Miracle-dz/UniFAR-FTUs huggingface dataset:
Identifying potential natural inhibitors of Brucella melitensis Methionyl-tRNA synthetase through an in-silico approach

Background Brucellosis is an infectious disease caused by bacteria of the genus Brucella. Although it is the most common zoonosis worldwide, there are increasing reports of drug resistance and cases of relapse after long term treatment with the existing drugs of choice. This study therefore aims at identifying possible natural inhibitors of Brucella melitensis Methionyl-tRNA synthetase through an in-silico approach. Methods Using PyRx 0.8 virtual screening software, the target was docked against a library of natural compounds obtained from edible African plants. The compound, 2-({3-[(3,5-dichlorobenzyl) amino] propyl} amino) quinolin-4(1H)-one (OOU) which is a co-crystallized ligand with the target was used as the reference compound. Screening of the molecular descriptors of the compounds for bioavailability, pharmacokinetic properties, and bioactivity was performed using the SWISSADME, pkCSM, and Molinspiration web servers respectively. The Fpocket and PLIP webservers were used to perform the analyses of the binding pockets and the protein ligand interactions. Analysis of the time-resolved trajectories of the Apo and Holo forms of the target was performed using the Galaxy and MDWeb servers. The lead compounds, Strophanthidin and Isopteropodin are present in Corchorus olitorius and Uncaria tomentosa (cat-claw) plants respectively. Results Isopteropodin had a binding affinity score of -8.9 kcal / ml with the target and had 17 anti-correlating residues in pocket 1 after molecular dynamics simulation. The complex formed by Isopteropodin and the target had a total RMSD of 4.408 and a total RMSF of 9.8067. However, Strophanthidin formed 3 hydrogen bonds with the target at ILE21, GLY262 and LEU294, and induced a total RMSF of 5.4541 at Pocket 1. Conclusion Overall, Isopteropodin and Strophanthidin were found to be better drug candidates than OOU and they showed potentials to inhibit the Brucella melitensis Methionyl-tRNA synthetase at Pocket 1, hence abilities to treat brucellosis. In vivo and in vitro investigations are needed to further evaluate the efficacy and toxicity of the lead compounds. Author Summary Strophanthidin and Isopteropodin showed potentials to inhibit the Brucella melitensis Methionyl-tRNA synthetase at Pocket 1 Both compounds can be used to treat brucellosis. Both compounds showed potentials of being safe to use in humans.
Influence of food matrix physico-chemical properties on the biophysics of digestion and in situ luminal viscosity

INFLUENCE OF FOOD MATRIX PHYSICO-CHEMICAL PROPERTIES ON THE BIOPHYSICS OF DIGESTION AND IN SITU LUMINAL VISCOSITY By FATEMAH M. ALHASAWI A Dissertation submitted to the School of Graduate Studies Rutgers, The State University of New Jersey In partial fulfillment of the requirements For the degree of Doctor of Philosophy Graduate Program in Food Science Written under the direction of Dr. Michael A. Rogers And approved by
Wild pigs mediate far-reaching agricultural impacts on tropical forest soil microbial communities

Edge effects, the altered abiotic and biotic conditions on the borders of natural areas, rarely extend more than a few hundred meters. Edge effects have rarely been linked to altered soil biota, which shape ecosystem processes including carbon storage, biogeochemical cycling, and plant performance. Here, we investigated if agriculturally-mediated increased wildlife populations affect soil biotic communities at a distance well over that of estimated edge effects when they move between agriculture and natural habitats using a 22-year fenced exclusion experiment in a primary rainforest in Peninsular Malaysia. We found that the presence of wildlife (mainly native pigs (Sus scrofa) that crop-raid in nearby oil palm plantations) was associated with higher bacterial diversity, and an altered community composition (mediated by changes in soil pH), and reduced abundances of symbiotic ectomycorrhizal fungi compared to soil in exclosures. There were only minor effects of pigs on soil chemistry or microclimate, so we suggest that changes in soil communities are driven by pigs’ leaf litter removal and alterations to plant composition. Our study highlights that indirect effects from agriculture can be transferred by wildlife >1 km into protected areas and this could have important repercussions for ecosystem processes and plant-soil feedbacks.
Comparing mRNA and sncRNA profiles during the maternal-to-embryonic transition in bovine IVF and scNT embryos

Abstract Production of embryos with high developmental competence by somatic cell nuclear transfer (scNT) is far less efficient than for in vitro fertilized (IVF) embryos, likely due to an accumulation of errors in genome reprogramming that results in aberrant expression of RNA transcripts, including messenger RNAs (mRNA) and, possibly, microRNAs (miRNA). Thus, our objectives were to use RNAseq to determine the dynamics of mRNA expression in early developing scNT and IVF embryos in the context of the maternal-to-embryonic transition (MET) and to correlate apparent transcriptional dysregulation in cloned embryos with miRNA expression profiles. Comparisons between scNT and IVF embryos indicated large scale transcriptome differences, which were most evident at the 8-cell and morula stages for genes associated with biological functions critical for the MET. For two miRNAs previously identified as differentially expressed in scNT morulae, miR-34a and miR-345, negative correlations with some predicted mRNA targets were apparent, though not widespread among the majority of predicted targets. Moreover, although large-scale aberrations in expression of mRNAs were evident during the MET in cattle scNT embryos, these changes were not consistently correlated with aberrations in miRNA expression at the same developmental stage, suggesting that other mechanisms controlling gene expression may be involved. Summary sentence Whereas large-scale aberrations in expression of mRNAs were evident during the maternal-to-embryonic transition in cattle scNT embryos, these changes were not consistently correlated with changes in miRNA expression at the same developmental stage. Graphical Abstract
Dermal exposure to the immunomodulatory antimicrobial chemical triclosan alters the skin barrier integrity and microbiome in mice.

Triclosan is an antimicrobial chemical used in healthcare settings that can be absorbed through the skin. Exposure to triclosan has been positively associated with food and aeroallergy and asthma exacerbation in humans and, although not directly sensitizing, has been demonstrated to augment the allergic response in a mouse model of asthma. The skin barrier and microbiome are thought to play important roles in regulating inflammation and allergy and disruptions may contribute to development of allergic disease. To investigate potential connections of the skin barrier and microbiome with immune responses to triclosan, SKH1 mice were exposed dermally to triclosan (0.5-2%) or vehicle for up to 7 consecutive days. Exposure to 2% triclosan for 5-7 days on the skin was shown to increase trans-epidermal water loss levels. Seven days of dermal exposure to triclosan decreased filaggrin 2 and keratin 10 expression, but increased filaggrin and keratin 14 protein along with the danger signal S100a8 and interleukin-4. Dermal exposure to triclosan for 7 days also altered the alpha and beta diversity of the skin and gut microbiome. Specifically, dermal triclosan exposure increased the relative abundance of the Firmicutes family, Lachnospiraceae on the skin but decreased the abundance of Firmicutes family, Ruminococcaceae in the gut. Collectively, these results demonstrate that repeated dermal exposure to the antimicrobial chemical triclosan alters the skin barrier integrity and microbiome in mice, suggesting that these changes may contribute to the increase in allergic immune responses following dermal exposure to triclosan.
A 41-Gene Pair Signature for Predicting the Pathological Response of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiation

Background and Purpose: Pathological response status is a standard reference for the early evaluation of the effect of neoadjuvant chemoradiation (nCRT) on locally advanced rectal cancer (LARC) patients. Various patients respond differently to nCRT, but identifying the pathological response of LARC to nCRT remains a challenge. Therefore, we aimed to identify a signature that can predict the response of LARC to nCRT. Material and Methods: The gene expression profiles of 111 LARC patients receiving fluorouracil-based nCRT were used to obtain gene pairs with within-sample relative expression orderings related to pathological response. These reversal gene pairs were ranked according to the mean decrease Gini index provided by the random forest algorithm to obtain the signature. This signature was verified in two public cohorts of 46 and 42 samples, and a cohort of 33 samples measured at our laboratory. In addition, the signature was used to predict disease-free survival benefits in a series of colorectal cancer datasets. Results: A 41-gene pair signature (41-GPS) was identified in the training cohort with an accuracy of 84.68% and an area under the receiver operating characteristic curve (AUC) of 0.94. In the two public test cohorts, the accuracy was 93.37 and 73.81%, with AUCs of 0.97 and 0.86, respectively. In our dataset, the AUC was 0.80. The results of the survival analysis show that 41-GPS plays an effective role in identifying patients who will respond to nCRT and have a better prognosis. Conclusion: The signature consisting of 41 gene pairs can robustly predict the clinical pathological response of LARC patients to nCRT.
Identification, Isolation, and Characterization of Medipeptins, Antimicrobial Peptides From Pseudomonas mediterranea EDOX

The plant microbiome is a vastly underutilized resource for identifying new genes and bioactive compounds. Here, we used Pseudomonas sp. EDOX, isolated from the leaf endosphere of a tomato plant grown on a small farm in the Netherlands. To get more insight into its biosynthetic potential, the genome of Pseudomonas sp. EDOX was sequenced and subjected to bioinformatic analyses. The genome sequencing analysis identified strain EDOX as a member of the Pseudomonas mediterranea. In silico analysis for secondary metabolites identified a total of five non-ribosomally synthesized peptides synthetase (NRPS) gene clusters, related to the biosynthesis of syringomycin, syringopeptin, anikasin, crochelin A, and fragin. Subsequently, we purified and characterized several cyclic lipopeptides (CLPs) produced by NRPS, including some of the already known ones, which have biological activity against several plant and human pathogens. Most notably, mass spectrometric analysis led to the discovery of two yet unknown CLPs, designated medipeptins, consisting of a 22 amino acid peptide moiety with varying degrees of activity against Gram-positive and Gram-negative pathogens. Furthermore, we investigated the mode of action of medipeptin A. The results show that medipeptin A acts as a bactericidal antibiotic against Gram-positive pathogens, but as a bacteriostatic antibiotic against Gram-negative pathogens. Medipeptin A exerts its potent antimicrobial activity against Gram-positive bacteria via binding to both lipoteichoic acid (LTA) and lipid II as well as by forming pores in membranes. Collectively, our study provides important insights into the biosynthesis and mode of action of these novel medipeptins from P. mediterranea EDOX.
Riparian forest restoration as sources of biodiversity and ecosystem functions in anthropogenic landscapes

Restoration of tropical riparian forests is challenging, since these ecosystems are the most diverse, dynamic, and complex physical and biological terrestrial habitats. This study tested whether biodiversity can predict ecosystem functions in a human-impacted tropical riparian forest. We explored the effects of several biodiversity components (taxonomic or functional groups) on different ecosystem functions associated with restored riparian forests Overall, 49% of the biodiversity components showed positive effects on ecosystem functions, each component to a different degree. In general, our results showed that both taxonomic and functional biodiversity had strong effects on ecosystem functions indicating that floral and faunal biodiversity enhanced the multifunctionality of these restored riparian tropical forests. These findings indicate that in restored riparian forests, recovery of biodiversity is followed by improvement in important ecosystem functions that are the basis for successful restoration. Future research and policy for restoration programs must focus on restoring elementary faunal and floral components of biodiversity in order to promote ecosystem multifunctionality.
B cell-intrinsic requirement for WNK1 kinase in T cell-dependent antibody responses

Migration and adhesion play critical roles in B cells, regulating recirculation between lymphoid organs, migration within lymphoid tissue and interaction with CD4+ T cells. However, there is limited knowledge of how B cells integrate chemokine receptor and integrin signaling with B cell activation to generate efficient humoral responses. Here we show that the WNK1 kinase, a regulator of migration and adhesion, is essential in B cells for T-dependent antibody responses. We demonstrate that WNK1 transduces signals from the BCR, CXCR5 and CD40, and using intravital imaging we show that WNK1 regulates migration of naive and activated B cells, and their interactions with T cells. Unexpectedly, we show that WNK1 is required for BCR- and CD40-induced proliferation, acting through the OXSR1 and STK39 kinases, and for efficient B cell-T cell collaboration in vivo. Thus, WNK1 is critical for humoral immune responses, by regulating B cell migration, adhesion and T cell-dependent activation. Summary The WNK1 kinase is essential in B cells for T-dependent antibody responses because it is activated by signaling from BCR, CXCR5 and CD40 and regulates B cell migration, adhesion, T-dependent activation, and differentiation into germinal center B cells and plasma cells.
(Un)common space in infant neuroimaging studies: A systematic review of infant templates

In neuroimaging, spatial normalization is an important step that maps an individual’s brain onto a template brain permitting downstream statistical analyses. Yet, in infant neuroimaging, there remain several technical challenges that have prevented the establishment of a standardized template for spatial normalization. Thus, many different approaches are used in the literature. To quantify the popularity and variability of these approaches in infant neuroimaging studies, we performed a systematic review of infant MRI studies from 2000 to 2020. Here, we present results from 833 studies meeting inclusion criteria. Studies were classified into 1) processing data in single subject space, 2) using a predefined, or “off the shelf”, template, 3) creating a study specific template or 4) using a hybrid of these methods. We found that across the studies in the systematic review, single subject space was the most used (no common space). This was the most used common space for DWI and structural MRI studies while fMRI studies preferred off the shelf atlases. We found a pattern such that more recently published studies are more commonly using off the shelf atlases. When considering special populations, preterm studies most used single subject space while, when no special populations were being analyzed, an off the shelf template was most common. The most used off the shelf templates were the UNC Infant Atlases (26.1%). Using a systematic review of infant neuroimaging studies, we highlight a lack of an established “standard” template brain in these studies.
SLURP-1 Controls Growth and Migration of Lung Adenocarcinoma Cells, Forming a Complex With α7-nAChR and PDGFR/EGFR Heterodimer

Secreted Ly6/uPAR-related protein 1 (SLURP-1) is a secreted Ly6/uPAR protein that negatively modulates the nicotinic acetylcholine receptor of α7 type (α7-nAChR), participating in control of cancer cell growth. Previously we showed, that a recombinant analogue of human SLURP-1 (rSLURP-1) diminishes the lung adenocarcinoma A549 cell proliferation and abolishes the nicotine-induced growth stimulation. Here, using multiplex immunoassay, we demonstrated a decrease in PTEN and mammalian target of rapamycin (mTOR) kinase phosphorylation in A549 cells upon the rSLURP-1 treatment pointing on down-regulation of the PI3K/AKT/mTOR signaling pathway. Decreased phosphorylation of the platelet-derived growth factor receptor type β (PDGFRβ) and arrest of the A549 cell cycle in the S and G2/M phases without apoptosis induction was also observed. Using a scratch migration assay, inhibition of A549 cell migration under the rSLURP-1 treatment was found. Affinity extraction demonstrated that rSLURP-1 in A549 cells forms a complex not only with α7-nAChR, but also with PDGFRα and epidermal growth factor receptor (EGFR), which are known to be involved in regulation of cancer cell growth and migration and are able to form a heterodimer. Knock-down of the genes encoding α7-nAChR, PDGFRα, and EGFR confirmed the involvement of these receptors in the anti-migration effect of SLURP-1. Thus, SLURP-1 can target the α7-nAChR complexes with PDGFRα and EGFR in the membrane of epithelial cells. Using chimeric proteins with grafted SLURP-1 loops we demonstrated that loop I is the principal active site responsible for the SLURP-1 interaction with α7-nAChR and its antiproliferative effect. Synthetic peptide mimicking the loop I cyclized by a disulfide bond inhibited ACh-evoked current at α7-nAChR, as well as A549 cell proliferation and migration. This synthetic peptide represents a promising prototype of new antitumor drug with the properties close to that of the native SLURP-1 protein.
The Effect of Yoga Meditation Practice on Young Adults’ Inhibitory Control: An fNIRS Study

Objectives: The present study aimed to test the effect of yoga meditation (YoMed) practice on inhibitory control of young adults. Methods: A total of 50 participants (23 male, 21–28 years old) from a university in Jinan, Shandong Province were enrolled in this study. Participants were randomly assigned to a YoMed group or a Control group. Participants’ basic information, physical activity, and inhibitory control were measured. A multi-channel continuous-wave near-infrared spectrometer was used to monitor the brain’s hemodynamic responses. Results: After the intervention, we found significant differences in Flanker tasks between the YoMed group and Control group. The accuracy in the YoMed group was higher than those in the Control group (p < 0.05). Analysis of fNIRS data showed that oxyhemoglobin (oxy-Hb) levels in the prefrontal cortex (PFC) increased in the YoMed group during the Flanker tasks after the YoMed intervention. Conclusion: YoMed has a temporarily promoting effect on the brain activation of young adults. It is an effective and appropriate exercise to improve the inhibitory control of young adults.
Percutaneous Mechanical Atherectomy Plus Thrombectomy Using the Rotarex®S Device Followed by a Drug-Coated Balloon for the Treatment of Femoropopliteal Artery In-stent Restenosis: A Prospective Single-Center, Single-Arm Efficacy Trial (PERMIT-ISR Trial)

Background: Studies investigating debulking devices with drug-coated balloons (DCBs) in the treatment of femoropopliteal (FP) artery in-stent restenosis (ISR) are limited. We aimed to evaluate the safety and midterm outcome of percutaneous mechanical atherectomy plus thrombectomy (MATH) using the Rotarex®S (Straub Medical, Wangs, Switzerland) catheter followed by a DCB in the treatment of FP-ISR. Methods: This study was a single-center single-arm trial. Patients with symptomatic (Rutherford category 2–5) de novo restenosis lesions of FP-ISR were treated with MATH and subsequent DCB. From June 2016 to May 2018, 59 patients with FP-ISR were enrolled. The primary endpoint was target lesion revascularization (TLR) and changes in the Rutherford category of the target limb at 12 months. Secondary endpoints included primary and secondary patency at 12 months, technical success rate, major adverse events, and ankle-brachial index (ABI). Risk factors for TLR were analyzed using Cox proportional hazard model. Results: The average follow-up time was 33 ± 8 months. The rate of technical success was 88.1% (52/59). Nine patients received bailout stenting. The rate of freedom from TLR was 84.7% (50/59) at 1 year, the Rutherford category changed at 12 months were significantly improved from baseline (p < 0.01). The primary patency rates and the secondary patency at the 12-month follow-ups were 82.5 and 92.5%, respectively. The ABI changed at 12 months were significantly improved from baseline (p < 0.01). Global limb anatomic staging system (GLASS) classification III [hazard ratio (HR) 18.44, 95% CI (1.57–215.99), p = 0.020] and postoperative Rutherford classification ≥4 [HR 8.28, 95% CI (1.85–37.06), p = 0.006] were identified as independent predictors of TLR. Conclusion: Our preliminary data suggested that MATH using a Rotarex®S catheter combined with DCB angioplasty is a safe, minimally invasive, and effective treatment for FP-ISR with favorable, immediate, and midterm outcomes. Clinical Trial Registration: http://www.chictr. org.cn, identifier [ChiCTR2000041380].
Circulating Levels of MicroRNAs Associated With Hypertension: A Cross-Sectional Study in Male and Female South African Participants

MicroRNAs are non-coding, post-transcriptional regulators of gene expression and their dysregulation has been associated with development of various diseases, including hypertension. Consequently, understanding their role in the pathogenesis and progression of disease is essential. Prior research focusing on microRNAs in disease has provided a basis for understanding disease prognosis and offered possible channels for therapeutic interventions. Herein, we aimed to investigate possible differences in the expression profiles of five microRNAs in the blood of participants grouped on the basis of their hypertension status. This was done to elucidate the possible roles played by these microRNAs in the development of hypertension. Using quantitative reverse transcription polymerase chain reaction, we evaluated the expression levels of miR-126-3p, 30a-5p, 182-5p, 30e-3p, and 1299 in the whole blood of 1456 participants, normotensive (n = 573), screen-detected hypertensive (n = 304) and known hypertensive (n = 579). The expression of miR-126-3p and 182-5p was significantly higher in known hypertensives relative to both screen-detected hypertensives and normotensives, and also in screen-detected hypertensives vs normotensives. A significant association between the expression of miR-126-3p, 182-5p, and 30a-5p and known hypertension was also evident. This study demonstrated dysregulated miR-126-3p, 182-5p, and 30a-5p expression in hypertension, highlighting the possible efficacy of these microRNAs as targets for the diagnosis of hypertension as well as the development of microRNA-based therapies.