Miracle-dz/UniFAR-FTUs huggingface dataset:
Probing the aggregated effects of purifying selection per individual on 1,380 medical phenotypes in the UK Biobank

Understanding the relationship between natural selection and phenotypic variation has been a long-standing challenge in human population genetics. With the emergence of biobank-scale datasets, along with new statistical metrics to approximate strength of purifying selection at the variant level, it is now possible to correlate a proxy of individual relative fitness with a range of medical phenotypes. We calculated a per-individual deleterious load score by summing the total number of derived alleles per individual after incorporating a weight that approximates strength of purifying selection. We assessed four methods for the weight, including GERP, phyloP, CADD, and fitcons. By quantitatively tracking each of these scores with the site frequency spectrum, we identified phyloP as the most appropriate weight. The phyloP-weighted load score was then calculated across 15,129,142 variants in 335,161 individuals from the UK Biobank and tested for association on 1,380 medical phenotypes. After accounting for multiple test correction, we observed a strong association of the load score amongst coding sites only on 27 traits including body mass, adiposity and metabolic rate. We further observed that the association signals were driven by common variants (derived allele frequency > 5%) with high phyloP score (phyloP > 2). Finally, through permutation analyses, we showed that the load score amongst coding sites had an excess of nominally significant associations on many medical phenotypes. These results suggest a broad impact of deleterious load on medical phenotypes and highlight the deleterious load score as a tool to disentangle the complex relationship between natural selection and medical phenotypes.
Transverse relaxation in supported and nonsupported phospholipid model membranes and the influence of ultraslow motions: A 31P‐NMR study

The effect of motions which are slow on the NMR time scale (in particular, lateral diffusion) on the 31P‐NMR transverse relaxation behavior of POPC (1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine) phospholipid membranes was studied by experiment and computer simulation. Two new membrane model systems (spherical supported vesicles) which exhibit some unique geometrical features and physical properties as well as the commonly used multilamellar vesicles, were applied for the measurement of the 31P‐NMR anisotropic transverse relaxation times. The known geometry of the new membrane model systems under study enables a direct comparison of the experimental transverse relaxation spectra with those obtained by a spectral simulation technique which considers random diffusion on the surface of a sphere as the dominant relaxation mechanism, where the sphere size corresponds to that used in the experiments. The transverse relaxation times obtained experimentally for the three model systems studied differ drasticall.
Unravelling the Complex Interplay of Transcription Factors Orchestrating Seed Oil Content in Brassica napus L.

Transcription factors (TFs) and their complex interplay are essential for directing specific genetic programs, such as responses to environmental stresses, tissue development, or cell differentiation by regulating gene expression. Knowledge regarding TF–TF cooperations could be promising in gaining insight into the developmental switches between the cultivars of Brassica napus L. , namely Zhongshuang11 (ZS11), a double-low accession with high-oil- content, and Zhongyou821 (ZY821), a double-high accession with low-oil-content. In this regard, we analysed a time series RNA-seq data set of seed tissue from both of the cultivars by mainly focusing on the monotonically expressed genes (MEGs). The consideration of the MEGs enables the capturing of multi-stage progression processes that are orchestrated by the cooperative TFs and, thus, facilitates the understanding of the molecular mechanisms determining seed oil content. Our findings show that TF families, such as NAC, MYB, DOF, GATA, and HD-ZIP are highly involved in the seed developmental process. Particularly, their preferential partner choices as well as changes in their gene expression profiles seem to be strongly associated with the differentiation of the oil content between the two cultivars. These findings are essential in enhancing our understanding of the genetic programs in both cultivars and developing novel hypotheses for further experimental studies.
Are Melanoides tuberculata and Tarebia granifera (Gastropoda, Thiaridae), suitable first intermediate hosts of Clonorchis sinensis in Vietnam?

BACKGROUND Two thiarid snail species, Melanoides tuberculata and Tarebia granifera have been reported as first intermediate hosts of the liver fluke Clonorchis sinensis; however, their role as true first intermediate hosts has not been verified. Thus, the present study aimed to clarify the suitability of these two snail species as first intermediate hosts of C. sinensis. This was accomplished by collecting snails from a highly endemic area for C. sinensis in Vietnam, the Thac Ba reservoir, and identifying shed cercariae using molecular techniques. We also conducted experimental infections of five snail species including M. tuberculata and T. granifera with eggs of C. sinensis. METHODOLOGY/PRINCIPAL FINDINGS A total of 11,985 snails, representing 10 species were sampled. Five snail species, M. tuberculata, T. granifera, Lymnaea swinhoei, Parafossarulus manchouricus, and Bithynia fuchsiana were found shedding cercariae with an overall prevalence of infection ranging from 0.7% to 11.5%. Seven cercarial types were recorded. Cercariae of C. sinensis were only found in Parafossarulus manchouricus. Using a multiplex PCR approach for detecting C. sinensis infection, the prevalence in P. manchouricus was 4.2%. Additionally, all five snail species were experimentally exposed to C. sinensis eggs, however only P. manchouricus was successfully infected with an infection rate of 7.87%. CONCLUSIONS/SIGNIFICANCE We confirmed that in the Thac Ba reservoir, Vietnam, the two thiarids, M. tuberculata and T. granifera are not suitable first intermediate hosts of C. sinensis. Only P. manchouricus was found infected by C. sinensis in nature, and was the only species that became infected experimentally.
Synthesis and characterization of novel organosoluble poly(aryl ether ketone)s and poly(aryl ether ketone sulfone)s containing 1,4-naphthylene units

Two monomers containing naphthalene, 4,4′-di(1-naphthoxy)benzophenone (DNOBN) and 4,4′-bis(1-naphthoxy)diphenyl sulfone (BNODPS), were prepared by the condensation reactions of 4,4′-difluorobenzophenone and 4,4′-dichlorodiphenyl sulfone with 1-naphthol, respectively. Novel poly(aryl ether ketone)s (PAEKs) and poly(aryl ether ketone sulfone)s containing 1,4-naphthylene units were synthesized from DNOBN and BNODPS via the electrophilic Friedel–Crafts acylation polycondensation with various aromatic diacid dichlorides, in the presence of anhydrous aluminum chloride and N-methyl-2-pyrrolidone in 1,2-dichloroethane. Because of the incorporation of 1,4-naphthylene units, the resulting PAEKs and poly(aryl ether ketone sulfone)s exhibited outstanding thermal stability and improved solubility in common organic solvents. The glass transition temperatures are above 200°C, and the temperatures at a 5% weight loss are above 548°C under nitrogen atmosphere. All these polymers are amorphous and can form strong, transparent, and flexible films with tensile strengths of 89.4–100.6 MPa, Young’s moduli of 2.13–2.65 GPa, and elongations at break of 15.5–25.3%. All these polymers had low dielectric constants of 2.70–2.89 at 1 MHz and low water sorption of 0.51–0.59%.
Improved cognitive function after kidney transplantation compared to hemodialysis

End‐stage renal disease is associated with chronic stress that in turn may result in endocrine changes, affect cognitive, and physical capacities and increase the risk for cardiovascular events. The objective of this study was to evaluate and characterize possible stress parameters and compare cognitive function in those patients. Physiological and biochemical stress parameters as well as cognitive function were assessed in 17 hemodialysis and 18 renal transplant patients and both groups were compared. Serum cortisol and interleukin‐6 levels were elevated in both groups but showed no significant difference. Cholesterol and low‐density lipoprotein levels were significantly higher in patients following renal transplantation. While heart rate variability was comparable in both groups, most cognitive tests showed better results in renal transplant patients. We showed that: (1) cognitive function may improve following renal transplantation; (2) standard biochemical stress parameters are not useful to discriminate stress in patients with chronic kidney disease; and (3) heart rate variability is unaltered in this setting.
Enhancing the performance of MnO by double carbon modification for advanced lithium-ion battery anodes

Porous hybrid materials with designed micro/nano-sub-structures have been recognized as promising anodes for lithium-ion batteries (LIBs) due to their high capacity and reliable performance. The low electrical conductivity and side-reactions at the interface of electrode/electrolyte prohibit their practical applications. Carbon material modification can effectively enhance the conductivity and mechanical properties, and suppress the direct contact between the electrode and electrolyte, leading to enhanced performance. Herein, unique porous MnO with micro/nano-architectures has been in situ decorated with carbon layers on the surface and by carbon nanotube doping between the particles (denoted as MnO@C/CNTs) by a catalytic chemical vapor deposition (CCVD) treatment. As anodes in LIBs, these MnO@C/CNTs exhibit remarkable cycling performance (1266 mA h g−1 after 300 cycles at 500 mA g−1) and good rate capability (850 mA h g−1 after 100 cycles at 100 mA g−1). The inspiring performance is associated with the carbon modified porous micro/nano-structure features which can buffer the volume expansion and promote the ion/electron transfer at the interface of electrode/electrolyte.
External Validation of a Predictive Model to Estimate Renal Function After Living Donor Nephrectomy

Supplemental Digital Content is available in the text. Background. Transplantation from living donor nephrectomy (LDN) is the best treatment for end-stage renal disease but observed decrease in donor renal function is a major concern. The aim of this study was to externally validate a predictive model to estimate 1-y postdonation estimated glomerular filtration rate (eGFR) and risk of chronic kidney disease (CKD) in living donors. Methods. All LDN performed at Necker Hospital from January 2006 to May 2018 were retrospectively included. Observed eGFR (using CKD-EPI formula) at 1-y post LDN was compared with the predicted eGFR calculated with a formula developed at Toulouse-Rangueil and based on predonation eGFR and age. Pearson correlation, receiver operating characteristics curve (ROC curve), and calibration curve were used to assess external validity of the proposed prognostic model to predict postoperative eGFR and occurrence of CKD in donors. Results. Four hundred donors were evaluated with a mean postoperative eGFR of 62.1 ± 14 mL/min/1.73m2. Significant correlation (Pearson r = 0.66; P < 0.001) and concordance (Bradley-Blackwood F = 49.189; P < 0.001) were observed between predicted and observed 1-y eGFR. Area under the receiver operating characteristic curve of the model relevant accuracy was 0.86 (95% CI, 0.82-0.89). Conclusions. This study externally validated the formula to predict 1-y postdonation eGFR. The calculator could be an accurate tool to improve the selection of living kidney donor candidate.
Development and characterization of pluronic lecithin organogel containing fluocinolone acetonide

Abstract The rabble-rousing skin condition can be conventionally treated, but due to some demerits, there is a need to find a novel approach with an appropriate release profile. The research work narrates the optimization of the topical delivery system of Fluocinolone acetonide loaded in pluronic lecithin organogel. The preliminary studies were carried out and, the ternary phase diagram was established by Chemix school version 3.60. The formulation was optimized by taking a different concentration of polymers as independent and viscosity and drug release (6 h) as dependent variables by applying 32 full factorial design. The optimized batch was further compared with marketed preparation and also kept for the stability study. The release profile of the optimized batch exhibited a sustained release of up to 6 h (77.00%). It gave ex vivo drug release up to 6 h (90.64%) which is more prolonged than marketed preparation and, cutaneous disposition was found to be higher. Besides, the texture analysis was compared to that of the marketed formulation of the drug. However, the proof of the effectiveness of the formulated pluronic lecithin organogel will require further in vivo study for future aspects. In a nutshell, the proposed formulation of fluocinolone acetonide is the simplest and promising dosage form for the treatment of psoriasis.
Analysis of thermal efficiency of a passive solar water heater

The analysis of thermal efficiency of a passive solar water heater is presented. The heater which has potential applications in agro-industries and homes, consisted of a single-glazed flat plate solar collector made up of an absorber plate and a transparent sheet of glass; water storage tanks and the stand. The absorber plate was made of mild steel which is a very good conductor of heat. Copper tube was used to form a loop on the mild steel absorber. Water in the loop is heated by the radiant energy trapped by the absorber. The system was tested experimentally under daytime load conditions at Nsukka, Nigeria, over the ambient temperature range of 21 to 31°C, and a daily global irradiation range of 8.3 to 17.4 MJ m -2 . Peak temperature rise of the heated water was about 83°C, while the maximum daily average useful efficiency was about 42%. It was deduced that the system can be operated successfully for agro-industries and home applications.
Abscisic acid regulates secondary cell-wall formation and lignin deposition in Arabidopsis thaliana through phosphorylation of NST1

Significance Lignin deposition in plants is affected by environmental stress, and stress-signaling involves increases in the levels of the plant hormone abscisic acid (ABA). Here we show, using a combination of biochemical and genetic approaches, how ABA can regulate lignin biosynthesis. This involves phosphorylation of the master lignin transcription factor NST1 by a family of protein kinases (SnRK2s) that are themselves activated by phosphorylation as a result of ABA recognition by its receptor. This work provides a basis for designing trees and other biomass plants that are better adapted to stress and climate change. Plant secondary cell-wall (SCW) deposition and lignification are affected by both seasonal factors and abiotic stress, and these responses may involve the hormone abscisic acid (ABA). However, the mechanisms involved are not clear. Here we show that mutations that limit ABA synthesis or signaling reduce the extent of SCW thickness and lignification in Arabidopsis thaliana through the core ABA-signaling pathway involving SnRK2 kinases. SnRK2.2. 3 and 6 physically interact with the SCW regulator NAC SECONDARY WALL THICKENING PROMOTING FACTOR 1 (NST1), a NAC family transcription factor that orchestrates the transcriptional activation of a suite of downstream SCW biosynthesis genes, some of which are involved in the biosynthesis of cellulose and lignin. This interaction leads to phosphorylation of NST1 at Ser316, a residue that is highly conserved among NST1 proteins from dicots, but not monocots, and is required for transcriptional activation of downstream SCW-related gene promoters. Loss of function of NST1 in the snd1 mutant background results in lack of SCWs in the interfascicular fiber region of the stem, and the Ser316Ala mutant of NST1 fails to complement this phenotype and ABA-induced lignin pathway gene expression. The discovery of NST1 as a key substrate for phosphorylation by SnRK2 suggests that the ABA-mediated core-signaling cascade provided land plants with a hormone-modulated, competitive desiccation-tolerance strategy allowing them to differentiate water-conducting and supporting tissues built of cells with thicker cell walls.
Extra Virgin Olive Oil Phenols Vasodilate Rat Mesenteric Resistance Artery via Phospholipase C (PLC)-Calcium Microdomains-Potassium Channels (BKCa) Signals

Recent evidence suggests that the reason Extra Virgin Olive Oil (EVOO) lowers blood pressure and reduces the risk of developing hypertension is partly due to minor components of EVOO, such as phenols. However, little is still known about the mechanism(s) through which EVOO phenols mediate anti-hypertensive effects. The aim of the present study was to investigate the mechanisms of action of EVOO phenols on mesenteric resistance arteries. A pressure myograph was used to test the effect of EVOO phenols on isolated mesenteric arteries in the presence of specific inhibitors of: (1) BKca channels (Paxillin, 10−5 M); (2) L-type calcium channels (Verapamil, 10−5 M); (3) Ryanodine receptor, RyR (Ryanodine, 10−5 M); (4) inositol 1,4,5-triphosphate receptor, IP3R, (2-Aminoethyl diphenylborinate, 2-APB, 3 × 10−3 M); (5) phospholipase C, PLC, (U73122, 10−5 M), and (6) GPCR-Gαi signaling, (Pertussis Toxin, 10−5 M). EVOO phenols induced vasodilation of mesenteric arteries in a dose-dependent manner, and this effect was reduced by pre-incubation with Paxillin, Verapamil, Ryanodine, 2-APB, U73122, and Pertussis Toxin. Our data suggest that EVOO phenol-mediated vasodilation requires activation of BKca channels potentially through a local increase of subcellular calcium microdomains, a pivotal mechanism on the base of artery vasodilation. These findings provide novel mechanistic insights for understanding the vasodilatory properties of EVOO phenols on resistance arteries.
Wintering bird communities are tracking climate change faster than breeding communities.

1. Global climate change is driving species' distributions towards the poles and mountain tops during both non-breeding and breeding seasons, leading to changes in the composition of natural communities. However, the degree of season differences in climate-driven community shifts has not been thoroughly investigated at large spatial scales. 2. We compared the rates of change in the community composition during both winter (non-breeding season) and summer (breeding) and their relation to temperature changes. 3. Based on continental-scale data from Europe and North America, we examined changes in bird community composition using the community temperature index (CTI) approach and compared the changes with observed regional temperature changes during 1980-2016. 4. CTI increased faster in winter than in summer. This seasonal discrepancy is probably because individuals are less site-faithful in winter, and can more readily shift their wintering sites in response to weather in comparison to the breeding season. Regional long-term changes in community composition were positively associated with regional temperature changes during both seasons, but the pattern was only significant during summer due to high annual variability in winter communities. Annual changes in community composition were positively associated with the annual temperature changes during both seasons. 5. Our results were broadly consistent across continents, suggesting some climate-driven restructuring in both European and North American avian communities. Because community composition has changed much faster during the winter than during the breeding season, it is important to increase our knowledge about climate-driven impacts during the less-studied non-breeding season.
Cortical hemodynamic mapping of subthalamic nucleus deep brain stimulation in Parkinsonian patients, using high-density functional near-infrared spectroscopy

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for idiopathic Parkinson’s disease. Despite recent progress, the mechanisms responsible for the technique’s effectiveness have yet to be fully elucidated. The purpose of the present study was to gain new insights into the interactions between STN-DBS and cortical network activity. We therefore combined high-resolution functional near-infrared spectroscopy with low-resolution electroencephalography in seven Parkinsonian patients on STN-DBS, and measured cortical haemodynamic changes at rest and during hand movement in the presence and absence of stimulation (the ON-stim and OFF-stim conditions, respectively) in the off-drug condition. The relative changes in oxyhaemoglobin [HbO], deoxyhaemoglobin [HbR], and total haemoglobin [HbT] levels were analyzed continuously. At rest, the [HbO], [HbR], and [HbT] over the bilateral sensorimotor (SM), premotor (PM) and dorsolateral prefrontal (DLPF) cortices decreased steadily throughout the duration of stimulation, relative to the OFF-stim condition. During hand movement in the OFF-stim condition, [HbO] increased and [HbR] decreased concomitantly over the contralateral SM cortex (as a result of neurovascular coupling), and [HbO], [HbR], and [HbT] increased concomitantly in the dorsolateral prefrontal cortex (DLPFC)—suggesting an increase in blood volume in this brain area. During hand movement with STN-DBS, the increase in [HbO] was over the contralateral SM and PM cortices was significantly lower than in the OFF-stim condition, as was the decrease in [HbO] and [HbT] in the DLPFC. Our results indicate that STN-DBS is associated with a reduction in blood volume over the SM, PM and DLPF cortices, regardless of whether or not the patient is performing a task. This particular effect on cortical networks might explain not only STN-DBS’s clinical effectiveness but also some of the associated adverse effects.
Electrophilic oxysterols: generation, measurement and protein modification

Abstract Cholesterol is an essential component of mammalian plasma membranes. Alterations in sterol metabolism or oxidation have been linked to various pathological conditions, including cardiovascular diseases, cancer, and neurodegenerative disorders. Unsaturated sterols are vulnerable to oxidation induced by singlet oxygen and other reactive oxygen species. This process yields reactive sterol oxidation products, including hydroperoxides, epoxides as well as aldehydes. These oxysterols, in particular those with high electrophilicity, can modify nucleophilic sites in biomolecules and affect many cellular functions. Here, we review the generation and measurement of reactive sterol oxidation products with emphasis on cholesterol hydroperoxides and aldehyde derivatives (electrophilic oxysterols) and their effects on protein modifications. Graphical Abstract