bluuebunny/crossref_metadata_2025_split huggingface dataset:
The knowledge and attitudes of psychiatrists towards antipsychotic long-acting injections in Nigeria
Authors: James Bawo O. , Omoaregba Joyce O. , Okonoda Kingsley M. , Otefe Edebi U. , Patel Maxine X. 
Published: July 2012

Background: Antipsychotic long-acting injections (LAIs) reduce covert nonadherence with medication in the clinical management of psychotic disorders. However, they are variably utilised by clinicians, especially in the long term. Factors including poor knowledge, stigma and perceived coercion can all adversely influence LAI utilisation. Previous research has emanated almost exclusively from developed countries. This study explores the knowledge and attitudes of psychiatrists and trainees in Nigeria towards LAIs. Methods: A cross-sectional study was undertaken among mental health professionals in Nigeria using a pre-existing questionnaire. Results: Participant psychiatrists ( n = 128) expressed positive attitudes towards LAIs. Their knowledge concerning LAIs and its side effects was fair. The participants reported that nearly half (41.7%) of their patients with a psychotic illness were on LAIs. Those who reported a high prescribing rate for LAIs (>40%) were more likely to endorse more positive ‘patient-centred attitudes’ ( p < 0.04). In contrast to previous reports, psychiatrists reported that patients were less likely to feel ashamed when on LAIs, though most endorsed the statement that force was required during LAI administration. Conclusion: The desirability of treatment by injections differs in Africa in comparison to Western cultures, possibly due to the increased potency that injections are perceived to have. This is perhaps evidenced by high rates reported for use of LAIs. Nigerian psychiatrists had positive attitudes to LAIs but their knowledge, particularly regarding side effects, was fair and needs to be improved. Providing information to patients prior to antipsychotic treatment may enhance informed consent in a country where medical paternalism is still relatively strong.
Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells
Authors: Vitali Caterina , Mingozzi Francesca , Broggi Achille , Barresi Simona , Zolezzi Francesca , Bayry Jagadeesh , Raimondi Giorgio , Zanoni Ivan , Granucci Francesca 
Published: July 2012

Abstract
There is evidence that dendritic cells (DCs) induce peripheral tolerance. Nevertheless, it is not known whether immature DCs in general are able to tolerize CD4+ T cells or if this is a prerogative of specialized subtypes. Here we show that, when autoantigen presentation is extended to all conventional mouse DCs, immature lymphoid tissue resident DCs are unable to induce autoantigen-specific regulatory T (iTreg) cell conversion. In contrast, this is an exclusive prerogative of steady-state migratory DCs. Because only lymph nodes host migratory DCs, iTreg cells develop and are retained solely in lymph nodes, and not in the spleen. Mechanistically, in cutaneous lymph nodes, DC-derived CCL22 contributes to the retention of iTreg cells. The importance of the local generation of iTreg cells is emphasized by their essential role in preventing autoimmunity.
Full reconstitution of human platelets in humanized mice after macrophage depletion
Authors: Hu Zheng , Yang Yong-Guang 
Published: July 2012

AbstractCotransplantation of human fetal thymic tissue and CD34+ fetal liver cells in nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) or NOD/SCID/γc−/− mice results in the development of multilineage human hematopoietic cells. In this study, we show that these humanized mice had extremely low levels of human platelets. The presence of human megakaryocytes at a normal concentration in the bone marrow suggests that human megakaryocytic differentiation occurred efficiently in these mice. Rapid increase in human platelets in blood to levels comparable with those of human peripheral blood mononuclear cells (PBMCs) after macrophage depletion indicates that mouse macrophages are responsible for the poor human platelet reconstitution in humanized mice. In support of this possibility, human platelets were rapidly rejected after infusion into untreated mice, but persisted in macrophage-depleted mice. These findings indicate that inhibition or depletion of recipient mouse macrophages may provide a useful means for evaluating human thrombopoiesis and platelet function in vivo using immunodeficient mice.
Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters
Authors: Lemonnier François , Couronné Lucile , Parrens Marie , Jaïs Jean-Philippe , Travert Marion , Lamant Laurence , Tournillac Olivier , Rousset Therese , Fabiani Bettina , Cairns Rob A. , Mak Tak , Bastard Christian , Bernard Olivier A. , de Leval Laurence , Gaulard Philippe 
Published: July 2012

Abstract
Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (TFH) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed TFH markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival.
Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS
Authors: Deeg H. Joachim , Scott Bart L. , Fang Min , Shulman Howard M. , Gyurkocza Boglarka , Myerson David , Pagel John M. , Platzbecker Uwe , Ramakrishnan Aravind , Radich Jerald P. , Sandmaier Brenda M. , Sorror Mohamed , Stirewalt Derek L. , Wilson Wendy A. , Storb Rainer , Appelbaum Frederick R. , Gooley Ted 
Published: July 2012

AbstractClonal cytogenetic abnormalities are a major risk factor for relapse after hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS). We determined the impact of the recently established 5-group cytogenetic classification of MDS on outcome after HCT. Results were compared with the impact of the International Prognostic Scoring System (IPSS) 3 cytogenetic risk groups, and the additional effect of a monosomal karyotype was assessed. The study included data on 1007 patients, 1-75 years old (median 45 years), transplanted from related (n = 547) or unrelated (n = 460) donors. Various conditioning regimens were used, and marrow, peripheral blood, or cord blood served as stem cell source. Both IPSS and 5-group cytogenetic risk classifications were significantly associated with post-HCT relapse and mortality, but the 5-group classification discriminated more clearly among the lowest- and highest-risk patients. A monosomal karyotype tended to further increase the rates of relapse and mortality, even after considering the IPSS or 5-group classifications. In addition, the pathologic disease category correlated with both relapse and mortality. Mortality was also impacted by patient age, donor type, conditioning regimen, platelet count, and etiology of MDS. Although mortality declined significantly in recent years, novel strategies are needed to overcome the barrier of high-risk cytogenetics.
Correlation between NIH composite skin score, patient-reported skin score, and outcome: results from the Chronic GVHD Consortium
Authors: Jacobsohn David A. , Kurland Brenda F. , Pidala Joseph , Inamoto Yoshihiro , Chai Xiaoyu , Palmer Jeanne M. , Arai Sally , Arora Mukta , Jagasia Madan , Cutler Corey , Weisdorf Daniel , Martin Paul J. , Pavletic Steven Z. , Vogelsang Georgia , Lee Stephanie J. , Flowers Mary E. D. 
Published: July 2012

Abstract
There are no validated criteria to measure skin response in chronic GVHD. In a prospectively assembled, multicenter cohort of patients with chronic GVHD (N = 458), we looked for correlation of change in several different scales recommended by the National Institutes of Health (NIH) Consensus with clinician and patient perception of change and overall survival. Of the clinician scales, the NIH composite 0-3 skin score was the only one that correlated with both clinician and patient perception of improvement or worsening. Of the patient-reported scales, the skin subscale of the Lee Symptom Scale was the only one that correlated with both clinician and patient perception of improvement or worsening. At study entry, NIH skin score 3 and Lee skin symptom score > 15 were both associated with worse overall survival. Worsening of NIH skin score at 6 months was associated with worse overall survival. Improvement in the Lee skin symptom score at 6 months was associated with improved overall survival. Our findings support the use of the NIH composite 0-3 skin score and the Lee skin symptom score as simple and sensitive measures to evaluate skin involvement in clinical trials as well as in the clinical monitoring of patients with cutaneous chronic GVHD.
The race for the prize: T-cell trafficking strategies for optimal surveillance
Authors: Lee Minyi , Mandl Judith N. , Germain Ronald N. , Yates Andrew J. 
Published: July 2012

Abstract
The initiation of T-cell responses requires rare precursors to locate a draining lymph node (dLN) and encounter dendritic cells (DCs) presenting peptide-major histocompatibility complexes (pMHCs). To locate this needle in the haystack rapidly, T cells face an optimization problem—what is the most efficient trafficking strategy for surveillance and recirculation through blood? Two extremes are scanning low numbers of DCs per node with frequent recirculation, or meticulous surveillance with infrequent recirculation. Naive T cells also require stimulation by self-pMHCs. To enable efficient location of both foreign and self, has evolution settled on an optimum time for T cells to spend surveying each lymph node? Using a data-driven mathematical model, we show the most efficient strategy for detecting antigen in a dLN depends on its abundance. Detection of low-density antigen is optimized with systemically slow transit. In contrast, at high densities or if dLN egress is restricted, rapid transit through other nodes is optimal. We argue that blood-lymph recirculation dynamics facilitate a trade-off, and are consistent with dominant roles for the very early detection of rare foreign antigens in a dLN, and the efficient accumulation of signals from systemically distributed self-antigens.
Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset
Authors: Harly Christelle , Guillaume Yves , Nedellec Steven , Peigné Cassie-Marie , Mönkkönen Hannu , Mönkkönen Jukka , Li Jianqiang , Kuball Jürgen , Adams Erin J. , Netzer Sonia , Déchanet-Merville Julie , Léger Alexandra , Herrmann Thomas , Breathnach Richard , Olive Daniel , Bonneville Marc , Scotet Emmanuel 
Published: July 2012

AbstractHuman peripheral Vγ9Vδ2 T cells are activated by phosphorylated metabolites (phosphoagonists [PAg]) of the mammalian mevalonate or the microbial desoxyxylulose-phosphate pathways accumulated by infected or metabolically distressed cells. The underlying mechanisms are unknown. We show that treatment of nonsusceptible target cells with antibody 20.1 against CD277, a member of the extended B7 superfamily related to butyrophilin, mimics PAg-induced Vγ9Vδ2 T-cell activation and that the Vγ9Vδ2 T-cell receptor is implicated in this effect. Vγ9Vδ2 T-cell activation can be abrogated by exposing susceptible cells (tumor and mycobacteria-infected cells, or aminobisphosphonate-treated cells with up-regulated PAg levels) to antibody 103.2 against CD277. CD277 knockdown and domain-shuffling approaches confirm the key implication of the CD277 isoform BTN3A1 in PAg sensing by Vγ9Vδ2 T cells. Fluorescence recovery after photobleaching (FRAP) experiments support a causal link between intracellular PAg accumulation, decreased BTN3A1 membrane mobility, and ensuing Vγ9Vδ2 T-cell activation. This study demonstrates a novel role played by B7-like molecules in human γδ T-cell antigenic activation and paves the way for new strategies to improve the efficiency of immunotherapies using Vγ9Vδ2 T cells.
Direct Cooperation Between Androgen Receptor and E2F1 Reveals a Common Regulation Mechanism for Androgen-Responsive Genes in Prostate Cells
Authors: Altintas D. M. , Shukla M. S. , Goutte-Gattat D. , Angelov D. , Rouault J. P. , Dimitrov S. , Samarut Jacques 
Published: July 2012

Abstract
We have studied the regulation of ATAD2 gene expression by androgens in prostate cells. ATAD2 is a coactivator of the androgen receptor (AR) and the MYC protein. We showed that ATAD2 expression is directly regulated by AR via an AR binding sequence (ARBS) located in the distal enhancer of its regulatory region. The gene is also regulated by the E2F1 transcription factor. Using knockdown and chromatin immunoprecipitation technique approaches, we could demonstrate that AR and E2F1 functionally collaborate and physically interact between each other. From the analysis of chromatin conformation, we conclude that this cooperation results from a chromatin looping over the ATAD2 promoter region between the ARBS and E2F1 binding site in an androgen-dependent manner. Furthermore, we could show that several genes overexpressed in prostate cancer and potentially involved in several aspects of tumor development have an ARBS and an E2F1 binding site in their regulatory regions and exhibit the same mechanism of regulation by both transcription factors as ATAD2.
Association with Nitric Oxide Synthase on Insulin Secretory Granules Regulates Glucokinase Protein Levels
Authors: Markwardt Michele L. , Nkobena Andongfac , Ding Shi-Ying , Rizzo Mark A. 
Published: July 2012

Abstract
Glucokinase (GCK) association with insulin-secretory granules is controlled by interaction with nitric oxide synthase (NOS) and is reversed by GCK S-nitrosylation. Nonetheless, the function of GCK sequestration on secretory granules is unknown. Here we report that the S-nitrosylation blocking V367M mutation prevents GCK accumulation on secretory granules by inhibiting association with NOS. Expression of this mutant is reduced compared with a second S-nitrosylation blocking GCK mutant (C371S) that accumulates to secretory granules and is expressed at levels greater than wild type. Even so, the rate of degradation for wild type and mutant GCK proteins were not significantly different from one another, and neither mutation disrupted the ability of GCK to be ubiquitinated. Furthermore, gene silencing of NOS reduced endogenous GCK content but did not affect β-actin content. Treatment of GCK(C371S) expressing cells with short interfering RNA specific for NOS also blocked accumulation of this protein to secretory granules and reduced expression levels to that of GCK(V367M). Conversely, cotransfection of catalytically inactive NOS increased GCK-mCherry levels. Expression of GCK(C371S) in βTC3 cells enhanced glucose metabolism compared with untransfected cells and cells expressing wild type GCK, even though this mutant has slightly reduced enzymatic activity in vitro. Finally, molecular dynamics simulations revealed that V367M induces conformational changes in GCK that are similar to S-nitrosylated GCK, thereby suggesting a mechanism for V367M-inhibition of NOS association. Our findings suggest that sequestration of GCK on secretory granules regulates cellular GCK protein content, and thus cellular GCK activity, by acting as a storage pool for GCK proteins.
Aerobic scope and cardiovascular oxygen transport is not compromised at high temperatures in the toadRhinella marina
Authors: Overgaard Johannes , Andersen Jonas L , Findsen Anders , Pedersen Pil B. M. , Hansen Kasper , Ozolina Karlina , Wang Tobias 
Published: July 2012

SummaryNumerous recent studies convincingly correlate the upper thermal tolerance limit of aquatic ectothermic animals to reduced aerobic scope, and ascribe the decline in aerobic scope to failure of the cardiovascular system at high temperatures. In the present study we investigate whether this "aerobic scope model" applies to an air-breathing and semi-terrestrial vertebrate Rhinella marina (formerly Bufo marinus). To quantify aerobic scope, we measured resting and maximal rate of oxygen consumption at temperatures ranging from 10 to 40°C. To include potential effects of acclimation, three groups of toads were acclimated chronically at 20, 25 and 30°C, respectively. The absolute difference between resting and maximal rate of oxygen consumption increased progressively with temperature and there was no significant decrease in aerobic scope, even at temperature immediately below the lethal limit (41-42°C). Hematological and cardio-respiratory variables were measured at rest and immediately after maximal activity at benign (30°C) and critically high (40°C) temperatures. Within this temperature interval, both resting and active heart rate increased, and there was no indication of respiratory failure, judged from high arterial oxygen saturation, PO2 and [HbO2]. With the exception of elevated resting metabolic rate for cold acclimated toads, we found few differences in the thermal responses between acclimation groups with regard to the cardio-metabolic parameters. In conclusion, we found no evidence for temperature induced cardio-respiratory failure in Rhinella marina indicating that maintenance of aerobic scope and oxygen transport is unrelated to the upper thermal limit of this air-breathing semi-terrestrial vertebrate.
Correlates of prolonged swimming performance in F2 hybrids of migratory and non-migratory threespine stickleback ecotypes
Authors: Dalziel Anne C. , Schulte Patricia M. 
Published: July 2012

SummaryDetermining which underlying traits contribute to differences in whole-animal performance can be difficult when many traits differ between individuals with high and low capacities. We have previously found that migratory (anadromous marine) and non-migratory (stream-resident) threespine stickleback (Gasterosteus aculeatus) populations have genetically based differences in prolonged swimming performance (Ucrit) that are associated with divergence of a number of candidate morphological and physiological traits (pectoral fin size and shape, body shape, pectoral muscle and heart size, and pectoral muscle metabolic enzyme activities). Here, we use F2 hybrid crosses to determine which traits are correlated with Ucrit when expressed in a largely randomized genetic background and a range of trait values for other divergent traits. We found that four of our 12 candidate traits were positively correlated with Ucrit in F2 hybrids and that the combined effects of ventricle mass, pectoral adductor mass, and adductor citrate synthase activity accounted for 17.9% of the variation in Ucrit. These data provide additional support for a causal role of muscle and heart size in mediating intra-specific differences in Ucrit, but indicate that many candidate morphological and biochemical traits do not have a strong effect on Ucrit when disassociated other divergent traits. However, the limited variation in Ucrit in our F2 hybrid families may have decreased our ability to detect correlations among these candidate traits and Ucrit. These data suggest that many traits, interactions among traits, and traits not measured in this study, affect prolonged swimming performance in threespine stickleback.
Functional morphology and bite performance of raptorial chelicerae of camel spiders (Solifugae)
Authors: van der Meijden Arie , Langer Franz , Boistel Renaud , Vagovic Patrik , Heethoff Michael 
Published: July 2012

SummarySolifugae are an understudied group of relatively large arachnids with well over 1.000 species distributed on almost all major continents. These highly active predators utilize their large chelicerae for feeding, defense, burrowing and mating. We investigated the differences in cheliceral morphology and performance of two ecologically divergent species from North-Africa; the cursorial Galeodes sp. and the burrowing Rhagodes melanus. Morphological data show differences in aspect ratio between the two species. Bite force measurements show Rhagodes (n=11) to be a much stronger biter than Galeodes (n=8), both in absolute maximum force (Rhagodes 5,63 N, Galeodes 2,12 N) and relative to cheliceral size. Synchrotron-μ-tomographies of one specimen for each species reveal large differences in physiological cross sectional area (PCSA) and estimated muscle stress, resulting in a much higher muscle stress in Rhagodes. The latter species also showed a longer muscle fiber length. Muscle volume and PCSA were found to differ between the two chelicerae in the two scanned specimens. Whereas Rhagodes reflects this morphological asymmetry in having a higher bite force in the right chelicera, Galeodes shows no such bias.
Induced synthesis of P450 Aromatase and 17β-estradiol by D-aspartate in frog brain
Authors: Burrone Lavina , Santillo Alessandra , Pinelli Claudia , Chieffi Baccari Gabriella , Di Fiore Maria Maddalena 
Published: July 2012

SummaryD-aspartic acid is an endogenous amino acid occurring in endocrine glands as well as in nervous system of various animal phyla. Our previous studies have provided evidence that D-Aspartate plays a role in induction of estradiol synthesis in gonads. Recently, we have also demonstrated that D-aspartic acid induces P450 aromatase mRNA expression in the frog (Pelophylax esculentus) testis. P450 aromatase is the key enzyme in the estrogen synthetic pathway, which irreversibly converts testosterone into 17β-estradiol. In this study, we firstly investigated the immunolocalisation of P450 aromatase in the frog brain P. esculentus, never described in amphibians. Therefore, to test the hypothesis that D-Aspartate mediates a local synthesis of P450 aromatase in the frog brain, we administered in vivo D-Aspartate to frog male and then assessed the brain aromatase expression, sex hormone levels as well as their receptor expressions. We found that D-Aspartate enhances brain aromatase expression (mRNA and protein) through CREB pathway. Then, P450 aromatase enzyme induces 17β-estradiol production from testosterone, with consequent increase of its receptor. Therefore, the regulation of D-Aspartate-mediated P450 aromatase expression could be an important step in the control of neuroendocrine regulations of the reproductive axis. On the other hand, we found that the sites of P450 aromatase immunoreactivity in the frog brain correspond to the areas known to be involved in neurosteroid synthesis.