Miracle-dz/UniFAR-FTUs huggingface dataset:
Rhizobium Nod Factor Signaling: Evidence for a G Protein–Mediated Transduction Mechanism

Rhizobium nodulation (Nod) factors are lipochitooligosaccharide signals that elicit key symbiotic developmental responses in the host legume root. In this study, we have investigated Nod factor signal transduction in the Medicago root epidermis by using a pharmacological approach in conjunction with transgenic plants expressing the Nod factor–responsive reporter construct pMtENOD12–GUS. Evidence for the participation of heterotrimeric G proteins in Nod factor signaling has come from three complementary observations: (1) the amphiphilic peptides mastoparan and Mas7, known G protein agonists, are able to mimic Nod factor–induced epidermal MtENOD12 expression; (2) growth of plants in nodulation-inhibiting conditions (10 mM NH4NO3) leads to a dramatic reduction in both Nod factor– and mastoparan-elicited gene expression; and (3) bacterial pertussis toxin, a well-characterized G protein antagonist, blocks the activities of both the Nod factor and mastoparan. In addition, we have found that antagonists that interfere with phospholipase C activity (neomycin and U73122) and Ca2+ influx/release (EGTA, La3+, and ruthenium red) block Nod factor/mastoparan activity. Taken together, these results are consistent with a Nod factor signal transduction mechanism involving G protein mediation coupled to the activation of both phosphoinositide and Ca2+ second messenger pathways.
Reasons for stimulant use among lation gay men in San Francisco: A comparison between methamphetamine and cocaine users

The literature on drug-using gay men has documented a strong relationship between methamphetamine (MA) use and high-risk sexual practices. Of particular concern is that MA use is associated with powerful sexual effects that may facilitate the transmission of HIV. As a group, Latino gay men show high risk for HIV infection, and such risk has been related to episodes of sex under the influence of drugs. However, little information exists about stimulant use among Latino gay men, and it is not known whether MA use in this population is similarly motivated by sexual effects. This study reports reasons for stimulant use in a sample of 300 Latino gay men randomly selected from social and sexual venues; only men who reported stimulant use in the last 6 months were included in the study. Of stimulant users, 51% (n=153) reported MA, 44% (n=133) reported cocaine, and 5% (n=14) reported crack as their “most frequently used stimulant” (MFS); reasons for use were assessed for the participant’s specific MFS. Reasons for stimulant use clustered by five main factors, including energy, sexual enhancement, social connection, coping with stressors, and focused work productivity. MA users gave reasons more frequently related to sexual enhancement (to have better sex, more sex, and more anal sex) whereas cocaine users gave reasons more often related to social connections (to be more sociable and to fit in with other gay men). These findings suggest that Latino gay men use stimulants for reasons that are important in their social, emotional, work, and sexual lives. Like non-Latino Whites, Latino gay men were found to rely on MA for reasons related to sexual enhancement, possibly to meet cultural expectations and norms of sexual prowess and sexual success in the gay community.
NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases

Background/Aims Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD). Methods One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing. Results None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined. Conclusions Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.
A novel fluorescent reporter detects plastic remodeling of mitochondria–ER contact sites

ABSTRACT Mitochondria–ER contact sites (MERCs) enable communication between the ER and mitochondria and serve as platforms for many cellular events, including autophagy. Nonetheless, the molecular organization of MERCs is not known, and there is no bona fide marker of these contact sites in mammalian cells. In this study, we designed a genetically encoded reporter using split GFP protein for labeling MERCs. We subsequently analyzed its distribution and dynamics during the cell cycle and under stressful cellular conditions such as starvation, apoptosis and ER stress. We found that MERCs are dynamic structures that undergo remodeling within minutes. Mitochondrial morphology, but not ER morphology, affected the distribution of MERCs. We also found that carbonyl cyanidem-chlorophenyl hydrazone (CCCP) and oligomycin A treatment enhanced MERC formation. The stimulations that led to apoptosis or autophagy increased the MERC signal. By contrast, increasing cellular lipid droplet load did not change the pattern of MERCs. Summary: A split GFP-based fluorescent reporter can be used to monitor the remodeling of mitochondria–ER contact sites
Heart Rate and Use of Beta-Blockers in Stable Outpatients with Coronary Artery Disease

Background Heart rate (HR) is an emerging risk factor in coronary artery disease (CAD). However, there is little contemporary data regarding HR and the use of HR-lowering medications, particularly beta-blockers, among patients with stable CAD in routine clinical practice. The goal of the present analysis was to describe HR in such patients, overall and in relation to beta-blocker use, and to describe the determinants of HR. Methods and Findings CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis of >50%, or chest pain associated with proven myocardial ischemia. A total of 33,438 patients from 45 countries in Europe, the Americas, Africa, Middle East, and Asia/Pacific were enrolled between November 2009 and July 2010. Most of the 33,177 patients included in this analysis were men (77.5%). Mean (SD) age was 64.2 (10.5) years, HR by pulse was 68.3 (10.6) bpm, and by electrocardiogram was 67.2 (11.4) bpm. Overall, 44.0% had HR≥70 bpm. Beta-blockers were used in 75.1% of patients and another 14.4% had intolerance or contraindications to beta-blocker therapy. Among 24,910 patients on beta-blockers, 41.1% had HR≥70 bpm. HR≥70 bpm was independently associated with higher prevalence and severity of angina, more frequent evidence of myocardial ischemia, and lack of use of HR-lowering agents. Conclusions Despite a high rate of use of beta-blockers, stable CAD patients often have resting HR≥70 bpm, which was associated with an overall worse health status, more frequent angina and ischemia. Further HR lowering is possible in many patients with CAD. Whether it will improve symptoms and outcomes is being tested. Trial Registration Controlled-Trials.com ISRCTN43070564
Measuring Joint Hypermobility Using the Beighton Scale in Children With Intellectual Disability

Purpose: To determine the feasibility and reliability of using the 9-point Beighton Hypermobility Score (9-BHS) with youth with intellectual disabilities using a least to most prompting technique. Method: One hundred one youth (5-18 years old) enrolled in the study. Two separate evaluations, separated by 3 to 4 weeks, were performed on 25 participants. Results: Ninety assented to the test, and 85 performed all 9-BHS maneuvers. Scores were not significantly different for age and gender, but participants with Down syndrome had significantly higher scores. Test-retest scores showed 80% to 90% agreement (n = 25). Cohen kappa ranged from moderate (0.41-0.60) to perfect (1.0) for the 9 maneuvers, and an ICC of 0.88 was found for total scores. Conclusion: The results demonstrate that the use of the 9-BHS in youth with intellectual disabilities in the manner described is feasible and reliable.
A new monoclinic polymorph of trans-dichloridodipyridinepalladium(II)

In the structure of the title compound, [PdCl2(C5H5N)2], the PdII atom is located on an inversion centre and the pyridine rings are coplanar. There is intermolecular π–π stacking between the pyridyl rings, with a centroid-to-centroid separation of 3.916 (1) Å. The structure is a new polymorph of two previously determined structures [Viossat, Dung & Robert (1993 ▶). Acta Cryst. C49, 84–85; Liao & Lee (2006 ▶). Acta Cryst. E62, m680–m681].
Extended follow-up of a cohort of british chemical workers exposed to formaldehyde.

BACKGROUND Formaldehyde is mutagenic and, when inhaled at high concentrations, carcinogenic in rats. Some epidemiologic studies have linked occupational exposure to formaldehyde with cancers of the nose, nasopharynx, and lung, but the evidence for human carcinogenicity has been inconsistent and requires clarification. METHODS We extended by 11 years the follow-up of an existing cohort of 14 014 men employed after 1937 at six British factories where formaldehyde was produced or used. Subjects had been identified from employment records, and their jobs had been classified for potential exposure to formaldehyde. Standardized mortality ratios (SMRs) were derived using the person-years method and were compared with the expected numbers of deaths for the national population. RESULTS During follow-up through December 31, 2000, 5185 deaths were recorded, including two from sino-nasal cancer (2.3 expected) and one from nasopharyngeal cancer (2.0 expected). Relative to the national population, mortality from lung cancer was increased among those who worked with formaldehyde, particularly in men in the highest of four estimated exposure categories (>2 ppm) (SMR = 1.58, 95% confidence interval = 1.40 to 1.78), and the increase persisted after adjustment for local geographic variations in mortality (SMR = 1.28, 95% confidence interval = 1.13 to 1.44). However, there was a statistically nonsignificant decrease in the risk of death from lung cancer with duration of high exposure (P(trend) =. 18), and this risk showed no trend with time since first high exposure (P(trend) =. 99). CONCLUSIONS The evidence for human carcinogenicity of formaldehyde remains unconvincing. Although a small effect on sino-nasal or nasopharyngeal cancer cannot be ruled out, a possible increase in the risk of lung cancer is a greater concern.
‘Hotspots’ of Antigen Presentation Revealed by Human Leukocyte Antigen Ligandomics for Neoantigen Prioritization

The remarkable clinical efficacy of the immune checkpoint blockade therapies has motivated researchers to discover immunogenic epitopes and exploit them for personalized vaccines. Human leukocyte antigen (HLA)-binding peptides derived from processing and presentation of mutated proteins are one of the leading targets for T-cell recognition of cancer cells. Currently, most studies attempt to identify neoantigens based on predicted affinity to HLA molecules, but the performance of such prediction algorithms is rather poor for rare HLA class I alleles and for HLA class II. Direct identification of neoantigens by mass spectrometry (MS) is becoming feasible; however, it is not yet applicable to most patients and lacks sensitivity. In an attempt to capitalize on existing immunopeptidomics data and extract information that could complement HLA-binding prediction, we first compiled a large HLA class I and class II immunopeptidomics database across dozens of cell types and HLA allotypes and detected hotspots that are subsequences of proteins frequently presented. About 3% of the peptidome was detected in both class I and class II. Based on the gene ontology of their source proteins and the peptide’s length, we propose that their processing may partake by the cellular class II presentation machinery. Our database captures the global nature of the in vivo peptidome averaged over many HLA alleles, and therefore, reflects the propensity of peptides to be presented on HLA complexes, which is complementary to the existing neoantigen prediction features such as binding affinity and stability or RNA abundance. We further introduce two immunopeptidomics MS-based features to guide prioritization of neoantigens: the number of peptides matching a protein in our database and the overlap of the predicted wild-type peptide with other peptides in our database. We show as a proof of concept that our immunopeptidomics MS-based features improved neoantigen prioritization by up to 50%. Overall, our work shows that, in addition to providing huge training data to improve the HLA binding prediction, immunopeptidomics also captures other aspects of the natural in vivo presentation that significantly improve prediction of clinically relevant neoantigens.
Net Expression Inhibits the Growth of Pancreatic Ductal Adenocarcinoma Cell PL45 In Vitro and In Vivo

Pancreatic ductal adenocarcinoma has a poor prognosis due to late diagnosis and a lack of effective therapeutic options. Thus, it is important to better understand its molecular mechanisms and to develop more effective treatments for the disease. The ternary complex factor Net, which exerts its strong inhibitory function on transcription of proto-oncogene gene c-fos by forming ternary complexes with a second transcription factor, has been suspected of being involved in pancreatic cancer and other tumors biology. In this study, we found that the majority of pancreatic ductal adenocarcinoma tissues and cell lines had weak or no expression of Net, whereas significantly high level of Net expression occurred in paired adjacent normal tissues we studied. Furthermore, using in vitro and in vivo model systems, we found that overexpression of Net inhibited cell growth and survival and induced cell apoptosis in human pancreatic ductal adenocarcinoma cell PL45; the mechanisms by which Net inhibited the cell cycle progression were mainly through P21-Cyclin D1/CDK4 Pathway. Our data thus suggested that Net might play an important role in pancreatic carcinogenesis, possibly by acting as a tumor suppressor gene.
Compound Heterozygote of a Novel Missense Mutation (p.K402T) and a Double Missense Mutation (p.[G71R;Y486D]) in Type II Crigler-Najjar Syndrome

362 C rigler-Najjar syndrome type II (CN-II; # Mendelian Inheritance in Man [MIM] 606785) is a moderate type of hereditary unconjugated hyperbilirubinemia caused by mutations of the bilirubin uridine diphosphate-glucuronosyltransferase gene UGT1A1 (1). Diagnosis of this syndrome is important in distinguishing it from the severe phenotype of hereditary unconjugated hyperbilirubinemia, known as Crigler-Najjar syndrome type I (CNI; MIM #218800). The serum bilirubin concentration of CN-I is more than 20 mg/dL (343mmol/L) and can reach 30 to 50 mg/dL (513–855mmol/L). Patients with CN-I are in danger of kernicterus and must receive daily phototherapy right from the neonatal period (2). They should undergo liver transplantation to avoid kernicterus. Hyperbilirubinemia in patients with CN-II is less severe than CN-I (1). The serum bilirubin concentration of CN-II is seldom harmful after the neonatal period. The serum bilirubin concentration of patients with CN-I or CN-II is often intermediate between the values specifying the 2 syndromes. Accurate diagnosis of the 2 syndromes is necessary for appropriate treatment. A phenobarbitalloading test is effective in differential diagnosis (3), but the results are not always clear, in which case genetic diagnosis is necessary. The cDNA of UGT1A1 was first cloned in 1991, and a large number of mutations have been found in patients with CN-I, CN-II, and Gilbert syndrome (GS; MIM #143500) (4,5). Mutations of UGT1A1 differ according to ethnic grouping. East Asians display many unique mutations; in particular, a major polymorphic mutation is c.211G>A: p.G71R in exon 1 of UGT1A1 (6). p.G71R reduces glucuronidation ability to less than 32% of wild type and is an important cause of Gilbert syndrome (7). One of the most important causes of CN-II in Asians is a double missense mutation, p.[G71R;Y486D] (8). This double mutation has hardly ever been detected in white and African populations.
Reproductive Health Care for Women with Spina Bifida

Women with spina bifida have unique health care concerns and as the life expectancy of this population increases, they are transitioning from adolescence to womanhood and entering their reproductive years with little information about what to expect. Likewise, their health care providers do not have the benefit of evidence-based research that comprehensively addresses the issues these women may face related to reproduction or aging. Few studies have focused on the effects that spina bifida may have on these women's reproductive systems, nor has attention been paid to the effects that possible reproductive endocrine changes may have on their disability. Needless to say, concerns about sexuality, sexual function, and pregnancy are just as important to these women as they are to their able-bodied counterparts.
Democratic Values and Teacher Self-Efficacy Perceptions: A Case of Pre-Service English Language Teachers in Turkey

This study investigated democratic values of pre-service English language teachers in relation to their teacher self-efficacy perceptions in a Turkish context. It also examined the possible relationships between gender, grade and democratic values and self- efficacy perceptions. A questionnaire survey was conducted with 294 pre-service teachers. Findings show that they had a high level of democratic values while senior students reported the highest rate of democratic values. Results did not show a significant difference between democratic values and gender. Participants also reported a moderately high level of self-efficacy. Lastly, correlation was found between their democratic values and self-efficacy perceptions.
Program development by stepwise refinement

The creative activity of programming--to be distinguished from coding--is usually taught by examples serving to exhibit certain techniques. It is here considered as a sequence of design decisions concerning the decomposition of tasks into subtasks and of data into data structures. The process of successive refinement of specifications is illustrated by a short but nontrivial example, from which a number of conclusions are drawn regarding the art and the instruction of programming.
A non-monotonic method for large-scale non-negative least squares

We present a new algorithm for solving the non-negative least-squares (NNLS) problem. Our algorithm extends the unconstrained quadratic optimization algorithm of Barzilai and Borwein (BB) [J. Barzilai and J. M. Borwein; Two-Point Step Size Gradient Methods. IMA J. Numer. Anal. 1988. ] to handle nonnegativity constraints. Our extension differs from other constrained BB variants in simple but crucial aspects, the most notable being our modification to the BB stepsize itself. Our stepsize computation takes into account the nonnegativity constraints, and is further refined by a stepsize scaling strategy. These changes, in combination with orthogonal projections onto the nonnegative orthant, yield an effective NNLS algorithm. We compare our algorithm with several competing approaches, including established bound-constrained solvers, popular BB-based methods, and also a specialised NNLS algorithm. On several synthetic and real-world datasets our method displays highly competitive empirical performance.
Referred speech-language and hearing complaints in the western region of São Paulo, Brazil

OBJECTIVE: The aim of this study was to characterize the epidemiological profile of the population attending primary health care units in the western region of the city of São Paulo, Brazil, highlighting referred speech-language and hearing complaints. METHOD: This investigation was a cross-sectional observational study conducted in primary health care units. Household surveys were conducted and information was obtained from approximately 2602 individuals, including (but not limited to) data related to education, family income, health issues, access to public services and access to health services. The speech-language and hearing complaints were identified from specific questions. RESULTS: Our results revealed that the populations participating in the survey were heterogeneous in terms of their demographic and economic characteristics. The prevalence of referred speech-language and hearing complaints in this population was 10%, and only half the users of the public health system in the studied region who had complaints were monitored or received specific treatment. CONCLUSIONS: The results demonstrate the importance of using population surveys to identify speech-language and hearing complaints at the level of primary health care. Moreover, these findings highlight the need to reorganize the speech-language pathology and audiology service in the western region of São Paulo, as well as the need to improve the Family Health Strategy in areas that do not have a complete coverage, in order to expand and improve the territorial diagnostics and the speech-language pathology and audiology actions related to the prevention, identification, and rehabilitation of human communication disorders.
A Space-Time Code Design for Omnidirectional Transmission in Massive MIMO Systems

Omnidirectional space-time coding has been proposed recently for massive multiple-input multiple-output (MIMO) systems to broadcast common information. In these systems, signals across all transmit antennas have constant power and their discrete Fourier transforms have constant power as well, where the number of discrete frequencies is the number of transmit antennas. When the number of transmit antennas is large, i.e., it is a massive MIMO system, signals received at these discrete angles have constant mean power at any instant time. Furthermore, spatial diversity can be achieved. In this letter, we propose a different design of such a transmission, where the sum of received signal powers in a few consecutive time slots is constant at any angle (not just discrete angles). The other two properties mentioned above, namely, constant transmission power across antennas at any instant time and achieving spatial diversity, are still maintained. Furthermore, it has the fast symbol-wise maximum-likelihood decoding.