Miracle-dz/UniFAR-FTUs huggingface dataset:
Conformational changes in glutaminyl-tRNA synthetases upon binding of the substrates and analogs using molecular docking and molecular dynamics approaches

Abstract Aminoacyl-tRNA synthetases (aaRSs) are considered as important components in protein translation as they facilitate the attachment of specific transfer RNA (tRNA) to form aminoacyl-tRNAs. Our study focused on understanding the crystal structure of Glutaminyl-tRNA synthetase (GlnRS) from Thermus thermophilus HB8 (PDB ID:5ZDO) and mechanism of formation of enzyme–substrate complex using substrates and its analogs by applying molecular dynamics simulation (MDS) to investigate the conformational changes. Least energy structure of TtGlnRS was considered to dock the enzyme substrates such as glutamine (Gln), glutamic acid (Glu), adenosine monophosphate (AMP), adenosine triphosphate (ATP), QSI and various substrate analogs (2MA, 4SU and 5MU) onto the active site of the enzyme. We focused on comparative analysis of binding specificity between Gln and Glu; similarly, ATP and AMP. Active site organization as observed by MDS analysis showed interactive changes associated with substrate and catalytically important loops. Study found that when tRNAGln specific for GlnRS was docked into the active site of the TtGlnRS enzyme it interacts with 2' OH on the ribose acceptor end of the tRNA. Upon validation with 50 ns MDS, the maximum deviations and conformational changes of secondary structural elements were observed to be high in the loop regions of enzyme–substrate complexes. Binding affinity of ATP to TtGlnRS was further proved by isothermal titration calorimetry. AbbreviationsaaRSs aminoacyl-tRNA synthetasesAMP adenosine monophosphateATP adenosine triphosphateGlide Grid-based LIgand Docking with EnergeticGlnRS glutaminyl-tRNA synthetaseGRAVY GRand AVerage of hydropathicitYGROMACS GROingen Machine for Chemical SimulationsHADDOCK High Ambiguity Driven protein–protein DOCKingITC isothermal titration calorimetry2MA 2-methyladenosine 5'-(dihydrogen phosphate)MDS molecular dynamics simulation5MU 5-methyluridine 5'-monophosphateNPT number of particles, pressure and temperatureNVT number of particles, volume and temperatureOPLS-AA optimized potential for liquid simulation all atomPDB Brookhaven Protein DatabankPME Particle-Mesh EwaldQSI 5'-o-[n-(l-Glutaminyl)-sulfamoyl]adenosineRg radius of gyrationRMSD root mean square deviationRMSF root mean square fluctuation4SU 4-thiouracil 5'-monophosphateSPC simple point chargetRNA transfer ribo nucleic acidTt Thermus thermophilusXP extra precision Communicated by Ramaswamy H. Sarma
An automated method for normalising large Landsat time series datasets to like values for change detection

The increased availability of Landsat imagery provides the opportunity to monitor changes in the land surface over long time frames. This paper presents an automated method for normalizing satellite images to a calibrated reference image using pseudo invariant features (PIFs). The method is repeatable, objective and fast, and has been used to prepare a large collection of Landsat images for flood inundation detection.
Treatment of Painful, Irreparable Partial Meniscal Defects With a Polyurethane Scaffold

Background: A biodegradable polyurethane scaffold was designed to fulfill a challenging clinical need in the treatment of patients with painful, irreparable partial meniscal defects. Hypothesis: The use of an acellular polyurethane scaffold for new tissue generation in irreparable, partial meniscal defects provides both midterm pain relief and improved functionality. Study Design: Case series; Level of evidence, 4. Methods: A total of 44 patients with irreparable, partial meniscal defects (29 medial and 15 lateral) were implanted with a polyurethane scaffold in a prospective, single-arm proof-of-principle study with a minimum 5-year follow-up. Clinical outcomes were measured with the visual analog scale (VAS) for pain, International Knee Documentation Committee (IKDC), and Knee injury and Osteoarthritis Outcome Score (KOOS) at baseline and at 2- and 5-year follow-up. Magnetic resonance imaging (MRI) was used to evaluate the meniscal implant and cartilage status of the index compartment. Kaplan-Meier time-to–treatment failure distributions were also performed. Removal of the scaffold, conversion to a meniscal transplant, or unicompartmental/total knee arthroplasty was used as endpoints. Results: Seven patients were lost to follow-up (15.9%). The patients who participated in this study showed significant clinical improvement after surgery (mean [±SD] at baseline, 2 years, and 5 years: 56.2 ± 21.6, 24.6 ± 22.7, and 19.3 ± 26.9, respectively [VAS]; 206.5 ± 79.7, 329.8 ± 108.9, and 333.6 ± 112.2, respectively [total KOOS]). MRI of the scaffolds showed a smaller sized implant when compared with the native meniscus with an irregular surface at 2- and 5-year follow-up. A stable cartilage status of the index compartment at 5-year follow-up was demonstrated in 46.7% of patients compared with the baseline status. During the follow-up period, 62.2% of the implants survived. At final follow-up, 66.7% of the medial scaffolds were still functioning versus 53.8% of the lateral scaffolds. Conclusion: A polyurethane meniscal implant can improve knee joint function and significantly reduce pain in patients with segmental meniscus deficiency up to 5 years after implantation. A stable cartilage status of the index compartment at 5-year follow-up was demonstrated in 46.7% of patients, calling into question the chondroprotective ability of the implant. In addition, a relatively high failure rate was noticed. Long-term and randomized controlled studies are mandatory to confirm the initial results and the reliability of this procedure.
Rates of niche and phenotype evolution lag behind diversification in a temperate radiation

Significance Alternative models of evolutionary processes suggest different associations between species diversification and trait evolution, but limited empirical evidence is available to test these models across large clades at global extents. Here we investigate the relative timing of species diversification and niche and phenotypic evolution across a global plant radiation (Saxifragales) with enormous phenotypic and habitat variation. We demonstrate strong temporal lags among rates, with increased diversification occurring first, followed by niche and phenotype. Accelerated diversification rates are coincident with mid-Miocene expansion of temperate biomes. Later increases in niche and phenotypic evolutionary rates argue against density-dependent diversification alone, indicating a major role for ecological opportunity. These results have broad implications for understanding diversification processes and the origin of present-day temperate biotas. Environmental change can create opportunities for increased rates of lineage diversification, but continued species accumulation has been hypothesized to lead to slowdowns via competitive exclusion and niche partitioning. Such density-dependent models imply tight linkages between diversification and trait evolution, but there are plausible alternative models. Little is known about the association between diversification and key ecological and phenotypic traits at broad phylogenetic and spatial scales. Do trait evolutionary rates coincide with rates of diversification, are there lags among these rates, or is diversification niche-neutral? To address these questions, we combine a deeply sampled phylogeny for a major flowering plant clade—Saxifragales—with phenotype and niche data to examine temporal patterns of evolutionary rates. The considerable phenotypic and habitat diversity of Saxifragales is greatest in temperate biomes. Global expansion of these habitats since the mid-Miocene provided ecological opportunities that, with density-dependent adaptive radiation, should result in simultaneous rate increases for diversification, niche, and phenotype, followed by decreases with habitat saturation. Instead, we find that these rates have significantly different timings, with increases in diversification occurring at the mid-Miocene Climatic Optimum (∼15 Mya), followed by increases in niche and phenotypic evolutionary rates by ∼5 Mya; all rates increase exponentially to the present. We attribute this surprising lack of temporal coincidence to initial niche-neutral diversification followed by ecological and phenotypic divergence coincident with more extreme cold and dry habitats that proliferated into the Pleistocene. A lack of density-dependence contrasts with investigations of other cosmopolitan lineages, suggesting alternative patterns may be common in the diversification of temperate lineages.
The relationship between the atherosclerotic cardiovascular disease risk score used in the prediction of cardiovascular disease risk and endocan

Objective: To date, there have been no studies investigating whether or not there is a correlation between the serum endocan level and the atherosclerotic cardiovascular disease (ASCVD) risk score that is frequently used in the determination of the risk of cardiovascular disease. If a single parameter such as endocan can provide reliable results which could be used in the prediction of the cardiovascular disease risk, the workload of the clinician would be lightened. The aim of this study was to investigate whether or not there is an association between the serum endocan level and the ASVCD risk score. Materials and Methods: This prospective, cross-sectional study included individuals age 40–79 years with risk factors calculated using the ASVCD score and individuals without any of those risk factors. In accordance with ASCVD risk calculation, each participant was questioned with respect to age, gender, height, weight, and lifestyle habits such as smoking, diseases, and medications. Systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and serum endocan levels were measured and recorded. The serum endocan levels and ASCVD scores were compared. Results: The study included 205 individuals, comprising 92 (44.9%) males and 113 (55.1%) females with a mean age of 50.7 ± 7.6 years. The 10-year atherosclerosis risk was determined as mean 6.32% ± 5.9% (range, 0.3%–27.3%). The mean serum endocan level was calculated as 1109.6 ± 1479.7 ng/mL. As the ASCVD risk score increased, no increase was detected in the serum endocan level. Conclusion: The results of the study suggested that the serum endocan level is not suitable for use in place of the ASCVD risk score as a predictor of cardiovascular disease risk.
Explicit Utilization of General Knowledge in Machine Reading Comprehension

To bridge the gap between Machine Reading Comprehension (MRC) models and human beings, which is mainly reflected in the hunger for data and the robustness to noise, in this paper, we explore how to integrate the neural networks of MRC models with the general knowledge of human beings. On the one hand, we propose a data enrichment method, which uses WordNet to extract inter-word semantic connections as general knowledge from each given passage-question pair. On the other hand, we propose an end-to-end MRC model named as Knowledge Aided Reader (KAR), which explicitly uses the above extracted general knowledge to assist its attention mechanisms. Based on the data enrichment method, KAR is comparable in performance with the state-of-the-art MRC models, and significantly more robust to noise than them. When only a subset (20%-80%) of the training examples are available, KAR outperforms the state-of-the-art MRC models by a large margin, and is still reasonably robust to noise.
Changes in Lactate-Producing and Lactate-Utilizing Bacteria in Relation to pH in the Rumen of Sheep During Stepwise Adaptation to a High-Concentrate Diet

Changes in the numbers and types of lactate-producing and lactate-utilizing bacteria in the rumen of sheep were followed during stepwise adaptation from a low- to a high-concentrate diet. The mean numbers of bacteria increased after each change in diet when increasing amounts of maize grain were substituted for maize stover. A surge in number of amylolytic bacteria always preceded an increase in lactate-utilizing bacteria, and with the final diet containing 71% grain and molasses the two groups tended to balance each other, which resulted in low lactic acid accumulation. The lactate utilizers thus played a key role in controlling the fermentation. Orderly shifts occurred among the predominating amylolytic and lactate-utilizing bacteria in response to the gradual decrease in ruminal pH as the amount of maize meal in the diet increased. Among the lactate utilizers, the succession began with acid-sensitive Veillonella and Selenomonas, which were superseded by more acid-tolerant Anaerovibrio and Propionibacterium. Among the amylolytic bacteria, Bacteroides was superseded by more acid-tolerant Lactobacillus and Eubacterium. The ecological succession of predominating genera was shown to be correlated significantly with ruminal pH and, more specifically, with the length of time as well as the extent to which the pH remained below a certain critical undefined value in the rumen, arbitrarily set at pH 6.00.
Sex differences in behavior and neuropharmacology of zebrafish

Sex is an important variable in biomedical research. The zebrafish (Danio rerio) is increasingly utilized as a powerful new model organism in translational neuroscience and pharmacology. Mounting evidence indicates important sex differences in zebrafish behavioral and neuropharmacological responses. Here, we discuss the role of sex in zebrafish central nervous system (CNS) models, their molecular mechanisms, recent findings and the existing challenges in this field. We also emphasize the growing utility of zebrafish models in translational neuropharmacological research of sex differences, fostering future CNS drug discovery and the search for novel sex‐specific therapies. Finally, we highlight the interplay between sex and environment in zebrafish models of sex‐environment correlations as an important strategy of CNS disease modeling using this aquatic organism.
A new selective medium for isolating Listeria spp. from heavily contaminated material

Food-associated outbreaks of human listeriosis have emphasized the importance and necessity of screening food for the presence of Listeria isolates-selective agar medium combining acriflavine (10 mg/liter) with ceftazidime (50 mg/liter) was developed. A total of 1,099 cheese production specimens were cultured, from which 157 Listeria isolates. (14.3%) grew. When compared with modified McBride agar, the acriflavine-ceftazidime agar recovered more Listeria isolates (98 versus 65%, P less than 0.001) more rapidly (57% after 48 h of incubation of the enrichment broth versus 35%, P less than 0.01) and in greater amounts. Acriflavine-ceftazidime selective agar medium proved to be a highly sensitive medium to recover Listeria spp. from heavily contaminated food products.
Impact of Distraction Osteogenesis Maxillary Expansion on the Internal Nasal Valve in Obstructive Sleep Apnea

Objective To assess the effect of distraction osteogenesis maxillary expansion (DOME) on objective parameters of the internal nasal valve and correlate findings with subjective outcomes. Study Design Retrospective cohort study. Setting Tertiary referral center. Subjects and Methods After Institutional Review Board approval, included subjects were those with obstructive sleep apnea, had undergone DOME from September 2014 to April 2018, and had cone beam computed tomography scans available before and after expansion. Measurement of the internal nasal valve parameters was performed with Invivo6 Software (version 6.0.3). Interrater reliability of all pre- and postexpansion parameters was measured. Patient-reported outcome measures included the Nasal Obstruction and Septoplasty Effectiveness Scale (NOSE) and Epworth Sleepiness Scale scores, and correlation between objective and subjective outcomes were evaluated by Spearman correlation analysis. Results Thirty-two subjects met inclusion criteria. All showed significant improvement in their subjective outcomes as well as an increase in their internal valve parameters. Significant correlation was observed between increased angles and improvement in postexpansion NOSE score (right angle, P = .024; left angle, P = .029). Conclusion DOME widens the internal nasal valve objectively (dimensions), which correlates significantly with subjective improvement (NOSE scores).
Occurrence of Anxiety and Depression among Stable COPD Patients and its Impact on Functional Capability.

INTRODUCTION Anxiety and depression are important but often under-diagnosed co-morbid conditions in patients with Chronic Obstructive Pulmonary Disease (COPD) which may affect the functional capacity of the patients. AIM To find out the proportion of depression and anxiety among stable COPD patients using a validated questionnaire suitable for use in clinic and the factors affecting their reduced functional capability as assessed by six-minute walk test. MATERIALS AND METHODS This was a descriptive cross-sectional study. Seventy five patients diagnosed with stable COPD in outpatient Department of Pulmonary Medicine in a tertiary care hospital, satisfying all inclusion criteria, were included in the study. They were examined clinically, categorized as per Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity assessment guideline and interviewed by designated interviewer using validated questionnaire for depression (Hamilton depression rating scale, HAM-D) and anxiety (State Trait Anxiety Inventory, STAI). The functional exercise capacity of the patient was assessed by six-minute walk test. Statistical analysis was performed using Minitab software (version16.1). RESULTS Among 75 stable COPD patients (68 male, 7 female), majority (32 out of 75) had both depression and anxiety, while only anxiety or depression was present in 9 each. The patients with depression had no significant difference in six-minute walk distance, change in heart rate and respiratory rate (p = 0.4186, 0.219 and 0.41 respectively) as compared to those without depression, but were found to be more dyspnoeic at the end of the test (p= 0.003). There was also no significant difference in walk distance in patients with high STAI score as compared to those with low STAI score (p= 0.276). CONCLUSION Both anxiety and depression were present in majority of the stable COPD patients. The presence of these co-morbid conditions had no significant effect on the functional status of the patients in the form of reduced six-minute walk distance, though they were more symptomatic than those without these co-morbidities.
Potentially Inappropriate Prescribing Among Older Persons: A Meta-Analysis of Observational Studies

PURPOSE Potentially inappropriate prescribing (PIP) is a common yet preventable medical error among older persons in primary care. It is uncertain whether PIP produces adverse outcomes in this population, however. We conducted a systematic review with meta-analysis to pool the adverse outcomes of PIP specific to primary care. METHOD We searched PubMed, Embase, CINAHL, Web of Science, Scopus, PsycINFO, and previous review articles for studies related to “older persons,” “primary care,” and “inappropriate prescribing. ” Two reviewers selected eligible articles, extracted data, and evaluated the risk of bias. Meta-analysis was conducted to pool studies with similar PIP criteria and outcome measures. RESULTS Of the 2,804 articles identified, we included 8 articles with a total of 77,624 participants. All included studies had cohort design and low risk of bias. Although PIP did not affect mortality (risk ratio [RR] 0.98; 95% CI, 0.93-1.05), it was significantly associated with the other available outcomes, including emergency room visits (RR 1.63; 95% CI, 1.32-2.00), adverse drug events (RR 1.34; 95% CI, 1.09-1.66), functional decline (RR 1.53; 95% CI, 1.08-2.18), health-related quality of life (standardized mean difference –0.26; 95% CI, –0.36 to –0.16), and hospitalizations (RR 1.25; 95% CI, 1.09-1.44). A majority of the pooled estimates had negligible heterogeneity. CONCLUSIONS This meta-analysis provides consolidated evidence on the wide-ranging impact of PIP among older persons in primary care. It highlights the need to identify PIP in primary care, calls for further research on PIP interventions in primary care, and points to the need to consider potential implications when deciding on the operational criteria of PIP.
Loss‐of‐function mutations in the melanocortin‐3 receptor gene confer risk for human obesity: A systematic review and meta‐analysis

The association between rare coding loss‐of‐function (LOF) mutations in the melanocortin receptor 3 (MC3R) gene and human obesity is controversial. To fill this gap of knowledge, we performed a systematic review and meta‐analysis of genetic association studies in all ages and ethnicities. Two reviewers independently performed risk of bias assessment and extracted data. We searched Medline, Embase, Web of Science Core Collection, BIOSIS Preview, CINAHL, ProQuest Dissertations & Theses, and reference lists of relevant studies. All case‐control, cross‐sectional, prospective, and retrospective studies that evaluated prevalence of rare (less than 1% frequency) coding partial/complete LOF mutations in MC3R among individuals with obesity and normal weight were included. Our systematic search identified 1925 references relevant to the present review. Six studies were deemed eligible. Meta‐analysis of 2969 individuals with obesity and 2572 with normal weight showed a positive association between rare heterozygous coding partial/complete LOF mutations in MC3R and obesity in children and adults of European, North African, and Asian ancestries (odds ratio = 3.07; 95% CI, 1.48‐7.00; P = 4.2 × 10−3). Our data demonstrates that rare partial/complete LOF mutations in the coding region of MC3R confer three‐time increased risk of obesity in humans, and implies that rare genetic variants with intermediate effects contribute to the missing heritability of obesity.
Dual Supervised Learning for Natural Language Understanding and Generation

Natural language understanding (NLU) and natural language generation (NLG) are both critical research topics in the NLP and dialogue fields. Natural language understanding is to extract the core semantic meaning from the given utterances, while natural language generation is opposite, of which the goal is to construct corresponding sentences based on the given semantics. However, such dual relationship has not been investigated in literature. This paper proposes a novel learning framework for natural language understanding and generation on top of dual supervised learning, providing a way to exploit the duality. The preliminary experiments show that the proposed approach boosts the performance for both tasks, demonstrating the effectiveness of the dual relationship.