Miracle-dz/UniFAR-FTUs huggingface dataset:
Nur77 Regulates Nondeletional Mechanisms of Tolerance in T Cells

Negative selection against highly self-reactive thymocytes is critical for preventing autoimmunity. Thymocyte deletion, anergy induction, and agonist selection are all forms of negative selection that can occur following a high-affinity TCR signal. Of Bim and Nur77, two TCR-induced proteins with proapoptotic function, Bim has been shown to be important for clonal deletion in several model systems, whereas Nur77 was often dispensable. However, Nur77 has been reported to influence other aspects of T cell development by mechanisms that may not be related to its proapoptotic function. In this study, we examined the role of Nur77 during thymocyte development in the presence and absence of Bim to separate apoptotic from nonapoptotic functions of Nur77. Polyclonal Bim−/− and Bim−/−Nur77−/− mice exhibited comparable accumulation of high-affinity signaled CD4+CD8+ double-positive thymocytes and CD8+ and CD4+ single-positive thymocytes. However, combined Bim and Nur77 deficiency increased the frequency of thymic Foxp3+ T regulatory cells and Foxp3−FR4hiCD73hi anergic phenotype CD4+ T cells compared with Bim−/− mice, suggesting that Nur77 expression impairs the development of nonconventional tolerance-inducing cell fates. Using the OT-I RIP-mOVA model, we found that Nur77 deficiency did not substantially impact clonal deletion nor did it exacerbate the defect in clonal deletion in the absence of Bim. However, additional loss of Nur77 in the absence of Bim led to diabetes induction, suggesting that Nur77 promotes tolerance in this context. Together, these data reveal novel nondeletional roles for Nur77 that differ between T cell subsets and have implications for self-tolerance.
Sexual knowledge, attitudes and activity of older people in Taipei, Taiwan.

AIMS We examined sexual activity and predictive factors among older people in Taipei, Taiwan. We aimed to characterize the older population engaged in sexual activity and determine influencing factors, exploring aspects of sexuality that may influence elders' health and quality of life (QOL). BACKGROUND Studies of sexual attitudes and behaviour have found that sexual difficulties are common among mature adults worldwide, influenced in men and women by physical health, ageing, psychosocial and cultural factors. DESIGN AND METHODS We conducted a community-based retrospective study involving a random sample of 412 men and 204 women over age 65. A questionnaire on demographics and social situations was administered, along with a Sexuality Knowledge and Attitudes Scale; 34 questions evaluated sexual knowledge and 18 evaluated sexual attitudes. RESULTS Two-hundred and twenty participants were sexually active (35.7%), 185 mainly with spouses (84.1%); frequency was 21.4 (SD 16.9) times per year (range: 1-120). Multiple logistic regressions identified five significant predictors of sexual activity: gender, age, being with spouse, sexual knowledge and sexual attitudes. Sexual activity was significantly associated with higher education levels, lower stress and more self-reported daily activities. CONCLUSIONS Our results agreed with Western studies linking sexual activity with better health and higher QOL in older adults. Older peoples' stress and daily activity levels are recognized quality-of-life measures; lower stress and more daily activities among sexually active older people suggests a connection between sexual activity and higher QOL. Increasing knowledge and improving attitudes about sexuality may help older people build healthier relationships and enhance health and QOL. Relevance to clinical practice. If healthcare professionals possess greater understanding of older peoples' sexuality, healthcare systems may find ways to increase sexual knowledge and foster healthier attitudes and relationships to improve older peoples' overall health and QOL.
Local and regional trends in the ground vegetation of beech forests 1 2

1 2 We sampled moss and vascular forest vegetation in five ancient beech forests from 3 northwest France, embracing in each a wide array of environmental conditions. Indirect 4 (PCA) and direct (RDA) gradient analysis were used to discern local and regional ecological 5 factors which explain the observed variation in species composition. Our results point to a 6 global factor encompassing a large array of soil and light conditions, unravelled when local 7 particularities of studied forests are partialled out. The humus form, numerically expressed by 8 the Humus Index, explains a large part of the observed variation in ground vegetation. Our 9 study confirmed opposite trends in vascular and moss species richness according to humus 10 condition. Ecological factors to which vascular and moss forest species respond at the 11 regional level can be estimated directly on the field by visually inspecting humus forms and 12 vegetation strata despite of the confounding influence of local factors. 13 14
Characterization of SRp46, a Novel Human SR Splicing Factor Encoded by a PR264/SC35 Retropseudogene

ABSTRACT The highly conserved SR family contains a growing number of phosphoproteins acting as both essential and alternative splicing factors. In this study, we have cloned human genomic and cDNA sequences encoding a novel SR protein designated SRp46. Nucleotide sequence analyses have revealed that the SRp46 gene corresponds to an expressed PR264/SC35 retropseudogene. As a result of mutations and amplifications, the SRp46 protein significantly differs from the PR264/SC35 factor, mainly at the level of its RS domain. Northern and Western blot analyses have established that SRp46 sequences are expressed at different levels in several human cell lines and normal tissues, as well as in simian cells. In contrast, sequences homologous to SRp46 are not present in mice. In vitro splicing studies indicate that the human SRp46 recombinant protein functions as an essential splicing factor in complementing a HeLa cell S100 extract deficient in SR proteins. In addition, complementation analyses performed with β-globin or adenovirus E1A transcripts and different splicing-deficient extracts have revealed that SRp46 does not display the same activity as PR264/SC35. These results demonstrate, for the first time, that an SR splicing factor, which represents a novel member of the SR family, is encoded by a functional retropseudogene.
Maintenance phase treatment of psychotic disorders in outpatients from Serbia – focus on long-term benzodiazepine use

Abstract Introduction: Prescribing trends in maintenance therapy of patients with primary psychotic disorders (PSD) may vary worldwide. Present study aimed to investigate prescription patterns in a sample of outpatients with PSD from Serbia. Methods: In a sample of 73 PSD outpatients we analysed the rate of antipsychotic polypharmacy and psychotropic polypharmacy, concomitant continual benzodiazepine use, and associations between therapy, psychotic symptoms and quality of life. Results: Maintenance therapy (median daily dose 321 mg of chlorpromazine equivalents) predominantly consisted of monotherapy with second generation antipsychotics (45.2%), followed by antipsychotic polypharmacy based on first and second generation combination (25.0%). The median number of psychotropic drugs was 3. Benzodiazepines were continually prescribed to more than 60% of patients (mean daily dose 2.9 ± 2.0 mg lorazepam equivalents). Patients with benzodiazepine use had significantly more psychotropic medications and more antipsychotic polypharmacy, poorer quality of life and more severe psychopathology in comparison to another group. Conclusion: The present study demonstrated new information regarding the prescription patterns of psychotropic drugs in outpatients with PSD in Serbia, amplified with clinically relevant information. This study also revealed distinct prescription patterns concerning antipsychotic/benzodiazepine polypharmacy. Overall, such findings are likely to contribute to improving clinical practice and care for patients with PSD in general. Keypoints Present exploratory research aimed to elucidate trends of antipsychotics polypharmacy and concomitant use of psychotropic medications including benzodiazepines in the maintenance treatment of outpatients with schizophrenia and other psychotic disorders, amplified with clinically relevant information (symptoms and quality of life). ‘Antipsychotic (AP) polypharmacy’ was defined as concurrent use of more than one AP for at least 1 month; ‘Psychotropic polypharmacy’ was defined as the combination of AP and a different class of psychotropic drugs medication for at least one month. The median number of prescribed psychotropic drugs was 3 (mean 3.1 ± 1.1) and the average AP daily dose was moderate (median 321 mg of chlorpromazine equivalents). However, the rates of AP polypharmacy (45.2%) and benzodiazepine prescription on a continual basis (>60%) found in our sample could be considered relatively high. Outpatients with higher AP daily dose and higher BPRS symptom score were receiving more benzodiazepines. For improvement of the local, as well as general clinical practice and care for patients with psychotic disorders, and for education in psychiatry, such analyses need to be done on a regular basis and on larger samples.
The effect of habitat on modern shark diversification

Sharks occupy marine habitats ranging from shallow, inshore environments to pelagic, and deepwaters, and thus provide a model system for testing how gross habitat differences have shaped vertebrate macroevolution. Palaeontological studies have shown that onshore lineages diversify more quickly than offshore taxa. Among onshore habitats, coral reef‐association has been shown to increase speciation rates in several groups of fishes and invertebrates. In this study, we investigated whether speciation rates are habitat dependent by generating the first comprehensive molecular timescale for shark divergence. Using phylogenetic comparative methods, we rejected the hypothesis that shelf (i.e. onshore) lineages have higher speciation rates compared to those occupying deepwater and oceanic (i.e. offshore) habitats. Our results, however, support the hypothesis of increased speciation rates in coral reef‐associated lineages within the Carcharhinidae. Our new timetree suggests that the two major shark lineages leading to the extant shark diversity began diversifying mostly after the end‐Permian mass extinction: the squalimorphs into deepwater and the galeomorphs into shelf habitats. We suggest that the breakdown of the onshore–offshore speciation rate pattern in sharks is mediated by success in deepwater environments through ecological partitioning, and in some cases, the evolution of morphological novelty.
Work redesign.

The key to easing the nurse shortage at your hospital: hang on to the nurses on your staff. To accomplish that, you need a work environment that gives nurses the support and tools they need to spend as much time as possible caring for patients. Seven organizations are doing just that with strategies that range from the ambitious to the mundane.
Hospital-level factors associated with report of physical activity in patients on mechanical ventilation across Washington State.

RATIONALE Use of physical and/or occupational therapy in the intensive care unit (ICU) is safe, feasible, and demonstrates improvements in functional status with early administration. Access to physical and/or occupational therapy in the ICU is variable, with little known regarding its use in community ICUs. OBJECTIVES Determine what proportion of hospitals across Washington State report use of physical activity in mechanically ventilated patients and investigate process of care factors associated with reported activity delivery. METHODS Cross-sectional telephone interview survey study of nurse managers in hospitals caring for patients on mechanical ventilation across Washington State in 2013. Survey responses were linked with hospital-level data available in the Washington State Department of Health Comprehensive Hospital Abstract Reporting System database. Chi-square testing was used to explore unadjusted associations between potential process of care factors and report on activity delivery. Two multivariable logistic regression models were developed to explore the association between presence of a mobility protocol and report on delivery of activity. MEASUREMENTS AND MAIN RESULTS We identified 54 hospitals caring for patients on mechanical ventilation; 47 participated in the survey (response rate, 85.5%). Nurse managers from 36 (76.6%) hospitals reported use of physical activity in patients on mechanical ventilation, with 22 (46.8%) reporting use of high-level physical activity (transferring to chair, standing or ambulating) and 24 (51.1%) reporting use in high-severity patients (patients requiring mechanical ventilation and/or vasopressors). Presence of a written ICU activity protocol (odds ratio [OR], 5.54; 95% confidence interval [CI], 1.60-19.18; P = 0.006), hospital volume (OR, 5.33; 95% CI, 1.54-18.48; P = 0.008), and academic affiliation (OR, 4.40; 95% CI, 1.23-15.63; P = 0.02) were associated with report of higher level activity. Presence of a written ICU activity protocol (OR, 6.00; 95% CI, 1.69-21.14; P = 0.005) and academic affiliation (OR, 4.50; 95% CI, 1.21-16.46; P = 0.02) were associated with report of delivery of physical activity to high-severity patients. CONCLUSIONS Nurse managers at three-fourths (76.6%) of eligible hospitals across Washington State reported use of physical activity in patients on mechanical ventilation. Hospital-level factors including hospital volume, academic affiliation, and presence of a mobility protocol were associated with report of higher level activity and delivery of activity to high-severity patients.
Apoptosis and angiogenesis are induced in the unstable coronary atherosclerotic plaque

ObjectiveApoptosis and angiogenesis may be involved in the pathogenesis of atherosclerosis and plaque destabilization. In this study, we investigated if apoptosis and angiogenesis were induced in the unstable human coronary atherosclerotic plaque compared to stable atherosclerotic plaque. MethodsAtherosclerotic plaques from patients with stable (n=9) and unstable angina (n=13) were obtained by directional coronary atherectomy performed during percutaneous transluminal coronary angioplasty. Apoptosis was detected by terminal deoxynucleotidyl transferase end labelling (TUNEL), as well as by immunostaining for caspase 3, Bax and Bcl-2. Neovascularization was determined by immunostaining for the endothelial cell-specific CD31, vascular endothelial growth factor (VEGF-A), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), hypoxia inducible factor-1&agr; (HIF-&agr;), and the sections were quantified blindly. ResultsThe apoptotic nuclei were more frequently found in the unstable coronary atherosclerotic plaques. When the number of apoptotic cells was quantified, an increased apoptotic index was found in the unstable plaques (P=0.04). The positive staining for caspase-3 was increased in the unstable plaques (P=0.0008), while no difference in either Bax or Bcl-2 was found between groups. Neovascularization, as evidenced by lumens surrounded by a CD31 positive endothelial layer, was more frequently present in the plaques from patients with unstable angina (P=0.04). The number of cells with positive staining for VEGF-A was increased in unstable plaques (P=0.005). No difference of Ang I, Ang II, HIF1-&agr; was found between groups. ConclusionsIn unstable human coronary plaques, apoptosis probably involving caspase 3 was found. The plaques had an increased neovascularization, probably induced by VEGF-A. These factors may contribute to explaining plaque destabilization and intraplaque haemorrhage.
A computational method for reliable gait event detection and abnormality detection for feedback in rehabilitation

In this paper, a gait event detection algorithm is presented that uses computer intelligence (fuzzy logic) to identify seven gait phases in walking gait. Two inertial measurement units and four force-sensitive resistors were used to obtain knee angle and foot pressure patterns, respectively. Fuzzy logic is used to address the complexity in distinguishing gait phases based on discrete events. A novel application of the seven-dimensional vector analysis method to estimate the amount of abnormalities detected was also investigated based on the two gait parameters. Experiments were carried out to validate the application of the two proposed algorithms to provide accurate feedback in rehabilitation. The algorithm responses were tested for two cases, normal and abnormal gait. The large amount of data required for reliable gait-phase detection necessitate the utilisation of computer methods to store and manage the data. Therefore, a database management system and an interactive graphical user interface were developed for the utilisation of the overall system in a clinical environment.
Current Directions in Psychological Science

The ability to suppress distractors is critical for the successful completion of goal-oriented behaviors. This is particularly true for everyday behaviors that take time to accomplish and are frequently interrupted by unpredicted events (e.g., spotting a sale on a favorite drink while searching a grocery store for an apple). For one to continue with the intended goal, attention to the distractor must be reactively suppressed (i.e., terminated) so that the goal-oriented behavior may resume. Such reactive suppression can be contrasted with a proactive mechanism that anticipates the appearance of a distractor and suppresses related sensory processing in advance. In this review, I consider three aspects of distractor suppression: (a) the distinction between proactive and reactive mechanisms, (b) the conditions under which reactive distractor rejection can be rapid, and (c) the neural and cognitive processes necessary for controlling proactive and reactive distractor suppression.
Antimony Uptake Systems in the Protozoan Parasite Leishmania and Accumulation Differences in Antimony-Resistant Parasites

ABSTRACT The first line drug against leishmaniasis consists of pentavalent antimony [Sb(V)], but there is general belief that the active form of the metal is the trivalent form [Sb(III)]. In this study, we have quantified the accumulation of Sb(V) and Sb(III) in Leishmania by using inductively coupled plasma mass spectrometry. The accumulation was studied in three Leishmania species at various life stages, sensitive or resistant to antimony. Both Sb(III) and Sb(V) are accumulated in promastigote and amastigote parasites, but through competition experiments with arsenite, we found that the routes of entry of Sb(V) and Sb(III) are likely to differ in Leishmania. The level of accumulation of either Sb(III) or Sb(V), however, was not correlated with the susceptibility of wild-type Leishmania cells to antimony. This suggests that other factors may also be implicated in the mode of action of the drugs. In contrast to metal susceptibility, resistance to Sb(III) correlated well with decreased antimony accumulation. This phenotype was energy dependent and highlights the importance of transport systems in drug resistance of this protozoan parasite.
Continuous Modulation of Action Potential Firing by a Unitary GABAergic Connection in the Globus Pallidus In Vitro

The firing patterns of neurons in the globus pallidus (GP) are affected by two major sources of GABAergic inhibition: striatal afferents and local axon collaterals. Local GABAergic GP-GP synapses display short-term depression (STD) and very sparse connectivity. At the high presynaptic firing rates typical in the GP, one would expect this STD to be complete, practically canceling the postsynaptic impact of the synapse. To investigate the apparent paradox of a synapse not affecting its postsynaptic neuron, we performed dual whole-cell recordings in acute brain slices from rats and recorded, for the first time, unitary IPSPs from a GP-GP GABAergic connection. We show that at high presynaptic firing rates the unitary connection continuously modulates the postsynaptic firing rate through a combination of large chloride driving force, unitary IPSP summation, and incomplete synaptic depression. Our findings indicate that, despite substantial STD and sparse connectivity, local GABAergic axon collaterals in the GP may echo the changes in presynaptic firing frequency across postsynaptic targets.
Interactions between Eurozone and US Booms and Busts: A Bayesian Panel Markov-Switching VAR Model

Interactions between the eurozone and US booms and busts and among major eurozone economies are analyzed by introducing a panel Markov-switching VAR model well suitable for a multi-country cyclical analysis. The model accommodates changes in low and high data frequencies and endogenous time-varying transition matrices of the country-specific Markov chains. The transition matrix of each Markov chain depends on its own past history and on the history of the other chains, thus allowing for modeling of the interactions between cycles. An endogenous common eurozone cycle is derived by aggregating country-specific cycles. The model is estimated using a simulation based Bayesian approach in which an efficient multi-move strategy algorithm is defined to draw common time-varying Markov-switching chains. Our results show that the US and eurozone cycles are not fully synchronized over the 1991-2013 sample period, with evidence of more recessions in the Eurozone. Shocks affect the US 1-quarter in advance of the eurozone, but these spread very rapidly among economies. An increase in the number of eurozone countries in recession increases the probability of the US to stay within recession, while the US recession indicator has a negative impact on the probability to stay in recession for eurozone countries. Turning point analysis shows that the cycles of Germany, France and Italy are closer to the US cycle than other countries. Belgium, Spain, and Germany, provide more timely information on the aggregate recession than Netherlands and France.
Ectopic expression of the microtubule‐dependent motor protein Eg5 promotes pancreatic tumourigenesis

Pancreatic cancer is a highly aggressive disease with a grim prognosis, due to its late diagnosis, propensity to rapidly metastasize, and resistance to therapy. The molecular events underlying this remain poorly defined. Here we report the overexpression and gene copy number gain of the microtubule‐dependent motor protein Eg5 in human pancreatic cancer samples. We also show that Eg5 expression correlates with clinicopathological parameters of pancreatic cancer and promotes anchorage‐independent cell growth and tumour formation in mice. In addition, Eg5 is up‐regulated in pancreatic cancer cell lines and enhances cell proliferation in an ATPase activity‐dependent manner. Our data further reveal that Eg5 overexpression causes the formation of multipolar spindles and multinucleation and induces the accumulation of polyploid cells. These findings demonstrate a role for Eg5 in pancreatic tumourigenesis and indicate a potential for targeting Eg5 in pancreatic cancer treatment. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.