Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel functions for ADF/cofilin in excitatory synapses - lessons from gene-targeted mice

Actin filaments (F-actin) are the major structural component of excitatory synapses. In excitatory synapses, F-actin is enriched in presynaptic terminals and in postsynaptic dendritic spines, and actin dynamics – the spatiotemporally controlled assembly and disassembly of F-actin – have been implicated in pre- and postsynaptic physiology, additionally to their function in synapse morphology. Hence, actin binding proteins that control actin dynamics have moved into the focus as regulators of synapse morphology and physiology. Actin depolymerizing proteins of the ADF/cofilin family are important regulators of actin dynamics, and several recent studies highlighted the relevance of cofilin 1 for dendritic spine morphology, trafficking of postsynaptic glutamate receptors, and synaptic plasticity. Conversely, almost nothing was known about the synaptic function of ADF, a second ADF/cofilin family member present at excitatory synapses, and it remained unknown whether ADF/cofilin is relevant for presynaptic physiology. To comprehensively characterize the synaptic function of ADF/cofilin we made use of mutant mice lacking either ADF or cofilin 1 or both proteins. Our analysis revealed presynaptic defects (altered distribution and enhanced exocytosis of synaptic vesicles) and behavioral abnormalities reminiscent of attention deficit-hyperactivity disorder in double mutants that were not present in single mutants. Hence, by exploiting gene-targeted mice, we demonstrated the relevance of ADF for excitatory synapses, and we unraveled novel functions for ADF/cofilin in presynaptic physiology and behavior.
Hyperprolactinaemia among infertile patients and its effect on sperm functions

Summary. The effects of hyperprolactinaemia on sperm function were investigated in 264 men with oligozoo‐, asthenozoo‐, or teratozoospermia and who were attending a male infertility clinic. None of the patients exhibited galactorrhea or complained of impotence. There was no correlation between abnormal values in spermiogram and hyperprolactinaemia. After multiple measurements of serum prolactin concentration, 15 cases (5.7%) were diagnosed as hyperprolactinaemic (≧ 10 ng ml−1). Six of these patients were taking cimetidine and six were taking anti‐anxiety drugs. Serum prolactin returned to the normal level after discontinuation of these drugs; thus these 12 cases were considered as drug‐induced hyperprolactinaemia. The other three patients were diagnosed as having pituitary microadenomas and received bromocriptine treatment; the serum prolactin levels normalized within 1 month. No changes in sperm concentration, motility or morphology were found after normalization of serum prolactin levels. Sperm fertilizing ability was monitored by the hamster test for 10 months in the three patients with pituitary microadenoma, and no improvement was observed. Results suggest that hyperprolactinaemia, which does not cause symptoms, has little effect on the impairment of sperm functions. Measurement of serum prolactin in infertile men could be justified, however, for early detection of pituitary adenomas.
Faking Dynamics of Ropes and Springs

This article presents a method to model flexible linear bodies: ropes, cords, springs, and the like, for animation production. The resulting models can easily be animated in a manner that convincingly fakes dynamic behavior. The models were animated using the keyframe animation system, which provides traditional spline-based control of the models' animatable parameters.
Emotional state, coping styles, and somatic variables in patients with chronic hepatitis C.

The authors in a cross-sectional study examined 113 patients with chronic hepatitis C (CHC) without widely progressed or decompensated liver disease. The patients were investigated for emotional state (depression, anxiety, coping styles) and somatic/sociodemographic variables. A high percentage of patients had positive scores for depression (22.4%) and anxiety (15.2%). Mode of acquisition (e.g., former drug abuse) and histological grade of liver damage had no significant influence on emotional state or coping strategies. Older patients (> or = 50 years) were significantly more depressed (P = 0.024). Patients with a recently diagnosed CHC (> 4 weeks, < 6 months) had significantly lower scores for depression (P = 0.003) and anxiety (P = 0.001) than the subgroup with a time interval since initial diagnosis of more than 5 years. Recently diagnosed CHC patients also showed the highest levels of problem-solving behavior. Patients who were advised not to undergo an interferon therapy were significantly more depressed (P = 0.001) and anxious (P = 0.028). Older patients with CHC and patients with a long period since CHC diagnosis or who were advised not to undergo interferon therapy should be carefully and regularly assessed for depression, anxiety, and inappropriate coping styles.
Preventive attitude of physicians to avoid OHSS in IVF patients.

The ovarian hyperstimulation syndrome (OHSS) is a dramatic iatrogenic complication of fertility treatment. There is no consensus about its prevention strategies. We assessed whether physicians modify their preventive attitude in relation to clinical risk factors and to the oestradiol response chart. Three case scenarios with three levels of risk factors for OHSS were constructed. For each case scenario, four different charts of the oestradiol curve were described (peak serum oestradiol of 3590 or 6590 pg/ml obtained after a shorter or longer period). At random, we sent three out of the 12 artificially constructed case scenarios to 573 physicians who are members of the European Society of Human Reproduction and Embryology (ESHRE). They were asked whether they would cancel the cycle, take preventive measures or proceed to a regular IVF. A total of 389 cases from 130 different physicians was analysed. Globally, in 23% of the cases the physicians would proceed to a regular IVF. This decision varied significantly according to the risk level (between 38% in low risk to 8% in high risk cases; P < 0.01) and in relation to the oestradiol curve (P < 0.01). In 11% of the cases they would cancel the cycle and in 66% take some preventive measures. Among the selected preventive measures, coasting was by far the most popular choice (60%), followed by the use of i.v. albumin or hydroxyaethyl starch solution (36%) and cryo-preservation of all embryos (33%). In view of the sparse data as to whether coasting is really an effective method, and on how it should be carried out, we suggest that there is an urgent need to evaluate coasting as a preventive method in a large randomized trial in order to properly assess its efficiency and to provide precise guidelines for its use.
Local temperature in curved spacetime

A physically meaningful local concept of temperature is introduced in quantum field theory on curved spacetime and applied to the example of a massless field on de Sitter space. It turns out in this model that the equilibrium (Gibbs) states which can be prepared by a geodesic observer have in general a varying temperature distribution in the neighbourhood of the geodesic and may not even allow for a consistent thermal interpretation close to the horizon. This result, which can be traced back to the Unruh effect, illustrates the failure of a global notion of temperature in curved spacetime and reveals the need for a local concept, as presented here.
The proteomic response of the mussel congeners Mytilus galloprovincialis and M. trossulus to acute heat stress: implications for thermal tolerance limits and metabolic costs of thermal stress

SUMMARY The Mediterranean blue mussel, Mytilus galloprovincialis, an invasive species in California, has displaced the more heat-sensitive native congener, Mytilus trossulus, from its former southern range, possibly due to climate change. By comparing the response of their proteomes to acute heat stress we sought to identify responses common to both species as well as differences that account for greater heat tolerance in the invasive. Mussels were acclimated to 13°C for four weeks and exposed to acute heat stress (24°C, 28°C and 32°C) for 1 h and returned to 13°C to recover for 24 h. Using two-dimensional gel electrophoresis and tandem mass spectrometry we identified 47 and 61 distinct proteins that changed abundance in M. galloprovincialis and M. trossulus, respectively. The onset temperatures of greater abundance of some members of the heat shock protein (Hsp) 70 and small Hsp families were lower in M. trossulus. The abundance of proteasome subunits was lower in M. galloprovincialis but greater in M. trossulus in response to heat. Levels of several NADH-metabolizing proteins, possibly linked to the generation of reactive oxygen species (ROS), were lower at 32°C in the cold-adapted M. trossulus whereas proteins generating NADPH, important in ROS defense, were higher in both species. The abundance of oxidative stress proteins was lower at 32°C in M. trossulus only, indicating that its ability to combat heat-induced oxidative stress is limited to lower temperatures. Levels of NAD-dependent deacetylase (sirtuin 5), which are correlated with lifespan, were lower in M. trossulus in response to heat stress. In summary, the expression patterns of proteins involved in molecular chaperoning, proteolysis, energy metabolism, oxidative damage, cytoskeleton and deacetylation revealed a common loci of heat stress in both mussels but also showed a lower sensitivity to high-temperature damage in the warm-adapted M. galloprovincialis, which is consistent with its expanding range in warmer waters.
The Approximate Number System Acuity Redefined: A Diffusion Model Approach

While all humans are capable of non-verbally representing numerical quantity using so-called the approximate number system (ANS), there exist considerable individual differences in its acuity. For example, in a non-symbolic number comparison task, some people find it easy to discriminate brief presentations of 14 dots from 16 dots while others do not. Quantifying individual ANS acuity from such a task has become an essential practice in the field, as individual differences in such a primitive number sense is thought to provide insights into individual differences in learned symbolic math abilities. However, the dominant method of characterizing ANS acuity—computing the Weber fraction (w)—only utilizes the accuracy data while ignoring response times (RT). Here, we offer a novel approach of quantifying ANS acuity by using the diffusion model, which accounts both accuracy and RT distributions. Specifically, the drift rate in the diffusion model, which indexes the quality of the stimulus information, is used to capture the precision of the internal quantity representation. Analysis of behavioral data shows that w is contaminated by speed-accuracy tradeoff, making it problematic as a measure of ANS acuity, while drift rate provides a measure more independent from speed-accuracy criterion settings. Furthermore, drift rate is a better predictor of symbolic math ability than w, suggesting a practical utility of the measure. These findings demonstrate critical limitations of the use of w and suggest clear advantages of using drift rate as a measure of primitive numerical competence.
Inflammation, Coagulation and Cardiovascular Disease in HIV-Infected Individuals

Background The SMART study was a trial of intermittent use of antiretroviral therapy (ART) (drug conservation [DC]) versus continuous use of ART (viral suppression [VS]) as a strategy to reduce toxicities, including cardiovascular disease (CVD) risk. We studied the predictive value of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer with CVD morbidity and mortality in HIV-infected patients who were enrolled in SMART beyond other measured CVD risk factors. Methods A blood sample was available in 5098 participants who were enrolled in the SMART study for the measurement of IL-6, hsCRP and D-dimer. Hazard ratios (HR) with 95% CI for CVD events were estimated for each quartile (Q) for each biomarker vs the 1st quartile and for 1 SD higher levels. For both treatment groups combined, unadjusted and adjusted HRs were determined using Cox regression models. Results There were 252 participants who had a CVD event over a median follow-up of 29 months. Adjusted HRs (95% CI) for CVD for Q4 vs Q1 were 4.65 (2.61, 8.29), 2.10 (1.40, 3.16), and 2.14 (1.38, 3.33) for IL-6, hsCRP and D-dimer, respectively. Associations were similar for the DC and VS treatment groups (interaction p-values were >0.30). The addition of the three biomarkers to a model that included baseline covariates significantly improved model fit (p<0.001). Area under the curve (AUC) estimates improved with inclusion of the three biomarkers in a model that included baseline covariates corresponding to other CVD risk factors and HIV factors (0.741 to 0.771; p<0.001 for difference). Conclusions In HIV-infected individuals, IL-6, hsCRP and D-dimer are associated with an increased risk of CVD independent of other CVD risk factors. Further research is needed to determine whether these biomarkers can be used to improve CVD risk prediction among HIV positive individuals.
The global burden of neurologic diseases

Editors' Note: Commenting on Chin and Vora's perspective on the global burden of neurologic diseases, Shubhakaran discusses specific challenges of neurology in India. Citing the retrospective study on primary CNS lymphoma by Holdoff et al., Chamberlain points out shortcomings in management of this disease and the need for randomized trials. Bhutada et al. disagree with the authors of the Clinical Reasoning article “Transient cervical cord swelling in monomelic …
Local mirror symmetry and type IIA monodromy of Calabi-Yau manifolds

We propose a monodromy invariant pairing Khol(X) H3(X _ ;Z) ! Q for a mirror pair of Calabi-Yau manifolds, (X; X _ ). This pairing is utilized implicitly in the previous calculations of the prepotentials for Gromov-Witten invariants. After identifying the pairing explicitly we interpret some hypergeometric series from the viewpoint of homo- logical mirror symmetry due to Kontsevich. Also we consider the local mirror symmetry limit to del Pezzo surfaces in Calabi-Yau 3-folds.
RCT comparing minimally with moderately rough implants. Part 1: clinical observations.

AIM This 1-year prospective RCT compared the outcome of minimally (turned) and moderately rough (TiUnite) implant surfaces. MATERIAL AND METHODS Two subgroups of patients were formed; one group (n = 10) where all teeth had been extracted due to severe periodontitis, another group (n = 8) with teeth in the antagonistic jaw with a history of periodontitis and some remaining medium pockets (4-6 mm). Implants (n = 85, 43 turned & 42 TiUnite) were installed randomly in each patient. After 3-6 months of submerged healing, healing abutments were connected, followed by final abutments 2 weeks later, all with the same surface characteristics as the supporting implant. Peri-implant parameters and intra-oral radiographs were recorded up to 1 year after abutment connection. RESULTS Two turned implants failed in the partial edentulous group during the initial healing period (CSR: 95%) and none of the TiUnite (CSR: 100%) surface. No statistically significant differences in clinical parameters could be observed between both surfaces. The partial edentulous subgroup showed more bone loss compared to the full edentulous subgroup. CONCLUSION Moderately rough implants have a similar clinical outcome (at 1 year of loading in periodontitis susceptible patients) compared to minimally rough implants.
Loss of functional ELOVL4 depletes very long-chain fatty acids (≥C28) and the unique ω-O-acylceramides in skin leading to neonatal death

Mutations in elongation of very long-chain fatty acid-4 (ELOVL4) are associated with autosomal dominant Stargardt-like macular degeneration (STGD3), with a five base-pair (5 bp) deletion mutation resulting in the loss of 51 carboxy-terminal amino acids and truncation of the protein. In addition to the retina, Elovl4 is expressed in a limited number of mammalian tissues, including skin, with unknown function(s). We generated a knock-in mouse model with the 5-bp deletion in the Elovl4 gene. As anticipated, mice carrying this mutation in the heterozygous state (Elovl4(+/del)) exhibit progressive photoreceptor degeneration. Unexpectedly, homozygous mice (Elovl4(del/del)) display scaly, wrinkled skin, have severely compromised epidermal permeability barrier function, and die within a few hours after birth. Histopathological evaluation of the Elovl4(del/del) pups revealed no apparent abnormality(ies) in vital internal organs. However, skin histology showed an abnormally-compacted outer epidermis [stratum corneum (SC)], while electron microscopy revealed deficient epidermal lamellar body contents, and lack of normal SC lamellar membranes that are essential for permeability barrier function. Lipid analyses of epidermis from Elovl4(del/del) mice revealed a global decrease in very long-chain fatty acids (VLFAs) (i.e., carbon chain > or =C28) in both the ceramide/glucosylceramide and the free fatty-acid fractions. Strikingly, Elovl4(del/del) skin was devoid of the epidermal-unique omega-O-acylceramides, that are key hydrophobic components of the extracellular lamellar membranes in mammalian SC. These findings demonstrate that ELOVL4 is required for generating VLFA critical for epidermal barrier function, and that the lack of epidermal omega-O-acylceramides is incompatible with survival in a desiccating environment.
Dietary Patterns, Metabolic Markers and Subjective Sleep Measures in Resident Physicians

Shiftwork is common in medical training and is necessary for 24-h hospital coverage. Shiftwork poses difficulties not only because of the loss of actual sleep hours but also because it can affect other factors related to lifestyle, such as food intake, physical activity level, and, therefore, metabolic patterns. However, few studies have investigated the nutritional and metabolic profiles of medical personnel receiving training who are participating in shiftwork. The aim of the present study was to identify the possible negative effects of food intake, anthropometric variables, and metabolic and sleep patterns of resident physicians and establish the differences between genders. The study included 72 resident physicians (52 women and 20 men) who underwent the following assessments: nutritional assessment (3-day dietary recall evaluated by the Adapted Healthy Eating Index), anthropometric variables (height, weight, body mass index, and waist circumference), fasting metabolism (lipids, cortisol, high-sensitivity C-reactive protein [hs-CRP], glucose, and insulin), physical activity level (Baecke questionnaire), sleep quality (Pittsburgh Sleep Quality Index; PSQI), and sleepiness (Epworth Sleepiness Scale; ESS). We observed a high frequency of residents who were overweight or obese (65% for men and 21% for women; p = 0.004). Men displayed significantly greater body mass index (BMI) values (p = 0.002) and self-reported weight gain after the beginning of residency (p = 0.008) than women. Poor diet was observed for both genders, including the low intake of vegetables and fruits and the high intake of sweets, saturated fat, cholesterol, and caffeine. The PSQI global scores indicated significant differences between genders (5.9 vs. 7.5 for women and men, respectively; p = 0.01). Women had significantly higher mean high-density lipoprotein cholesterol (HDL-C; p < 0.005), hs-CRP (p = 0.04), and cortisol (p = 0.009) values than men. The elevated prevalence of hypertriglyceridemia and abnormal values of low-density lipoprotein cholesterol (LDL-C; >100 mg/dL) were observed in most individuals. Higher than recommended hs-CRP levels were observed in 66% of the examined resident physicians. Based on current recommendations, a high prevalence of low sleep quality and excessive daytime sleepiness was identified. These observations indicate the need to monitor health status and develop actions to reassess the workload of medical residency and the need for permission to perform extra night shifts for medical residents to avoid worsening health problems in these individuals.
Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein–related proteins and phosphoinositides

Sterols are moved between cellular membranes by nonvesicular pathways whose functions are poorly understood. In yeast, one such pathway transfers sterols from the plasma membrane (PM) to the endoplasmic reticulum (ER). We show that this transport requires oxysterol-binding protein (OSBP)–related proteins (ORPs), which are a large family of conserved lipid-binding proteins. We demonstrate that a representative member of this family, Osh4p/Kes1p, specifically facilitates the nonvesicular transfer of cholesterol and ergosterol between membranes in vitro. In addition, Osh4p transfers sterols more rapidly between membranes containing phosphoinositides (PIPs), suggesting that PIPs regulate sterol transport by ORPs. We confirmed this by showing that PM to ER sterol transport slows dramatically in mutants with conditional defects in PIP biosynthesis. Our findings argue that ORPs move sterols among cellular compartments and that sterol transport and intracellular distribution are regulated by PIPs.
Life history correlates of fecal bacterial species richness in a wild population of the blue tit Cyanistes caeruleus

Very little is known about the normal gastrointestinal flora of wild birds, or how it might affect or reflect the host's life-history traits. The aim of this study was to survey the species richness of bacteria in the feces of a wild population of blue tits Cyanistes caeruleus and to explore the relationships between bacterial species richness and various life-history traits, such as age, sex, and reproductive success. Using PCR-TGGE, 55 operational taxonomic units (OTUs) were identified in blue tit feces. DNA sequencing revealed that the 16S rRNA gene was amplified from a diverse range of bacteria, including those that shared closest homology with Bacillus licheniformis, Campylobacter lari, Pseudomonas spp. , and Salmonella spp. For adults, there was a significant negative relationship between bacterial species richness and the likelihood of being detected alive the following breeding season; bacterial richness was consistent across years but declined through the breeding season; and breeding pairs had significantly more similar bacterial richness than expected by chance alone. Reduced adult survival was correlated with the presence of an OTU most closely resembling C. lari; enhanced adult survival was associated with an OTU most similar to Arthrobacter spp. For nestlings, there was no significant change in bacterial species richness between the first and second week after hatching, and nestlings sharing the same nest had significantly more similar bacterial richness. Collectively, these results provide compelling evidence that bacterial species richness was associated with several aspects of the life history of their hosts.