Miracle-dz/UniFAR-FTUs huggingface dataset:
BRCT-domain protein BRIT1 influences class switch recombination

Significance Class switch recombination (CSR), a B-cell–specific reaction essential for optimal antibody responses, proceeds through the deliberate generation of DNA breaks. Although these breaks are obligatory intermediates of class switching, their improper resolution not only impairs immune responses but also promotes oncogenic translocations. The pathways and mechanisms that participate in the repair of such lesions are yet to be fully elucidated. In this work, we have identified a BRCT domain containing protein BRIT1 as an effector of the DNA repair phase of CSR. We show that B cells lacking BRIT1 are impaired in undergoing class switching due to an inability to repair DNA breaks efficiently. This work thus has significant implications in both immunity and cancer. DNA double-strand breaks (DSBs) serve as obligatory intermediates for Ig heavy chain (Igh) class switch recombination (CSR). The mechanisms by which DSBs are resolved to promote long-range DNA end-joining while suppressing genomic instability inherently associated with DSBs are yet to be fully elucidated. Here, we use a targeted short-hairpin RNA screen in a B-cell lymphoma line to identify the BRCT-domain protein BRIT1 as an effector of CSR. We show that conditional genetic deletion of BRIT1 in mice leads to a marked increase in unrepaired Igh breaks and a significant reduction in CSR in ex vivo activated splenic B cells. We find that the C-terminal tandem BRCT domains of BRIT1 facilitate its interaction with phosphorylated H2AX and that BRIT1 is recruited to the Igh locus in an activation-induced cytidine deaminase (AID) and H2AX-dependent fashion. Finally, we demonstrate that depletion of another BRCT-domain protein, MDC1, in BRIT1-deleted B cells increases the severity of CSR defect over what is observed upon loss of either protein alone. Our results identify BRIT1 as a factor in CSR and demonstrate that multiple BRCT-domain proteins contribute to optimal resolution of AID-induced DSBs.
The DnaJ Gene Family in Pepper (Capsicum annuum L.): Comprehensive Identification, Characterization and Expression Profiles

The DnaJ proteins which function as molecular chaperone played critical roles in plant growth and development and response to heat stress (HS) and also called heat shock protein 40 based on molecular weight. However, little was reported on this gene family in pepper. Recently, the release of the whole pepper genome provided an opportunity for identifying putative DnaJ homologous. In this study, a total of 76 putative pepper DnaJ genes (CaDnaJ01 to CaDnaJ76) were identified using bioinformatics methods and classified into five groups by the presence of the complete three domains (J-domain, zinc finger domain, and C-terminal domain). Chromosome mapping suggested that segmental duplication and tandem duplication were occurred in evolution. The multiple stress-related cis-elements were found in the promoter region of these CaDnaJ genes, which indicated that the CaDnaJs might be involved in the process of responding to complex stress conditions. In addition, expression profiles based on RNA-seq showed that the 47 CaDnaJs were expressed in at least one tissue tested. The result implied that they could be involved in the process of pepper growth and development. qRT-PCR analysis found that 80.60% (54/67) CaDnaJs were induced by HS, indicated that they could participated in pepper response to high temperature treatments. In conclusion, all these results would provide a comprehensive basis for further analyzing the function of CaDnaJ members and be also significant for elucidating the evolutionary relationship in pepper.
Is this trail too crowded? A choice experiment to evaluate tradeoffs and preferences of park visitors in Garibaldi Park, British Columbia

Large crowds in parks can be a problem for park managers and visitors. However, perceptions of crowding are difficult to measure due to coping mechanisms deployed by park visitors. Furthermore, perceptions of crowding should not be measured in isolation, but rather as part of a suite of conditions that comprise the visitors’ outdoor experience. We used a dichotomous choice experiment with visual images and eight attributes to estimate park users’ utilities associated with their visitor experience in Garibaldi Provincial Park in British Columbia, Canada. Our visual method allowed us to control for background view and compare user preferences on hiking trails with preferences at final destinations. We find that utilities are more sensitive to crowding at viewpoints than to other aspects of the outdoor experience. Thus, visitor satisfaction and crowding perceptions are more likely to be defined by where visitors have these encounters rather than the total number of encounters.
The impact of dialysis modality on arterial stiffness in patients with end-stage renal disease

Background: Arterial stiffness determined by brachial–ankle pulse wave velocity (baPWV) has been established as a powerful predictor of cardiovascular mortality in hemodialysis (HD) patients. There are, however, few studies regarding the comparative impact of different renal replacement therapies (RRTs) on PWV. Therefore, we conducted a cross-sectional study to compare arterial wall properties and cardiac function between patients treated with continuous ambulatory peritoneal dialysis (CAPD) and those with HD who were matched for age, dialysis duration, and blood pressure. Methods: baPWV and transthoracic echocardiography (TTE) were performed in HD patients (n = 23) after 1 h of midweek dialysis session and CAPD patients (n = 26) with empty abdomen after drainage of dialysate. The baseline data were retrospectively reviewed. Results: baPWV was significantly higher in HD patients than in CAPD patients (18.1 ± 2.8 vs. 16.1 ± 2.7 m/s, p = 0.015). TTE revealed significantly increased E/E′, left atrial volume index (LAVI), and inferior vena cava (IVC) diameter index in HD patients compared with CAPD patients (p < 0.05). In a multivariate regression analysis adjusted for dialysis modality, age, systolic BP, residual glomerular filtration rate, diabetes, and echocardiographic parameters, HD was independently associated with increased baPWV. Conclusion: This study showed that HD patients had significantly increased arterial stiffness and severe diastolic dysfunction compared with CAPD patients.
An overview of patient safety climate in the VA.

OBJECTIVE To assess variation in safety climate across VA hospitals nationally. STUDY SETTING Data were collected from employees at 30 VA hospitals over a 6-month period using the Patient Safety Climate in Healthcare Organizations survey. STUDY DESIGN We sampled 100 percent of senior managers and physicians and a random 10 percent of other employees. At 10 randomly selected hospitals, we sampled an additional 100 percent of employees working in units with intrinsically higher hazards (high-hazard units [HHUs]). DATA COLLECTION Data were collected using an anonymous survey design. PRINCIPAL FINDINGS We received 4,547 responses (49 percent response rate). The percent problematic response--lower percent reflecting higher levels of patient safety climate--ranged from 12.0-23.7 percent across hospitals (mean=17.5 percent). Differences in safety climate emerged by management level, clinician status, and workgroup. Supervisors and front-line staff reported lower levels of safety climate than senior managers; clinician responses reflected lower levels of safety climate than those of nonclinicians; and responses of employees in HHUs reflected lower levels of safety climate than those of workers in other areas. CONCLUSIONS This is the first systematic study of patient safety climate in VA hospitals. Findings indicate an overall positive safety climate across the VA, but there is room for improvement.
Genetic inactivation of the adenosine A2A receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis

Studies with multiple sclerosis patients and animal models of experimental autoimmune encephalomyelitis (EAE) implicate adenosine and adenosine receptors in modulation of neuroinflammation and brain injury. Although the involvement of the A1 receptor has been recently demonstrated, the role of the adenosine A2A receptor (A2AR) in development of EAE pathology is largely unknown. Using mice with genetic inactivation of the A2A receptor, we provide direct evidence that loss of the A2AR exacerbates EAE pathology in mice. Compared with wild‐type mice, A2AR knockout mice injected with myelin oligodendroglia glycoprotein peptide had a higher incidence of EAE and exhibited higher neurological deficit scores and greater decrease in body weight. A2AR knockout mice displayed increased inflammatory cell infiltration and enhanced microglial cell activation in cortex, brainstem, and spinal cord. In addition, demyelination and axonal damage in brainstem were exacerbated, levels of Th1 cytokines increased, and Th2 cytokines decreased. Collectively, these findings suggest that extracellular adenosine acting at A2ARs triggers an important neuroprotective mechanism. Thus, the A2A receptor is a potential target for therapeutic approaches to multiple sclerosis.
Millimeter wave dosimetry of human skin

To identify the mechanisms of biological effects of mm waves it is important to develop accurate methods for evaluating absorption and penetration depth of mm waves in the epidermis and dermis. The main characteristics of mm wave skin dosimetry were calculated using a homogeneous unilayer model and two multilayer models of skin. These characteristics included reflection, power density (PD), penetration depth (δ), and specific absorption rate (SAR). The parameters of the models were found from fitting the models to the experimental data obtained from measurements of mm wave reflection from human skin. The forearm and palm data were used to model the skin with thin and thick stratum corneum (SC), respectively. The thin SC produced little influence on the interaction of mm waves with skin. On the contrary, the thick SC in the palm played the role of a matching layer and significantly reduced reflection. In addition, the palmar skin manifested a broad peak in reflection within the 83–277 GHz range. The viable epidermis plus dermis, containing a large amount of free water, greatly attenuated mm wave energy. Therefore, the deeper fat layer had little effect on the PD and SAR profiles. We observed the appearance of a moderate SAR peak in the therapeutic frequency range (42–62 GHz) within the skin at a depth of 0.3–0.4 mm. Millimeter waves penetrate into the human skin deep enough (δ = 0.65 mm at 42 GHz) to affect most skin structures located in the epidermis and dermis. Bioelectromagnetics 29:65–70, 2008. © 2007 Wiley‐Liss, Inc.
The Results of Surgical Treatment for Adult Scoliosis

This study was done to define and characterize those adult patients with scoliosis who will have problems of pain and/or progression leading to a surgical procedure and to review the results of these surgical procedures. The authors reviewed the cases of 49 adult patients who had undergone surgical treatment for scoliosis (average follow-up, 34 months; range, 24-140 months). The patients were categorized according to age, which allowed analysis of the data comparing age and the incidence and level of pain, age versus the degree of curvature, and age versus the incidence of progression. The relative incidence of pain and progression as indications for surgery were found to vary with respect to age. In the younger groups, progression was more often the indication for surgery than in the older groups. The Younger groups also had larger curves than did the older groups, on average. The degree of pain was not found to correlate with the magnitude of the deformity. Surgical Complications occurred in 20 patients; however, 14 of these were minor complications during the perioperative period, which did result in any sequelae. Surgical treatment can be done with a relatively low serious complication rate and good results in terms of pain relief and reasonable correction of the deformity.
Macroeconomic performance index: a new approach to calculation of economic wellbeing

ABSTRACT Since the rise of the global financial crisis, there has been revival of interest in performance indexes that measure the overall stance of the economy and the wellbeing of households. Such indexes typically consist of inflation, growth, employment and long-term interest rates. We develop such an index by appending exchange rate and weighting each variable by the inverse of its variance in order to prevent the more volatile variable to dominate the index. We call this macroeconomic performance index (MPI) and argue that such an index better explains the overall economic stance especially in emerging economies. We generate the index using data from three emerging economies, namely Turkey, Brazil and Poland. Our analysis indicates that the index has a nonlinear structure and hence we analyse its behaviour using threshold autoregressive (TAR) model. It is observed that MPI captures the economic stance and main economic incidents quite successfully in each subject country. To further see the relevance of the MPI, we run TAR cointegration analysis with consumer confidence indexes (CCIs) for the subject countries with TAR cointegration test. The results indicate long-term relationship between the MPI and CCI in all three countries.
Aggression in Young Adults — A Matter of Short Sleep and Social Jetlag?

Evening orientation and sleep duration have been linked with aggression and problematic behaviors, but no study has used an explicit aggression questionnaire. The present study used the Buss-Perry Aggression Questionnaire based on physical aggression, verbal aggression, anger, and hostility, as well as questionnaires on the timing of sleep and sleep duration to assess this relationship in young adult men. The Composite Scale of Morningness was used to assess circadian preference; sleep-wake variables (wake time and sleep onset time on weekdays and on weekend days) were used to calculate midpoint of sleep, social jetlag, and sleep duration. Results indicated that sleep duration correlated negatively with verbal aggression, physical aggression, and anger. Short sleepers were more aggressive. Using multivariate analysis of variance, shorter sleep duration was a significant predictor of verbal aggression and anger. Concerning physical aggression, social jetlag also contributed to the model. Morningness-eveningness was associated with the hostility scale with eveningness related to higher hostility. Men scored higher than women in physical and verbal aggression.
Identification of Novel Epstein-Barr Virus MicroRNA Genes from Nasopharyngeal Carcinomas

ABSTRACT MicroRNAs (miRNAs) represent a conserved class of small noncoding RNAs that are found in all higher eukaryotes as well as some DNA viruses. miRNAs are 20 to 25 nucleotides in length and have important regulatory functions in biological processes such as embryonic development, cell differentiation, hormone secretion, and metabolism. Furthermore, miRNAs have been implicated in the pathology of various diseases, including cancer. miRNA expression profiles not only classify different types of cancer but also may even help to characterize distinct tumor stages, therefore constituting a valuable tool for prognosis. Here we report the miRNA profile of Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) tissue samples characterized by cloning and sequencing. We found that all EBV miRNAs from the BART region are expressed in NPC tissues, whereas EBV miRNAs from the BHRF1 region are not found. Moreover, we identified two novel EBV miRNA genes originating from the BART region that have not been found in other tissues or cell lines before. We also identified three new human miRNAs which might be specific for nasopharyngeal tissues. We further show that a number of different cellular miRNAs, including miR-15a and miR-16, are up- or downregulated in NPC tissues compared to control tissues. We found that the tumor suppressor BRCA-1 is a target of miR-15a as well as miR-16, suggesting a miRNA role in NPC pathogenesis.
Predictors of long-term survival with pulmonary metastasectomy for osteosarcomas and soft tissue sarcomas.

AIM The control of pulmonary metastases is important for long-term survival of the patients with osteosarcomas and soft tissue sarcomas. METHODS To evaluate the efficacy of aggressive pulmonary metastasectomy for those patients, we reviewed 105 cases (44 osteosarcomas, and 61 soft tissue sarcomas) treated in our hospital. RESULTS The number of metastases was only the significant risk factor for the curability of the metastasectomy (logistic regression analysis, P=0.0274). The 5-year and 10-year survival rate were 43.6% and 32%. The curability was only independent prognostic factor on multivariate analysis (P=0.0008). CONCLUSIONS Early detection of pulmonary metastasis, multimodal perioperative treatment, and design for minimizing the volume of resected lung tissues will enable complete and repeat resections for the achievement of long-term survival.
Evaluation of orthostatic hypotension: relationship of a new self-report instrument to laboratory-based measures.

OBJECTIVE To compare measured autonomic deficits (composite autonomic severity score [CASS]) with a brief self-report scale we developed to measure severity of symptoms of orthostatic hypotension. PATIENTS AND METHODS Patients were recruited in 2 phases: from August to October 2002 and in April 2004. All patients underwent full evaluation in the autonomic laboratory, from which a CASS of autonomic deficits was derived. Patients also completed the 5-item self-report Orthostatic Grading Scale, which inquires about symptoms of orthostatic intolerance due to orthostatic hypotension (eg, severity, frequency, and interference with daily activities). RESULTS Of 145 patients, 97 (67%) had orthostatic hypotension. The 5-item scale demonstrated strong internal consistency (coefficient alpha=.91). Patients with orthostatic hypotension had significantly higher scores on each questionnaire item and CASS subscores than those without orthostatic hypotension. The scale items correlated significantly with each of the CASS subscores, maximally with the CASS adrenergic subscore. CONCLUSIONS Orthostatic hypotension is not the only cause of reduced orthostatic tolerance, and some patients may have orthostatic hypotension but be asymptomatic. Results of this study indicate that this 5-item questionnaire is a reliable and valid measure of the severity of symptoms of orthostatic hypotension and that it can supplement laboratory-based measures to provide a rapid, more complete clinical assessment. This questionnaire would also be useful as a brief screening device for orthostatic intolerance to aid physicians in identifying patients who may have orthostatic hypotension.
The testes‐specific bZip type transcription factor Tisp40 plays a role in ER stress responses and chromatin packaging during spermiogenesis

We previously reported that the spermatid‐specific transcription factor Tisp40 functions through UPRE and CRE. To investigate Tisp40 function in vivo, we generated TISP40(–/–) mice. TISP40(–/–) mice were born at expected ratios, were healthy, and mutant males bred normally. However, the ER stress‐response protein Grp78/BiP accumulated in the TISP40(–/–) testis and RAMP4 (Ribosome‐associated membrane protein 4) mRNA level was up‐regulated. Disruption of TISP40 caused ER stress and activation of caspase 12 but not caspase 9, leading to apoptosis of meiotic/postmeiotic germ cells. On the other hand, DAPI staining and electron microscopy revealed that epididymal sperm nuclei were abnormally relaxed in the TISP40(–/–) testis, a phenotype that was independent of the expression and maturation of transition proteins and protamines but due to abnormally retained histones. Histones localized to the cytoplasm as well as to the nucleus and were also retained in epididymal sperm. Histones H2A and H4 were dramatically up‐regulated and the acetylation of H2A, H2B and H4 was also enhanced in the TISP40(–/–) testis. Taken together, we conclude that Tisp40 plays an important role in the unfolded protein response of the testis and in regulating the maturation of sperm head nuclei.
A new Late Cretaceous iguanomorph from North America and the origin of New World Pleurodonta (Squamata, Iguania)

Iguanomorpha (stem + crown Iguania) is a diverse squamate clade with members that predominate many modern American lizard ecosystems. However, the temporal and palaeobiogeographic origins of its constituent crown clades (e.g. Pleurodonta (basilisks, iguanas, and their relatives)) are poorly constrained, mainly due to a meagre Mesozoic-age fossil record. Here, we report on two nearly complete skeletons from the Late Cretaceous (Campanian) of North America that represent a new and relatively large-bodied and possibly herbivorous iguanomorph that inhabited a semi-arid environment. The new taxon exhibits a mosaic of anatomical features traditionally used in diagnosing Iguania and non-iguanian squamates (i.e. Scleroglossa; e.g. parietal foramen at the frontoparietal suture, astragalocalcaneal notch in the tibia, respectively). Our cladistic analysis of Squamata revealed a phylogenetic link between Campanian-age North American and East Asian stem iguanomorphs (i.e. the new taxon + Temujiniidae). These results and our evaluation of the squamate fossil record suggest that crown pleurodontans were restricted to the low-latitude Neotropics prior to their early Palaeogene first appearances in the mid-latitudes of North America.
Distinct alterations in colonic morphology and physiology in two rat models of enhanced stress-induced anxiety and depression-like behaviour

Stress and anxiety are important causal and exacerbating factors in functional gastro-intestinal (GI) disorders such as irritable bowel syndrome. Stress affects GI motility, faecal transit and visceral pain sensitivity. Additionally, permeability and function of the gut epithelium, which acts as a barrier between the external environment and the body's internal milieu is altered by stress. However, the effects of an enhanced stress response on colonic morphology require further investigation. We have used two animal models of stress and anxiety, the maternally separated (MS) and Wistar Kyoto (WKY) rats to examine colonic morphology. These rats exhibit increased anxiety behaviours, visceral hypersensitivity and increased stress-induced defecation in the open field arena. At a morphological level, increased mucus secretion and an associated elevation in the number of mucosal goblet cells was observed in the high anxiety rats. Additionally, the mucosal layer was flattened in MS and WKY rats, a finding indicative of mild mucosal damage. Furthermore, the muscular layer of the distal colon in these animals was thickened, an observation that may have implications for faecal transit and visceral pain perception. This study provides evidence of altered colonic function and morphology in two animal models with a heightened response to stress.