the detection of mild Alzheimer's disease and mild cognitive impairment?

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Cacho, Jesús; Benito-León, Julián; García-García, Ricardo; Fernández-Calvo, Bernardino; Vicente-Villardón, José Luis; Mitchell, Alex J

2010-01-01

There is currently a need to develop tools to identify patients with mild AD and mild cognitive impairment (MCI). We determined the validity and reliability of a brief, easily administered cognitive screening battery consisting of fusion of two well-known brief tests (Mini-Mental Status Examination [MMSE] and Clock Drawing Test [CDT]) (Mini-clock) to differentiate between patients with mild AD, MCI, and healthy control subjects. 66 consecutive patients with mild AD, 21 with MCI, and 66 healthy controls seen in a memory clinic setting were compared. Receiver operating characteristic (ROC) curve analysis was used to calculate the cut-off value permitting discrimination between mild AD, MCI, and healthy control subjects. Interrater and test-retest reliability were also assessed. Mean cognitive scores for patients with AD, MCI, and control subjects on all two individual tests were significantly different (for each, p Mini-clock was higher than that obtained with MMSE or CDT in differentiating mild AD from controls (0.973 vs. 0.952 and 0.881, respectively) and MCI from controls (0.855 vs. 0.821 and 0.779, respectively). Test-retest reliability for the Mini-clock was 0.99, meanwhile interrater reliability was 0.87. The mean time to complete the test for all subjects was 8 min and 50 s. The Mini-clock is highly sensitive and specific in the detection of mild AD and reasonably accurate when attempting to separate MCI from health controls. It has a high interrater and test-retest reliability, can be quickly administered, and does not require major training.

Profiling helper T cell subset gene expression in deer mice

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Hjelle Brian

2006-08-01

Full Text Available Abstract Background Deer mice (Peromyscus maniculatus are the most common mammals in North America and are reservoirs for several zoonotic agents, including Sin Nombre virus (SNV, the principal etiologic agent of hantavirus cardiopulmonary syndrome (HCPS in North America. Unlike human HCPS patients, SNV-infected deer mice show no overt pathological symptoms, despite the presence of virus in the lungs. A neutralizing IgG antibody response occurs, but the virus establishes a persistent infection. Limitations of detailed analysis of deer mouse immune responses to SNV are the lack of reagents and methods for evaluating such responses. Results We developed real-time PCR-based detection assays for several immune-related transcription factor and cytokine genes from deer mice that permit the profiling of CD4+ helper T cells, including markers of Th1 cells (T-bet, STAT4, IFNγ, TNF, LT, Th2 cells (GATA-3, STAT6, IL-4, IL-5 and regulatory T cells (Fox-p3, IL-10, TGFβ1. These assays compare the expression of in vitro antigen-stimulated and unstimulated T cells from individual deer mice. Conclusion We developed molecular methods for profiling immune gene expression in deer mice, including a multiplexed real-time PCR assay for assessing expression of several cytokine and transcription factor genes. These assays should be useful for characterizing the immune responses of experimentally- and naturally-infected deer mice.

A REVIEW OF MILD COMBUSTION AND OPEN FURNACE DESIGN CONSIDERATION

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M.M. Noor

2012-12-01

Full Text Available Combustion is still very important to generate energy. Moderate or Intense Low-oxygen Dilution (MILD combustion is one of the best new technologies for clean and efficient combustion. MILD combustion has been proven to be a promising combustion technology in industrial applications with decreased energy consumption due to the uniformity of its temperature distribution. It is clean compared to traditional combustion due to producing low NOx and CO emissions. This article provides a review and discussion of recent research and developments in MILD. The issue and applications are summarized, with some suggestions presented on the upgrading and application of MILD in the future. Currently MILD combustion has been successfully applied in closed furnaces. The preheating of supply air is no longer required since the recirculation inside the enclosed furnace already self-preheats the supply air and self-dilutes the oxygen in the combustion chamber. The possibility of using open furnace MILD combustion will be reviewed. The design consideration for open furnace with exhaust gas re-circulation (EGR was discussed.

iAB-RBC-283: A proteomically derived knowledge-base of erythrocyte metabolism that can be used to simulate its physiological and patho-physiological states

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Palsson Bernhard O

2011-07-01

Full Text Available Abstract Background The development of high-throughput technologies capable of whole cell measurements of genes, proteins, and metabolites has led to the emergence of systems biology. Integrated analysis of the resulting omic data sets has proved to be hard to achieve. Metabolic network reconstructions enable complex relationships amongst molecular components to be represented formally in a biologically relevant manner while respecting physical constraints. In silico models derived from such reconstructions can then be queried or interrogated through mathematical simulations. Proteomic profiling studies of the mature human erythrocyte have shown more proteins present related to metabolic function than previously thought; however the significance and the causal consequences of these findings have not been explored. Results Erythrocyte proteomic data was used to reconstruct the most expansive description of erythrocyte metabolism to date, following extensive manual curation, assessment of the literature, and functional testing. The reconstruction contains 281 enzymes representing functions from glycolysis to cofactor and amino acid metabolism. Such a comprehensive view of erythrocyte metabolism implicates the erythrocyte as a potential biomarker for different diseases as well as a 'cell-based' drug-screening tool. The analysis shows that 94 erythrocyte enzymes are implicated in morbid single nucleotide polymorphisms, representing 142 pathologies. In addition, over 230 FDA-approved and experimental pharmaceuticals have enzymatic targets in the erythrocyte. Conclusion The advancement of proteomic technologies and increased generation of high-throughput proteomic data have created the need for a means to analyze these data in a coherent manner. Network reconstructions provide a systematic means to integrate and analyze proteomic data in a biologically meaning manner. Analysis of the red cell proteome has revealed an unexpected level of complexity in

Ecklonia cava Polyphenol Has a Protective Effect against Ethanol-Induced Liver Injury in a Cyclic AMP-Dependent Manner

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Haruka Yamashita

2015-06-01

Full Text Available Previously, we showed that Ecklonia cava polyphenol (ECP treatment suppressed ethanol-induced increases in hepatocyte death by scavenging intracellular reactive oxygen species (ROS and maintaining intracellular glutathione levels. Here, we examined the effects of ECP on the activities of alcohol-metabolizing enzymes and their regulating mechanisms in ethanol-treated hepatocytes. Isolated hepatocytes were incubated with or without 100 mM ethanol. ECP was dissolved in dimethylsulfoxide. ECP was added to cultured cells that had been incubated with or without ethanol. The cells were incubated for 0–24 h. In cultured hepatocytes, the ECP treatment with ethanol inhibited cytochrome P450 2E1 (CYP2E1 expression and activity, which is related to the production of ROS when large quantities of ethanol are oxidized. On the other hand, ECP treatment with ethanol increased the activity of alcohol dehydrogenase (ADH and aldehyde dehydrogenase. These changes in activities of CYP2E1 and ADH were suppressed by treatment with H89, an inhibitor of protein kinase A. ECP treatment with ethanol enhanced cyclic AMP concentrations compared with those of control cells. ECP may be a candidate for preventing ethanol-induced liver injury via regulating alcohol metabolic enzymes in a cyclic AMP-dependent manner.

Mild Cognitive Impairment in Parkinson's Disease-What Is It?

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Weil, Rimona S; Costantini, Alyssa A; Schrag, Anette E

2018-03-10

Mild cognitive impairment is a common feature of Parkinson's disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson's disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson's disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson's disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson's disease. Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson's disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson's provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia. Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson's disease.

Detection of Mild Emphysema by Computed Tomography Density Measurements

International Nuclear Information System (INIS)

Vikgren, J.; Friman, O.; Borga, M.; Boijsen, M.; Gustavsson, S.; Bake, B.; Tylen, U.; Ekberg-Jansson, A.

2005-01-01

Purpose: To assess the ability of a conventional density mask method to detect mild emphysema by high-resolution computed tomography (HRCT); to analyze factors influencing quantification of mild emphysema; and to validate a new algorithm for detection of mild emphysema. Material and Methods: Fifty-five healthy male smokers and 34 never-smokers, 61-62 years of age, were examined. Emphysema was evaluated visually, by the conventional density mask method, and by a new algorithm compensating for the effects of gravity and artifacts due to motion and the reconstruction algorithm. Effects of the reconstruction algorithm, slice thickness, and various threshold levels on the outcome of the density mask area were evaluated. Results: Forty-nine percent of the smokers had mild emphysema. The density mask area was higher the thinner the slice irrespective of the reconstruction algorithm and threshold level. The sharp algorithm resulted in increased density mask area. The new reconstruction algorithm could discriminate between smokers with and those without mild emphysema, whereas the density mask method could not. The diagnostic ability of the new algorithm was dependent on lung level. At about 90% specificity, sensitivity was 65-100% in the apical levels, but low in the rest of the lung. Conclusion: The conventional density mask method is inadequate for detecting mild emphysema, while the new algorithm improves the diagnostic ability but is nevertheless still imperfect

Digit Symbol Performance in Mild Dementia and Depression.

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Hart, Robert P.; And Others

1987-01-01

Patients with mild dementia of the Alzheimer's type (DAT), patients with major depression, and normal control subjects completed the Wechsler Adult Intelligence Scale (WAIS) Digit Symbol test of incidental memory. Though mild DAT and depressed patients had equivalent deficits in psychomotor speed, DAT patients recalled fewer digit-symbol items.…

Integration of genome-scale metabolic networks into whole-body PBPK models shows phenotype-specific cases of drug-induced metabolic perturbation.

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Cordes, Henrik; Thiel, Christoph; Baier, Vanessa; Blank, Lars M; Kuepfer, Lars

2018-01-01

Drug-induced perturbations of the endogenous metabolic network are a potential root cause of cellular toxicity. A mechanistic understanding of such unwanted side effects during drug therapy is therefore vital for patient safety. The comprehensive assessment of such drug-induced injuries requires the simultaneous consideration of both drug exposure at the whole-body and resulting biochemical responses at the cellular level. We here present a computational multi-scale workflow that combines whole-body physiologically based pharmacokinetic (PBPK) models and organ-specific genome-scale metabolic network (GSMN) models through shared reactions of the xenobiotic metabolism. The applicability of the proposed workflow is illustrated for isoniazid, a first-line antibacterial agent against Mycobacterium tuberculosis , which is known to cause idiosyncratic drug-induced liver injuries (DILI). We combined GSMN models of a human liver with N-acetyl transferase 2 (NAT2)-phenotype-specific PBPK models of isoniazid. The combined PBPK-GSMN models quantitatively describe isoniazid pharmacokinetics, as well as intracellular responses, and changes in the exometabolome in a human liver following isoniazid administration. Notably, intracellular and extracellular responses identified with the PBPK-GSMN models are in line with experimental and clinical findings. Moreover, the drug-induced metabolic perturbations are distributed and attenuated in the metabolic network in a phenotype-dependent manner. Our simulation results show that a simultaneous consideration of both drug pharmacokinetics at the whole-body and metabolism at the cellular level is mandatory to explain drug-induced injuries at the patient level. The proposed workflow extends our mechanistic understanding of the biochemistry underlying adverse events and may be used to prevent drug-induced injuries in the future.

Impact of Mild versus Moderate Intensity Aerobic Walking Exercise ...

African Journals Online (AJOL)

2014-03-01

Mar 1, 2014 ... Objective: To compare the effects of mild and moderate intensity treadmill walking exercises on markers of bone ... second group (B) received mild intensity aerobic exercise training. ..... Using functional loading to influence.

Molecular imaging of serotonin degeneration in mild cognitive impairment.

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Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

2017-09-01

Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic

Preliminary questions before studying mild traumatic brain injury outcome.

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Fayol, P; Carrière, H; Habonimana, D; Dumond, J-J

2009-07-01

To point out from the literature the issues in mild traumatic brain injury outcome. METHODOLOGY-RESULTS: The literature review allows to point out several different factors involved in the difficulty to study mild traumatic brain injury: mild traumatic brain injury definition, postconcussional syndrome definition, diagnosis threshold, severity and functional symptoms outcome, neuropsychological tests, unspecific syndrome feature, individual factors, confounding factors and treatment interventions. The mild traumatic brain injury outcome study is complicated by the definitions issues and especially their practical use and by the multiplicity and the intricate interrelationships among involved factors. The individual outcome and social cost weight is widely emphasized for an event still considered as medically trivial. The well-ordered preventive interventions necessity and the targeted treatment programs need for the persisting postconcussive symptoms complete our critical review.

Gait, dual task and history of falls in elderly with preserved cognition, mild cognitive impairment, and mild Alzheimer's disease

OpenAIRE

Ansai, Juliana H.; Andrade, Larissa P.; Rossi, Paulo G.; Takahashi, Anielle C.M.; Vale, Francisco A.C.; Rebelatto, Jos? R.

2017-01-01

Background Studies with functional and applicable methods and new cognitive demands involving executive function are needed to improve screening, prevention and rehabilitation of cognitive impairment and falls. Objective to identify differences in gait, dual task performances, and history of falls between elderly people with preserved cognition, mild cognitive impairment and mild Alzheimer's disease. Method A cross-sectional study was conducted. The sample consisted of 40 community-dwelling o...

[Self-treatment with baking soda can lead to severe metabolic alkalosis].

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Jensen, Sara; Skriver, Signe

2014-12-15

This case report describes a 66-year-old man, previously healthy besides mild hypertension. He ingested a self-made folk remedy consisting of baking soda and water against acid reflux in dosages that resulted in severe metabolic alkalosis (pH 7.8). Diagnosing and treating MA is easy and cheap, but if the condition is not treated, consequences can be severe. The challenge is to uncover patients' use of non prescription medications and folk remedies in the diagnostic process. Having this information it is possible to prevent MA in both high- and low-risk patients.

Metabolic consequences of stress during childhood and adolescence.

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Pervanidou, Panagiota; Chrousos, George P

2012-05-01

Stress, that is, the state of threatened or perceived as threatened homeostasis, is associated with activation of the stress system, mainly comprised by the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system normally functions in a circadian manner and interacts with other systems to regulate a variety of behavioral, endocrine, metabolic, immune, and cardiovascular functions. However, the experience of acute intense physical or emotional stress, as well as of chronic stress, may lead to the development of or may exacerbate several psychologic and somatic conditions, including anxiety disorders, depression, obesity, and the metabolic syndrome. In chronically stressed individuals, both behavioral and neuroendocrine mechanisms promote obesity and metabolic abnormalities: unhealthy lifestyles in conjunction with dysregulation of the stress system and increased secretion of cortisol, catecholamines, and interleukin-6, with concurrently elevated insulin concentrations, lead to development of central obesity, insulin resistance, and the metabolic syndrome. Fetal life, childhood, and adolescence are particularly vulnerable periods of life to the effects of intense acute or chronic stress. Similarly, these life stages are crucial for the later development of behavioral, metabolic, and immune abnormalities. Developing brain structures and functions related to stress regulation, such as the amygdala, the hippocampus, and the mesocorticolimbic system, are more vulnerable to the effects of stress compared with mature structures in adults. Moreover, chronic alterations in cortisol secretion in children may affect the timing of puberty, final stature, and body composition, as well as cause early-onset obesity, metabolic syndrome, and type 2 diabetes mellitus. The understanding of stress mechanisms leading to metabolic abnormalities in early life may lead to more effective prevention and intervention strategies of obesity

Mild Dehydration Does Not Influence Performance Or Skeletal Muscle Metabolism During Simulated Ice Hockey Exercise In Men.

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Palmer, Matthew S; Heigenhauser, George J F; Duong, MyLinh; Spriet, Lawrence L

2017-04-01

This study determined whether mild dehydration influenced skeletal muscle glycogen use, core temperature or performance during high-intensity, intermittent cycle-based exercise in ice hockey players vs. staying hydrated with water. Eight males (21.6 ± 0.4 yr, 183.5 ± 1.6 cm, 83.9 ± 3.7 kg, 50.2 ± 1.9 ml·kg -1 ·min -1 ) performed two trials separated by 7 days. The protocol consisted of 3 periods (P) containing 10 × 45-s cycling bouts at ~133% VO 2max , followed by 135 s of passive rest. Subjects drank no fluid and dehydrated during the protocol (NF), or maintained body mass by drinking WATER. Muscle biopsies were taken at rest, immediately before and after P3. Subjects were mildly dehydrated (-1.8% BM) at the end of P3 in the NF trial. There were no differences between the NF and WATER trials for glycogen use (P1+P2; 350.1 ± 31.9 vs. 413.2 ± 33.2, P3; 103.5 ± 16.2 vs. 131.5 ± 18.9 mmol·kg dm -1 ), core temperature (P1; 37.8 ± 0.1 vs. 37.7 ± 0.1, P2; 38.2 ± 0.1 vs. 38.1 ± 0.1, P3; 38.3 ± 0.1 vs. 38.2 ± 0.1 °C) or performance (P1; 156.3 ± 7.8 vs. 154.4 ± 8.2, P2; 150.5 ± 7.8 vs. 152.4 ± 8.3, P3; 144.1 ± 8.7 vs. 148.4 ± 8.7 kJ). This study demonstrated that typical dehydration experienced by ice hockey players (~1.8% BM loss), did not affect glycogen use, core temperature, or voluntary performance vs. staying hydrated by ingesting water during a cycle-based simulation of ice hockey exercise in a laboratory environment.

FGF21 as a hepatokine, adipokine, and myokine in metabolism and diseases

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Nobuyuki eItoh

2014-07-01

Full Text Available Fibroblast growth factor (FGF family members are mostly secreted as signaling proteins with diverse functions in development and metabolism. FGF21 is a unique FGF with metabolic, but not proliferative activities. FGF21 is mostly induced by different kinds of stress and acts though FGF receptor 1c with β−Klotho as a cofactor in an endocrine or, in parts, autocirne/paracrine manner. Hepatic FGF21 directly acts on white adipocytes to inhibit lipolysis and acts through the brain to increase systemic glucocorticoid levels and suppress physical activity in response to starvation. It also protects against dioxin toxicity. Adipocytic FGF21 induces the browning of white adipose tissue (WAT and activates brown adipocytes in response to cold exposure. It also acts as an upstream effector of adiponectin in white adipocytes. Myocytic FGF21 protects against diet-induced obesity and insulin resistance, induces the browning of WAT, and protects against cardiac hypertrophy. In addition, Fgf21 polymorphisms are possibly related with metabolic diseases and FGF21 are biomarker of metabolic diseases. These findings indicate that FGF21 plays roles as a hepatokine, adipokine, and myokine in metabolism, injury protection, and diseases.

Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

Science.gov (United States)

Castellano, Christian-Alexandre; Baillargeon, Jean-Patrice; Nugent, Scott; Tremblay, Sébastien; Fortier, Mélanie; Imbeault, Hélène; Duval, Julie; Cunnane, Stephen C

2015-01-01

To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

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Christian-Alexandre Castellano

Full Text Available To investigate whether cerebral metabolic rate of glucose (CMRglu is altered in normal weight young women with polycystic ovary syndrome (PCOS who exhibit mild insulin resistance.Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR. A battery of cognitive tests was administered to evaluate working memory, attention and executive function.The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035 compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018. A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05. Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group.The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

Mild Cognitive Impairment and Progession to Dementia: New Findings

Science.gov (United States)

... David C. Spencer, MD Steven Karceski, MD Mild cognitive impairment and progression to dementia New findings John C.S. ... exami- nations showed that 534 persons had mild cognitive impairment, or MCI (see About MCI, following sec- tion). ...

Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.

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Mary Cloud B Ammons

Full Text Available Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.

Therapeutic potential of Mediator complex subunits in metabolic diseases.

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Ranjan, Amol; Ansari, Suraiya A

2018-01-01

The multisubunit Mediator is an evolutionary conserved transcriptional coregulatory complex in eukaryotes. It is needed for the transcriptional regulation of gene expression in general as well as in a gene specific manner. Mediator complex subunits interact with different transcription factors as well as components of RNA Pol II transcription initiation complex and in doing so act as a bridge between gene specific transcription factors and general Pol II transcription machinery. Specific interaction of various Mediator subunits with nuclear receptors (NRs) and other transcription factors involved in metabolism has been reported in different studies. Evidences indicate that ligand-activated NRs recruit Mediator complex for RNA Pol II-dependent gene transcription. These NRs have been explored as therapeutic targets in different metabolic diseases; however, they show side-effects as targets due to their overlapping involvement in different signaling pathways. Here we discuss the interaction of various Mediator subunits with transcription factors involved in metabolism and whether specific interaction of these transcription factors with Mediator subunits could be potentially utilized as therapeutic strategy in a variety of metabolic diseases. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

The Possible Role of Smoking and Mild Inflammation on Iron, Copper Ions and Related Metalloproteins in Male Volunteers Working in Radiation Field

International Nuclear Information System (INIS)

Bahgat, M.M.; Amer, M.M.; Michael, M.I.; El Daly, E.S.

2009-01-01

Oxidative stress implies that cells have intact pro-oxidant/anti-oxidant systems that continuously generate and detoxify oxidants during normal aerobic metabolism. When additional oxidative events occur, the pro-oxidant systems out balance the anti-oxidant, potentially producing oxidative damage to lipids, proteins, carbohydrates, and nucleic acids ultimately leading to cell death in severe oxidative stress. A disturbance in pro-oxidant/anti-oxidant systems results from a myriad of different oxidative challenges, including radiation, metabolism of environmental pollutants and administered drugs and immune system response to disease or infection. Forty male volunteers have participated in this study to evaluate the effect of smoking and mild infection on ferric and copper ions, related metalloproteins and glutathione peroxidase in males working in the radiation fields. The results denoted that those two stress ors added further imbalance in the pro oxidant-antioxidant status

Insulin Resistance Predicts Medial Temporal Hypermetabolism in Mild Cognitive Impairment Conversion to Alzheimer Disease

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Willette, Auriel A.; Modanlo, Nina

2015-01-01

Alzheimer disease (AD) is characterized by progressive hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans. Peripheral insulin resistance (IR) increases AD risk. No studies have examined associations between FDG metabolism and IR in mild cognitive impairment (MCI) and AD, as well as MCI conversion to AD. We studied 26 cognitively normal (CN), 194 MCI (39 MCI-progressors, 148 MCI-stable, 2 years after baseline), and 60 AD subjects with baseline FDG-PET from the Alzheimer’s Disease Neuroimaging Initiative. Mean FDG metabolism was derived for AD-vulnerable regions of interest (ROIs), including lateral parietal and posteromedial cortices, medial temporal lobe (MTL), hippocampus, and ventral prefrontal cortices (vPFC), as well as postcentral gyrus and global cerebrum control regions. The homeostasis model assessment of IR (HOMA-IR) was used to measure IR. For AD, higher HOMA-IR predicted lower FDG in all ROIs. For MCI-progressors, higher HOMA-IR predicted higher FDG in the MTL and hippocampus. Control regions showed no associations. Higher HOMA-IR predicted hypermetabolism in MCI-progressors and hypometabolism in AD in medial temporal regions. Future longitudinal studies should examine the pathophysiologic significance of the shift from MTL hyper- to hypometabolism associated with IR. PMID:25576061

Type II membrane protein CD69 regulates the formation of resting T-helper memory.

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Shinoda, Kenta; Tokoyoda, Koji; Hanazawa, Asami; Hayashizaki, Koji; Zehentmeier, Sandra; Hosokawa, Hiroyuki; Iwamura, Chiaki; Koseki, Haruhiko; Tumes, Damon J; Radbruch, Andreas; Nakayama, Toshinori

2012-05-08

Memory T-helper (Th) lymphocytes are crucial for the maintenance of acquired immunity to eliminate infectious pathogens. We have previously demonstrated that most memory Th lymphocytes reside and rest on stromal niches of the bone marrow (BM). Little is known, however, regarding the molecular basis for the generation and maintenance of BM memory Th lymphocytes. Here we show that CD69-deficient effector CD4 T lymphocytes fail to relocate into and persist in the BM and therefore to differentiate into memory cells. Consequently, CD69-deficient CD4 T cells fail to facilitate the production of high-affinity antibodies and the generation of BM long-lived plasma cells in the late phase of immune responses. Thus, CD69 is critical for the generation and maintenance of professional memory Th lymphocytes, which can efficiently help humoral immunity in the late phase. The deficit of immunological memory in CD69-deficient mice also highlights the essential role of BM for the establishment of Th memory.

Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation

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Victoria Ryg-Cornejo

2016-01-01

Full Text Available Naturally acquired immunity to malaria develops only after years of repeated exposure to Plasmodium parasites. Despite the key role antibodies play in protection, the cellular processes underlying the slow acquisition of immunity remain unknown. Using mouse models, we show that severe malaria infection inhibits the establishment of germinal centers (GCs in the spleen. We demonstrate that infection induces high frequencies of T follicular helper (Tfh cell precursors but results in impaired Tfh cell differentiation. Despite high expression of Bcl-6 and IL-21, precursor Tfh cells induced during infection displayed low levels of PD-1 and CXCR5 and co-expressed Th1-associated molecules such as T-bet and CXCR3. Blockade of the inflammatory cytokines TNF and IFN-γ or T-bet deletion restored Tfh cell differentiation and GC responses to infection. Thus, this study demonstrates that the same pro-inflammatory mediators that drive severe malaria pathology have detrimental effects on the induction of protective B cell responses.

Implication of snail in metabolic stress-induced necrosis.

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Cho Hee Kim

2011-03-01

Full Text Available Necrosis, a type of cell death accompanied by the rupture of the plasma membrane, promotes tumor progression and aggressiveness by releasing the pro-inflammatory and angiogenic cytokine high mobility group box 1. It is commonly found in the core region of solid tumors due to hypoxia and glucose depletion (GD resulting from insufficient vascularization. Thus, metabolic stress-induced necrosis has important clinical implications for tumor development; however, its regulatory mechanisms have been poorly investigated.Here, we show that the transcription factor Snail, a key regulator of epithelial-mesenchymal transition, is induced in a reactive oxygen species (ROS-dependent manner in both two-dimensional culture of cancer cells, including A549, HepG2, and MDA-MB-231, in response to GD and the inner regions of a multicellular tumor spheroid system, an in vitro model of solid tumors and of human tumors. Snail short hairpin (sh RNA inhibited metabolic stress-induced necrosis in two-dimensional cell culture and in multicellular tumor spheroid system. Snail shRNA-mediated necrosis inhibition appeared to be linked to its ability to suppress metabolic stress-induced mitochondrial ROS production, loss of mitochondrial membrane potential, and mitochondrial permeability transition, which are the primary events that trigger necrosis.Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression.

The Manners of Liberalism: A Question of Limits.

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Allen, William B.

1982-01-01

The argument that liberal education leads people to substitute intellectual tolerance or ambiguity for righteous indignation is criticized, with reference to Harriet Beecher Stowe's portrayal of Thomas Jefferson, his liberalism, and democratic manners. (MSE)

Theory and experimental validation of SPLASH (Single Panel Lamp and Shroud Helper).

Energy Technology Data Exchange (ETDEWEB)

Larsen, Marvin Elwood; Porter, Jason M.

2005-06-01

The radiant heat test facility develops test sets providing well-characterized thermal environments, often representing fires. Many of the components and procedures have become standardized to such an extent that the development of a specialized design tool was appropriate. SPLASH (Single Panel Lamp and Shroud Helper) is that tool. SPLASH is implemented as a user-friendly program that allows a designer to describe a test setup in terms of parameters such as lamp number, power, position, and separation distance. Thermal radiation is the dominant mechanism of heat transfer and the SPLASH model solves a radiation enclosure problem to estimate temperature distributions in a shroud providing the boundary condition of interest. Irradiance distribution on a specified viewing plane is also estimated. This document provides the theoretical development for the underlying model. A series of tests were conducted to characterize SPLASH's ability to analyze lamp and shroud systems. The comparison suggests that SPLASH succeeds as a design tool. Simplifications made to keep the model tractable are demonstrated to result in estimates that are only approximately as uncertain as many of the properties and characteristics of the operating environment.

Farmakologisk behandling af mild ukompliceret hypertension i almen praksis

DEFF Research Database (Denmark)

Paulsen, Maja Skov; Christensen, Bo; Søndergaard, Jens

2013-01-01

pressure 90-99 mmHg; no diabetes or cardiovascular disease) did not reduce mortality or morbidity. The evidence for pharmacotherapy in patients having mild/uncomplicated hypertension is weak. However, current Danish guidelines have taken this into consideration in their recommendations of pharmacotherapy......Hypertension is an important risk factor for cardiovascular disease. In Denmark, patients with hypertension are primarily managed in primary care. A recent Cochrane review concluded that pharmacotherapy of patients with mild hypertension (systolic blood pressure 140-159 mmHg; diastolic blood...... to patients with mild/uncomplicated hypertension....

Ask yeast how to burn your fats: lessons learned from the metabolic adaptation to salt stress.

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Pascual-Ahuir, Amparo; Manzanares-Estreder, Sara; Timón-Gómez, Alba; Proft, Markus

2018-02-01

Here, we review and update the recent advances in the metabolic control during the adaptive response of budding yeast to hyperosmotic and salt stress, which is one of the best understood signaling events at the molecular level. This environmental stress can be easily applied and hence has been exploited in the past to generate an impressively detailed and comprehensive model of cellular adaptation. It is clear now that this stress modulates a great number of different physiological functions of the cell, which altogether contribute to cellular survival and adaptation. Primary defense mechanisms are the massive induction of stress tolerance genes in the nucleus, the activation of cation transport at the plasma membrane, or the production and intracellular accumulation of osmolytes. At the same time and in a coordinated manner, the cell shuts down the expression of housekeeping genes, delays the progression of the cell cycle, inhibits genomic replication, and modulates translation efficiency to optimize the response and to avoid cellular damage. To this fascinating interplay of cellular functions directly regulated by the stress, we have to add yet another layer of control, which is physiologically relevant for stress tolerance. Salt stress induces an immediate metabolic readjustment, which includes the up-regulation of peroxisomal biomass and activity in a coordinated manner with the reinforcement of mitochondrial respiratory metabolism. Our recent findings are consistent with a model, where salt stress triggers a metabolic shift from fermentation to respiration fueled by the enhanced peroxisomal oxidation of fatty acids. We discuss here the regulatory details of this stress-induced metabolic shift and its possible roles in the context of the previously known adaptive functions.

Walking Our Talk in the Neighborhoods: Partnerships between Professionals and Natural Helpers. Building Community Partnerships in Child Welfare, Part Three. Family to Family: Tools for Rebuilding Foster Care.

Science.gov (United States)

Annie E. Casey Foundation, Baltimore, MD.

The Family to Family initiative has encouraged states to reconceptualize, redesign, and reconstruct their foster care systems. By 1996, the initiative was being implemented in five states, five Georgia counties, and Los Angeles County, California. This paper describes some of the ways natural helpers can assist professionals achieve the necessary…

Drinking of chokeberry juice from the ecological farm Dzieciolowo and distensibility of brachial artery in men with mild hypercholesterolemia.

Science.gov (United States)

Poreba, Rafal; Skoczynska, Anna; Gac, Pawel; Poreba, Malgorzata; Jedrychowska, Iwona; Affelska-Jercha, Anna; Turczyn, Barbara; Wojakowska, Anna; Oszmianski, Jan; Andrzejak, Ryszard

2009-01-01

The aim of the study was to estimate the influence of drinking chokeberry juice on the endothelial function in men with mild hypercholesterolemia. It was shown that chronic treatment with flavonoids improves vascular function and reduces cardiovascular remodelling by increasing NO release from endothelial cells. A group of 35 men diagnosed with mild hypercholesterolemia (mean age: 53.9 +-5.8 years), with no earlier pharmacological treatment, were enrolled to the study. In all men, assessment of endothelial function, and serum lipids level were carried out at four time points: at the beginning of the studies, after 6 weeks of regular drinking of chokeberry juice, after 6 weeks without drinking the juice, then after repeated 6 weeks of drinking chokeberry juice. During the study, significant decreases in serum total cholesterol, LDL cholesterol and triglycerides levels were observed. A statistically significant increase in serum nitric oxide (NO) concentration and in the flow mediated dilatation (FMD) were observed. At the beginning, FMD > or = 7 % was present in 13 of 35 subjects (37.1 %). After 6 weeks of regular chokeberry juice drinking, FMD > or = 7 % was present in 29 of 35 subjects (82.9 %). However, after 6 weeks abstaining from drinking the juice and repeated exposure to 6 weeks drinking of chokeberry juice, FMD > or = 7 % was present in all studied subjects. Regular drinking of chokeberry juice has a beneficial effect on endothelial function and lipid metabolism in men with mild hypercholesterolemia.

A sibship with a mild variant of Zellweger syndrome

NARCIS (Netherlands)

Barth, P. G.; Schutgens, R. B.; Wanders, R. J.; Heymans, H. S.; Moser, A. E.; Moser, H. W.; Bleeker-Wagemakers, E. M.; Jansonius-Schultheiss, K.; Derix, M.; Nelck, G. F.

1987-01-01

A mild variant of Zellweger (cerebro-hepato-renal) syndrome was diagnosed in male and female siblings aged 7 and 2 years. They had mild facial dysmorphia, moderate psychomotor retardation, tapetoretinal degeneration, sensorineural deafness and hepatomegaly. Ultrastructural examination of a liver

IL-6 Production by TLR-Activated APC Broadly Enhances Aged Cognate CD4 Helper and B Cell Antibody Responses In Vivo.

Science.gov (United States)

Brahmakshatriya, Vinayak; Kuang, Yi; Devarajan, Priyadharshini; Xia, Jingya; Zhang, Wenliang; Vong, Allen Minh; Swain, Susan L

2017-04-01

Naive CD4 T cell responses, especially their ability to help B cell responses, become compromised with aging. We find that using APC pretreated ex vivo with TLR agonists, polyinosinic-polycytidylic acid and CpG, to prime naive CD4 T cells in vivo, restores their ability to expand and become germinal center T follicular helpers and enhances B cell IgG Ab production. Enhanced helper responses are dependent on IL-6 production by the activated APC. Aged naive CD4 T cells respond suboptimally to IL-6 compared with young cells, such that higher doses are required to induce comparable signaling. Preactivating APC overcomes this deficiency. Responses of young CD4 T cells are also enhanced by preactivating APC with similar effects but with only partial IL-6 dependency. Strikingly, introducing just the activated APC into aged mice significantly enhances otherwise compromised Ab production to inactivated influenza vaccine. These findings reveal a central role for the production of IL-6 by APC during initial cognate interactions in the generation of effective CD4 T cell help, which becomes greater with age. Without APC activation, aging CD4 T cell responses shift toward IL-6-independent Th1 and CD4 cytotoxic Th cell responses. Thus, strategies that specifically activate and provide Ag to APC could potentially enhance Ab-mediated protection in vaccine responses. Copyright © 2017 by The American Association of Immunologists, Inc.

Mild hybrids with CVT: comparison of electrical and mechanical torque assist

NARCIS (Netherlands)

Druten, van R.M.; Serrarens, A.F.A.; Vroemen, B.G.; Tillaart, van den E.L.; de Haas, J.

2001-01-01

This paper evaluates two mild hybrid drive trains for a mid-class passenger car with a gasoline engine by means of comptuer simulation. The term mild hybrid is used for vehicles with sustained electric propulsion. The mild hybrid drive trains both have a Continuously Variable Transmission (CVT) with

Artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP): preparation and immunological analysis of vaccine efficacy.

Science.gov (United States)

Masuko, Kazutaka; Wakita, Daiko; Togashi, Yuji; Kita, Toshiyuki; Kitamura, Hidemitsu; Nishimura, Takashi

2015-01-01

To elucidate the immunologic mechanisms of artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP), which indicated a great vaccine efficacy in human cancers, we prepared ovalbumin (OVA)-H/K-HELP by conjugating killer and helper epitopes of OVA-model tumor antigen via a glycine-linker. Vaccination of C57BL/6 mice with OVA-H/K-HELP (30 amino acids) but not with short peptides mixture of class I-binding peptide (8 amino-acids) and class II-binding peptide (17 amino-acids) combined with adjuvant CpG-ODN (cytosine-phosphorothioate-guanine oligodeoxynucleotides), induced higher numbers of OVA-tetramer-positive CTL with concomitant activation of IFN-γ-producing CD4(+) Th1 cells. However, replacement of glycine-linker of OVA-H/K-HELP with other peptide-linker caused a significant decrease of vaccine efficacy of OVA-H/K-HELP. In combination with adjuvant CpG-ODN, OVA-H/KHELP exhibited greater vaccine efficacy compared with short peptides vaccine, in both preventive and therapeutic vaccine models against OVA-expressing EG-7 tumor. The elevated vaccine efficacy of OVAH/K-HELP might be derived from the following mechanisms: (i) selective presentation by only professional dendritic cells (DC) in vaccinated draining lymph node (dLN); (ii) a long-term sustained antigen presentation exerted by DC to stimulate both CTL and Th1 cells; (iii) formation of three cells interaction among DC, Th and CTL. In comparative study, H/K-HELP indicated stronger therapeutic vaccine efficacy compared with that of extended class I synthetic long peptide, indicating that both the length of peptide and the presence of Th epitope peptide were crucial aspects for preparing artificially synthesized H/K-HELP vaccine. Copyright © 2014 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Institutional traditions in teachers' manners of teaching

Science.gov (United States)

Lundqvist, Eva; Almqvist, Jonas; Östman, Leif

2012-03-01

The aim of this article is to make a close case study of one teacher's teaching in relation to established traditions within science education in Sweden. The teacher's manner of teaching is analysed with the help of an epistemological move analysis. The moves made by the teacher are then compared in a context of educational philosophy and selective tradition. In the analyses the focus is to study the process of teaching and learning in action in institutionalised and socially shared practices. The empirical material consists of video recordings of four lessons with the same group of students and the same teacher. The students are all in Year 7 in a Swedish 9-year compulsory school. During these lessons the students work with a subject area called "Properties of materials". The results show that the teacher makes a number of different moves with regard to how to proceed and come to a conclusion about what the substances are. Many of these moves are special in that they indicate that the students need to be able to handle the procedural level of school science. These moves do not deal directly with the knowledge production process, but with methodological aspects. The function of the moves turns the students' attention from one source of knowledge to another. The moves are aimed at helping the students to help themselves, since it is through their own activity and their own thinking that learning takes place. This is characteristic in the teacher's manner of teaching. When compared in a context of educational philosophy, this manner of teaching has similarities with progressentialism; a mixture of essentialism and progressivism. This educational philosophy is a central aspect of what is called the academic tradition—a selective tradition common in science education in Sweden between 1960 and 1990.

Co-infection of Sweet Orange with Severe and Mild Strains of Citrus tristeza virus Is Overwhelmingly Dominated by the Severe Strain on Both the Transcriptional and Biological Levels

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Shimin Fu

2017-08-01

Full Text Available Citrus tristeza is one of the most destructive citrus diseases and is caused by the phloem-restricted Closterovirus, Citrus tristeza virus. Mild strain CTV-B2 does not cause obvious symptoms on indicators whereas severe strain CTV-B6 causes symptoms, including stem pitting, cupping, yellowing, and stiffening of leaves, and vein corking. Our laboratory has previously characterized changes in transcription in sweet orange separately infected with CTV-B2 and CTV-B6. In the present study, transcriptome analysis of Citrus sinensis in response to double infection by CTV-B2 and CTV-B6 was carried out. Four hundred and eleven transcripts were up-regulated and 356 transcripts were down-regulated prior to the onset of symptoms. Repressed genes were overwhelmingly associated with photosynthesis, and carbon and nucleic acid metabolism. Expression of genes related to the glycolytic, oxidative pentose phosphate (OPP, tricarboxylic acid cycle (TCA pathways, tetrapyrrole synthesis, redox homeostasis, nucleotide metabolism, protein synthesis and post translational protein modification and folding, and cell organization were all reduced. Ribosomal composition was also greatly altered in response to infection by CTV-B2/CTV-B6. Genes that were induced were related to cell wall structure, secondary and hormone metabolism, responses to biotic stress, regulation of transcription, signaling, and secondary metabolism. Transport systems dedicated to metal ions were especially disturbed and ZIPs (Zinc Transporter Precursors showed different expression patterns in response to co-infection by CTV-B2/CTV-B6 and single infection by CTV-B2. Host plants experienced root decline that may have contributed to Zn, Fe, and other nutrient deficiencies. Though defense responses, such as, strengthening of the cell wall, alteration of hormone metabolism, secondary metabolites, and signaling pathways, were activated, these defense responses did not suppress the spread of the pathogens

Deoxyribonucleic acid methylation and gene expression of PPARGC1A in human muscle is influenced by high-fat overfeeding in a birth-weight-dependent manner

DEFF Research Database (Denmark)

Brøns, Charlotte; Jacobsen, Stine; Nilsson, Emma

2010-01-01

Context: Low birth weight (LBW) and unhealthy diets are risk factors of metabolic disease including type 2 diabetes (T2D). Genetic, nongenetic, and epigenetic data propose a role of the key metabolic regulator peroxisome proliferator-activated receptor gamma, coactivator 1alpha (PPARGC1A......) in the development of T2D. Objective: Our objective was to investigate gene expression and DNA methylation of PPARGC1A and coregulated oxidative phosphorylation (OXPHOS) genes in LBW and normal birth weight (NBW) subjects during control and high-fat diets. Design, Subjects, and Main Outcome Measures: Twenty young...... healthy men with LBW and 26 matched NBW controls were studied after 5 d high-fat overfeeding (+50% calories) and after a control diet in a randomized manner. Hyperinsulinemic-euglycemic clamps were performed and skeletal muscle biopsies excised. DNA methylation and gene expression were measured using...

Superovulation Induced Changes of Lipid Metabolism in Ovaries and Embryos and Its Probable Mechanism.

Directory of Open Access Journals (Sweden)

Li-Ya Wang

Full Text Available This research was intended to investigate the fetal origins of changed birth weight of the offspring born through assisted reproductive technology (ART. The association between hormone and lipid metabolism or body weight has been generally accepted, and as the basic and specific treatment in ART procedure, gonadotropin stimulation might have potential effects on intrauterine lipid metabolism. In our studies, the mice were superovulated with two doses of gonadotropin. The cholesterol metabolism in ovaries and the triglyceride metabolism in embryos were analyzed. The results showed gonadotropin probably accelerated luteinization and induced a longer time follicle development and ovulation, which resulted in histological and morphological alteration of ovary, and increased the cholesterol content and the expressions of steroidogenesis-related genes. In embryos, gonadotropin increased lipid accumulation and decreased fatty acid synthesis in a dose-dependent manner. Moreover, the changes of fatty acid composition were also shown in superovulation groups. Our studies firstly provided the evidence that the superovulation might affect the maternal and fetal lipid metabolism. These variations of lipid metabolism in our results may be associated with birth weight of ART infants.

Pheromone-sensing neurons regulate peripheral lipid metabolism in Caenorhabditis elegans.

Science.gov (United States)

Hussey, Rosalind; Stieglitz, Jon; Mesgarzadeh, Jaleh; Locke, Tiffany T; Zhang, Ying K; Schroeder, Frank C; Srinivasan, Supriya

2017-05-01

It is now established that the central nervous system plays an important role in regulating whole body metabolism and energy balance. However, the extent to which sensory systems relay environmental information to modulate metabolic events in peripheral tissues has remained poorly understood. In addition, it has been challenging to map the molecular mechanisms underlying discrete sensory modalities with respect to their role in lipid metabolism. In previous work our lab has identified instructive roles for serotonin signaling as a surrogate for food availability, as well as oxygen sensing, in the control of whole body metabolism. In this study, we now identify a role for a pair of pheromone-sensing neurons in regulating fat metabolism in C. elegans, which has emerged as a tractable and highly informative model to study the neurobiology of metabolism. A genetic screen revealed that GPA-3, a member of the Gα family of G proteins, regulates body fat content in the intestine, the major metabolic organ for C. elegans. Genetic and reconstitution studies revealed that the potent body fat phenotype of gpa-3 null mutants is controlled from a pair of neurons called ADL(L/R). We show that cAMP functions as the second messenger in the ADL neurons, and regulates body fat stores via the neurotransmitter acetylcholine, from downstream neurons. We find that the pheromone ascr#3, which is detected by the ADL neurons, regulates body fat stores in a GPA-3-dependent manner. We define here a third sensory modality, pheromone sensing, as a major regulator of body fat metabolism. The pheromone ascr#3 is an indicator of population density, thus we hypothesize that pheromone sensing provides a salient 'denominator' to evaluate the amount of food available within a population and to accordingly adjust metabolic rate and body fat levels.

Altered AKT1 and MAPK1 Gene Expression on Peripheral Blood Mononuclear Cells and Correlation with T-Helper-Transcription Factors in Systemic Lupus Erythematosus Patients

Directory of Open Access Journals (Sweden)

Sonia Garcia-Rodriguez

2012-01-01

Full Text Available Kinases have been implicated in the immunopathological mechanisms of Systemic Lupus Erythematosus (SLE. v-akt murine-thymoma viral-oncogene-homolog 1 (AKT1 and mitogen-activated-protein-kinase 1 (MAPK1 gene expressions in peripheral mononuclear cells from thirteen SLE patients with inactive or mild disease were evaluated using quantitative real-time reverse-transcription polymerase-chain-reaction and analyzed whether there was any correlation with T-helper (Th transcription factors (TF gene expression, cytokines, and S100A8/S100A9-(Calprotectin. Age- and gender-matched thirteen healthy controls were examined. AKT1 and MAPK1 expressions were upregulated in SLE patients and correlated with Th17-(Retinoic acid-related orphan receptor (ROR-C, T-regulatory-(Treg-(Transforming Growth Factor Beta (TGFB-2, and Th2-(interleukin (IL-5-related genes. MAPK1 expression correlated with Th1-(IL-12A, T-box TF-(T-bet, Th2-(GATA binding protein-(GATA-3, and IL-10 expressions. IL-10 expression was increased and correlated with plasma Tumor Necrosis Factor (TNF-α and Th0-(IL-2, Th1-(IL-12A, T-bet, GATA3, Treg-(Forkhead/winged-helix transcription factor- (FOXP-3, and IL-6 expressions. FOXP3 expression, FOXP3/RORC, and FOXP3/GATA3 expression ratios were increased. Plasma IL-1β, IL-12(p70, Interferon-(IFN-γ, and IL-6 cytokines were augmented. Plasma IL-1β, IL-6, IL-2, IFN-γ, TNF-α, IL-10, and IL-13 correlated with C-reactive protein, respectively. Increased Calprotectin correlated with neutrophils. Conclusion, SLE patients presented a systemic immunoinflammatory activity, augmented AKT1 and MAPK1 expressions, proinflammatory cytokines, and Calprotectin, together with increased expression of Treg-related genes, suggesting a regulatory feedback opposing the inflammatory activity.

The Copper Metabolism MURR1 Domain protein 1 (COMMD1) modulates the aggregation of misfolded protein species in a client-specific manner

NARCIS (Netherlands)

W.I.M. Vonk (Willianne I.); V. Kakkar (Vaishali); P. Bartuzi (Paulina); D. Jaarsma (Dick); R. Berger (Ruud); M.A. Hofker (Marten); L.W.J. Klomp (Leo W.); C. Wijmenga (Cisca); H. Kampinga (Harm); B. van de Sluis (Bart)

2014-01-01

textabstractThe Copper Metabolism MURR1 domain protein 1 (COMMD1) is a protein involved in multiple cellular pathways, including copper homeostasis, NF-κB and hypoxia signalling. Acting as a scaffold protein, COMMD1 mediates the levels, stability and proteolysis of its substrates (e.g. the

The use of transgenic animals to study lipoprotein metabolism

Energy Technology Data Exchange (ETDEWEB)

Rubin, E.M.; Plump, A.S.

1993-12-01

The application of transgenic technology to lipoprotein metabolism and atherosclerosis was first reported in 1988. Today, a large percentage of the genes involved in lipoprotein metabolism have been overexpressed in mice, and a substantial number of these same genes have been disrupted by homologous recombination in embryonic stem (ES) cells. The utility of animal models of lipoprotein metabolism and atherosclerosis is far-reaching given the complex nature of these systems. There are at least 17 known genes directly involved in lipoprotein metabolism and likely dozens more may be involved. This massive network of interacting factors has necessitated the development of in vivo systems which can be subject to genetic manipulation. The power of overexpression is obvious: elucidating function in a relatively controlled genetic environment in which the whole system is present and operational. The not-so-obvious problem with transgenics is ``background,`` or for purposes of the current discussion, the mouse`s own lipoprotein system. With the advent of gene knockout, we have been given the ability to overcome ``background.`` By recreating the genetic complement of the mouse we can alter a system in essentially any manner desired. As unique tools, and in combination with one another, the overexpression of foreign genes and the targeted disruption or alteration of endogenous genes has already and will continue to offer a wealth of information on the biology of lipoprotein metabolism and its effect on atherosclerosis susceptibility.

The measurement of the nigrostriatal dopaminergic function and glucose metabolism in patients with movement disorders

Energy Technology Data Exchange (ETDEWEB)

Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Shima, Fumio; Kato, Motohiro (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine)

1992-12-01

The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with [sup 18]F-Dopa and [sup 18]F-FDG respectively. The [sup 18]F-Dopa uptake in the striatum (the caudate head and the putamen) decreased in patients with Parkinson's disease but was relatively unaffected in the caudate. The cerebral glucose metabolism was normal in patients with Parkinson's disease. The [sup 18]F-Dopa uptake in the striatum also decreased in cases of atypical parkinsonism and in cases of progressive supranuclear palsy, but there was no difference in the uptake between the caudate and the putamen. The glucose metabolism decreased in the cerebral hemisphere including the striatum; this finding was also different from those of Parkinson's disease. A normal [sup 18]F-Dopa uptake in the striatum with a markedly decreased striatal glucose metabolism and a mildly decreased cortical glucose metabolism was observed in cases of Huntington's disease and Wilson's disease. The [sup 18]F-Dopa uptake in the striatum increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of [sup 18]F-Dopa uptake and glucose metabolism were thus observed in the various movement disorders. These results suggest that the measurements of the [sup 18]F-Dopa uptake and the cerebral glucose metabolism would be useful for the evaluation of the striatal function in various movement disorders. (author).

The measurement of the nigrostriatal dopaminergic function and glucose metabolism in patients with movement disorders

Energy Technology Data Exchange (ETDEWEB)

Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Shima, Fumio; Kato, Motohiro [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1992-12-01

The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with [sup 18]F-Dopa and [sup 18]F-FDG respectively. The [sup 18]F-Dopa uptake in the striatum (the caudate head and the putamen) decreased in patients with Parkinson's disease but was relatively unaffected in the caudate. The cerebral glucose metabolism was normal in patients with Parkinson's disease. The [sup 18]F-Dopa uptake in the striatum also decreased in cases of atypical parkinsonism and in cases of progressive supranuclear palsy, but there was no difference in the uptake between the caudate and the putamen. The glucose metabolism decreased in the cerebral hemisphere including the striatum; this finding was also different from those of Parkinson's disease. A normal [sup 18]F-Dopa uptake in the striatum with a markedly decreased striatal glucose metabolism and a mildly decreased cortical glucose metabolism was observed in cases of Huntington's disease and Wilson's disease. The [sup 18]F-Dopa uptake in the striatum increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of [sup 18]F-Dopa uptake and glucose metabolism were thus observed in the various movement disorders. These results suggest that the measurements of the [sup 18]F-Dopa uptake and the cerebral glucose metabolism would be useful for the evaluation of the striatal function in various movement disorders. (author).

The role of water metabolism in the heat stress syndrome with the use of radioisotopes in cattle

International Nuclear Information System (INIS)

Abdel-Samiee, A.M.

1982-01-01

Due to the importance of water metabolism in thermo - regulation especially under heat stress, this investigation was carried out to study the effect of high ambient temperature, separated from other climatic factors which were maintained constant, on live body weight, water metabolism components, total body water, total body solids, water turnover rate, biological half life - time of tritiated water and rectal temperature and cardiorespiratory rate. Twelve dry friesian cows of 3 - years old were placed in metabolic cages inside climatic chambers. Animals were subjected to two successive treatments. First, mild treatment, where the environmental temperature and relative humidity were kept constant at 16 C and 62%, respective for 7 - hours a day. The second treatment (heat stress treatment), where the environmental temperature and relative humidity were 39 C and 62% R.H.,respectively for 7 hours a day

Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury.

Science.gov (United States)

Weil, Zachary M; Gaier, Kristopher R; Karelina, Kate

2014-10-01

Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period. Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability. Here, we injured mice either once or twice separated by three or 20days. Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task. A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point. In contrast, when the second injury occurred substantially later (20days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury. The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy. These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial

Pattern of airway inflammation and remodelling in mild persistent atopic asthma and in mild persistent asthma related to gastroesophageal reflux.

Science.gov (United States)

Dal Negro, R W; Guerriero, M; Micheletto, C

2012-12-01

The increase of basement membrane thickness (BMAT) represents a structural feature described as commonly characterizing airway remodelling in asthma, even if the non-atopic condition had been investigated only episodically from this point of view. Gastrooesophageal-reflux is a pathological condition which can frequently cause and/or sustain asthma in non-atopic individuals. The aim of the study was to measure BMT; some inflammatory mediators in BAL; cys-leucotrienes (LTE4) in urine; e-NO, and BHR to Methacholine (MCh) in mild atopic and in mild non-atopic, GER-related asthma. After their informed consent, 25 mild atopic (40.9 years +/- 13.1 sd, FEV1 = 95.9% pred. +/- 12.9 sd) and 39 non-atopic, GER-related asthmatics (57.3 years +/- 14.2 ds, FEVY1 = 101.3% pred. +/- 12.2 sd), nonsmoker and of a comparable asthma duration, underwent measurements of basal lung function and bronchial response to MCh (PD20 FEV1); endobronchial biopsies and BAL (in the right middle lobe), and a 24-h gastroesophageal pHmetry. Atopic GER-related asthma showed two distinct patterns of airway inflammation. The eosinophilic contribution to airway inflammation was systematically prevailing in the former group, such as: EOS = 10.7% +/- 13.4 sd vs 2.0% +/- 2.8 sd, p = 0.001; ECP = 344.9 mcg/l +/- 635.9 sd vs 59.2 mcg/l +/- 75.1 sd, p = 0.001. Data from the present study are suggesting that persistent mild atopic and mild GER-related asthma seem to represent two distinct phenotypes of asthma in terms of airway remodelling, and in particular of BMT involvement.

Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet

NARCIS (Netherlands)

Shi, W.; Hegeman, M.A.; Dartel, van D.A.M.; Tang, J.; Suarez, M.; Swarts, H.; Hee, van der B.; Arola, L.; Keijer, J.

2017-01-01

Scope: Metabolic flexibility is the ability to switch metabolism between carbohydrate oxidation (CHO) and fatty acid oxidation (FAO) and is a biomarker for metabolic health. The effect on metabolic health of nicotinamide riboside (NR) as an exclusive source of vitamin B3 is unknown and is examined

Mild Aphasia: Is This the Place for an Argument?

Science.gov (United States)

Armstrong, Elizabeth; Fox, Sarah; Wilkinson, Ray

2013-01-01

Purpose: Individuals with mild aphasia often report significant disruption to their communication despite seemingly minor impairment. This study explored this phenomenon through examining conversations of a person with mild aphasia engaging in argumentation--a skill she felt had significantly deteriorated after her stroke. Method: A person with…

Dim Light at Night Disrupts Molecular Circadian Rhythms and Affects Metabolism

Science.gov (United States)

Fonken, Laura K.; Aubrecht, Taryn G.; Meléndez-Fernández, O. Hecmarie; Weil, Zachary M.; Nelson, Randy J.

2014-01-01

With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms which are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electrical lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to nighttime light and investigated changes in the circadian system and body weight. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night attenuate core circadian clock rhythms in the SCN at both the gene and protein level. Moreover, circadian clock rhythms were perturbed in the liver by nighttime light exposure. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide mechanistic evidence for how mild changes in environmental lighting can alter circadian and metabolic function. PMID:23929553

Effect of silver ion, carbon dioxide, and oxygen on ethylene action and metabolism

International Nuclear Information System (INIS)

Beyer, E.M. Jr.

1979-01-01

The relationship between ethylene action and metabolism was investigated in the etiolated pea seedling (Pisum sativum L. cv. Alaska) by inhibiting ethylene action with Ag + , high CO 2 , and low O 2 and then determining if ethylene metabolism was inhibited in a similar manner. Ag + (100 milligrams per liter) was clearly the most potent antiethylene treatment. Ag + pretreatment inhibited the growth retarding action of 0.2 microliters per liter ethylene by 48% and also inhibited the incorporation of 14 C 2 H 4 into pea tips by the same amount. As the ethylene concentration was increased from 0.2 to 30 microliters per liter, the effectiveness of Ag + in reducing ethylene action and metabolism declined in a similar fashion. Although Ag + significantly inhibited the incorporation of 14 C 2 H 4 into tissue metabolites, the oxidation of 14 C 2 H 4 to 14 CO 2 was unaffected. CO 2 (7%) inhibited ethylene-induced growth retardation but its effectiveness diminished at a greater rate than that of Ag + with increasing ethylene concentration. High CO 2 had just the opposite effect of Ag + since it inhibited 14 C 2 H 4 oxidation to 14 CO 2 without affecting tissue incorporation. In contrast to Ag + , CO 2 did not inhibit ethylene action and metabolism to exactly the same extent, and the inhibition of metabolism did not rapidly decline with increasing 14 C 2 H 4 concentration. However, high CO 2 did alter the ratio of 14 C 2 H 4 tissue incorporation to 14 CO 2 production in a manner consistent with changes in ethylene effectiveness. Lowering the O 2 concentration to 5% reduced ethylene-induced growth retardation and inhibited 14 C 2 H 4 tissue incorporation and oxidation to 14 CO 2 by 26 and 45%, respectively. Low O 2 reduced pea seedling growth under these conditions thereby severely limiting its usefulness as a specific antiethylene treatment

Effects of sustained sleep restriction on mitogen-stimulated cytokines, chemokines and T helper 1/ T helper 2 balance in humans.

Directory of Open Access Journals (Sweden)

John Axelsson

Full Text Available BACKGROUND: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. METHODS: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00-07.00 h followed by 5 days with restricted sleep (03.00-07.00 h. On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-α, interleukin (IL -1β, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1 after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA. Also leukocyte numbers, mononuclear cells and cortisol were analysed. RESULTS: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05. A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-α and MCP-1 in the late evening and early night hours (p's<.05. In addition, all variables varied across the 24 h day. CONCLUSIONS: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.

Evolution of diagnostic criteria and assessments for Parkinson's disease mild cognitive impairment.

Science.gov (United States)

Goldman, Jennifer G; Holden, Samantha K; Litvan, Irene; McKeith, Ian; Stebbins, Glenn T; Taylor, John-Paul

2018-04-01

Mild cognitive impairment has gained recognition as a construct and a potential prodromal stage to dementia in both Alzheimer's disease and Parkinson's disease (PD). Although mild cognitive impairment has been recognized in the Alzheimer's disease field, it is a relatively more recent topic of interest in PD. Recent advances include the development of diagnostic criteria for PD mild cognitive impairment to provide more uniform definitions for clinical and research use. Studies reveal that mild cognitive impairment in PD is frequent, but also heterogeneous, with variable clinical presentations, differences in its progression to dementia, and likely differences in underlying pathophysiology. Application of the International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment Task Force diagnostic criteria has provided insights regarding cognitive measures, functional assessments, and other key topics that may require additional refinement. Furthermore, it is important to consider definitions of PD mild cognitive impairment in the landscape of other related Lewy body disorders, such as dementia with Lewy bodies, and in the context of prodromal and early-stage PD. This article examines the evolution of mild cognitive impairment in concept and definition, particularly in PD, but also in related disorders such as Alzheimer's disease and dementia with Lewy bodies; the development and application of International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment diagnostic criteria; and insights and future directions for the field of PD mild cognitive impairment. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Perioperative corticosteroids for intermittent and mild persistent asthma

OpenAIRE

Hiroto Matsuse; Terufumi Shimoda; Ikuko Machida; Yuki Kondo; Tetsuya Kawano; Sachiko Saeki; Shinya Tomari; Kazuko Mitsuta; Chizu Fukushima; Yasushi Obase; Shigeru Kohno

2002-01-01

Objectives: Asthmatics are considered to be at high risk for pulmonary complications during general anesthesia with tracheal intubation. The purpose of the present study was to determine the usefulness of perioperative corticosteroids for mild asthmatics in preventing perioperative exacerbation of asthma. Methods: Airway hyperresponsiveness to inhaled methacholine was determined in patients with intermittent (n = 27) and mild persistent (n = 48) asthma before general anesthesia who underwe...

T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production.

Science.gov (United States)

Zhu, Jinfang

2015-09-01

Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these "type 2 immune response-related" cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses. In this review, I will focus on the signaling pathways and key molecules that determine the differentiation of naïve CD4 T cells into Th2 cells, and how the expression of Th2 cytokines, especially IL-4 and IL-13, is regulated in Th2 cells. The similarities and differences in the differentiation of Th2 cells, IL-4-producing T follicular helper (Tfh) cells and ILC2s as well as their relationships will also be discussed. Published by Elsevier Ltd.

CD21+ (B2 antigen+) cell decrement and CD4+CD29+ (helper-inducer) cell increment suggest an activation of cell immune reactivity in multiple sclerosis.

Science.gov (United States)

Gambi, D; Porrini, A M; Giampietro, A; Macor, S

1991-08-01

Two-color flow cytometric analysis on peripheral blood lymphocytes of 35 untreated multiple sclerosis (MS) patients, 17 other medical disease (OMD) patients and 14 healthy control (HC) subjects was performed to evaluate the levels of different T and B cell subpopulations. In MS patients we observed an increase in CD4+CD29+ helper-inducer cells but this increase was not related to the different phases of the disease. We hypothesize that this change is related to the reduction of CD21+ cells expressing B2 antigen, a 140 kDa molecule disappearing after B cell activation. An increased level of CD4+CD45RA- (helper-inducer-like cells) and a reduction of CD4+CD29- (suppressor-inducer-like cells) were also present in our patients. These findings demonstrate an immune 'disequilibrium' in MS, which is linked with an increased level of CD25+ cells expressing the interleukin-2 (IL-2) receptor. IL-2, besides being a T cell growth factor, is also a B cell growth factor. These data let us hypothesize that an activation of the immune response is present in MS.

T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production

Science.gov (United States)

Zhu, Jinfang

2015-01-01

Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these “type 2 immune response-related” cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses. In this review, I will focus on the signaling pathways and key molecules that determine the differentiation of naïve CD4 T cells into Th2 cells, and how the expression of Th2 cytokines, especially IL-4 and IL-13, is regulated in Th2 cells. The similarities and differences in the differentiation of Th2 cells, IL-4-producing T follicular helper (Tfh) cells and ILC2s as well as their relationships will also be discussed. PMID:26044597

Lymphocyte Glucose and Glutamine Metabolism as Targets of the Anti-Inflammatory and Immunomodulatory Effects of Exercise

Directory of Open Access Journals (Sweden)

Frederick Wasinski

2014-01-01

Full Text Available Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight association between metabolism and function in these cells was suggested to introduce the possibility of several pathologies resulting from the inability of lymphocytes to meet their nutrient demands under a given condition. In fact, disruptions in lymphocyte metabolism and function have been observed in different inflammatory, metabolic, and autoimmune pathologies. Regular physical exercise and physical activity offer protection against several chronic pathologies, and this benefit has been associated with the anti-inflammatory and immunomodulatory effects of exercise/physical activity. Chronic exercise induces changes in lymphocyte functionality and substrate metabolism. In the present review, we discuss whether the beneficial effects of exercise on lymphocyte function in health and disease are associated with modulation of the glucose and glutamine metabolic pathways.

Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis.

Science.gov (United States)

Martel, Britta C; Litman, Thomas; Hald, Andreas; Norsgaard, Hanne; Lovato, Paola; Dyring-Andersen, Beatrice; Skov, Lone; Thestrup-Pedersen, Kristian; Skov, Søren; Skak, Kresten; Poulsen, Lars K

2016-06-01

Atopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. In this study, we used microarray analysis to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared to skin from healthy controls and from lesional psoriasis skin. The primary aim was to identify differentially expressed genes involved in skin barrier formation and inflammation, and to compare our results with those reported for patients with moderate and severe AD. In contrast to severe AD, expression of the majority of genes associated with skin barrier formation was unchanged or upregulated in patients with mild AD compared to normal healthy skin. Among these, no significant differences in the expression of filaggrin (FLG) and loricrin at both mRNA and protein level were found in lesional skin from patients with mild AD, despite the presence of heterozygous FLG mutations in the majority of patients with mild extrinsic AD. Several inflammation-associated genes such as S100A9, MMP12, CXCL10 and CCL18 were highly expressed in lesional skin from patients with mild psoriasis and were also increased in patients with mild extrinsic and intrinsic AD similar to previous reports for severe AD. Interestingly, expression of genes involved in inflammatory responses in intrinsic AD resembled that of psoriasis more than that of extrinsic AD. Overall, differences in expression of inflammation-associated genes found among patients with mild intrinsic and extrinsic AD correlated with previous findings for patients with severe intrinsic and extrinsic AD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stereotypes: A Preliminary Report on Mannerisms and Blindisms.

Science.gov (United States)

Leonhardt, M.

1990-01-01

The article describes current research on stereotypes in a group of blind children in Barcelona, Spain. Mannerisms and blindisms covering a range of verbal and motor behavior are defined and discussed, as are the variables of behavior related to them. (Author/DB)

Sex-specific metabolic profiles of androgens and its main binding protein SHBG in a middle aged population without diabetes

DEFF Research Database (Denmark)

Piontek, Uwe; Wallaschofski, Henri; Kastenmüller, Gabi

2017-01-01

The role of androgens in metabolism with respect to sex-specific disease associations is poorly understood. Therefore, we aimed to provide molecular signatures in plasma and urine of androgen action in a sex-specific manner using state-of-the-art metabolomics techniques. Our study population...