Miracle-dz/UniFAR-FTUs huggingface dataset:
Ocular Vestibular-Evoked Myogenic Potential Amplitudes Elicited at 4 kHz Optimize Detection of Superior Semicircular Canal Dehiscence

Introduction: High-resolution temporal bone computed tomography (CT) is considered the gold standard for diagnosing superior semicircular canal dehiscence (SCD). However, CT has been shown over-detect SCD and provide results that may not align with patient-reported symptoms. Ocular vestibular-evoked myogenic potentials (oVEMPs)—most commonly conducted at 500 Hz stimulation—are increasingly used to support the diagnosis and management of SCD. Previous research reported that stimulation at higher frequencies such as 4 kHz can have near-perfect sensitivity and specificity in detecting radiographic SCD. With a larger cohort, we seek to understand the sensitivity and specificity of 4 kHz oVEMPs for detecting clinically significant SCD, as well as subgroups of radiographic, symptomatic, and surgical SCD. We also investigate whether assessing the 4 kHz oVEMP n10-p15 amplitude rather than the binary n10 response alone would optimize the detection of SCD. Methods: We conducted a cross-sectional study of patients who have undergone oVEMP testing at 4 kHz. Using the diagnostic criteria proposed by Ward et al., patients were determined to have SCD if dehiscence was confirmed on temporal bone CT by two reviewers, patient-reported characteristic symptoms, and if they had at least one positive vestibular or audiometric test suggestive of SCD. Receiver operating characteristic (ROC) analysis was conducted to identify the optimal 4 kHz oVEMP amplitude cut-off. Comparison of 4 kHz oVEMP amplitude across radiographic, symptomatic, and surgical SCD subgroups was conducted using the Mann-Whitney U test. Results: Nine hundred two patients (n, ears = 1,804) underwent 4 kHz oVEMP testing. After evaluating 150 temporal bone CTs, we identified 49 patients (n, ears = 61) who had radiographic SCD. Of those, 33 patients (n, ears = 37) were determined to have clinically significant SCD. For this study cohort, 4 kHz oVEMP responses had a sensitivity of 86.5% and a specificity of 87.8%. ROC analysis demonstrated that accounting for the inter-amplitude of 4 kHz oVEMP was more accurate in detecting SCD than the presence of n10 response alone (AUC 91 vs. 87%). Additionally, using an amplitude cut-off of 15uV reduces false positive results and improves specificity to 96.8%. Assessing 4 kHz oVEMP response across SCD subgroups demonstrated that surgical and symptomatic SCD cases had significantly higher amplitudes, while radiographic SCD cases without characteristic symptoms had similar amplitudes compared to cases without evidence of SCD. Conclusion: Our results suggest that accounting for 4 kHz oVEMP amplitude can improve detection of SCD compared to the binary presence of n10 response. The 4 kHz oVEMP amplitude cut-off that maximizes sensitivity and specificity for our cohort is 15 uV. Our results also suggest that 4 kHz oVEMP amplitudes align better with symptomatic SCD cases compared to cases in which there is radiographic SCD but no characteristic symptoms.
Synergy Screening Identifies a Compound That Selectively Enhances the Antibacterial Activity of Nitric Oxide

Antibiotic resistance poses a serious threat to global health. To reinforce the anti-infective arsenal, many novel therapeutic strategies to fight bacterial infections are being explored. Among them, anti-virulence therapies, which target pathways important for virulence, have attracted much attention. Nitric oxide (NO) defense systems have been identified as critical for the pathogenesis of various bacteria, making them an appealing therapeutic target. In this study, we performed chemical screens to identify inhibitors of NO detoxification in Escherichia coli. We found that 2-mercaptobenzothiazole (2-MBT) can potently inhibit cellular detoxification of NO, achieving a level of inhibition that resembled the effect of genetically removing Hmp, the dominant detoxification enzyme under oxygenated conditions. Further analysis revealed that in the presence of NO, 2-MBT impaired the catalysis of Hmp and synthesis of Hmp and other proteins, whereas in its absence there were minimal perturbations to growth and protein synthesis. In addition, by studying the structure-activity relationship of 2-MBT, we found that both sulfur atoms in 2-MBT were vital for its inhibition of NO detoxification. Interestingly, when 2-mercaptothiazole (2-MT), which lacked the benzene ring, was used, differing biological activities were observed, although they too were NO dependent. Specifically, 2-MT could still prohibit NO detoxification, though it did not interfere with Hmp catalysis; rather, it was a stronger inhibitor of protein synthesis and it reduced the transcript levels of hmp, which was not observed with 2-MBT. Overall, these results provide a strong foundation for further exploration of 2-MBT and 2-MT for therapeutic applications.
Drug Weaponry to Fight Against SARS-CoV-2

The current outbreak of SARS-CoV-2 virus has caused a large increase in mortality and morbidity associated with respiratory diseases. Huge efforts are currently ongoing to develop a vaccine against this virus. However, alternative approaches could be considered in the fight against this disease. Among other strategies, structural-based drug design could be an effective approach to generate specific molecules against SARS-CoV-2, thus reducing viral burden in infected patients. Here, in addition to this structural approach, we also revise several therapeutic strategies to fight against this viral threat. Furthermore, we report ACE-2 genetic polymorphic variants affecting residues involved in close contacts with SARS-CoV-2 that might be associated to different infection risks. These analyses could provide valuable information to predict the course of the disease.
A Novel Potentially Pathogenic Rare Variant in the DNAJC7 Gene Identified in Amyotrophic Lateral Sclerosis Patients From Mainland China

Variants in the DNAJC7 gene have been shown to be novel causes of amyotrophic lateral sclerosis (ALS). However, the contributions of DNAJC7 mutations in Asian ALS patients remain unclear. In this study, we screened rare pathogenic variants in the DNAJC7 gene in a cohort of 578 ALS patients from Mainland China. A novel, rare, putative pathogenic variant c.712A>G (p.R238G) was identified in one sporadic ALS patient. The carrier with this variant exhibited symptom onset at a relatively younger age and experienced rapid disease progression. Our results expand the pathogenic variant spectrum of DNAJC7 and indicate that variants in the DNAJC7 gene may also contribute to ALS in the Chinese population.
Feasibility and Functional Outcome of Robotic Assisted Kidney Transplantation Using Grafts With Multiple Vessels: Comparison to Propensity Matched Contemporary Open Kidney Transplants Cohort

Introduction: The aim of the study was to report the perioperative and functional results of Robotic assisted kidney transplantation (RAKT) in Grafts with multiple vessels (GMVs) and compare it to the results of Open kidney transplantation (OKT) with GMVs. Materials and Methods: Patients undergoing RAKT from living donors using GMVs were reviewed from prospectively collected RAKT database at our institution between March 2013 and March 2018. Patient undergoing Open kidney transplantation (OKT) using GMVs served as controls. Ex-vivo bench surgical reconstruction of GMVs was done according to specific anatomy. Propensity score matching was used to balance the sample size in the two groups. Results: Of 153 RAKT and OKT procedures, 86 cases were eligible for propensity score matching for the statistically significant variables (standardized difference >0.10) and 43 procedures were assigned to each group. Median anastomoses, total and cold ischemia and rewarming times did not differ significantly between the RAKT and OKT groups. In comparison with OKT in GMVs we found that RAKT with GMVs had less pain score on post op 2nd day (p = 0.03). There was also a significant difference in mean analgesic requirement (p = 0.02), hospital stay (p = 0.05) and incision length (p = 0.04). Most of the major, minor surgical, and medical postoperative complications were comparable between the two groups except for wound related events (p = 0.002). Conclusion: Multiplicity of renal vessels in RAKT does not adversely affect patient or graft survival compared with the OKT. Satisfactory functional outcome can be achieved by RAKT similar to OKT in GMVs. RAKT seems to have advantage over OKT in that it is less invasive and has the potential to cause fewer low grade complications. Small sample size and short follow-up are the main limitations of the study.
miR-138 Function and Its Targets on Mouse Mammary Epithelial Cells

miRNA was 20～25 nt endogenous non-coding RNA. miRNAs are encoded small RNAs that hybridize with messenger RNAs, resulting in degradation or translational inhibition of targeted transcripts. In order to investigate the function of miR-138 on mouse mammary epithelial cells, technique for gene silencing-miRNA inhibitor (anti-miRNA) was applied to make miR-138 silence, qRT-PCR was showed valid for inhibitor miR-138. And Western blot, CASY(r)-technology was put in use to study some change of mouse mammary epithelial cells after miR138 inhibitor. It was shown that miR-138 suppresses the exepress of PRL-R(P 0.05). It was proved that miR-138 can inhibit activity and proliferation of mouse mammary epithelial cells after miR-138 inhibitor(P 0.01). HPLC was used to study expression of β-casin mouse mammary epithelial cells after miR-138 inhibitor, it shows down express ofβ-casin(P 0.05). Results indicated that the target of miR-138 was PRL-R, miR-138 suppresses translation of PRL-R. MiR-138 suppressed the viable and proliferation of mouse mammary epithelial cells.
Screening the Olive Tree Phyllosphere: Search and Find Potential Antagonists Against Pseudomonas savastanoi pv. savastanoi

Olive knot (OK) is a widespread bacterial disease, caused by Pseudomonas savastanoi pv. savastanoi (Pss), which currently has not effective control methods. The use of naturally occurring microbial antagonists, such as bacteria, as biocontrol agents could be a strategy to manage this disease. The objective of this work was to select bacteria from olive tree phyllosphere able to antagonize Pss using in vitro and in planta experiments. The elucidation of their modes of action and the potential relationship between antagonism and bacteria origin has been investigated, as well. To this end, 60 bacterial isolates obtained from the surface and inner tissues of different organs (leaves, twigs, and knots), from two olive cultivars of varying susceptibilities to OK, were screened for their in vitro antagonistic effect against Pss. A total of 27 bacterial strains were able to significantly inhibit Pss growth, being this effect linked to bacteria origin. Strains from OK-susceptible cultivar and colonizing the surface of plant tissues showed the strongest antagonistic potential. The antagonistic activity was potentially due to the production of volatile compounds, siderophores and lytic enzymes. Bacillus amyloliquefaciens P41 was the most effective antagonistic strain and their capacity to control OK disease was subsequently assayed using in planta experiments. This strain significantly reduces OK disease severity (43.7%), knots weight (55.4%) and population size of Pss (26.8%), while increasing the shoot dry weight (55.0%) and root water content (39.6%) of Pss-infected olive plantlets. Bacterial isolates characterized in this study, in particular B. amyloliquefaciens P41, may be considered as promising biocontrol candidates for controlling OK disease.
Protein Plasticity and its Role in Cellular Functions

The contribution of redox active properties of cysteines in intrinsically disordered regions (IDRs) of proteins is not very well acknowledged. Despite of providing structural stability and rigidity, intrinsically disordered cysteines are exceptional redox sensors and the redox status of the protein defines its structure. Experimental evidence suggests that the conformational heterogeneity of cysteines in intrinsically disordered proteins (IDPs) is related to numerous functions including regulation, structural changes and fuzzy complex formation. The unusual plasticity of IDPs make them suitable candidate to interact with many clients under specific conditions. Binding capabilities, dimerization and folding or unfolding nature of IDPs upon interaction with multiple clients assign distinct conformational changes associated with disulfide formation. Here we are going to focus on redox activity of IDPs, their dramatic roles that are not only restricted to cellular redox homeostasis and signaling pathways but also provide antioxidant, anti-apoptotic, binding and interactive power.
Early life stress targets the transcriptional signature and functional properties of voltage gated-sodium (Nav) channels in hippocampal NG2+ glia.

Background: The detrimental effects of early life stress (ELS) on brain development and mental health are well established. While studies have identified myelination and oligodendrocytes as targets of ELS across species, knowledge about the precise molecular mechanisms and cell populations involved is still lacking. NG2+ cells are a particularly interesting subpopulation, comprising oligodendrocyte precursor cells with unique properties, as they form synapses with neurons and respond to stress hormones. Methods: Using a mouse model of ELS, we performed molecular profiling in hippocampal NG2+ cells at early postnatal and adult stages. To further dissect the impact of glucocorticoids on ELS-induced transcriptional changes, we integrated our data with Chip-seq data on genomic binding sites of the glucocorticoid receptor (GR). The functional relevance of one candidate, Scn7a, was confirmed by electrophysiological recordings in hippocampal NG2+ cells. Results: ELS targeted the hippocampal NG2+ cell transcriptome, and the observed molecular changes correlated with the ELS-induced increase of corticosterone. The overlap analysis with Chip-seq data on genomic binding sites of the GR revealed nine overlapping genes. Amongst these, Scn7a, coding for a subunit of sodium channels, remained upregulated until adulthood in ELS animals. Upregulation of Scn7a was accompanied by an increase in the density of voltage-gated sodium channel activated currents in hippocampal NG2+ cells. Conclusions: Our findings indicate that ELS specifically targets the transcriptional profile and electrophysiological properties of hippocampal NG2+ glia. Considering that voltage-gated sodium channels are important for NG2+ cell-to-neuron communication, our findings suggest novel insights into the pathophysiology of stress related mental disorders.
A generic decision-making ability predicts psychopathology in adolescents and young adults and is reflected in distinct brain connectivity patterns

Decision-making underpins many important facets of our lives. Here, we assessed if a general ability factor underpins decision-making abilities. Using factor analysis of 32 decision-making measures in 830 adolescents and young adults, we identified a common factor we refer to as ‘decision acuity’ that was distinct from IQ and reflected advantageous decision-making abilities. Decision acuity decreased with low general social functioning and aberrant thinking. Crucially, decision acuity and IQ had dissociable neural signatures in terms of resting-state functional connectivity involving specific neural networks. Finally, decision acuity was reliable and its relationship with functional connectivity was stable when measured in the same individuals 18 months later. We conclude that our behavioural and brain data demonstrate a new cognitive construct encapsulating ability to perform decision-making across distinct domains, and that the expression of this construct may be important for understanding psychopathology.
Inferring protein sequence-function relationships with large-scale positive-unlabeled learning

Machine learning can infer how protein sequence maps to function without requiring a detailed understanding of the underlying physical or biological mechanisms. It’s challenging to apply existing supervised learning frameworks to large-scale experimental data generated by deep mutational scanning (DMS) and related methods. DMS data often contain high dimensional and correlated sequence variables, experimental sampling error and bias, and the presence of missing data. Importantly, most DMS data do not contain examples of negative sequences, making it challenging to directly estimate how sequence affects function. Here, we develop a positive-unlabeled (PU) learning framework to infer sequence-function relationships from large-scale DMS data. Our PU learning method displays excellent predictive performance across ten large-scale sequence-function data sets, representing proteins of different folds, functions, and library types. The estimated parameters pinpoint key residues that dictate protein structure and function. Finally, we apply our statistical sequence-function model to design highly stabilized enzymes.
Role of selective Bioactive Compounds as an Angiotensin Converting Enzyme Inhibitor

Hypertension is one of a major reason of mortality and morbidity and it is associated with heart and renal disease. The aim of this study is to find out the antihypertensive role of bioactive compounds from selected medicinal plants targeting ACE molecule which so far is not known. The plants taken in this study were Moringa oleifera, Azadirachta indica, and Hibiscus sabdariffa. The nitric oxide and superoxide scavenging property vary from 39.50% to 68% and 37.67 % to 75.50 %. respectively. The inhibition of ACE activity was found maximally in methanolic extract of A. indica (74 %), followed by H. sabdariffa (73.4%), and least in M. oleifera (71.8 %). The bioactive chloroform fraction was characterized for the presence of compound using standard techniques such as LCMS and NMR (13C-NMR 1H-NMR). The results revealed the presence of beta-sitosterol in M. oleifera, azadiradionolide in A. indica and hibiscitrin in H. sabdariffa. The compounds have shown significant low binding energy for hibiscitrin (−12.3kcal/mol), beta-sitosterol (−11.2kcal/mol) and azadiradionolide (−11.3kcal/mol) indicating the high efficacy of binding on the enzyme. While, binding energy of drug captopril was −5.6kcal/mol & enalpril - 8.1kcal/mol in the same pocket of the ACE molecule. Upon subjecting molecular dynamic simulation results indicated that beta sitosterol complex provided more compactness than the hibiscitrin and azadiradionolide compounds. The current study delivers a new perspective for the drug development against systolic blood pressure regulation and also opens new horizons for considering alternate highly potent drug target for hypertension.
Loss of Polycomb Protein EZH2 causes major depletion of H3K27 and H3K9 tri-methylation and developmental defects in the fungus Podospora anserina

Selective gene silencing is key to development. The H3K27me3 enriched heterochromatin maintains transcription repression established during early development and regulates cell fate. Conversely, H3K9me3 enriched heterochromatin prevents differentiation but constitutes a permanent protection against transposable element. We exploited the fungus Podospora anserina, a valuable alternative to higher eukaryote models to question the biological relevance and interplay of these two distinct heterochromatin conformations. We found that H3K27me3 and H3K9me3 modifications are mutually exclusive within gene-rich regions but not within repeats. Lack of PaKmt6 EZH2-like enzyme resulted in loss of H3K27me3 and in significant H3K9me3 reduction, whereas lack of PaKmt1 SU(VAR)3-9-like enzyme caused loss of H3K9me3 only. We established that P. anserina developmental programs require H3K27me3 mediated silencing unlike most fungi studied to date. Our findings provide new insight into roles of these histone marks and into the relationship between chromatin modifications and development.
Annual reproductive cycle and growth of the pen shell Atrina maura (Pterioidea: Pinnidae) on sand-bottom culture in the Ensenada Pabellones lagoon system, Gulf of California, Mexico

Abstract The reproductive cycle and growth of the pen shell, Atrina maura, which was cultured in the Ensenada Pabellones lagoon system, Gulf of California, from March 2008 to March 2009, is described in this article. Histological techniques and the condition index were used to determine its reproductive condition. The sex ratio was 0.57 females:1.72 males within the population studied. There were no differences (χ2, p < 0.05) in shell length (SL) between males and females. The mean length of the sampled specimens ranged between 50.99 ± 4.86 mm and 218.16 ± 8.87 mm. The histological results confirmed that A. maura is a gonochoristic organism that presents synchronic development of the gonads. The maturity and spawning phases were observed throughout the study period, with the exception of March and May 2008. The frequency of the gonad development stages obtained per month suggests that this species reproduced two times annually, with one important reproductive period from June to September, a minor reproductive period from November to February, and two resting periods as follows: July to August and January to February 2009.
Live imaging of avian embryos revealing a new head precursor map and the role for the anterior mesendoderm in brain development

We investigated the initial stages of head development using a new method to randomly label chicken epiblast cells with enhanced green fluorescent protein, and tracking the labeled cells. This analysis was combined with grafting mCherry-expressing quail nodes, or node-derived anterior mesendoderm (AME). These live imagings provided a new conception of the cellular mechanisms regulating brain and head ectoderm development. Virtually all anterior epiblast cells are bipotent for the development into the brain or head ectoderm. Their fate depends on the positioning after converging to the AME. When two AME tissues exist following the ectopic node graft, the epiblast cells converge to the two AME positions and develop into two brain tissues. The anterior epiblast cells bear gross regionalities that already correspond to the forebrain, midbrain, and hindbrain axial levels shortly after the node is formed. Therefore, brain portions that develop with the graft-derived AME are dependent on graft positioning.
Exploiting oxalotrophic bacteria to control Aspergillus niger lung infections

The opportunistic pathogen Aspergillus affects a record number of people worldwide. Many aspects of the ecology of Aspergillus spp. are linked to human pathogenesis, but not their ability to manipulate their environmental pH and enhance infectious potential via the secretion of oxalic acid. Here we showed that co-culturing with bacteria able to degrade oxalic acid (oxalotrophic bacteria) effectively suppress the pH shift induced by A. niger, and thereby arrest fungal growth. In 3D-cell culture systems infected with A. niger, co-inoculation with as little as 10 cells of an oxalotrophic bacterium was sufficient to return pH, Ca2+ and oxalic acid concentrations to the physiological values of uninfected cells. This is the first demonstration of the use of bacteria to control the infection potential of A. niger. This approach shifts the focus to the manipulation of the host environment as part of potential interventions to fight opportunistic fungal pathogens.