Miracle-dz/UniFAR-FTUs huggingface dataset:
Promotion of endocytosis efficiency through an ATP‐independent mechanism at rat calyx of Held terminals

At rat calyx of Held terminals, ATP was required not only for slow endocytosis, but also for rapid phase of compensatory endocytosis. An ATP‐independent form of endocytosis was recruited to accelerate membrane retrieval at increased activity and temperature. ATP‐independent endocytosis primarily involved retrieval of pre‐existing membrane, which depended on Ca2+ and the activity of neutral sphingomyelinase but not clathrin‐coated pit maturation. ATP‐independent endocytosis represents a non‐canonical mechanism that can efficiently retrieve membrane at physiological conditions without competing for the limited ATP at elevated neuronal activity.
Newborn Cystic Fibrosis Pigs Have a Blunted Early Response to an Inflammatory Stimulus.

RATIONALE Studies suggest that inappropriate responses to proinflammatory stimuli might contribute to inflammation in cystic fibrosis (CF) lungs. However, technical challenges have made it difficult to distinguish whether altered responses in CF airways are an intrinsic defect or a secondary effect of chronic disease in their tissue of origin. The CF pig model provides an opportunity to study the inflammatory responses of CF airways at birth, before the onset of infection and inflammation. OBJECTIVES To test the hypothesis that acute inflammatory responses are perturbed in porcine CF airways. METHODS We investigated the inflammatory responses of newborn CF and non-CF pig airways following a 4-hour exposure to heat-killed Staphylococcus aureus, in vivo and in vitro. MEASUREMENTS AND MAIN RESULTS Following an in vivo S. aureus challenge, markers of inflammation were similar between CF and littermate control animals through evaluation of bronchoalveolar lavage and tissues. However, transcriptome analysis revealed genotype-dependent differences as CF pigs showed a diminished host defense response compared with their non-CF counterparts. Furthermore, CF pig airways exhibited an increase in apoptotic pathways and a suppression of ciliary and flagellar biosynthetic pathways. Similar differences were observed in cultured airway epithelia from CF and non-CF pigs exposed to the stimulus. CONCLUSIONS Transcriptome profiling suggests that acute inflammatory responses are dysregulated in the airways of newborn CF pigs.
MUC1-C promotes the suppressive immune microenvironment in non-small cell lung cancer

ABSTRACT The cancer immune microenvironment is of importance for the effectiveness of immunotherapy; however, its dysregulation is poorly understood. The MUC1-C oncoprotein is aberrantly overexpressed in non-small cell lung cancer (NSCLC) and has been linked to the induction of PD-L1. The present work investigated the effects of targeting MUC1-C in an immuno-competent MUC1 transgenic (MUC1.Tg) mouse model. We show that Lewis Lung Carcinoma cells expressing MUC1-C (LLC/MUC1) exhibit upregulation of PD-L1 and suppression of interferon-γ (IFN-γ). In studies of LLC/MUC1 cells growing in vitro and as tumors in MUC1.Tg mice, treatment with the MUC1-C inhibitor, GO-203, was associated with the downregulation of PD-L1 and induction of IFN-γ. The results further demonstrate that targeting MUC1-C results in enhanced effector function of CD8+ tumor-infiltrating lymphocytes (TILs) as evidenced by increased expression of the activation marker CD69, the degranulation marker CD107α, and granzyme B. Notably, targeting MUC1-C was also associated with marked increases in TIL-mediated killing of LLC/MUC1 cells. Analysis of gene expression data sets further showed that overexpression of MUC1 in NSCLCs correlates negatively with CD8, IFNG and GZMB, and that decreases in CD8 and IFNG are associated with poor clinical outcomes. These findings in LLC/MUC1 tumors and in NSCLCs indicate that MUC1-C→PD-L1 signaling promotes the suppression of CD8+ T-cell activation and that MUC1-C is a potential target for reprogramming of the tumor microenvironment.
A review of brain stimulation methods to treat substance use disorders

BACKGROUND Substance use disorders (SUDs) are a leading cause of disability worldwide. While several pharmacological and behavioral treatments for SUDs are available, these may not be effective for all patients. Recent studies using non-invasive neuromodulation techniques including Repetitive Transcranial Magnetic Stimulation (rTMS), Transcranial Direct Current Stimulation (tDCS), and Deep Brain Stimulation (DBS) have shown promise for SUD treatment. OBJECTIVE Multiple studies were evaluated investigating the therapeutic potential of non-invasive brain stimulation techniques in treatment of SUDs. METHOD Through literature searches (eg, PubMed, Google Scholar), 60 studies (2000-2017) were identified examining the effect of rTMS, tDCS, or DBS on cravings and consumption of SUDs, including tobacco, alcohol, cannabis, opioids, and stimulants. RESULTS rTMS and tDCS demonstrated decreases in drug craving and consumption, while early studies with DBS suggest similar results. Results are most encouraging when stimulation is targeted to the Dorsolateral Prefrontal Cortex (DLPFC). CONCLUSIONS Short-term treatment with rTMS and tDCS may have beneficial effects on drug craving and consumption. Future studies should focus on extending therapeutic benefits by increasing stimulation frequency and duration of treatment. SCIENTIFIC SIGNIFICANCE The utility of these methods in SUD treatment and prevention are unclear, and warrants further study using randomized, controlled designs. (Am J Addict 2018;27:71-91).
Choice of Allograft in Patients Requiring Intestinal Transplantation: A Critical Review

Intestinal transplantation (ITx) is indicated in patients with irreversible intestinal failure (IF) and life-threatening complications related to total parenteral nutrition (TPN). ITx can be classified into three main types. Isolated intestinal transplantation (IITx), that is, transplantation of the jejunoileum, is indicated in patients with preserved liver function. Combined liver-intestine transplantation (L-ITx), that is, transplantation of the liver and the jejunoileum, is indicated in patients with liver failure related to TPN. Thus, patients with cirrhosis or advanced fibrosis should receive a combined allograft, while patients with lower grades of liver fibrosis can usually safely undergo ITx. Reflecting their degree of sickness, the waitlist mortality rate and the early posttransplant outcomes of patients receiving L-ITx are worse than IITx. However, L-ITx is associated with better long-term graft and patient survival. Multivisceral transplantation (MVTx), that is, transplantation of the organs dependent on the celiac axis and superior mesenteric artery, can be classified into full MVTx if it includes the liver and modified MVTx if it does not. The most common indications for MVTx are extensive portomesenteric thrombosis and diffuse gastrointestinal pathology such as motility disorders and polyposis syndrome. Every patient with IF should undergo a multidisciplinary evaluation by an experienced ITx team.
The Absence of DHHC3 Affects Primary and Latent Herpes Simplex Virus 1 Infection

ABSTRACT UL20, an essential herpes simplex virus 1 (HSV-1) protein, is involved in cytoplasmic envelopment of virions and virus egress. We reported recently that UL20 can bind to a host protein encoded by the zinc finger DHHC-type containing 3 (ZDHHC3) gene (also known as Golgi-specific DHHC zinc finger protein [GODZ]). Here, we show for the first time that HSV-1 replication is compromised in murine embryonic fibroblasts (MEFs) isolated from GODZ−/− mice. The absence of GODZ resulted in blocking palmitoylation of UL20 and altered localization and expression of UL20 and glycoprotein K (gK); the expression of gB and gC; and the localization and expression of tegument and capsid proteins within HSV-1-infected MEFs. Electron microscopy revealed that the absence of GODZ limited the maturation of virions at multiple steps and affected the localization of virus and endoplasmic reticulum morphology. Virus replication in the eyes of ocularly HSV-1-infected GODZ−/− mice was significantly lower than in HSV-1-infected wild-type (WT) mice. The levels of UL20, gK, and gB transcripts in the corneas of HSV-1-infected GODZ−/− mice on day 5 postinfection were markedly lower than in WT mice, whereas only UL20 transcripts were reduced in trigeminal ganglia (TG). In addition, HSV-1-infected GODZ−/− mice showed notably lower levels of corneal scarring, and HSV-1 latency reactivation was also reduced. Thus, normal HSV-1 infectivity and viral pathogenesis are critically dependent on GODZ-mediated palmitoylation of viral UL20. IMPORTANCE HSV-1 infection is widespread. Ocular infection can cause corneal blindness; however, approximately 70 to 90% of American adults exposed to the virus show no clinical symptoms. In this study, we show for the first time that the absence of a zinc finger protein called GODZ affects primary and latent infection, as well as reactivation, in ocularly infected mice. The reduced virus infectivity is due to the absence of the GODZ interaction with HSV-1 UL20. These results strongly suggest that binding of UL20 to GODZ promotes virus infectivity in vitro and viral pathogenesis in vivo.
Early Life Health Interventions and Academic Achievement

This paper studies the effect of improved early life health care on mortality and long-run academic achievement in school. We use the idea that medical treatments often follow rules of thumb for assigning care to patients, such as the classification of Very Low Birth Weight (VLBW ), which assigns infants special care at a specific birth weight cutoff. Using detailed administrative data on schooling and birth records from Chile and Norway, we establish that children who receive extra medical care at birth have lower mortality rates and higher test scores and grades in school. These gains are in the order of 0.15–0.22 standard deviations.
Impact of obstructive sleep apnea in transsphenoidal pituitary surgery: An analysis of inpatient data

Although previous studies have reported increased perioperative complications among obstructive sleep apnea (OSA) patients undergoing any surgery requiring general anesthesia, there is a paucity of literature addressing the impact of OSA on postoperative transsphenoidal surgery (TSS) complications. The aim of this study was to analyze postoperative outcomes in transsphenoidal pituitary surgery patients with OSA. Secondarily, we examined patient characteristics and comorbidities.
The Spanish-Version of the Subjective Vitality Scale: Psychometric Properties and Evidence of Validity

Abstract The Subjective Vitality Scale (SVS) assess the subjective experience of being full of energy and alive, a clinically relevant outcome measure of positive psychological well-being. The purpose of this paper was to translate the 7-item SVS into Spanish and examine its psychometric properties. In Study 1 (n = 790 adolescents) and Study 2 (n = 130 athletes) reliability and exploratory factor analysis (EFA) were carried out. In Study 1 and Study 3 (n = 197 dancers) evidence of validity of inferences based on SVS scores estimating relationships with other variables (life satisfaction, global self-esteem and emotional and physical exhaustion) was obtained. In Study 2 invariance across time was tested. Finally in Study 3, the factorial structure was cross-validated using confirmatory factor analysis (CFA). Results of EFA showed a one-factor solution. CFA also supported a unidimensional factor structure for the Spanish 6-item SVS (RMSEA = .050 (90% CI = .00, .080); NNFI = . 993; CFI = . 996). Reliability analysis indicated a strong internal consistency in all study samples (α ranged from .82 to .89). Further, results from multi-sample analysis supported the replicability of SVS factor structure across time. Finally, the SVS scores showed the expected correlations patterns (all them significant, p < .01) with the measured outcomes. In conclusion, the Spanish version of the SVS demonstrated adequate psychometric properties, indicating that the scale can be confidently used to measure the experience of possessing energy and aliveness; furthermore, differences across time can be meaningfully carried out.
Cognitive Function Among Antiretroviral Treatment–Naive Individuals Infected With Human Immunodeficiency Virus Type 1 Subtype G Versus CRF02_AG in Nigeria

Background Human immunodeficiency virus type 1 (HIV-1) subtype has been shown to be associated with disease progression. We compared cognitive function between individuals infected with HIV-1 subtype G and CRF02_AG in Nigeria. Methods For this cross-sectional study, samples were analyzed from 146 antiretroviral-naive participants. Genotypic analysis of plasma HIV RNA was performed by nested polymerase chain reaction of protease and reverse transcriptase genes, and sequences were aligned with curated HIV-1 subtype references. Cognitive status was determined using demographically adjusted T scores and global deficit score (GDS) obtained from a comprehensive neuropsychological test battery. Results A total of 76 (52.1%) participants were infected with CRF02_AG, 48 (32.8%) with subtype G, and 22 (15.1%) with other HIV-1 strains. In a multivariable linear regression adjusting for plasma HIV RNA, CD4 count, and depression score, mean global T score was lower among subtype G-infected compared with CRF02_AG-infected participants (mean difference, -3.0 [95% confidence interval {CI}, -5.2, to -.7]; P = .011). Also, T scores were significantly lower among subtype G- than CRF02_AG-infected participants for the speed of information processing, executive function, and verbal fluency ability domains. Adjusting for similar variables in a logistic regression, the odds of global cognitive impairment (GDS ≥0.5) were 2.2 times higher among subtype G compared with CRF02_AG-infected participants (odds ratio, 2.2 [95% CI, .9-5.4]; P = .078). Conclusions Cognitive performance was significantly worse among antiretroviral-naive individuals with HIV-1 subtype G vs CRF02_AG infection. Further studies are required to characterize the mechanistic basis for these differences.
Predictors of depression among patients on art in a rural health district in North West Cameroon

ABSTRACT Depression in people living with HIV/AIDS (acquired immune-deficiency syndrome) (PLWHA) increases risky HIV transmission behaviour, disease progression to AIDS, negatively affects drug adherence and is thus a risk for the development of drug-resistant strains. This study sought to identify predictors of depression in rural Cameroon. A cross-sectional analytic study was carried out from September 2013 to November 2013 in the Mbengwi district hospital of the North West region. We measured depression (PHQ-9 (nine-item Patient Health Questionnaire)), clinical and demographic characteristics of patients on antiretroviral therapy (ART). Means, proportions and a stepwise logistic regression model were fit to describe participants’ characteristics and predictors of depression in the study population. Of the 202 recruited patients, 58(28.7%) had a positive depression screen. Independent predictors of depression included monthly income less than 20,000 FCFA (US$40), (adjusted odds ratio (aOR) = 2.47; 95% CI = 1.18–5.18), CD4 count <200 cls/µl (aOR = 7.56; 95% CI = 2.46–23.30) and presence of AIDS symptoms (aOR = 4.29; 95% CI = 2.09–8.81). There was no significant correlation between duration on ART, marital status, age, gender and depression. Early diagnosis and treatment of depressed patients need to be incorporated into intervention programmes, which might improve patient outcomes. More research is needed to investigate the impact of antidepressant therapy in PLWHA on the evolution of treatment.
Intestinal Epithelial Cell Endoplasmic Reticulum Stress and Inflammatory Bowel Disease Pathogenesis: An Update Review

The intestinal epithelial cells serve essential roles in maintaining intestinal homeostasis, which relies on appropriate endoplasmic reticulum (ER) function for proper protein folding, modification, and secretion. Exogenous or endogenous risk factors with an ability to disturb the ER function can impair the intestinal barrier function and activate inflammatory responses in the host. The last decade has witnessed considerable progress in the understanding of the functional role of ER stress and unfolded protein response (UPR) in the gut homeostasis and its significant contribution to the pathogenesis of inflammatory bowel disease (IBD). Herein, we review recent evidence supporting the viewpoint that deregulation of ER stress and UPR signaling in the intestinal epithelium, including the absorptive cells, Paneth cells, goblet cells, and enteroendocrine cells, mediates the action of genetic or environmental factors driving colitis in experimental animals and IBD patients. In addition, we highlight pharmacologic application of chaperones or small molecules that enhance protein folding and modification capacity or improve the function of the ER. These molecules represent potential therapeutic strategies in the prevention or treatment of IBD through restoring ER homeostasis in intestinal epithelial cells.
Ventral, but not dorsal, hippocampus inactivation impairs reward memory expression and retrieval in contexts defined by proximal cues

The hippocampus (HPC) has been widely implicated in the contextual control of appetitive and aversive conditioning. However, whole hippocampal lesions do not invariably impair all forms of contextual processing, as in the case of complex biconditional context discrimination, leading to contention over the exact nature of the contribution of the HPC in contextual processing. Moreover, the increasingly well‐established functional dissociation between the dorsal (dHPC) and ventral (vHPC) subregions of the HPC has been largely overlooked in the existing literature on hippocampal‐based contextual memory processing in appetitively motivated tasks. Thus, the present study sought to investigate the individual roles of the dHPC and the vHPC in contextual biconditional discrimination (CBD) performance and memory retrieval. To this end, we examined the effects of transient post‐acquisition pharmacological inactivation (using a combination of GABAA and GABAB receptor agonists muscimol and baclofen) of functionally distinct subregions of the HPC (CA1/CA3 subfields of the dHPC and vHPC) on CBD memory retrieval. Additional behavioral assays including novelty preference, light‐dark box and locomotor activity test were also performed to confirm that the respective sites of inactivation were functionally silent. We observed robust deficits in CBD performance and memory retrieval following inactivation of the vHPC, but not the dHPC. Our data provides novel insight into the differential roles of the ventral and dorsal HPC in reward contextual processing, under conditions in which the context is defined by proximal cues.
Stabilisation of the trend in prevalence of childhood overweight and obesity in Spain: 2001-11.

BACKGROUNDS To ascertain whether the prevalence of childhood overweight and obesity had stabilised in Spain, in the same way as in other developed countries. METHODS Data were drawn from the 2001, 2006 and 2011 Spanish National Health Surveys. We estimated overweight and obesity on the basis of body mass index, and then calculated the prevalence of overweight and obesity for each year studied among boys and girls, respectively, in two different age groups; 5 -9 and 10 -15 years. The statistical significance of the trend in prevalence was evaluated using the chi-squared test. RESULTS The trend in the prevalence of overweight was not significant, with the magnitude generally proving similar in 2006 and 2011, e.g. prevalence among girls was 37.2% in 2006 and 37.5% in 2011 in the 5-9 age group, and 17.7% in 2006 and 17.5% in 2011 in the 10-15 age group. The magnitude of the prevalence of obesity in each sex and age group was similar across the 3 years of study, except in the case of boys aged 5-9 years, among whom a significant downward trend was observed, with prevalence declining from 16.8% in 2001 to 14.4% in 2006 and 12.6% in 2011. CONCLUSION In Spain, the prevalence of childhood overweight and obesity stabilised during the first decade of the present century.
Influence of excessive exercise on immunity, metabolism, and gut microbial diversity in an overtraining mice model

The purpose of this study was to evaluate the negative influence of excessive exercise on immunity, substance and energy metabolism as well as gut microbiota in mice. Firstly, an overtraining model of Male Kunming mice was established by high‐intensity swimming exercise for 4 weeks. Then, a series of evaluation indicators, including the routine blood analysis, immune organ coefficient, digestive enzymes, and aquaporins expression levels of small intestine and colon tissue, histological examinations of liver, spleen, small intestine, and colon, were determined based on this model. Furthermore, 16S rRNA gene sequencing was also employed to measure the microbial composition in gut. The results found that immune parameters, substance and energy metabolism of all mice was altered and disturbed after high‐intensity swimming for 4 weeks, led to an atrophy of thymus and spleen as well as abnormal structural changes in liver when compared to non‐swimming mice. Besides, excessive swimming mice had lower microbial diversity compared to non‐swimming mice. However, there was no significant difference in gut microbial taxa between the two groups. The data indicated that excessive exercise exhibits negative impacts on immunity, substance and energy metabolism as well as gut microbial diversity.
Practical considerations for large-scale gut microbiome studies

Abstract First insights on the human gut microbiome have been gained from medium-sized, cross-sectional studies. However, given the modest portion of explained variance of currently identified covariates and the small effect size of gut microbiota modulation strategies, upscaling seems essential for further discovery and characterisation of the multiple influencing factors and their relative contribution. In order to guide future research projects and standardisation efforts, we here review currently applied collection and preservation methods for gut microbiome research. We discuss aspects such as sample quality, applicable omics techniques, user experience and time and cost efficiency. In addition, we evaluate the protocols of a large-scale microbiome cohort initiative, the Flemish Gut Flora Project, to give an idea of perspectives, and pitfalls of large-scale faecal sampling studies. Although cryopreservation can be regarded as the gold standard, freezing protocols generally require more resources due to cold chain management. However, here we show that much can be gained from an optimised transport chain and sample aliquoting before freezing. Other protocols can be useful as long as they preserve the microbial signature of a sample such that relevant conclusions can be drawn regarding the research question, and the obtained data are stable and reproducible over time.
The Cytogenetic Effect of Copper in Experimental Hypocupermic Goats

1. Department of animal medicine and infectious diseases. (Animal Medicine) Faculty of veterinary medicine-Sadat city university. Sadat city, Egypt 2. Department of animal medicine and infectious diseases. (infectious diseases) Faculty of veterinary medicineSadat city university. Sadat city, Egypt 3. Department of Parasitology and Animal Diseases. Veterinary Research Division, National Research Center, Dokki, Egypt.