Miracle-dz/UniFAR-FTUs huggingface dataset:
Combining animal personalities with transcriptomics resolves individual variation within a wild‐type zebrafish population and identifies underpinning molecular differences in brain function

Resolving phenotype variation within a population in response to environmental perturbation is central to understanding biological adaptation. Relating meaningful adaptive changes at the level of the transcriptome requires the identification of processes that have a functional significance for the individual. This remains a major objective towards understanding the complex interactions between environmental demand and an individual's capacity to respond to such demands. The interpretation of such interactions and the significance of biological variation between individuals from the same or different populations remain a difficult and under‐addressed question. Here, we provide evidence that variation in gene expression between individuals in a zebrafish population can be partially resolved by a priori screening for animal personality and accounts for >9% of observed variation in the brain transcriptome. Proactive and reactive individuals within a wild‐type population exhibit consistent behavioural responses over time and context that relates to underlying differences in regulated gene networks and predicted protein–protein interactions. These differences can be mapped to distinct regions of the brain and provide a foundation towards understanding the coordination of underpinning adaptive molecular events within populations.
Psychotropic prescribing in Catalonia: results from an epidemiological study.

BACKGROUND Mental disorders (MDs) are mainly treated in primary care (PC), where psychotropic drug (PSD) prescribing is highly prevalent. Prescription of PSD is associated with clinical and non-clinical factors. PURPOSE To describe the patterns of PSD prescribing over a 12-month period and to determine the factors associated with this in a PC population. METHODS Cross-sectional study. Data were collected on 3815 patients, via patient interview, on sociodemographics and MDs [Diagnostic and Statistical Manual of Mental Disorders (DSM-IV criteria)]. Computerized records provided data on PSD prescribing. Multilevel logistic regressions assessed the factors that influence prescribing. RESULTS Thirty-four per cent of PC patients were prescribed PSDs >12 months, with anxiolytics being the most commonly prescribed (22%). Fifty-three per cent of patients with any MD in this 12-month period were prescribed PSDs; however, 25% of patients without any of these disorders were also prescribed these medications. Higher rates of prescribing were associated with female gender, older age, presence of MD, being a househusband/housewife, consulting about psychological problems, increasing number of consultations and higher self-perceived disability. PSDs were less likely to be prescribed to patients born outside Spain and those consulting about physical conditions. PSD prescribing was higher in patients previously married and antipsychotic prescribing was higher in patients never married. No statistically significant associations were found between PSD prescription and education. CONCLUSIONS PSD prescribing rates are high in Catalonia and are associated with a number of clinical and non-clinical factors. A significant proportion of patients are receiving these drugs in the absence of MD. These findings need to be considered when prescribing in PC.
Translation of Maternal TATA-Binding Protein mRNA Potentiates Basal but Not Activated Transcription in Xenopus Embryos at the Midblastula Transition

ABSTRACT Early embryonic development in Xenopus laevis is characterized by transcriptional repression which is relieved at the midblastula stage (MBT). Here we show that the relative abundance of TATA-binding protein (TBP) increases robustly at the MBT and that the mechanism underlying this increase is translation of maternally stored TBP RNA. We show that TBP is rate-limiting in egg extract under conditions that titrate nucleosome assembly. Precocious translation of TBP mRNA in Xenopus embryos facilitates transcription before the MBT, without requiring TBP to be prebound to the promoter before injection. This effect is transient in the absence of chromatin titration and is sustained when chromatin is titrated. These data show that translational regulation of TBP RNA contributes to limitations on the transcriptional capacity before the MBT. Second, we examined the ability of trans-acting factors to contribute to promoter activity before the MBT. Deletion of cis-acting elements does not affect histone H2B transcription in egg extract, a finding indicative of limited trans-activation. Moreover, in the context of the intact promoter, neither the transcriptional activator Oct-1, nor TBP, nor TFIID enable transcriptional activation in vitro. HeLa cell extract, however, reconstitutes activated transcription in mixed extracts. These data suggest a deficiency in egg extract cofactors required for activated transcription. We show that the capacity for activated H2B transcription is gradually acquired at the early gastrula transition. This transition occurs well after the blastula stage when the basal transcription machinery can first be complemented with TBP.
Annual Variability in Seed Production by Woody Plants and the Masting Concept: Reassessment of Principles and Relationship to Pollination and Seed Dispersal

By analyzing 296 published and unpublished data sets describing annual variation in seed output by 144 species of woody plants, this article addresses the following questions. Do plant species naturally fall into distinct groups corresponding to masting and nonmasting habits? Do plant populations generally exhibit significant bimodality in annual seed output? Are there significant relationships between annual variability in seed production and pollination and seed dispersal modes, as predicted from economy of scale considerations? We failed to identify distinct groups of species with contrasting levels of annual variability in seed output but did find evidence that most polycarpic woody plants seem to adhere to alternating supra‐annual schedules consisting of either high or low reproduction years. Seed production was weakly more variable among wind‐pollinated taxa than animal‐pollinated ones. Plants dispersed by mutualistic frugivores were less variable than those dispersed by either inanimate means or animals that predominantly behave as seed predators. We conclude that there are no objective reasons to perpetuate the concept of mast fruiting in the ecological literature as a shorthand to designate a distinct biological phenomenon. Associations between supra‐annual variabiity in seed output and pollination and seed dispersal methods suggest the existence of important reproductive correlates that demand further investigation.
Utilization of Nerve Conduction Studies for the Diagnosis of Polyneuropathy in Patients with Diabetes: A Retrospective Analysis of a Large Patient Series

Background: Diabetic polyneuropathy (DPN) is a disabling complication of diabetes mellitus. A population-based analysis of physician utilization of nerve conduction studies (NCS) for the assessment of DPN was conducted. Methods: All electrodiagnostic encounters over a 30-month period using a computer-based neurodiagnostic instrument linked to a data registry were analyzed retrospectively. The DPN case definition was abnormal sural and peroneal nerve conduction. Results: The study cohort consisted of a total of 63,779 electrodiagnostic encounters performed by 3468 physician practices. Primary care and internal medicine physicians represented 80.1% of the practices and accounted for 65.7% of the encounters. Endocrinologists represented 4.6% of the practices and 20.1% of the encounters. The demographics of patients were 52.7% female; 63.4 ± 11.8 (mean ± standard deviation) years (age); 168.1 ± 10.9 cm (height); 92.2 ± 22.6 kg (weight); and 32.6 ± 7.2 kg/m2 (body mass index). The most common peroneal abnormality was F-wave latency (33.6%). The sural nerve response latency and amplitude parameters had similar abnormality rates (58.3 and 62.7%). DPN was identified in 52.6% of the encounters; in another 19.3% no neuropathy was found. Conclusions: For over 70% of the patients, the specific diagnostic question of the presence of DPN was addressed by NCS with evidence-based criteria. The demographic features were strongly associated with risk of diabetes and DPN, suggesting that NCS were applied to appropriate demographic subgroups. The rate of DPN was also comparable to levels seen by academic electromyography laboratories. In 32.6% of the encounters the NCS suggested a posttest diagnosis other than DPN. This rate was similar to the results of referral to traditional electromyography laboratories. This study demonstrated that NCS using computer-based electrodiagnostic equipment was a suitable tool for the diagnosis of DPN. Furthermore, this technology permits examination of DPN in large populations.
Immunohistofluorescence Analysis of Myofibroblast Transdifferentiation in Human Corneas With Bullous Keratopathy

Purpose: To detect the transdifferentiation of keratocytes into myofibroblasts in human corneas with bullous keratopathy and to examine the relation of such transdifferentiation to the clinical course of the disease. Methods: Twenty patients with bullous keratopathy who underwent penetrating keratoplasty were enrolled in the study. Corneal buttons collected during surgery were examined for expression of α-smooth muscle actin (αSMA) by immunoblot analysis and by immunofluorescence analysis of whole-mount preparations. The course of bullous keratopathy was evaluated from clinical charts. Results: Immunoblot analysis revealed a marked increase in αSMA expression in some corneas affected by bullous keratopathy. Immunofluorescence analysis revealed that αSMA was expressed in myofibroblastic cells in the stroma of 10 of the 20 corneas examined. Expression of αSMA was detected in subjects with a clinical history of corneal epithelial erosion from 12 months after the onset of clinical stromal edema. In contrast, in subjects without a clinical history of epithelial erosion, αSMA expression was not detected until at least 27 months after the onset of stromal edema. The incidence of αSMA expression in stromal cells was not significantly associated with topical steroid administration. Conclusions: Transdifferentiation of keratocytes into myofibroblasts was observed in human corneas affected by bullous keratopathy. Such transdifferentiation occurred earlier after the onset of stromal edema in patients with a clinical history of epithelial erosion than in those without such a history.
Do the Noncaffeine Ingredients of Energy Drinks Affect Metabolic Responses to Heavy Exercise?

Abstract Pettitt, RW, Niemeyer, JD, Sexton, PJ, Lipetzky, A, and Murray, SR. Do the noncaffeine ingredients of energy drinks affect metabolic responses to heavy exercise? J Strength Cond Res 27(7): 1994–1999, 2013—Energy drinks (EDs) such as Red Bull (RB) are marketed to enhance metabolism. Secondary ingredients of EDs (e.g., taurine) have been purported to improve time trial performance; however, little research exists on how such secondary ingredients affect aerobic metabolism during heavy exercise. The purpose of this study was to investigate the effect of the secondary ingredients of RB on aerobic metabolism during and subsequent to heavy exercise. In double-blind, counterbalanced, and crossover fashion, 8 recreationally trained individuals completed a graded exercise test to determine the gas exchange threshold (GET). Subjects returned on 2 separate occasions and ingested either a 245 ml serving of RB or a control (CTRL) drink with the equivalent caffeine before engaging in two 10-minute constant-load cycling bouts, at an intensity equivalent to GET, with 3 minutes of rest between bouts. Accumulated liters of O2 (10 minutes) were higher for the first bout (17.1 ± 3.5 L) vs. the second bout (16.7 ± 3.5 L) but did not differ between drinks. Similarly, excess postexercise oxygen consumption was higher after the initial bout (RB mean, 2.6 ± 0.85 L; CTRL mean, 2.9 ± 0.90 L) vs. the second bout (RB mean, 1.5 ± 0.85 L; CTRL mean, 1.9 ± 0.87 L) but did not differ between drinks. No differences occurred between drinks for measures of heart rate or rating of perceived exertion. These results indicate that the secondary ingredients contained in a single serving of RB do not augment aerobic metabolism during or subsequent to heavy exercise.
Proximal hindlimb flexion in the horse: effect on movement symmetry and implications for defining soundness.

REASONS FOR PERFORMING THE STUDY Flexion tests are a common tool during the prepurchase and clinical lameness examination, yet studies quantifying the effect of flexion, apart from distal forelimb flexion in sound horses, are sparse. OBJECTIVES To investigate the effect of proximal hindlimb flexion on perceivable and measurable changes in movement symmetry in horses with objective movement symmetry falling within the margins of 'sound'. METHODS Thirteen horses, selected based on objective movement symmetry, were instrumented with inertial sensors on left and right tuber coxae and over the os sacrum. Vertical movement symmetry was quantified at trot before and after proximal hindlimb flexion, with a repeat of flexion after 5 min. Video recordings of the horses were assessed visually. RESULTS Proximal hindlimb flexion introduced additive changes in movement symmetry to the individual baseline movement, with a tendency towards smaller effects with increasing stride number. The main systematic effect was a decrease in upward movement of the os sacrum following mid-stance of the flexed limb and an increase in upward movement following mid-stance of the nonflexed limb, also manifesting in a 'hip hike' of the flexed limb; these findings reflected increased movement asymmetry following flexion. Depending on individual baseline asymmetry, flexion can also increase movement symmetry. CONCLUSIONS Proximal hindlimb flexion can exacerbate subtle asymmetry when performed carefully. Variation in measured symmetry following flexion within and between horses showed that the individual response to flexion is highly variable. POTENTIAL RELEVANCE Proximal hindlimb flexion may elevate the asymmetry of a slightly lame limb above the threshold for visibility, thus assisting in the clinical gait examination. Further work is needed to examine the causes for a positive response to flexion and possible differences between sound and lame horses as well as horses of different athletic disciplines.
Inappropriate prescribing predicts adverse drug events in older adults.

BACKGROUND Explicit measures of potentially inappropriate prescribing, such as the Beers criteria, have been associated with risk for adverse drug events (ADEs). However, no such link has been established for actual inappropriate prescribing using implicit measures. OBJECTIVE To determine whether an implicit measure of inappropriate prescribing can predict ADE risk. METHODS Patients were veterans aged 65 years and older who were seen in primary care clinics and participated in a randomized controlled trial of a pharmacist-physician collaborative intervention. Inappropriate prescribing was determined at baseline, using the 2003 Beers criteria as an explicit measure and the Medication Appropriateness Index (MAI) as an implicit measure. A modified MAI scoring approach was designed to target ADE risk and was used in addition to standard scoring. ADEs that occurred during the 3 months following baseline were assessed by patient interview and plausibility verification by blinded pharmacist review. Logistic regression analysis was used to determine whether inappropriate prescribing predicted risk for an ADE, controlling for potential confounding factors. RESULTS Of 236 patients, 34 (14.4%) experienced an ADE. Inappropriate prescribing was common at baseline, with 48.7% of patients receiving a Beers criteria drug and 98.7% of patients having an inappropriate rating on at least 1 MAI criterion. Modified MAI scoring, but not other measures of inappropriate prescribing, significantly predicted ADE risk. For every unit increase in modified MAI score (3.1 +/- 3.5; mean +/- SD), the adjusted 3-month odds of an ADE increased 13% (OR 1.13; 95% CI 1.02 to 1.26). For example, patients with a modified MAI score of 3, near the precise mean score of 3.1, were at a nearly 40% greater risk for an ADE compared with patients with a score of zero. CONCLUSIONS Implicit measurement of actual inappropriate prescribing predicted ADE risk, an important clinical outcome. This finding helps confirm the validity of prior studies that have relied on explicit measures to link potentially inappropriate prescribing to adverse health outcomes.
Desiccating Stress–Induced Chemokine Expression in the Epithelium Is Dependent on Upregulation of NKG2D/RAE-1 and Release of IFN-γ in Experimental Dry Eye

The Th1-associated chemokines CXCL9, CXCL10, and CXCL11 coordinate migration of CXCR3+ Th1 cells. The objective of this study was to evaluate the role of the innate immune system in stimulating chemokine expression in an experimental model of dry eye and bridge the gap between innate and adaptive immunity. Desiccating stress (DS) induced very early (6 h) expression and production of Th1-associated chemokines in cornea and conjunctiva of C57BL/6 and RAG1 knockout (KO) mice, demonstrating that chemokine expression does not require innate T cells. We then demonstrated that activating the innate immune system prior to adoptive transfer of T cells to RAG1KO mice increased disease severity. Interestingly, lack of induction of chemokines CXCL9, CXCL10, and CXCL11 in IFN-γKO mice provided evidence that their expression requires IFN-γ for induction. Treatment of RAG1KO mice with anti-NK1.1 prevented the increase of CXCL9, CXCL10, and CXCL11 in response to DS, compared with isotype controls. Additionally, DS increased the expression of NKG2D in the conjunctiva. The expression of the NKG2D ligand, retinoic acid early inducible gene 1, also increased at the ocular surface at both the protein and gene levels. Neutralization of NKG2D at the ocular surface decreased the expression of CXCL9, CXCL10, CXCL11, and IFN-γ. In summary, upregulation of CXCL9, CXCL10, and CXCL11 expression in experimental dry eye is T cell–independent, requiring IFN-γ–producing NKG2D+ NK cells that are activated in response to DS-induced stress signals. This study provides insight into the events that trigger the initial immune response in dry eye pathology.
Citric acid or orange juice for the 13C‐urea breath test: the impact of pH and gastric emptying

: There is an ongoing debate about the optimal test drink to be used in the 13C‐urea breath test (13C‐UBT). We recently reported that a citric acid solution is the optimal test drink in the 13C‐UBT, because it provides a high 13CO2 recovery and the excellent accuracy of the test appears optimal compared to other test meals. Orange juice, because of a better taste, is also propagated as a test drink in the 13C‐UBT.
The inhibition of hepatic bile acids transporters Ntcp and Bsep is involved in the pathogenesis of isoniazid/rifampicin-induced hepatotoxicity

Abstract Co-treatment of isoniazid (INH) and rifampicin (RFP) is well known for clinically apparent liver injury. However, the mechanism of INH/RFP-induced liver injury is controversial. Emerging evidence shows links between inhibition of bile acids transporters and drug-induced liver injury (DILI). The present study investigates whether sodium taurocholate cotransporting polypeptide (NTCP/Ntcp; SLC10A1) and bile salt export pump (BSEP/Bsep; ABCB11) are involved in the anti-tuberculosis medicines induced liver injury. ICR female mice were intragastrically treated with INH (50 or 100 mg/kg), RFP (100 or 200 mg/kg), or the combination of INH/RFP (50 + 100 mg/kg or 100 + 200 mg/kg) for 14 consecutive days. Liver histopathological examination, serum biochemical and liver malondialdehyde tests were evaluated. Apparent histopathological alterations and hepatic oxidative stress showed in INH (100 mg/kg), RFP (200 mg/kg) and their combination group. The hepatoxic effect was also indicated by increased serum biomarkers, such as aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (DBil), total bilirubin (TBil) and total bile acids (TBA). Both doses of INH/RFP administration significantly down-regulated the expression of Ntcp and Bsep in liver. Furthermore, the combination of INH and RFP displayed stronger effect on the expression of Ntcp compared with the corresponding dose of INH or RFP alone. In conclusion, down-regulated expression of hepatic Ntcp and Bsep might play an important role in the development of INH and RFP induced liver injury.
Characteristics of migraine visual aura in Southern Brazil and Northern USA

Background: Migraine aura, made up of one or more neurological symptoms arising from the cortex or brainstem, is a complex neurological phenomenon. Visual aura is the most frequent aura manifestation. Studying the subjective components of visual aura makes it possible to identify common characteristics. Objective: To thoroughly describe the characteristics of migraine visual aura in patients with migraine with aura. Methods: We performed a retrospective, descriptive study of the visual aura of 122 migraine patients collected at two headache clinics in the Americas. This study was designed to determine the characteristics of a typical visual aura. Results: The most common features of the visual aura in our study are that it occurs before the headache with a gap of less than 30 minutes, lasts 5 to 30 minutes, has a gradual onset, usually begins peripherally, is unilateral, and shimmers. Furthermore, the location of typical visual aura in the visual field has no fixed relationship to headache laterality, is slightly more often without color, and is often described as small bright dots and zigzag lines. Blurred vision, not typically considered to be an aura phenomenon of cortical origin, is in fact the most frequently reported visual symptom. Conclusions: Migraine visual aura is heterogeneous and pleomorphic, and some of our findings run contrary to common beliefs.
Identification of protective cell surface proteins in ribosomal fractions from Salmonella typhimurium

Cell surface antigen preparations from Salmonella typhimurium SR-11 prepared by either trichloroacetic acid extraction or boiling in sodium dodecyl sulfate were able to protect C3H/HeJ, C3H/HeDub, and A/J mice. Some of the proteins found in these preparations were shown to exist in the protective ribosomal fraction isolated from S. typhimurium SR-11. Passage of ribosomes isolated from S. typhimurium SR-11 and 6707 through a Sepharose 2B column removed the protective immunogen from 6707 ribosomes but did not completely remove it from SR-11 ribosomes. Immunity to salmonella infection in C3H/HeJ mice induced by ribosomal vaccines may be dependent on the presence of cell surface proteins in the ribosomal fraction.