Miracle-dz/UniFAR-FTUs huggingface dataset:
A common trans-acting factor is involved in transcriptional regulation of neurotransmitter genes by cyclic AMP

Activation of neurotransmitter receptors can regulate transcription in postsynaptic cells through the actions of second messengers. Trans-synaptic regulation of transcription appears to be an important mechanism controlling the synthesis of molecules involved in neuronal signaling, especially neuropeptides. Proenkephalin, vasoactive intestinal polypeptide, and somatostatin have been shown to be transcriptionally regulated by the second messenger, cyclic AMP (cAMP), as has the catecholamine synthesizing enzyme tryosine hydroxylase. cAMP-inducible elements have been mapped within these genes, and trans-acting factors which bind to several such elements have been identified. With the discovery that individual neurons generally contain multiple transmitters within their synaptic terminals, it has become important to understand in detail the mechanisms by which the synthesis of transmitters can be coregulated. Here we compare the structure and function of the proenkephalin cAMP-inducible enhancer with the mapped cAMP-inducible elements of the vasoactive intestinal polypeptide, somatostatin, and tyrosine hydroxylase genes and a putative cAMP-inducible element in the proto-oncogene c-fos. We have previously shown that the proenkephalin enhancer is composed of two different elements, ENKCRE-1 and ENKCRE-2. We show here that one of these, ENKCRE-2, is structurally similar to elements found within the vasoactive intestinal polypeptide, somatostatin, and tyrosine hydroxylase genes and binds a trans-acting factor that is competed for both in cotransfection experiments (in vivo) and in DNase I footprint assays (in vitro) by these other elements. The c-fos element has similar structural requirements to confer transcriptional induction by cAMP but competes less strongly. Protein purified by affinity chromatography with the ENKCRE-2 sequence binds to each of these elements. A second element within the proenkephalin cAMP-inducible enhancer, ENKCRE-1, binds a factor that is not competed for by these other genes and is therefore distinct. This analysis suggests a potential mechanism of transcriptional coregulation of the neuronally expressed genes investigated in this study and also demonstrates that multiple factors are involved in transcriptional activation by cAMP.
General functions for human survival and mortality

General functions for human survival and mortality may support a possibility of general mechanisms in human ageing. We discovered that the survival and mortality curves could be described very simply and accurately by the Weibull survival function with age-dependent shape parameter. The age-dependence of shape parameter determines the shape of the survival and mortality curves and tells the nature of the ageing rate. Especially, the progression of shape parameter with age may be explained by the increase of interaction among vital processes or the evolution of susceptibility to faults with age. Age-related diseases may be attributed to the evolution of susceptibility to faults with age.
Prevalence of Alzheimer's disease and dementia in two communities: Nigerian Africans and African Americans.

OBJECTIVE This article reports on a prevalence study of dementia and Alzheimer's disease among two groups of subjects with the same ethnic background but widely differing environments. METHOD The study was conducted among residents aged 65 years and older in two communities: Yorubas (N = 2,494) living in Ibadan, Nigeria, and African Americans (N = 2,212 in the community and N = 106 in nursing homes) living in Indianapolis, Indiana. The study design consisted of a screening stage followed by a clinical assessment stage for selected subjects on the basis of their performance on the screening tests. RESULTS The age-adjusted prevalence rates of dementia (2.29%) and Alzheimer's disease (1.41%) in the Ibadan sample were significantly lower than those in the Indianapolis sample, both in the community-dwelling subjects alone (4.82% and 3.69%, respectively) and in the combined nursing home and community samples (8.24% and 6.24%, respectively). The prevalence rates of dementia and Alzheimer's disease increased consistently with advancing age in both study groups. CONCLUSIONS To the authors' knowledge, this is the first study, using the same research method at the two sites, to report significant differences in rates of dementia and Alzheimer's disease in two different communities with similar ethnic origins.
The Population-Based Health Effect of Hand, Foot and Mouth Disease in Children in Shanghai

Background: An effective enterovirus 71 (EV71) vaccine is needed to control the annual outbreaks of hand, foot and mouth disease (HFMD) in China. Adequate epidemiologic data relating to HFMD are needed to make decisions about appropriate public health interventions and implementation of the new EV71 vaccine. Methods: We analyzed the population-based epidemiologic characteristics, clinical outcome and laboratory investigation of the 2011 HFMD outbreak in children based on the citywide surveillance system in Shanghai. Results: The incidence rate of HFMD was 25.8 per 1000 in children <10 years of age in Shanghai in 2011, ranging from 2.5 per 1000 in the age group 7 to 9.9 years to 48.4 per 1000 in the age group 3 to 3.9 years. Children 1 to 1.9 years were at the highest risk of developing severe complications and most susceptible to HFMD. Boys and migrant children had significantly increased risks of contracting HFMD and developing severe disease. More institutional clusters/outbreaks occurred in the winter peak months than in the summer peak months. Migrant young children played a central role in the spread of HFMD in the community. EV71 was identified in 39.7% of mild HFMD outpatients, 47.4% of hospitalized patients, 92.1% of severe inpatients with complications, 50% of outbreaks and 38.8% of clusters in institutions. Conclusion: HFMD and EV71 infections have a significant health effect on Shanghai children.
A Double-Blind, Placebo-Controlled Pilot Study of Galantamine to Improve Cognitive Dysfunction in Minimally Symptomatic Bipolar Disorder

Objective: There is increasing evidence that cognitive impairment is common in patients with bipolar disorder. The purpose of this study was to determine whether galantamine augmentation improved cognition in patients with euthymic bipolar disorder. In addition, the effect of galantamine on clinical measures of functioning and psychopathology was assessed. Method: This study was a randomized double-blind, placebo-controlled, parallel design examining the impact of galantamine augmentation on cognition and other clinical measures in 30 patients during the course of 3 months. Sixteen subjects who completed baseline and follow-up second neuropsychological testing were evaluable (10 with galantamine and 6 with placebo). Results: The galantamine group showed improved performance on the California Verbal Learning Test total learning and the placebo group showed improved performance on the 2 Delis-Kaplan Executive Functioning System trail-making conditions and category fluency. Conclusions: Episodic memory performance was improved in the galantamine treatment group but did not improve in the placebo group. In contrast, performance on 2 of the processing speed measures showed significant improvement in the placebo condition, whereas that of the patients treated with galantamine did not improve. Galantamine may thus have specific benefits for episodic memory, but not processing speed, in patients with cognitive impairment as part of bipolar disorder.
Critical thinking in the language classroom: Teacher beliefs and methods

In recent years, English language teaching and research in the Sultanate of Oman has witnessed a significant increase in the emphasis upon critical thinking skills development alongside language proficiency. Fostering a perspective of commitment to teaching critical thinking skills in line with the English language courses, this paper reports on a study conducted at the Language Centre at Sultan Qaboos University. In particular, it explores English language teachers’ conceptual definitions of critical thinking, their beliefs about the significance of critical thinking for language teaching and connections between critical thinking and language teaching methods. The results of the study’s survey, supported by concrete examples from the classroom, suggest that the ultimate majority of those teachers (96%) recognise the central role played by critical thinking in effective language pedagogy. The results also indicate teachers’ preference for aligning their teaching methods with the functional-communicative approach, related to Ennis’ (2011) critical thinking categories. They also suggest a predisposition for employing practical aspects of critical thinking teaching methodologies in the English language classroom to more holistically prepare students for further academic studies and their future careers in the workplace.
Effects of myocardial postconditioning on the recruitment of endothelial progenitor cells.

BACKGROUND Ischemic postconditioning (PostC), brief repetitive cycles of ischemia and reperfusion during early reperfusion, is suggested to protect the myocardium in patients with stent thrombosis-elevation myocardial infarction (STEMI) by improved endothelial dysfunction and alteration of cytokine release. These mechanisms are also of importance for the recruitment of endothelial progenitor cells (EPC), an endogenous repair mechanism for re-endothelialization and neoangiogenesis. The aim of this study was to investigate the effect of PostC on recruitment of EPC. METHODS EPC were analyzed in 20 patients with STEMI randomized to receive four cycles of PostC following percutaneous coronary intervention (PCI) or conventional PCI. Different subpopulations of EPC were quantified immediately and on day 4 using flow cytometry. Myocardium at risk, and infarct size was determined by cardiovascular magnetic resonance. RESULTS There was no influence of PostC on the number of different EPC (CD34(+) , CD133(+) , CD34(+) CD133(+) , CD34(+) KDR(+) , CD34(-) CD133(+) KDR(+) , CD34(+) CD133(+) KDR(+) ). Left ventricular ejection fraction, myocardium at risk, and infarct size did not correlate to the mobilization of EPC. There was an inverse correlation between the symptom-to-balloon time and the mobilization of progenitor precursor cells (CD34(+) cells: R =-0.527, P = 0.02; CD133(+) cells: R =-0.624, P = 0.004; CD34(+) CD133(+) cells: R =-0.466, P = 0.04). DISCUSSION Ischemic PostC did not result in improved mobilization of EPC in STEMI patients. The recruitment of progenitor cells seems to be related to the duration of ischemia rather than the size of the ischemic myocardial area. More effort is needed to understand the changes of endothelial surface markers by PostC and their role in EPC recruitment and homing.
Automated microscopy system for mosaic acquisition and processing

An automatic mosaic acquisition and processing system for a multiphoton microscope is described for imaging large expanses of biological specimens at or near the resolution limit of light microscopy. In a mosaic, a larger image is created from a series of smaller images individually acquired systematically across a specimen. Mosaics allow wide‐field views of biological specimens to be acquired without sacrificing resolution, providing detailed views of biological specimens within context. The system is composed of a fast‐scanning, multiphoton, confocal microscope fitted with a motorized, high‐precision stage and custom‐developed software programs for automatic image acquisition, image normalization, image alignment and stitching. Our current capabilities allow us to acquire data sets comprised of thousands to tens of thousands of individual images per mosaic. The large number of individual images involved in creating a single mosaic necessitated software development to automate both the mosaic acquisition and processing steps. In this report, we describe the methods and challenges involved in the routine creation of very large scale mosaics from brain tissue labelled with multiple fluorescent probes.
Hidden autoantibodies against common serum proteins in murine systemic lupus erythematosus. Detection by in vitro plaque-forming cell assay

The autoantibodies found in human and murine systemic lupus erythematosus (SLE) are generally directed against cells or components of cells such as nuclear antigens. This predilection may be due to the unusual immunogenicity of certain autoantigens, or to unusual patterns of antibody crossreactivity. Alternatively, the observed spectrum of reactivities may reflect the in vivo absorption of those autoantibodies directed against soluble antigens. To test whether hitherto undetected autoantibodies against serum proteins might exist in murine SLE, we developed assays that were independent of the possibility of absorption of autoantibodies by serum autoantigens; large numbers of plaque- forming cells (PFC) directed against mouse albumin and mouse transferrin were easily detected in the spleens of MRL/Mp-lpr/lpr, BXSB, and NZB mice. The secreted antibodies were relatively specific for the mouse proteins, since only limited cross-reactivity was seen with albumin and transferrins of other species in inhibition experiments. The production of these hidden antibodies could not be the result of diffuse polyclonal B cell activation, since the PFC to mouse transferrins and albumin were not always accompanied by comparable numbers of PFC against related albumins and transferrins. The results indicate that autoantibody production in murine lupus is a generalized phenomenon, not limited to the production of autoantibodies to nuclear or other cell-bound antibodies. However, the relative specificity of the autoantibodies for self-antigens indicates that diffuse polyclonal B cell activation cannot be the mechanism responsible, and argues that a selective mechanism, probably driven by antigen, accounts for production of autoantibodies in SLE.
Accounting Conservatism and Short Selling: Evidence from China

Using China's shortâ€ selling pilot program as a quasiâ€ experiment, we find that the prospect of short selling has significantly increased conditional accounting conservatism among firms that are eligible for short selling, consistent with a short sellersâ€™ disciplining effect hypothesis. When short selling takes position ex post, accounting conservatism starts to decrease with an increased downward pressure on stock prices. Moreover, the shortâ€ selling effect of increased conditional accounting conservatism becomes stronger for stateâ€ owned enterprises, and this effect is accompanied by an increase of unconditional conservatism. As corroborating evidence to support the disciplining hypothesis, we show that accounting conservatism is significantly decreased for firms that are removed from the shortâ€ selling eligibility list. Our results are robust after considering the endogeneity issue in measuring downward stock price pressure, and after constructing the control firms by using both a propensity score matching method and an alternative measure for accounting conservatism. Overall, we provide important evidence on the feedback effects that the capital market has on firm financial reporting.
Profile of glaucoma in a major eye hospital in north India.

PURPOSE To study the clinical profile and distribution of various subtypes of glaucoma in a referral practice in North India. METHOD A retrospective analysis was done of 2425 patients who attended the glaucoma clinic in a tertiary eye-care centre for five years from January 1995 to December 1999. A detailed history was obtained and a thorough examination was performed, including gonioscopy, disc assessment, applanation tonometry and automated perimetry. Diurnal variation of IOP and provocative tests for glaucoma were done where applicable. RESULT Primary angle closure glaucoma (PACG) was the most common glaucoma subtype. The primary open angle glaucoma (POAG) to the PACG ratio was 37:63. Chronic angle closure glaucoma (CACG) was the most common PACG subtype. The majority of CACG cases were relatively asymptomatic. Male dominance was seen for POAG, juvenile open angle glaucoma (JOAG), CACG, normal tension glaucoma (NTG) and secondary glaucomas. Female dominance was seen for ocular hypertension (OHT), acute or intermittent ACG and developmental glaucomas. The mean age in years at presentation was POAG:60.54 years (males 61.54 years, females 59.01 years) and PACG: 55.13 years (males 57.25 years, females 53.60). The three common secondary glaucomas were: glaucoma secondary to adherent leucoma, aphakic and pseudophakic glaucomas and traumatic glaucomas. Advanced glaucoma was detected in 42 to 53% of patients and bilateral blindness in 8 to 14% of patients in various subtypes. CONCLUSION Compared to Caucasians, glaucoma patients in North India seem to present nearly a decade earlier and the disease is more advanced at presentation. While PACG is the most commonly encountered glaucoma, NTG and exfoliative glaucoma are relatively rare.
Postnatal ablation of osteoblast Smad4 enhances proliferative responses to canonical Wnt signaling through interactions with &bgr;-catenin

Summary Canonical Wnt (cWnt) signaling through &bgr;-catenin regulates osteoblast proliferation and differentiation to enhance bone formation. We previously reported that osteogenic action of &bgr;-catenin is dependent on BMP signaling. Here, we further examined interactions between cWnt and BMP in bone. In osteoprogenitors stimulated with BMP2, &bgr;-catenin localizes to the nucleus, physically interacts with Smad4, and is recruited to DNA-binding transcription complexes containing Smad4, R-Smad1/5 and TCF4. Furthermore, Tcf/Lef-dependent transcription, Ccnd1 expression and proliferation all increase when Smad4, 1 or 5 levels are low, whereas TCF/Lef activities decrease when Smad4 expression is high. The ability of Smad4 to antagonize transcription of Ccnd1 is dependent on DNA-binding activity but Smad4-dependent transcription is not required. In mice, conditional deletion of Smad4 in osterix+ cells increases mitosis of cells on trabecular bone surfaces as well as in primary osteoblast cultures from adult bone marrow and neonatal calvaria. By contrast, ablation of Smad4 delays differentiation and matrix mineralization by primary osteoblasts in response to Wnt3a, indicating that loss of Smad4 perturbs the balance between proliferation and differentiation in osteoprogenitors. We propose that Smad4 and Tcf/Lef transcription complexes compete for &bgr;-catenin, thus restraining cWnt-dependent proliferative signals while favoring the matrix synthesizing activity of osteoblasts.
The Changing Nature Of Risks

Introduction Human life has always been fraught with risks. But until the first decades of the 19 century, risks were accepted as more or less natural in the sense that they were directly associated with human activity rather than with failures of systems or equipment. Accidents happened as a part of work (which often took place at home), during major building works, when travelling on land or at sea – and of course during wars. This perception changed dramatically after September 15, 1830, when William Huskisson became the first victim of a train accident. The occasion was the opening of the Liverpool and Manchester Railway and the train that hit the unfortunate Mr. Huskisson was George Stephenson’s Rocket. More accidents soon followed, involving exploding boilers, derailings, head-on collisions, collapsing bridges, and so on. (As an aside, the first recorded automobile death took place in Ireland on August 31, 1869, when a woman, Mary Ward, was thrown from and fell under the wheels of an experimental steam car built by her cousins. In 2002, road traffic accidents worldwide were estimated to kill 1.2 million people, with at least 20 million people being injured or disabled.) The crucial change that took place in the 19 century was that accidents became associated with the technological systems that people designed, built, and used as part of work, in the name of progress and civilisation. Suddenly, accidents happened not only because the people involved, today referred to as people at the sharp end, did something wrong or because of an act of nature, but also because a human-made system failed. Furthermore, the failures were no longer simple, such as a scaffolding falling down or a wheel axle breaking. The failures were complex, in the sense that they usually defied the immediate understanding of the people at the sharp end. In short, their knowledge and competence was about how to do their work, and not about how the technology worked or functioned. Before this change happened, people could take reasonable precautions against accidents at work because they understood the tools and artefacts they used sufficiently well. After this change had happened, that was no longer the case.
Delayed Sleep Timing and Symptoms in Adults With Attention-Deficit/Hyperactivity Disorder: A Controlled Actigraphy Study

Patients with attention-deficit/hyperactivity disorder (ADHD) often exhibit disrupted sleep and circadian rhythms. Determination of whether sleep disturbance and/or circadian disruption are differentially associated with symptom severity is necessary to guide development of future treatment strategies. Therefore, we measured sleep and ADHD symptoms in participants aged 19–65 who met the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) criteria for ADHD and insomnia without psychiatric comorbidities by monitoring actigraphy and daily sleep logs for 2 wks, as well as the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), the ADHD Rating Scale (ADHD-RS), and a clinic-designed sleep behavior questionnaire. Principal components analysis identified correlated circadian- and sleep-related variables in all participants with ADHD who completed the study (n = 24). The identified components were entered into a backwards stepwise linear regression analysis, which indicated that delayed sleep timing and increased sleepiness (ESS) (but not sleep duration or sleep efficiency) significantly predicted greater severity of both hyperactive-impulsive and inattentive ADHD symptoms (p < .05 for partial regression coefficients). In addition, combined subtypes had the most impaired age-adjusted sleep quality (PSQI scores; p < .05 compared with healthy controls; n = 13), and 91.7% of them reported going to bed late due to being “not tired/too keyed up to sleep” compared with 57.2% and 50% of inattentive and symptom-controlled participants, respectively (p < .05). In conclusion, the results of this study suggest that ADHD symptom severity correlates with delayed sleep timing and daytime sleepiness, suggesting that treatment interventions aimed at advancing circadian phase may improve daytime sleepiness. In addition, ADHD adults with combined hyperactive-impulsive and inattentive symptoms have decreased sleep quality as well as the delayed sleep timing of predominately inattentive subtypes. (Author correspondence: rfargason@uab.edu)