Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular cloning and functional characterization of GmAAPTs from soybean (Glycine max)

ABSTRACT Aminoalcoholphosphotransferase (AAPT) utilizes diacylglycerols and cytidine diphosphate-choline/ethanolamine as substrates for the synthesis of phosphatidylcholine (PC)/phosphatidylethanolamine (PE). Plant AAPTs involved in phospholipid metabolism mediate diverse physiological processes; however, little is known about their functions in triacylglycerol (TAG) metabolism and seed germination. In the present study, we isolated and characterized two AAPTs, GmAAPT1 and GmAAPT2, from soybean (Glycine max). GmAAPT1 and GmAAPT2 exhibited strong similarity in their amino acid contents and expression patterns, and both were found to localize to the endoplasmic reticulum and Golgi apparatus. In vitro enzymatic analyses showed that GmAAPT1 and GmAAPT2 contributed to PC and PE synthesis and exhibited choline/ethanolamine phosphotransferase-like enzymatic properties. The overexpression of GmAAPT1 and GmAAPT2 in Arabidopsis led to reduced levels of seed TAG and polyunsaturated fatty acids and decreased seed germination under freezing stress. Together, these findings suggest that GmAAPTs mediate TAG metabolism and negatively regulate seed freezing tolerance.
Nanodiscs: A toolkit for membrane protein science

Membrane proteins are involved in numerous vital biological processes, including transport, signal transduction and the enzymes in a variety of metabolic pathways. Integral membrane proteins account for up to 30% of the human proteome and they make up more than half of all currently marketed therapeutic targets. Unfortunately, membrane proteins are inherently recalcitrant to study using the normal toolkit available to scientists, and one is most often left with the challenge of finding inhibitors, activators and specific antibodies using a denatured or detergent solubilized aggregate. The Nanodisc platform circumvents these challenges by providing a self‐assembled system that renders typically insoluble, yet biologically and pharmacologically significant, targets such as receptors, transporters, enzymes, and viral antigens soluble in aqueous media in a native‐like bilayer environment that maintain a target's functional activity. By providing a bilayer surface of defined composition and structure, Nanodiscs have found great utility in the study of cellular signaling complexes that assemble on a membrane surface. Nanodiscs provide a nanometer scale vehicle for the in vivo delivery of amphipathic drugs, therapeutic lipids, tethered nucleic acids, imaging agents and active protein complexes. This means for generating nanoscale lipid bilayers has spawned the successful use of numerous other polymer and peptide amphipathic systems. This review, in celebration of the Anfinsen Award, summarizes some recent results and provides an inroad into the current and historical literature.
Investigating and dealing with publication bias and other reporting biases in meta‐analyses of health research: A review

A P value, or the magnitude or direction of results can influence decisions about whether, when, and how research findings are disseminated. Regardless of whether an entire study or a particular study result is unavailable because investigators considered the results to be unfavorable, bias in a meta‐analysis may occur when available results differ systematically from missing results. In this article, we summarize the empirical evidence for various reporting biases that lead to study results being unavailable for inclusion in systematic reviews, with a focus on health research. These biases include publication bias and selective nonreporting bias. We describe processes that systematic reviewers can use to minimize the risk of bias due to missing results in meta‐analyses of health research, such as comprehensive searches and prospective approaches to meta‐analysis. We also outline methods that have been designed for assessing risk of bias due to missing results in meta‐analyses of health research, including using tools to assess selective nonreporting of results, ascertaining qualitative signals that suggest not all studies were identified, and generating funnel plots to identify small‐study effects, one cause of which is reporting bias.
Impact of Neointimal Condition and Platelet Reactivity on Intrastent Thrombus at Long-Term Follow-up After 2nd- and 3rd-Generation Drug-Eluting Stent Implantation　- Insights From a Coronary Angioscopy and Pharmacodynamic Study.

BACKGROUND Although the incidence of very late stent failure (VLSF) is reduced with newer generation drug-eluting stent (DES), the mechanism of VLSF has not been fully explored.Methods and Results:This study evaluated both local vascular healing using coronary angioscopy and systemic factors determined by platelet reactivity at long-term follow-up after 2nd- and 3rd-generation DES implantation in patients with acute coronary syndrome. Coronary angioscopy was performed to assess neointimal coverage (NIC), yellow color (YC) grade and presence of thrombus. The obtained findings were compared with 2nd- and 3rd-DES. Platelet aggregation was assessed by light transmittance aggregometry. 100 consecutive patients were prospectively enrolled: 2nd- (n=50) and 3rd-DES (n=50). 3rd-DES patients had significantly higher NIC grade and lower YC grade compared with 2nd-DES. The presence of thrombus was tended to be lower with 3rd-DES than with 2nd-DES (8% vs. 18%, P=0.11). Patients with thrombus had significantly higher maximum platelet aggregation and higher prevalence of high on-treatment platelet reactivity (HPR) than those without thrombus. Multivariable analysis showed stent strut exposure and HPR as independent predictors of thrombus. CONCLUSIONS Newer generation DES contribute to better vascular healing depending on the degree of neointimal coverage. In addition to local factors at the stented lesion, systemic factors such as degree of platelet reactivity might also contribute to VLSF.
Detection and evaluation of haemophilic arthropathy: Which tools may be considered more reliable

Progressive arthropathy is the main cause of morbidity in patients with severe haemophilia. Diagnostic imaging can detect even subclinical arthropathy and impact prophylactic treatment. However, in most clinical settings the regular joint evaluation and follow‐up are based on clinical evaluation and patient's personal reporting of problems, while diagnostic imaging is not regularly employed.
Spontaneous motor-behavior abnormalities in two Drosophila models of neurodevelopmental disorders

Abstract Mutations in hundreds of genes cause neurodevelopmental disorders with abnormal motor behavior alongside cognitive deficits. Boys with fragile X syndrome (FXS), a leading monogenic cause of intellectual disability, often display repetitive behaviors, a core feature of autism. By direct observation and manual analysis, we characterized spontaneous-motor-behavior phenotypes of Drosophila dfmr1 mutants, an established model for FXS. We recorded individual 1-day-old adult flies, with mature nervous systems and prior to the onset of aging, in small arenas. We scored behavior using open-source video-annotation software to generate continuous activity timelines, which were represented graphically and quantitatively. Young dfmr1 mutants spent excessive time grooming, with increased bout number and duration; both were rescued by transgenic wild-type dfmr1+ . By two grooming-pattern measures, dfmr1-mutant flies showed elevated repetitions consistent with perseveration, which is common in FXS. In addition, the mutant flies display a preference for grooming posterior body structures, and an increased rate of grooming transitions from one site to another. We raise the possibility that courtship and circadian rhythm defects, previously reported for dfmr1 mutants, are complicated by excessive grooming. We also observed significantly increased grooming in CASK mutants, despite their dramatically decreased walking phenotype. The mutant flies, a model for human CASK-related neurodevelopmental disorders, displayed consistently elevated grooming indices throughout the assay, but transient locomotory activation immediately after placement in the arena. Based on published data identifying FMRP-target transcripts and functional analyses of mutations causing human genetic neurodevelopmental disorders, we propose the following proteins as candidate mediators of excessive repetitive behaviors in FXS: CaMKIIα, NMDA receptor subunits 2A and 2B, NLGN3, and SHANK3. Together, these fly-mutant phenotypes and mechanistic insights provide starting points for drug discovery to identify compounds that reduce dysfunctional repetitive behaviors.
When and why telepressure and technostress creators impair employee well-being

Objectives. This article describes the effects of two specific information and communication technology (ICT) demands (telepressure, technostress creators) on employee well-being, and investigates a mediating effect of detachment (Study 1) and moderating effects of technostress inhibitors on the effects of ICT demands on well-being (Study 2) and detachment (Study 3). Methods. Three quantitative studies with employees (Study 1, N = 296; Study 2, N = 142; Study 3, N = 316) were conducted. Results. The results support the negative effect of ICT demands on several well-being indicators. They also show how detachment mediates the effect of telepressure on well-being (Study 1) and how technostress inhibitors moderate the effect of technostress creators on well-being (Study 2). Technostress inhibitors further buffer negative effects of technostress creators on detachment (Study 3). Conclusion. Interventions to reduce negative consequences of ICTs by increasing the level of technostress inhibitors (e.g., technical support) or facilitating employee detachment (e.g., through communication policies) are derived. The findings confirm that general models explaining stress and well-being are applicable to new forms of job demands and extend existing empirical support for the effect of ICT demands on well-being. Future research should investigate the interplay between the studied variables within a moderated mediation model.
Molecular mechanism of selective substrate engagement and inhibitor disengagement of cysteine synthase

O-acetyl serine sulfhydrylase (OASS), referred to as cysteine synthase (CS), synthesizes cysteine from O-acetyl serine (OAS) and sulfur in bacteria and plants. The inherent challenge for CS is to overcome 4 to 6 log-folds stronger affinity for its natural inhibitor, serine acetyltransferase (SAT), as compared with its affinity for substrate, OAS. Our recent study showed that CS employs a novel competitive-allosteric mechanism to selectively recruit its substrate in the presence of natural inhibitor. In this study, we trace the molecular features that control selective substrate recruitment. To generalize our findings, we used CS from three different bacteria (Haemophilus, Salmonella, and Mycobacterium) as our model systems and analyzed structural and substrate-binding features of wild-type CS and its ∼13 mutants. Results show that CS uses a noncatalytic residue, M120, located 20 Å away from the reaction center, to discriminate in favor of substrate. M120A and background mutants display significantly reduced substrate binding, catalytic efficiency, and inhibitor binding. Results shows that M120 favors the substrate binding by selectively enhancing the affinity for the substrate and disengaging the inhibitor by 20 to 286 and 5- to 3-folds, respectively. Together, M120 confers a net discriminative force in favor of substrate by 100- to 858-folds.
Misdiagnosis: Burnout, moral injury, and implications for the electronic health record

Burnout is a long-term stress reaction marked by emotional exhaustion, depersonalization, and a lack of sense of personal accomplishment. Burnout in clinicians is receiving significant attention. Some have proposed that clinicians are experiencing symptoms of moral injury, defined as "perpetrating, failing to prevent, bearing witness to, or learning about acts that transgress deeply held moral beliefs and expectations. " Current efforts to improve the electronic health record (EHR) have focused on improving the user experience to reduce burden that has been identified as a contributing factor to provider burnout. However, if EHRs are contributing to moral injury, improvements to user experience will not eliminate the effects on providers. Current research has not evaluated the risk for moral injury resulting from the use of EHRs. This Perspective reviews the differences between burnout and moral injury, discusses the implications for clinicians using EHRs, and highlights the need for research to better define the problem.
Low intermittent flow promotes rat mesenchymal stem cell differentiation in logarithmic fluid shear device.

Bone marrow mesenchymal stem cells are an ideal candidate for bone tissue engineering due to their osteogenic potential. Along with chemical, mechanical signals such as fluid shear stress have been found to influence their differentiation characteristics. But the range of fluid shear experienced in vivo is too wide and difficult to generate in a single device. We have designed a microfluidic device that could generate four orders of shear stresses on adherent cells. This was achieved using a unique hydraulic resistance combination and linear optimization to the lesser total length of the circuit, making the device compact and yet generating four logarithmically increasing shear stresses. Numerical simulation depicts that, at an inlet velocity of 160 μl/min, our device generated shear stresses from 1.03 Pa to 1.09 mPa. In this condition, we successfully cultured primary rat bone marrow mesenchymal stem cells (rBMSCs) in the device for a prolonged period of time in the incubator environment (four days). Higher cell proliferation rate was observed in the intermittent flow at 1.09 mPa. At 10 mPa, both upregulation of osteogenic genes and higher alkaline phosphatase activity were observed. These results suggest that the intermittent shear of the order of 10 mPa can competently enhance osteogenic differentiation of rBMSCs compared to static culture.
Phylogenomics and species delimitation for effective conservation of manta and devil rays

Practical biodiversity conservation relies on delineation of biologically meaningful units. Manta and devil rays (Mobulidae) are threatened worldwide, yet morphological similarities and a succession of recent taxonomic changes impede the development of an effective conservation strategy. Here, we generate genome‐wide single nucleotide polymorphism (SNP) data from a geographically and taxonomically representative set of manta and devil ray samples to reconstruct phylogenetic relationships and evaluate species boundaries under the general lineage concept. We show that nominal species units supported by alternative data sources constitute independently evolving lineages, and find robust evidence for a putative new species of manta ray in the Gulf of Mexico. Additionally, we uncover substantial incomplete lineage sorting indicating that rapid speciation together with standing variation in ancestral populations has driven phylogenetic uncertainty within Mobulidae. Finally, we detect cryptic diversity in geographically distinct populations, demonstrating that management below the species level may be warranted in certain species. Overall, our study provides a framework for molecular genetic species delimitation that is relevant to wide‐ranging taxa of conservation concern, and highlights the potential for genomic data to support effective management, conservation and law enforcement strategies.
Effect of Repetitive Administration of a Next-generation Sensory Organization Test in Adults With and Without Vestibular Dysfunction

Supplemental Digital Content is available in the text Hypothesis: The overall aim was to assess the effects of repetitive testing on performance on a next-generation Sensory Organization Test (NG-SOT). Background: The psychometric properties of sensory organization assessment with a next-generation posturography device are not fully characterized. Thus, a better understanding of the reliability of the NG-SOT is required to support its use as an outcome measure. Methods: Forty adults (20 vestibular-impaired) participated. Test–retest reliability was determined using the interclass correlation coefficient [ICC (3,1)] for the composite, somatosensory, vision, vestibular, and visual preference scores. Learning effects were assessed by analyzing the change in the composite score over time. Results: Analyzing the NG-SOT scores across all participants produced the following interclass correlation coefficients [95% confidence interval (CI)]: composite = 0.95 (0.92, 0.97), somatosensory = 0.20 (−0.06, 0.44), vision = 0.93 (0.88, 0.96), vestibular = 0.91 (0.85, 0.94), and visual preference = 0.19 (−0.07, 0.43). The mean differences (95% CI; p value) for the composite score between administrations were: 2.7 (1.0, 4.4; 0.002) for visits 1 and 2; 1.4 (−0.3, 3.1; 0.099) for visits 2 and 3; 0.7 (−1.0, 2.4; 0.403) for visits 3 and 4; and 0.4 (−1.3, 2.1; 0.653) for visits 4 and 5. Conclusions: Test–retest reliability was excellent for the composite, vision, and vestibular scores, but it was poor for the somatosensory and visual preference scores. A learning effect for the composite score was identified, but performance was stable after two administrations. Changes in the composite score that are greater than 6.5 points exceed the measurement error for the test.
Laparoscopic mediastinal approach for retrosternal gastric conduit cancer after esophagectomy

The prognosis of esophageal cancer has improved, but the incidence of gastric conduit cancer has increased. Gastric conduit cancer is difficult to treat because current treatment options are highly invasive; in particular, surgical procedures have high mortality and modality. Treatment through the retrosternal route usually requires sternotomy, which often causes lethal osteomyelitis. To prevent lethal complications and reduce invasiveness, we used the laparoscopic mediastinal approach. Here, we report a successful case using the laparoscopic mediastinal approach for the treatment of gastric conduit cancer through the retrosternal route. Despite a few concerns, this approach can be a treatment option for gastric conduit cancer through the retrosternal route.
Assessment of mustard vesicant lung injury and anti‐TNF‐α efficacy in rodents using live‐animal imaging

Nitrogen mustard (NM) causes acute lung injury, which progresses to fibrosis. This is associated with a macrophage‐dominant inflammatory response and the production of proinflammatory/profibrotic mediators, including tumor necrosis factor alpha (TNF‐α). Herein, we refined magnetic resonance imaging (MRI) and computed tomography (CT) imaging methodologies to track the progression of NM‐induced lung injury in rodents and assess the efficacy of anti‐TNF‐α antibody in mitigating toxicity. Anti‐TNF‐α antibody was administered to rats (15 mg/kg, every 8 days, intravenously) beginning 30 min after treatment with phosphate‐buffered saline control or NM (0.125 mg/kg, intratracheally). Animals were imaged by MRI and CT prior to exposure and 1–28 days postexposure. Using MRI, we characterized acute lung injury and fibrosis by quantifying high‐signal lung volume, which represents edema, inflammation, and tissue consolidation; these pathologies were found to persist for 28 days following NM exposure. CT scans were used to assess structural components of the lung and to register changes in tissue radiodensities. CT scans showed that in control animals, total lung volume increased with time. Treatment of rats with NM caused loss of lung volume; anti‐TNF‐α antibody mitigated this decrease. These studies demonstrate that MRI and CT can be used to monitor lung disease and the impact of therapeutic intervention.
Can we obtain in vivo transmural mean hoop stress of the aortic wall without knowing patient-specific material properties and residual deformations?

It is well known that residual deformations/stresses alter the mechanical behavior of arteries, e.g. the pressure-diameter curves. In an effort to enable personalized analysis of the aortic wall stress, approaches have been developed to incorporate experimentally-derived residual deformations into in vivo loaded geometries in finite element simulations using thick-walled models. Solid elements are typically used to account for “bending-like” residual deformations. Yet, the difficulty in obtaining patient-specific residual deformations and material properties has become one of the biggest challenges of these thick-walled models. In thin-walled models, fortunately, static determinacy offers an appealing prospect that allows for the calculation of the thin-walled membrane stress without patient-specific material properties. The membrane stress can be computed using forward analysis by enforcing an extremely stiff material property as penalty treatment, which is referred to as the forward penalty approach. However, thin-walled membrane elements, which have zero bending stiffness, are incompatible with the residual deformations, and therefore, it is often stated as a limitation of thin-walled models. In this paper, by comparing the predicted stresses from thin-walled models and thick-walled models, we demonstrate that the transmural mean hoop stress is the same for the two models and can be readily obtained from in vivo clinical images without knowing the patient-specific material properties and residual deformations. Computation of patient-specific mean hoop stress can be greatly simplified by using membrane model and the forward penalty approach, which may be clinically valuable.
SUV39H1 is a New Client Protein of Hsp90 Degradated by Chaetocin as a Novel C-Terminal Inhibitor of Hsp90

Hsp90 is often overexpressed with activated form in cancer cells, and many key cellular proteins are dependent upon the Hsp90 machinery (these proteins are called “client protein”). Nowadays, more client proteins and more inhibitors of Hsp90 are being discovered. Chaetocin has been identified as an inhibitor of histone methyl transferase SUV39H1. Herein, we find that Chaetocin is an inhibitor of Hsp90 which binds to the C-terminal of Hsp90α. Chaetocin inhibited a variety of Hsp90 client proteins including AMl1-ETO and BCL-ABL, the mutant fusion-protein in the K562 and HL-60 cells. SUV39H1 mediates epigenetic events in the pathophysiology of hematopoietic disorders. We found that inhibition of Hsp90 by Chaetocin and 17-AAG had ability to induce degradation of SUV39H1 through proteasome pathway. In addition, SUV39H1 interacted with Hsp90 through co-chaperone HOP. These results suggest that SUV39H1 belongs to a client protein of Hsp90. Moreover, Chaetocin was able to induce cell differentiation in the two cells in the concentration range of Hsp90 inhibition. Altogether, our results demonstrate that SUV39H1 is a new client protein of Hsp90 degradated by Chaetocin as a novel C-terminal inhibitor of Hsp90. The study establishes a new relationship of Chaetocin and SUV39H1, and paves an avenue for exploring a new strategy to target SUV39H1 by inhibition of Hsp90 in leukemia.