Miracle-dz/UniFAR-FTUs huggingface dataset:
The long tale of the calcium activated Cl− channels in olfactory transduction

ABSTRACT Ca2+-activated Cl− currents have been implicated in many cellular processes in different cells, but for many years, their molecular identity remained unknown. Particularly intriguing are Ca2+-activated Cl− currents in olfactory transduction, first described in the early 90s. Well characterized electrophysiologically, they carry most of the odorant-induced receptor current in the cilia of olfactory sensory neurons (OSNs). After many attempts to determine their molecular identity, TMEM16B was found to be abundantly expressed in the cilia of OSNs in 2009 and having biophysical properties like those of the native olfactory channel. A TMEM16B knockout mouse confirmed that TMEM16B was indeed the olfactory Cl− channel but also suggested a limited role in olfactory physiology and behavior. The question then arises of what the precise role of TMEM16b in olfaction is. Here we review the long story of this channel and its possible roles.
Advance Refundings of Municipal Bonds

Municipal bonds are often "advance refunded. " Bonds that are not yet callable are defeased by creating a trust that pays the interest up to the call date, and pays the call price. New debt, generally at lower interest rates, is issued to fund the trust. Issuing new securities generally has zero net present value. In this case, however, value is destroyed for the issuer through the pre-commitment to call. We estimate that for the typical bond in an advance refunding, the option value lost to the municipality is approximately 1% of the par value not including fees. This translates to an aggregate value lost of over $4 billion from 1996 to 2009 for the bonds in our sample, which are roughly half of the universe of advance refunded bonds that traded during the period. The worst 5% of the transactions represent a destruction of $2.9 billion for taxpayers. We discuss various motives for the transaction, and argue that a major one is the need for short-term budget relief. Advance refunding enables the issuer to borrow for current operating activities in exchange for higher interest payments after the call date. We find that municipalities in states with poor governance generally destroy the most value by advance refunding.
‘Fluid fields’ and the dynamics of risk in social research

In recent decades social scientists have expanded their understanding of risk in the field to extend from concern with participants to awareness of how researchers themselves may be exposed to a variety of physical, emotional, ethical and professional ‘dangers’. A variety of accounts have exposed the kinds of risks concerned with fieldwork, many of which are difficult to anticipate. However, this article takes a further step forward in considering the ways in which risks combine in the field, the coalescence of risk in particular circumstances, and the ways in which risk should be understood as dynamic and unpredictable. The article concludes that these considerations require researchers to take a leading role in assessing the risks that they face, that risks should not be considered as uniform for all team members in conjunction with projects involving multiple researchers, and that researchers should receive greater training on appropriate risk management in an effort to change the prevailing research culture in many institutions.
Inflammation-associated Cell Cycle–independent Block of Apoptosis by Survivin in Terminally Differentiated Neutrophils

Survivin has received great attention due to its expression in many human tumors and its potential as a therapeutic target in cancer. Survivin expression has been described to be cell cycle–dependent and restricted to the G2-M checkpoint, where it inhibits apoptosis in proliferating cells. In agreement with this current view, we found that survivin expression was high in immature neutrophils, which proliferate during differentiation. In contrast with immature cells, mature neutrophils contained only little or no survivin protein. Strikingly, these cells reexpressed survivin upon granulocyte/macrophage colony-stimulating factor (CSF) or granulocyte CSF stimulation in vitro and under inflammatory conditions in vivo. Moreover, survivin-deficient mature neutrophils were unable to increase their lifespan after survival factor exposure. Together, our findings demonstrate the following: (a) overexpression of survivin occurs in primary, even terminally differentiated cells and is not restricted to proliferating cells; and (b) survivin acts as an inhibitor of apoptosis protein in a cell cycle–independent manner. Therefore, survivin plays distinct and independent roles in the maintenance of the G2-M checkpoint and in apoptosis control, and its overexpression is not restricted to proliferating cells. These data provide new insights into the regulation and function of survivin and have important implications for the pathogenesis, diagnosis, and treatment of inflammatory diseases and cancer.
Genome-scale metabolic models as platforms for strain design and biological discovery

Genome-scale metabolic models (GEMs) have been developed and used in guiding systems’ metabolic engineering strategies for strain design and development. This strategy has been used in fermentative production of bio-based industrial chemicals and fuels from alternative carbon sources. However, computer-aided hypotheses building using established algorithms and software platforms for biological discovery can be integrated into the pipeline for strain design strategy to create superior strains of microorganisms for targeted biosynthetic goals. Here, I described an integrated workflow strategy using GEMs for strain design and biological discovery. Specific case studies of strain design and biological discovery using Escherichia coli genome-scale model are presented and discussed. The integrated workflow presented herein, when applied carefully would help guide future design strategies for high-performance microbial strains that have existing and forthcoming genome-scale metabolic models.
Endogenous CHRNA7-ligand SLURP1 as a potential tumor suppressor and anti-nicotinic factor in pancreatic cancer

Smoking is associated with increased risk and poorer prognosis of pancreatic ductal adenocarcinoma (PDAC). Nicotine acts through cholinergic nicotinic receptors, preferentially α7 (CHRNA7) that also binds the endogenous ligand SLURP1 (Secreted Ly-6/uPAR-Related Protein 1). The clinical significance of SLURP1 and its interaction with nicotine in PDAC are unclear. We detected similar levels of SLURP1 in sera from healthy donors and patients with chronic pancreatitis or PDAC; higher preoperative values were associated with significantly better survival in patients with resected tumors. Pancreatic tissue was not a source of circulating SLURP1 but contained diverse CHRNA7-expressing cells, preferentially epithelial and immune, whereas stromal stellate cells and a quarter of the tumor cells lacked CHRNA7. The CHRNA7 mRNA levels were decreased in PDAC, and CHRNA7high-PDAC patients lived longer. In CHRNA7high COLO357 and PANC-1 cultures, opposing activities of SLURP1 (anti-malignant/CHRNA7-dependent) and nicotine (pro-malignant/CHRNA7-infidel) were exerted without reciprocally interfering with receptor binding or downstream signaling. These data suggested that the ligands act independently and abolish each other’s effects through a mechanism resembling functional antagonism. Thus, SLURP1 might represent an inborn anti-PDAC defense being sensitive to and counteracting nicotine. Boosting SLURP1-CHRNA7 interaction might represent a novel strategy for treatment in high-risk individuals, i.e., smokers with pancreatic cancer.
Aging and Oxidative Stress Decrease Pineal Elongation Factor 2: In Vivo Protective Effect of Melatonin in Young Rats Treated With Cumene Hydroperoxide

We studied the alterations of Elongation Factor 2 (eEF2) in the pineal gland of aged rats as well as the possible protective role of exogenous melatonin on these changes in young rats treated with cumene hydroperoxide (CH), a compound that promotes lipid peroxidation and inhibits protein synthesis. The study was performed using male Wistar rats of 3 (control), 12, and 24 months and 3‐month‐old rats treated with CH, melatonin, and CH plus melatonin. We found that pineal eEF‐2 is affected by aging and CH, these changes being prevented by exogenous melatonin in the case of CH‐treated rats. The proteomic studies show that many other proteins are affected by aging and oxidative stress in the pineal gland. The results suggest that one of the possible mechanisms underlying pineal gland dysfunction during aging is the effect of lipid peroxidation on eEF‐2, which is a key component of protein synthesis machinery. J. Cell. Biochem. 118: 182–190, 2017. © 2016 Wiley Periodicals, Inc.
Quality of life in schizophrenic patients: the influence of sociodemographic and clinical characteristics and satisfaction with social support.

OBJECTIVE To evaluate the relationship of sociodemographic and clinical characteristics and satisfaction with social support with the quality of life of schizophrenic patients. METHODOLOGY This study included a sample of 268 participants. An interview was conducted to obtain sociodemographic and clinical data, supplemented with two assessment tools used to evaluate quality of life (World Health Organization Quality of Life instrument-Abbreviated version - WHOQOL-Bref) and satisfaction with social support (Social Support Satisfaction Scale - SSSS). Descriptive and inferential analyses were performed. RESULTS Most individuals were male (63.4%), with a mean age of 45.4 years, single (85.4%), living with their family (62.3%) and unemployed (90.3%). As for clinical characteristics, most had the disease for less than 20 years (50.7%), and 55.6% had at least one hospitalization within the last 5 years. Being employed and having had no hospitalization within the last 5 years were positively correlated with one or more WHOQOL-Bref domains. The results of the variables intimacy (p<0.001) and satisfaction with friends (p<0.001) were independently related to the total WHOQOL-Bref score. CONCLUSION Having a job, having had no hospitalization within the last 5 years and having greater satisfaction with social support are factors that positively influence quality of life among schizophrenics. It is therefore crucial that the psychosocial rehabilitation of patients with schizophrenia take these factors into account, increasing the support network, preventing relapses and promoting occupational activities.
Sex differences in fear conditioning in posttraumatic stress disorder

Background: Women are twice as likely as men to develop Posttraumatic Stress Disorder (PTSD). Abnormal acquisition of conditioned fear has been suggested as a mechanism for the development of PTSD. While some studies of healthy humans suggest that women are either no different or express less conditioned fear responses during conditioning relative to men, differences in the acquisition of conditioned fear between men and women diagnosed with PTSD has not been examined. Methods: Thirty-one participants (18 men; 13 women) with full or subsyndromal PTSD completed a fear conditioning task. Participants were shown computer-generated colored circles that were paired (CSþ) or unpaired (CSÀ) with an aversive electrical stimulus and skin conductance levels were assessed throughout the task. Results: Repeated measures ANOVA indicated a significant sex by stimulus interaction during acquisition. Women had greater differential conditioned skin conductance responses (CS þ trials compared to CSÀ trials) than did men, suggesting greater acquisition of conditioned fear in women with PTSD. Conclusions: In contrast to studies of healthy individuals, we found enhanced acquisition of conditioned fear in women with PTSD. Greater fear conditioning in women may either be a pre-existing vulnerability trait or an acquired phenomenon that emerges in a sex-dependent manner after the development of PTSD. Characterizing the underlying mechanisms of these differences is needed to clarify sex-related differences in the pathophysiology of PTSD. Women develop posttraumatic stress disorder (PTSD) at twice the rate of men, despite greater trauma exposure in men (Adamson et al., 2008; Breslau et al., 1998). Fear conditioning has been proposed as a core process in the development of PTSD (Orr et al., 2000; Pitman et al., 2000). During traumatic stress exposure, severe and prolonged threat result in a cascade of biological stress responding (Pitman et al., 2001) leading to the release of stress hormones and neuromodulators that are believed to enhance fear conditioning and memory consolidation, subsequently resulting in chronic symptoms that are characteristic of PTSD (Pitman, 1989; Pitman et al., 2000). However, little is known about potential sex differences in conditioning mechanisms associated with PTSD. presentations of the now conditioned stimuli are sufficient to elicit a conditioned response (CR) because of the prior CSeUCS associations. In conditioning models of PTSD, it is believed that neutral environmental cues present at the time of trauma exposure become associated with fear and arousal such that these previously innocuous stimuli can trigger conditioned fear responses even when danger is no longer …
RNA-Seq of Early-Infected Poplar Leaves by the Rust Pathogen Melampsora larici-populina Uncovers PtSultr3;5, a Fungal-Induced Host Sulfate Transporter

Biotroph pathogens establish intimate interactions with their hosts that are conditioned by the successful secretion of effectors in infected tissues and subsequent manipulation of host physiology. The identification of early-expressed pathogen effectors and early-modulated host functions is currently a major goal to understand the molecular basis of biotrophy. Here, we report the 454-pyrosequencing transcriptome analysis of early stages of poplar leaf colonization by the rust fungus Melampsora larici-populina. Among the 841,301 reads considered for analysis, 616,879 and 649 were successfully mapped to Populus trichocarpa and M. larici-populina genome sequences, respectively. From a methodological aspect, these results indicate that this single approach is not appropriate to saturate poplar transcriptome and to follow transcript accumulation of the pathogen. We identified 19 pathogen transcripts encoding early-expressed small-secreted proteins representing candidate effectors of interest for forthcoming studies. Poplar RNA-Seq data were validated by oligoarrays and quantitatively analysed, which revealed a highly stable transcriptome with a single transcript encoding a sulfate transporter (herein named PtSultr3;5, POPTR_0006s16150) showing a dramatic increase upon colonization by either virulent or avirulent M. larici-populina strains. Perspectives connecting host sulfate transport and biotrophic lifestyle are discussed.
CAN HYPOTHETICAL, QUESTIONS PREDICT ACTUAL, PARTICIPATION IN PUBLIC PROGRAMS? A FIELD VALIDITY TEST USING A PROVISION POINT MECHANISM

Niagara Mohawk Power Corporation utilized a demand revealing public good mechanism to implement a green electricity program for provision of renewable energy and planting trees. This GreenChoiceTM program provided an opportunity to test the reliability of contingent valuation for predicting actual participation levels. In this study, participation levels predicted by hypothetical open-ended and dichotomous choice questions are compared to a reference level obtained from the actual GreenChoiceTM program. This approach represents an important improvement over past public goods contingent valuation validity tests which have relied on voluntary contribution mechanisms to elicit actual willingness to pay, and thus are likely to overestimate hypothetical bias because of free riding. Yet, even with a demand revealing mechanism and controlling for awareness, hypothetical participation levels obtained from dichotomous choice responses are found to significantly exceed actual contributions. In contrast, open-ended responses predict actual contribution levels, in that hypothetical open-ended responses are not significantly different from actual responses. Calibration of hypothetical responses is also explored.
Estimating the Threshold Surface Density of Gp120-CCR5 Complexes Necessary for HIV-1 Envelope-Mediated Cell-Cell Fusion

Reduced expression of CCR5 on target CD4+ cells lowers their susceptibility to infection by R5-tropic HIV-1, potentially preventing transmission of infection and delaying disease progression. Binding of the HIV-1 envelope (Env) protein gp120 with CCR5 is essential for the entry of R5 viruses into target cells. The threshold surface density of gp120-CCR5 complexes that enables HIV-1 entry remains poorly estimated. We constructed a mathematical model that mimics Env-mediated cell-cell fusion assays, where target CD4+CCR5+ cells are exposed to effector cells expressing Env in the presence of a coreceptor antagonist and the fraction of target cells fused with effector cells is measured. Our model employs a reaction network-based approach to describe protein interactions that precede viral entry coupled with the ternary complex model to quantify the allosteric interactions of the coreceptor antagonist and predicts the fraction of target cells fused. By fitting model predictions to published data of cell-cell fusion in the presence of the CCR5 antagonist vicriviroc, we estimated the threshold surface density of gp120-CCR5 complexes for cell-cell fusion as ∼20 µm −2. Model predictions with this threshold captured data from independent cell-cell fusion assays in the presence of vicriviroc and rapamycin, a drug that modulates CCR5 expression, as well as assays in the presence of maraviroc, another CCR5 antagonist, using sixteen different Env clones derived from transmitted or early founder viruses. Our estimate of the threshold surface density of gp120-CCR5 complexes necessary for HIV-1 entry thus appears robust and may have implications for optimizing treatment with coreceptor antagonists, understanding the non-pathogenic infection of non-human primates, and designing vaccines that suppress the availability of target CD4+CCR5+ cells.
Molecular features of early onset adult myelodysplastic syndrome

Myelodysplastic syndromes are typically diseases of older adults. Patients in whom the onset is early may have distinct molecular and clinical features or reflect a demographic continuum. The identification of differences between “early onset” patients and those diagnosed at a traditional age has the potential to advance understanding of the pathogenesis of myelodysplasia and may lead to formation of distinct morphological subcategories. We studied a cohort of 634 patients with various subcategories of myelodysplastic syndrome and secondary acute myeloid leukemia, stratifying them based on age at presentation and clinical parameters. We then characterized molecular abnormalities detected by next-generation deep sequencing of 60 genes that are commonly mutated in myeloid malignancies. The number of mutations increased linearly with age and on average, patients >50 years of age had more mutations. TET2, SRSF2, and DNMT3A were more commonly mutated in patients >50 years old compared to patients ≤50 years old. In general, patients >50 years of age also had more mutations in spliceosomal, epigenetic modifier, and RAS gene families. Although there are age-related differences in molecular features among patients with myelodysplasia, most notably in the incidence of SRSF2 mutations, our results suggest that patients ≤50 years old belong to a disease continuum with a distinct pattern of early onset ancestral events.
Guduchi (Tinospora cordifolia): Biological and Medicinal properties, a review

Guduchi (Tinospora cordifolia) is commonly known as rasayana plant and its rejuvenating property is well reported in Ayurvedic and other ancient literature. It is a fairly common plant of the dry deciduous forests growing over hedges and small trees. Various parts of the plant are being prescribed in Ayurveda and other systems of medicine as a monoherbal or polyherbal preparation. In India, various extracts of the plant are used as a remedy for many diseases and are included in various polyherbal preparations used for the treatment of diabetes, hepatitis, etc. Since each part of guduchi has some medicinal property, it is very much commercially exploitable. During the last few decades considerable progress has been achieved regarding its biological activity and medicinal applications. Hence, it can be chosen as a source for the development of industrial products for treatment of various diseases. We have put an effort to compile available literature on research work done for this plant mainly on its therapeutic utility till recent, from the early beginning. This review gives a bird view of the main biological activities, pharmacological actions and medicinal applications of guduchi extracts and also biological activities of few guduchi compounds isolated.
Role of annealing conditions of LPCVD thin silicon films in the changing of the residue stress for MEMS application

The effect of the crystal structure of silicon LPCVD thin films on the initial residue stress and changes under post deposition treatment was investigated. It is shown that initial residue stress as-deposited films are under compression regardless of the crystal structure. Sharp change of the residue stress from compressive to tensile is a result of post annealing of amorphous silicon films at temperature above 650°C. Two temperature ranges of post annealing with minimal or free residual stress for amorphous silicon films were observed. The initial residual stress of polysilicon films is strongly depending on deposition condition as well as composition and concentration of gas environment. The post annealing time has a weak effect on the change of residual stress. Noticeable time effects were observed only for amorphous films at a temperature about 600°C.
Laparoscopic cholecystectomy: a prospective cohort study assessing the impact of grade of operating surgeon on operative time and 30‐day morbidity

INTRODUCTION There is an increasing trend towards day case surgery for uncomplicated gallstone disease. The challenges of maximising training opportunities are well recognised by surgical trainees and the need to demonstrate timely progression of competencies is essential. Laparoscopic cholecystectomy provides the potential for excellent trainee learning opportunities. Our study builds upon previous work by assessing whether measures of outcome are still affected when cases are stratified based on procedural difficulty. MATERIAL AND METHODS A prospective cohort study of all laparoscopic cholecystectomies conducted at a district general hospital between 2009 and 2014, performed under the care of a single consultant. The operative difficulty was determined using the Cuschieri classification. The primary endpoint was duration of operation. Secondary endpoints included length of hospital stay, delayed discharge rate and 30‐day morbidity. RESULTS A total of 266 laparoscopic cholecystectomies were performed during the study period. Mean operative time for all consultant‐led cases was 52.5 minutes compared with 51.4 minutes for trainees (P = 0.67 unpaired t‐test). When cases were stratified for difficulty, consultant‐led cases were on average 5 minutes faster. Median duration of hospital stay was equivalent in both groups and there was no statistical difference in re‐attendance (12.9% vs. 15.3% P = 0.59) or re‐admission rates (3.2% vs. 8.1% P = 0.10) at 30 days. CONCLUSIONS Our study provides evidence that laparoscopic cholecystectomy provides a good training opportunity for surgical trainees without being detrimental to patient outcome. We recommend that, in selected patients, under consultant supervision, laparoscopic cholecystectomy can be performed primarily by the surgical trainee without impacting on patient outcome or theatre scheduling.