Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring Differential Gene Expression Profiles Of Dero (Allodero) Hylae In Their Parasitic And Free-Living Forms

Parasitism is ubiquitous in nature, yet little is known about the evolutionary mechanisms that lead to a parasitic lifestyle. Facultative parasites can switch between free-living and parasitic lifestyles, which may provide an opportunity to study the genetic mechanisms underlying a transition to parasitism. The oligochaete Dero (Allodero) hylae is a facultative parasite commonly found within the ureter of various anuran species, such as the Cuban Tree Frog (Osteopilus septentrionalis). Dero hylae makes passage through the frog’s cloaca, where it then infects the ureter. In the ureter, the worm loses free-living characteristics such as hair setae, dorsal setae, a digestive tract, and fossa with gills as it transitions to a parasitic lifestyle. Dero hylae may be expelled from its host during urination, when this occurs the worm will reacquire free-living characteristics. The focus of this study is to compare the differential gene expression profiles observed when this rapid morphological change takes place. Specimens of D. hylae were collected from wild Cuban Tree Frogs and either flash-frozen for their parasitic stage RNA profile or cultured for two weeks to produce their free-living stage and then flash-frozen. Using the sequenced RNA, a de novo transcriptome was assembled and differential gene expression RNA Tag-Seq analysis between the free-living and parasitic life forms was analyzed. Based on these results, we have identified 213 genes differentially expressed transcripts between the two life forms, 190 of these being up-regulated in the free-living life form. While over half of the differential genes recovered did not recover any significant BLAST hits, many of these genes did provide insight into which molecular signals are potentially used by D. hylae to lose and subsequently regrow their setae, digestive tract, and gills. This analysis provides significant insight into which differentially expressed genes are linked to drastic morphological changes observed in this rare oligochaete parasitism across the free-living and parasitic forms of D. hylae.
Illuminating the druggable genome through patent bioactivity data

The patent literature is a potentially valuable source of bioactivity data. The SureChEMBL database (https://www.surechembl.org/) is a publicly available large-scale resource that contains compounds extracted on a daily basis from the full text, images and attachments of patent documents, through an automated text and image-mining pipeline. In this paper we describe a process to prioritise 3.7 million life science relevant patents obtained from SureChEMBL, according to how likely they were to contain bioactivity data for potent small molecules on less-studied targets, according to the classification developed by the Illuminating the Druggable Genome (IDG) project. The overall goal was to select a smaller number of patents that could be manually curated and incorporated into the ChEMBL database. We describe the approach taken, the results obtained, and provide some illustrative examples.
Sex-biased proteomic response to tomato spotted wilt virus infection of the salivary glands of Frankliniella occidentalis, the western flower thrips

Successful transmission of tomato spotted wilt virus (TSWV) by Frankliniella occidentalis requires robust infection of the salivary glands (SGs) and virus delivery to plants during salivation. Feeding behavior and transmission efficiency are sexually-dimorphic traits of this thrips vector species. Proteins secreted from male and female SG tissues, and the effect of TSWV infection on the thrips SG proteome are unknown. To begin to discern thrips factors that facilitate virus infection of SGs and transmission by F. occidentalis, we used gel- and label-free quantitative and qualitative proteomics to address two hypotheses: (i) TSWV infection modifies the composition and/or abundance of SG-expressed proteins in adults; and (ii) TSWV has a differential effect on the male and female SG proteome and secreted saliva. Our study revealed a sex-biased SG proteome for F. occidentalis, and TSWV infection modulated the SG proteome in a sex-dependent manner as evident by the number, differential abundance, identities and generalized roles of the proteins. Male SGs exhibited a larger proteomic response to the virus than female SGs. Intracellular processes modulated by TSWV in males indicated perturbation of SG cytoskeletal networks and cell-cell interactions (basement membrane, BM and extracellular matrix proteins, ECM), and subcellular processes consistent with a metabolic slow-down under infection. Several differentially-abundant proteins in infected male SGs play critical roles in viral life cycles of other host-virus pathosystems. In females, TSWV modulated processes consistent with tissue integrity and active translational and transcriptional regulation. A core set of proteins known for their roles in plant cell-wall degradation and protein metabolism were identified in saliva of both sexes, regardless of virus infection status. Saliva proteins secreted by TSWV- infected adults indicated energy generation, consumption and protein turnover, with an enrichment of cytoskeletal/BM/ECM proteins and tricarboxylic acid cycle proteins in male and female saliva, respectively. The nonstructural TSWV protein NSs - a multifunctional viral effector protein reported to target plant defenses against TSWV and thrips - was identified in female saliva. This study represents the first description of the SG proteome and secretome of a thysanopteran and provides many candidate proteins to further unravel the complex interplay between the virus, insect vector, and plant host.
Discovering Patterns in Bipartite Networks

Bipartite networks constitute an especially important type of network that can be widely applied to model and study several intricate systems in many scientific areas, being also theoretically related to several network models and concepts. However, given a bipartite network the identification of specific recurrent patterns of interest often represents a substantial challenge. In the present work, we apply the coincidence methodology for translating data into networks as a means for automatically identifying repeating interconnection patterns in given bipartite networks. The important issue of normalization of the links strength is also addressed. Though the method is illustrated with respect to foodweb networks, its application is general and encompasses many other subjects and areas.
Hippocampal Place-like Signal in Latent Social Space

During navigation, the hippocampus represents physical places like coordinates on a map; similar location-like signals have been seen in sensory and concept spaces. It is unclear just how general this hippocampal place code is, however: does it map places in wholly non-perceivable spaces, without locations being instructed or reinforced and during navigation-like behavior? To search for such a signal, we imaged participants’ brains while they played a naturalistic, narrative-based social interaction game, and modeled their relationships as a kind of navigation through social space. Two independent samples showed hippocampal place-like signals in both region-based and whole-brain representational similarity analyses, as well as decoding and average pattern similarity analyses; the effects were not explained by other measures of the behavior or task information. We also replicated and extended previous findings of hippocampal tracking of the egocentric angle in social space. These results are the first demonstration of complete domain generality in hippocampal place representation. One-Sentence Summary hippocampal place-like signal in non-perceivable and unreinforced space during naturalistic navigational behavior. Significance statement The hippocampus is a brain structure known to encode maps of physical spaces; this study shows that it also maps fully abstract, latent and uninstructed spaces. People played a naturalistic social interaction game while their brains were scanned. Hippocampal brain activity correlated with the fictional characters’ locations in an abstract social space framed by axes of affiliation and power, despite the participants never being exposed to a perceivable spatial representation. This mapping was present across multiple analyses and two samples, demonstrating that the brain system responsible for spatial mapping maps our social interactions too.
In vitro and in silico analysis proving DPP4 inhibition and diabetes-associated gene network modulation by a polyherbal formulation: Nisakathakadi Kashaya.

Dipeptidyl-peptidase IV (DPP4) inhibitors are an important class of anti-diabetic drugs recognised for their systemic biological actions. Polyherbal preparations like Ayurveda formulations are considered to be ideal sources for discovering novel DPP4 inhibitors owing to their rich phytochemical composition. The current study reports the DPP4 inhibitory potential of a clinically established Ayurvedic anti-diabetic formulation Nisakathakadi Kashaya (NK) using in vitro assay and substantiates it by identifying potential bioactives responsible for DPP4 inhibition using computational biology tools. NK showed a dose-dependent DPP4 inhibition with an IC50 of 2.06 μg GAE/mL, and the molecular docking and simulation studies showed three compounds, namely Terchebin, Locaracemoside B and 1,2,4,6 Tetra o Galloyl Beta D Glucose having stable interactions with DPP4 similar to the standard drug Vildagliptin. Further, for the reason that polyherbal formulations exert a network pharmacology mode of action, in silico analysis was carried out to identify the other putative phytochemical-protein networks modulated by NK. The complex pharmacological network of the formulation was explored further using a subnetwork of diabetes proteins and their relationship with diabetes-associated comorbidities. A number of key targets like TNFα, TGFβ1, SOD1, SOD2, AKT1, DPP4 and GLP1R were identified in the protein-protein interaction network that is vital to diabetic progression and complications. A combination of in vitro and in silico methods allowed us to prove the DPP4 inhibition potential of NK as well as provided insights into the possible pharmacological networking through which NK potentially exerts its systemic effect in diabetes management.Communicated by Ramaswamy H. Sarma.
Network Analysis Reveals the Molecular Bases of Statin Pleiotropy That Vary with Genetic Background

Atorvastatin is a highly successful drug prescribed to lower cholesterol and prevent cardiovascular disease in millions of people. Though much of its effect comes from inhibiting a key enzyme in the cholesterol biosynthetic pathway, genes in this pathway interact with genes in other pathways, resulting in 15% of patients suffering painful muscular side effects and 50% having inadequate responses. ABSTRACT Many approved drugs are pleiotropic: for example, statins, whose main cholesterol-lowering activity is complemented by anticancer and prodiabetogenic mechanisms involving poorly characterized genetic interaction networks. We investigated these using the Saccharomyces cerevisiae genetic model, where most genetic interactions known are limited to the statin-sensitive S288C genetic background. We therefore broadened our approach by investigating gene interactions to include two statin-resistant genetic backgrounds: UWOPS87-2421 and Y55. Networks were functionally focused by selection of HMG1 and BTS1 mevalonate pathway genes for detection of genetic interactions. Networks, multilayered by genetic background, were analyzed for key genes using network centrality (degree, betweenness, and closeness), pathway enrichment, functional community modules, and Gene Ontology. Specifically, we found modification genes related to dysregulated endocytosis and autophagic cell death. To translate results to human cells, human orthologues were searched for other drug targets, thus identifying candidates for synergistic anticancer bioactivity. IMPORTANCE Atorvastatin is a highly successful drug prescribed to lower cholesterol and prevent cardiovascular disease in millions of people. Though much of its effect comes from inhibiting a key enzyme in the cholesterol biosynthetic pathway, genes in this pathway interact with genes in other pathways, resulting in 15% of patients suffering painful muscular side effects and 50% having inadequate responses. Such multigenic complexity may be unraveled using gene networks assembled from overlapping pairs of genes that complement each other. We used the unique power of yeast genetics to construct genome-wide networks specific to atorvastatin bioactivity in three genetic backgrounds to represent the genetic variation and varying response to atorvastatin in human individuals. We then used algorithms to identify key genes and their associated FDA-approved drugs in the networks, which resulted in the distinction of drugs that may synergistically enhance the known anticancer activity of atorvastatin.
Investigation of Hyperbolic Metamaterials

Composites designed by employing metal/dielectric composites coupled to the components of the incident electromagnetic (EM) fields are named metamaterials (MMs), and they display features not observed in nature. This type of artificial media has attracted great interest, resulting in groundbreaking theory that bridges the gap between EM and photonic phenomena. Practical applications of MMs have been delayed due to the high losses related to the use of metallic composites, on top of the challenges in manufacturing nanoscale, three-dimensional structures. Novel materials—for instance, graphene or transparent-conducting oxides (TCOs), employed for the production of multilayered MMs—can significantly suppress undesirable losses. It is worthwhile noting that three-layered nanocomposites enable an increase in the frequency range of the surface wave. This work analyzes recent progress in the physics of multilayered MMs. We deliver an outline of key notions, such as effective medium approximation, and present multilayered MMs based on the three-layered structure. An overview of graphene multilayered MMs reveals their ability to support Ferrell–Berreman (FB) modes. We also describe the tunable properties of the multilayered MMs.
High-resolution mobile optical 3D scanner with color mapping

A high-resolution mobile handheld scanning device suitable for 3D data acquisition and analysis for forensic investigations, rapid prototyping, design, quality management, and archaeology with a measurement volume of approximately 325 mm x 200 mm x 100mm and a lateral object resolution of 170 µm developed at our institute is introduced. The scanners weight is 4.4 kg with an optional color DLSR camera. The PC for measurement control and point calculation is included inside the housing. Power supply is realized by rechargeable batteries. Possible operation time is between 30 and 60 minutes. The object distance is between 400 and 500 mm, and the scan time for one 3D shot may vary between 0.1 and 0.5 seconds. The complete 3D result is obtained a few seconds after starting the scan. For higher quality 3D and color images the scanner is attachable to tripod use. Measurement objects larger than the measurement volume must be acquired partly. The different resulting datasets are merged using a suitable software module. The scanner has been successfully used in various applications.
Computational Metabolomics Reveals the Potential Mechanism of Matrine Mediated Metabolic Network Against Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a complex issue in cancer treatment in the world at present. Matrine is the main active ingredient isolated from Sophora flavescens air and possesses excellent antitumor effects in HCC. However, the specific underlying mechanisms, especially the possible relationships between the anti-HCC effect of matrine and the related metabolic network of HCC, are not yet clear and need further clarification. In this study, an integrative metabolomic-based bioinformatics algorithm was designed to explore the underlying mechanism of matrine on HCC by regulating the metabolic network. Cell clone formation, invasion, and adhesion assay were utilized in HCC cells to evaluate the anti-HCC effect of matrine. A cell metabolomics approach based on LC-MS was used to obtain the differential metabolites and metabolic pathways regulated by matrine. The maximum activity contribution score model was developed and applied to calculate high contribution target genes of matrine, which could regulate a metabolic network based on the coexpression matrix of matrine-regulated metabolic genes and targets. Matrine significantly repressed the clone formation and invasion, enhanced cell–cell adhesion, and hampered cell matrix adhesion in SMMC-7721 cells. Metabolomics results suggested that matrine markedly regulated the abnormal metabolic network of HCC by regulating the level of choline, creatine, valine, spermidine, 4-oxoproline, D-(+)-maltose, L-(−)-methionine, L-phenylalanine, L-pyroglutamic acid, and pyridoxine, which are involved in D-glutamine and D-glutamate metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, etc. Our proposed metabolomic-based bioinformatics algorithm showed that the regulating metabolic networks of matrine exhibit anti-HCC effects through acting on MMP7, ABCC1, PTGS1, etc. At last, MMP7 and its related target β-catenin were validated. Together, the metabolomic-based bioinformatics algorithm reveals the effects of the regulating metabolic networks of matrine in treating HCC relying on the unique characteristics of the multitargets and multipathways of traditional Chinese medicine.
Physical performance and glycemic control under SGLT-2-inhibitors in patients with type 2 diabetes and established atherosclerotic cardiovascular diseases or high cardiovascular risk (PUSH): Design of a 4-week prospective observational study

Background Type 2 diabetes (T2D) is associated with limitation in physical performance. Results from animal studies report enhancement of physical performance in T2D rodents treated with sodium glucose cotransporter 2 inhibitors (SGLT2is). However, in human patients with T2D and established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular risk, the impact of guideline directed SGLT2i medication on physical performance has not been sufficiently examined. Objectives The main objectives of this study are thus firstly, to assess the changes in physical performance after 4 weeks of exercise therapy in patients with established ASCVD or high cardiovascular risk categorized into three groups according to their glycemic control at baseline. Secondly, to investigate the association of glycemic control at baseline and new guideline directed antidiabetic treatment (inadequate glycemic control and diabetes + new SGLT2i vs. adequate glycemic control and diabetes vs. no diabetes) with change in physical performance. Methods and design This is a 4-week prospective observational study of 450 participants with established ASCVD or high cardiovascular risk with or without T2D and without previous SGLT2i medication undergoing exercise therapy during inpatient rehabilitation in a single center in Switzerland. Upon admission, participants are categorized into 3 groups of 150 participants each according to their glycemic control. Group I consisting of participants with inadequately controlled T2D defined as mean fasting plasma glucose (FPG) of ≥7 mmol/L, who are consequently administered new treatment with an SGLT2i. Group II comprises of participants with adequately controlled T2D with mean FPG of <7 mmol/L requiring no antidiabetic medication change. Group III consists of participants with no diabetes and mean FPG of ≤ 5.5 mmol/L. Primary outcomes are 6-min walk distance and rate of perceived exertion. Secondary outcomes are echocardiographic parameters (left ventricular mass index; global longitudinal strain average; end-diastolic volume), fatigue, muscle, metabolic, and anthropometric measures. Ethics and dissemination This study is conducted in accordance with the Declaration of Helsinki with ethical approval from the Cantonal Ethical Commission of Bern, Switzerland. The results will be published in a peer-reviewed journal. The implementation and reporting will be according to the SPIRIT guidelines. Study protocol registration https://www.clinicaltrials. gov/, identifier: NCT03422263.
Evaluation of the learning curve for robotic single-anastomosis duodenal–ileal bypass with sleeve gastrectomy

Background The robotic surgical system is being used in various bariatric procedures. However, only a few studies with very small sample size are present on robotic single-anastomosis duodenal–ileal bypass with sleeve gastrectomy (SADI-S). Moreover, to date, the learning curve of robotic SADI-S has been poorly evaluated yet. Objective This retrospective study aimed to estimate the learning curve of robotic SADI-S. Methods 102 consecutive patients who underwent robotic SADI-S between March 2020 and December 2021 were included. Textbook outcome standard was performed to comprehensively evaluate clinical outcome of robotic SADI-S. Based on the textbook outcome, we evaluated the learning curve of robotic SADI-S by the cumulative sum (CUSUM) method. Results The mean operative time was 186.13 ± 36.91 min. No conversion to laparotomy or deaths occurred during the study period. The rate of complications was 6.9% (n = 7), of which major complications were identified in 2.9% (n = 3), including 2 gastric leakages and 1 respiratory failure. A total of 60 patients reached the textbook outcome standard. The rate of textbook outcome was positive and was steadily increasing after the number of surgical cases accumulated to the 58th case. Taking the 58th case as the boundary, all the patients were divided into the learning stage group (the first 58 patients) and mastery stage group (the last 44 patients). The rate of complications, proportion of abdominal drainage tubes and postoperative hospital stay were significantly higher in the learning stage group compared with the mastery stage group (P < 0.05). No significant difference was observed between the two groups in terms of patient demographic data, operative times, reoperations and readmission. Conclusion Robotic SADI-S is a feasible and reproducible surgical technique with a learning curve of 58 cases.