Miracle-dz/UniFAR-FTUs huggingface dataset:
PMEPA1 and NEDD4 control the proton production of osteoclasts by regulating vesicular trafficking

Osteoclast bone resorption activity is critically regulated to maintain bone homeostasis. Osteoclasts resorb bone by producing protons and acid hydrolase via lysosomal secretion, however, a detailed mechanism remains elusive. PMEPA1 is a vesicular membrane protein, which binds to the NEDD4 family member of ubiquitin ligases. We have previously reported that Pmepa1 is highly expressed in bone resorbing osteoclasts, and regulates bone resorption. Here, we investigated the mechanism of bone resorption regulated by PMEPA1. Mutant mice lacking NEDD4‐binding domains of PMEPA1 displayed enhanced bone volume, and reduced bone resorption activity in comparison with those of WT mice. Analysis with pH‐sensitive fluorescence probe revealed that proton secretion from osteoclasts significantly decreased in Pmepa1 mutant osteoclasts. Immunofluorescence analysis revealed that PMEPA1 was colocalized with NEDD4, V0A3, and V0D2 subunits of vacuolar ATPase, which regulate the proton production of osteoclasts. In addition, Nedd4 knockdown reduced bone resorption and proton secretion of osteoclasts. Furthermore, Pmepa1 mutation and Nedd4 knockdown altered the cytoplasmic distribution of components of V‐ATPase and expression of autophagy‐related proteins, suggesting that lysosomal secretion is affected. Collectively, these findings indicate that PMEPA1 controls proton secretion from osteoclasts via NEDD4 by regulating vesicular trafficking, and NEDD4 is an important regulator of bone resorption.
Local translation in perisynaptic and perivascular astrocytic processes – a means to ensure astrocyte molecular and functional polarity?

ABSTRACT Together with the compartmentalization of mRNAs in distal regions of the cytoplasm, local translation constitutes a prominent and evolutionarily conserved mechanism mediating cellular polarization and the regulation of protein delivery in space and time. The translational regulation of gene expression enables a rapid response to stimuli or to a change in the environment, since the use of pre-existing mRNAs can bypass time-consuming nuclear control mechanisms. In the brain, the translation of distally localized mRNAs has been mainly studied in neurons, whose cytoplasmic protrusions may be more than 1000 times longer than the diameter of the cell body. Importantly, alterations in local translation in neurons have been implicated in several neurological diseases. Astrocytes, the most abundant glial cells in the brain, are voluminous, highly ramified cells that project long processes to neurons and brain vessels, and dynamically regulate distal synaptic and vascular functions. Recent research has demonstrated the presence of local translation at these astrocytic interfaces that might regulate the functional compartmentalization of astrocytes. In this Review, we summarize our current knowledge about the localization and local translation of mRNAs in the distal perisynaptic and perivascular processes of astrocytes, and discuss their possible contribution to the molecular and functional polarity of astrocytes. Summary: This Review summarizes our current knowledge about mRNA distribution and local translation in astrocytes.
Ribosome occupancy profiles are conserved between structurally and evolutionarily related yeast domains

Abstract Motivation Protein synthesis is a non-equilibrium process, meaning that the speed of translation can influence the ability of proteins to fold and function. Assuming that structurally similar proteins fold by similar pathways, the profile of translation speed along an mRNA should be evolutionarily conserved between related proteins to direct correct folding and downstream function. The only evidence to date for such conservation of translation speed between homologous proteins has used codon rarity as a proxy for translation speed. There are, however, many other factors including mRNA structure and the chemistry of the amino acids in the A- and P-sites of the ribosome that influence the speed of amino acid addition. Results Ribosome profiling experiments provide a signal directly proportional to the underlying translation times at the level of individual codons. We compared ribosome occupancy profiles (extracted from five different large-scale yeast ribosome profiling studies) between related protein domains to more directly test if their translation schedule was conserved. Our analysis reveals that the ribosome occupancy profiles of paralogous domains tend to be significantly more similar to one another than to profiles of non-paralogous domains. This trend does not depend on domain length, structural classes, amino acid composition or sequence similarity. Our results indicate that entire ribosome occupancy profiles and not just rare codon locations are conserved between even distantly related domains in yeast, providing support for the hypothesis that translation schedule is conserved between structurally related domains to retain folding pathways and facilitate efficient folding. Availability and implementation Python3 code is available on GitHub at https://github.com/DanNissley/Compare-ribosome-occupancy. Supplementary information Supplementary data are available at Bioinformatics online.
Gestational age at birth and child special educational needs: a UK representative birth cohort study

Objective To examine the association between gestational age at birth across the entire gestational age spectrum and special educational needs (SENs) in UK children at 11 years of age. Methods The Millennium Cohort Study is a nationally representative longitudinal sample of children born in the UK during 2000–2002. Information about the child’s birth, health and sociodemographic factors was collected when children were 9 months old. Information about presence and reasons for SEN was collected from parents at age 11. Adjusted relative risks (aRRs) were estimated using modified Poisson regression, accounting for confounders. Results The sample included 12 081 children with data at both time points. The overall prevalence of SEN was 11.2%, and it was inversely associated with gestational age. Among children born <32 weeks of gestation, the prevalence of SEN was 27.4%, three times higher than among those born at 40 weeks (aRR=2.89; 95% CI 2.02 to 4.13). Children born early term (37–38 weeks) were also at increased risk for SEN (aRR=1.33; 95% CI 1.11 to 1.59); this was the same when the analysis was restricted to births after labour with spontaneous onset. Birth before full term was more strongly associated with having a formal statement of SEN or SEN for multiple reasons. Conclusion Children born at earlier gestational ages are more likely to experience SEN, have more complex SEN and require support in multiple facets of learning. This association was observed even among children born early-term and when labour began spontaneously.
Synthesis of boron nitride nanowires

A chemical method has been developed for synthesizing boron nitride nanowires through the reaction of a mixture gas of nitrogen (N2) and ammonia (NH3) over nanoscale α-FeB particles at 1100 °C. Boron content in the product comes from the α-FeB catalyst itself. Transmission electron microscopic image indicates an abundant quantity of BN nanowires with diameter about 20 nm and length up to several tens of microns. The product has also been characterized by high-resolution electron microscopy and electron energy loss spectrometer. The perfectly straight lattice fringes with an interlayer spacing of about 0.333 nm corresponding to d0002 spacing of h-BN indicate that the BN nanowires are well crystallized. Also, a growth mechanism has been speculated.
The effect of the menstrual cycle on the sense of touch, grip strength and manual dexterity of dental students

Objectives. This study aimed to evaluate through comparative tests the effect of the menstrual cycle on levels of depression, sleep quality and grip strength, fingertip touch and manual dexterity of students in the Dental Faculty. Methods. The study sample was formed from female students of the Dental Faculty. The total 70 participants comprised 31 from the first year and 39 from the final year. Evaluations were made in two different consecutive phases of the menstrual cycle. Data were collected using the Beck depression inventory (BDI), the Pittsburgh sleep quality index (PSQI), handgrip and lateral grip strength measurements, fingertip two-point discrimination sensory measurement, the Semmes–Weinstein monofilament test, the O’Connor tweezers skill test and the Purdue pegboard test. Results. A statistically significant difference was determined between the menstrual and ovulation phase measurements of the BDI, PSQI, Semmes–Weinstein monofilament test (right), the O’Connor tweezers skill test and Purdue pegboard test (right + left), and the Purdue Pegboard test (total and assembly) (p < 0.05). Conclusions. The menstrual cycle does not affect the sense of touch, grip strength and simple hand skills. However, task-focused skills requiring care and the manual dexterity needed for the use of instruments are affected.
Introducing ferromagnetism and anisotropic magnetoresistance in monolayer CVD graphene by nitrogen doping

We demonstrate a method to dope monolayer chemical vapor deposited (CVD) graphene with nitrogen and make it ferromagnetic. CVD graphene was first functionalized with hydroxyl groups by treating with H2O2 in the presence of UV light and then annealed in ammonia gas to dope it with nitrogen. Magnetization measurements showed a ferromagnetic hysteresis loop at low temperatures with a coercivity of 222 Oe at 2 K. We also investigated the effect of a change in the angle of the applied magnetic field on the anisotropic magnetoresistance effect (AMR) in the doped CVD graphene devices. Graphene shows positive AMR for temperatures from 2 K to 50 K, negative AMR at 100 K and 150 K, and no AMR for temperatures higher than 150 K. A maximum AMR of 0.92% was observed at 2 K for an in-plane magnetic field of 30 kOe. Magnetic force microscopy also confirms the introduction of magnetism in CVD graphene after doping, and electron spin resonance spectroscopy shows resonance when scanned in a magnetic field, which confirms the presence of unpaired electrons in doped graphene. The process introduced in this paper for nitrogen doping of graphene with attendant magnetism could pave the way for the applications of graphene in spintronics and other devices.
Visualization and Documentation of Capsule and Melanin Production in Cryptococcus neoformans

Cryptococcus neoformans is an opportunistic fungal pathogen primarily targeting immunosuppressed populations in both resource‐rich and resource‐limited nations. Successful treatment is limited to a few antifungals that have become compromised by cryptococcal resistance, leading to intensive research seeking new drug candidates. Two distinguishing hallmarks of this species are the ability to develop a polysaccharide capsule and melanization of the fungal cells. These also act as virulence factors, protecting this pathogen in the host as well as in the environment. Here we describe two classic methods to document capsule and melanin. Although initially described and documented several decades ago, these methods remain relevant in spite of the advent of more sophisticated methodology, due in part to their simplicity and cost efficiency. © 2021 Wiley Periodicals LLC.
Sex differences in mapping and rhythm outcomes of a repeat atrial fibrillation ablation

Objective The risk of procedure-related complications and rhythm outcomes differ between men and women after atrial fibrillation catheter ablation (AFCA). We evaluated whether consistent sex differences existed in mapping and rhythm outcomes in repeat ablation procedures. Methods Among 3282 patients in the registry, we analysed 443 consecutive patients (24.6% female, 58.5±10.3 years old, 61.5% with paroxysmal atrial fibrillation) who underwent a second AFCA. We compared the clinical factors, mapping, left atrial (LA) pressure, complications and long-term clinical recurrences after propensity score matching. Results LA volume index (43.1±18.6 vs 35.8±11.6 mL/m2, p<0.001) was higher, but LA dimension (40.0±6.8 vs 41.6±6.3 mm, p=0.018), LA voltage (0.94±0.55 vs 1.20±0.68 mV, p=0.002) and pericardial fat volume (89.5±43.1 vs 122.1±53.9 cm3, p<0.001) were lower in women with repeat ablation than in their male counterparts. Pulmonary vein (PV) reconnections were lower (58.7% vs 74.9%, p=0.001), but the proportion of extra-PV triggers (27.5% vs 17.0%, p=0.026) and elevated LA pulse pressures (79.7% vs 63.7%, p=0.019) was significantly higher in women than in men. There was no significant sex difference in the rate of procedure-related complications (4.6% vs 4.2%, p=0.791). During a 31-month (8–60) median follow-up, clinical recurrences were significantly higher in women after both the de novo procedure (log-rank p=0.039, antiarrhythmic drug (AAD)-free log-rank p<0.001) and the second procedure (log-rank p=0.006, AAD-free log-rank p=0.093). Female sex (HR 1.51, 95% CI 1.06 to 2.15, p=0.023), non-paroxysmal atrial fibrillation (HR 1.78, 95% CI 1.30 to 2.34, p<0.010) and extra-PV triggers (HR 1.88, 95% CI 1.28 to 2.75, p=0.001) were independently associated with clinical recurrences after repeat procedures. Conclusions During repeat AFCA procedures, PV reconnections were lower in women than in men, and the existence of extra-PV triggers and an LA pressure elevation were more significant, which resulted in poor rhythm outcomes. Trial registration number NCT02138695.
2‐Hydroxy‐5‐nitrobenzaldehyde phenylhydrazone

In the title compound, C13H11N3O3, the mol­ecule is essentially planar, the dihedral angle between the benzene rings being 5.31 (10)°. The nitro group meta to the phenyl­hydrazone substituent is almost coplanar with the ring to which it is attached, with a dihedral angle of 3.09 (12)° between the plane of the nitro group and the phenol ring plane. In the crystal structure, inter­molecular N—H⋯O and C—H⋯O inter­actions inter­connect the mol­ecules into a three-dimensional framework. In addition, the crystal packing is stabilized by weak π–π inter­actions [centroid–centroid distance = 3.7279 (11) A].
Differential expression of αVβ3 and αVβ6 integrins in prostate cancer progression

Neuroendocrine prostate cancer (NEPrCa) arises de novo or after accumulation of genomic alterations in pre-existing adenocarcinoma tumors in response to androgen deprivation therapies. We have provided evidence that small extracellular vesicles released by PrCa cells and containing the αVβ3 integrin promote neuroendocrine differentiation of PrCa in vivo and in vitro. Here, we examined αVβ3 integrin expression in three murine models carrying a deletion of PTEN (SKO), PTEN and RB1 (DKO), or PTEN, RB1 and TRP53 (TKO) genes in the prostatic epithelium; of these three models, the DKO and TKO tumors develop NEPrCa with a gene signature comparable to those of human NEPrCa. Immunostaining analysis of SKO, DKO and TKO tumors shows that αVβ3 integrin expression is increased in DKO and TKO primary tumors and metastatic lesions, but absent in SKO primary tumors. On the other hand, SKO tumors show higher levels of a different αV integrin, αVβ6, as compared to DKO and TKO tumors. These results are confirmed by RNA-sequencing analysis. Moreover, TRAMP mice, which carry NEPrCa and adenocarcinoma of the prostate, also have increased levels of αVβ3 in their NEPrCa primary tumors. In contrast, the αVβ6 integrin is only detectable in the adenocarcinoma areas. Finally, analysis of 42 LuCaP patient-derived xenografts and primary adenocarcinoma samples shows a positive correlation between αVβ3, but not αVβ6, and the neuronal marker synaptophysin; it also demonstrates that αVβ3 is absent in prostatic adenocarcinomas. In summary, we demonstrate that αVβ3 integrin is upregulated in NEPrCa primary and metastatic lesions; in contrast, the αVβ6 integrin is confined to adenocarcinoma of the prostate. Our findings suggest that the αVβ3 integrin, but not αVβ6, may promote a shift in lineage plasticity towards a NE phenotype and might serve as an informative biomarker for the early detection of NE differentiation in prostate cancer.
Refill Reminder Preference and Inhaled Corticosteroid Adherence Among Patients with Asthma.

CONTEXT Refill reminders can help patients improve adherence to inhaled corticosteroid (ICS) therapy. However, little is known about patient preferences for reminder type or whether patients who express a preference differ from patients who do not. OBJECTIVES To describe patient preferences for ICS prescription refill reminder type and to compare baseline ICS therapy adherence, measured as proportion of days covered (PDC) 1 year before initiating preference-based reminders, between patients who did and did not express a preference. DESIGN This substudy within a randomized multi-intervention study was conducted at Kaiser Permanente Colorado. Adults with asthma randomized to intervention were offered the opportunity to choose text, telephone, or email reminders. Patients who did and did not provide a preference were compared by baseline characteristics using log-binomial models. MAIN OUTCOME MEASURE(S) The primary outcomes were reminder preference and type. RESULTS A total of 1497 of 4545 patients (32.9%) expressed a preference; 789 (52.7%) chose text. The adjusted relative risk (aRR) of not providing a preference increased with decreasing PDC (PDC of 0.50 to < 0.80: aRR, 1.14; 95% confidence interval [CI], 1.04-1.25; PDC < 0.5: aRR, 1.76; 95% CI, 1.59-1.95) compared with patients with a PDC of 0.80 or greater. CONCLUSION Among patients who expressed a preference, text reminders were preferred. Patients who expressed a preference had higher baseline adherence. Further research is needed to determine whether expressing a preference for a refill reminder type is itself associated with adherence. Given that offering the opportunity to choose a reminder type only engaged a subset of patients, further work is needed to understand how best to leverage technology-enabled communication outreach to help patients optimize adherence.
COVID-19 prevalence and predictors in United States adults during peak stay-at-home orders

Background Early recognition of COVID-19 cases is essential for effective public health measures aimed at isolation of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS–COV-2). The objective of this study was to describe characteristics, self-reported symptoms, and predictors of testing positive for SARS-CoV-2 infection in a community-based sample. Methods and findings This was a cross-sectional nationwide survey of adults in the US conducted between April 24 through May 13, 2020. The survey targeted a representative sample of approximately 5,000 respondents. The rate of COVID-19 cases and testing, most frequently reported symptoms, symptom severity, treatment received, impact of COVID-19 on mental and physical health, and factors predictive of testing positive were assessed. Most of the 5,203 participants (85.6%) reported no COVID-19-like symptoms. Of the 747 (14.5%) participants reporting COVID-19-like symptoms, 367 (49.1%) obtained a diagnostic test. Eighty-nine participants (24.3%) reported a positive COVID-19 test result, representing 1.7% of the total sample. For those testing positive, the most common symptoms were dry cough, fever, and shortness of breath/difficulty breathing. Those who tested positive were more likely to report greater symptom severity versus those who tested negative. Severe dry cough, new loss of taste or smell, trouble waking up, living with someone experiencing symptoms, recent international travel, respiratory issues, and reporting ethnicity of Black or African American were predictive of testing positive. Conclusions This study assessed the impact of COVID-19 using community-level self-reported data across the US during the peak of most stay at home’ orders. Self-reported symptoms and risk factors identified in this study are consistent with the clinical profile emerging for COVID-19. In the absence of widespread testing, this study demonstrates the utility of a representative US community-based sample to provide direct-reported symptoms and outcomes to quickly identify high-risk individuals who are likely to test positive and should consider taking greater precautions.
Cardiac troponin release following left bundle branch pacing

Left bundle branch pacing (LBBP) has emerged as an alternative to His bundle pacing (HBP) to achieve physiologic ventricular stimulation. The extent of myocardial injury during permanent LBBP implantation is currently not known. The aim of the study was to prospectively assess the extent of myocardial injury during LBBP implantation. Cardiac troponin (cTn) levels were measured at baseline and 6–12 h following permanent LBBP. The number of attempts to achieve LBBP was documented. Troponin levels were measured in a control population undergoing other electrophysiology procedures including HBP, other devices involving right ventricular (RV) pacing, radiofrequency ablation for atrial fibrillation (AF) and supraventricular tachycardia (SVT). Significant elevation of troponin (SET) was defined as threefold increase above the upper reference limit (URL) for cTn. Between December 2019 and April 2020, 204 were prospectively enrolled: LBBP in 98 and Control group 106 (SVT, 55; AF, 20; HBP, 17; other devices, 14). SET (>3× URL) was seen in 49.4% of patients in the LBBP group compared to 58.4% in the control group (p = .23). Peak troponin levels were greater in the control group compared to the LBBP group (230.3 ± 320.1 vs. 87.4 ± 71.3 pg/ml; p = .0001). Compared to LBBP (49.4%), SET was observed less frequently following HBP (17.5%; p = .01), and other device implantation (29%; p = .15). Patients requiring >2 attempts (n = 33) had significantly higher incidence of SET compared to <2 attempts (n = 56; 66.7% vs. 39.3%; p = .01). LBBP implantation is associated with myocardial injury. Asymptomatic troponin release following LBBP is less than or comparable to other interventional electrophysiology procedures.
Artemisia annua – Importance in Traditional Medicine and Current State of Knowledge on the Chemistry, Biological Activity and Possible Applications

Abstract Artemisia annua (annual mugwort) is a species that has long been used in traditional Asian medicine, mainly Chinese and Hindu. The species is widespread and known as a medicinal plant not only in Asia but also in Europe, in both Americas, and Australia. The species has become a subject of particular interest due to the 2015 Nobel Prize awarded for detecting the sesquiterpene lactone artemisinin in it and proving its antimalarial activities. The raw materials obtained from this species are Artemisiae annuae folium and Artemisiae annuae herba. The leaves are a raw material in the Chinese Pharmacopoeia and Vietnamese Pharmacopoeia. Both raw materials are in the International Pharmacopoeia published by the WHO. The main components of these raw materials are mainly specific sesquiterpene lactones, essential oil, flavonoids, coumarins, and phenolic acids. In traditional Asian medicine, the species is used, for example, in the treatment of jaundice and bacterial dysentery, as an antipyretic agent in malaria and tuberculosis, in the treatment of wounds and haemorrhoids, and in viral, bacterial, and autoimmune diseases. Professional pharmacological studies conducted today have confirmed its known traditional applications and explain previously unknown mechanisms of its biological action and have also found evidence of new directions of biological activity, including, among others, anti-inflammatory, analgesic, antioxidant, antitumour, and nephroprotective activities. The species is of growing importance in the cosmetics industry.