Miracle-dz/UniFAR-FTUs huggingface dataset:
Myosins, an Underestimated Player in the Infectious Cycle of Pathogenic Bacteria

Myosins play a key role in many cellular processes such as cell migration, adhesion, intracellular trafficking and internalization processes, making them ideal targets for bacteria. Through selected examples, such as enteropathogenic E. coli (EPEC), Neisseria, Salmonella, Shigella, Listeria or Chlamydia, this review aims to illustrate how bacteria target and hijack host cell myosins in order to adhere to the cell, to enter the cell by triggering their internalization, to evade from the cytosolic autonomous cell defense, to promote the biogenesis of intracellular replicative niche, to disseminate in tissues by cell-to-cell spreading, to exit out the host cell, and also to evade from macrophage phagocytosis. It highlights the diversity and sophistication of the strategy evolved by bacteria to manipulate one of their privileged targets, the actin cytoskeleton.
Adsorption—Desorption Dynamics of Alcohols on H-Beta and H-CMK Zeolites Nanocrystallites Studied by Quartz Crystal Microbalance Method

The quartz crystal microbalance (QCM) method was used to study the adsorption–desorption dynamics of alcohols on the zeolite nanocrystallites (diameter, 200 nm). The mass transfer of C1–C4 alcohols on zeolites H-Beta and H-CMK nanocrystallites in the pulse and steady-flow modes at 100 °C and p/ps < 0.04 was studied with the QCM method. Experimental results show that the adsorption–desorption dynamics of various alcohols on the nanocrystallites is governed by diffusion in micropores, which is characterized by effective diffusion coefficients Defmicro = 10−13 to 10−15 cm2 s−1. Slow mass transfer of alcohols in the micropores of zeolites indicates natural limitations on the rate of the acid–base heterogeneously catalytic reactions over these solids.
Solid-Contact Potentiometric Sensors Based on Main-Tailored Bio-Mimics for Trace Detection of Harmine Hallucinogen in Urine Specimens

All-solid-state potentiometric sensors have attracted great attention over other types of potentiometric sensors due to their outstanding properties such as enhanced portability, simplicity of handling, affordability and flexibility. Herein, a novel solid-contact ion-selective electrode (SC-ISE) based on poly(3,4-ethylenedioxythiophene) (PEDOT) as the ion-to-electron transducer was designed and characterized for rapid detection of harmine. The harmine-sensing membrane was based on the use of synthesized imprinted bio-mimics as a selective material for this recognition. The imprinted receptors were synthesized using acrylamide (AA) and ethylene glycol dimethacrylate (EGDMA) as functional monomer and cross-linker, respectively. The polymerization process was carried out at 70 °C in the presence of dibenzoyl peroxide (DBO) as an initiator. The sensing membrane in addition to the solid-contact layer was applied to a glassy-carbon disc as an electronic conductor. All performance characteristics of the presented electrode in terms of linearity, detection limit, pH range, response time and selectivity were evaluated. The sensor revealed a wide linearity over the range 2.0 × 10−7–1.0 × 10−2 M, with a detection limit of 0.02 µg/mL and a sensitivity slope of 59.2 ± 0.8 mV/hamine concentration decade. A 40 mM Britton–Robinson (BR) buffer solution at pH of 6 was used for all harmine measurements. The electrode showed good selectivity towards harmine over other common interfering ions, and maintained a stable electrochemical response over two weeks. After applying the validation requirements, the proposed method revealed good performance characteristics. Method precision, accuracy, bias, trueness, repeatability, reproducibility, and uncertainty were also evaluated. These analytical capabilities support the fast and direct assessment of harmine in different urine specimens. The analytical results were compared with the standard liquid chromatographic method. The results obtained demonstrated that PEDOT/PSS was a promising solid-contact ion-to-electron transducer material in the development of harmine-ISE. The electrodes manifested enhanced stability and low cost, which provides a wide number of potential applications for pharmaceutical and forensic analysis.
Synthetic thick filaments: A new avenue for better understanding the myosin super-relaxed state in healthy, disease, and mavacamten-treated cardiac systems.

A hallmark feature of myosin-II is that it can spontaneously self-assemble into bipolar synthetic thick filaments (STFs) in low ionic strength buffers, thereby serving as a reconstituted in-vitro model for muscle thick filament. While these STFs have been extensively used for structural characterization, their functional evaluation has been limited. In this report, we show that myosins in STFs mirror the more electrostatic and cooperative interactions that underlie the energy-sparing super-relaxed (SRX) state, which are not seen using shorter myosin sub-fragments, heavy meromyosin (HMM) and myosin subfragment-1 (S1). Using these STFs, we show several pathophysiological insults in hypertrophic cardiomyopathy, including the R403Q myosin mutation, phosphorylation of myosin light chains, and increased ADP:ATP ratio destabilize the SRX population. Furthermore, wild-type myosin containing STFs, but not S1, HMM, or STFs-containing R403Q myosin, recapitulated the ADP-induced destabilization of the SRX state. Studies involving a clinical-stage small molecule inhibitor, mavacamten, showed that it is not only more effective in increasing myosin SRX population in STFs than in S1 or HMM , but it also increases myosin SRX population equally well in STFs made of healthy and disease-causing R403Q myosin. Importantly, we also found that pathophysiological perturbations such as elevated ADP concentration weakens the mavacamten's ability to increase the myosin SRX population, suggesting that mavacamten-bound myosin heads are not permanently protected in the SRX state but can be recruited into action. These findings collectively emphasize that STFs serve as a valuable tool to provide novel insights into the myosin SRX state in healthy, disease, and therapeutic conditions.
Immunoinformatics-guided designing and in silico analysis of epitope-based polyvalent vaccines against multiple strains of human coronavirus (HCoV)

ABSTRACT Objectives The group of human coronaviruses (HCoVs) consists of some highly pathogenic viruses that have caused several outbreaks in the past. The newly emerged strain of HCoV, the SARS-CoV-2 is responsible for the recent global pandemic that has already caused the death of hundreds of thousands of people due to the lack of effective therapeutic options. Methods In this study, immunoinformatics methods were used to design epitope-based polyvalent vaccines which are expected to be effective against four different pathogenic strains of HCoV i.e., HCoV-OC43, HCoV-SARS, HCoV-MERS, and SARS-CoV-2. Results The constructed vaccines consist of highly antigenic, non-allergenic, nontoxic, conserved, and non-homologous T-cell and B-cell epitopes from all the four viral strains. Therefore, they should be able to provide strong protection against all these strains. Protein-protein docking was performed to predict the best vaccine construct. Later, the MD simulation and immune simulation of the best vaccine construct also predicted satisfactory results. Finally, in silico cloning was performed to develop a mass production strategy of the vaccine. Conclusion If satisfactory results are achieved in further in vivo and in vitro studies, then the vaccines designed in this study might be effective as preventative measures against the selected HCoV strains.
Altered VDAC-HK association and apoptosis in mouse peripheral blood lymphocytes exposed to diabetic condition: an in vitro and in vivo study

Abstract Increased apoptotic lymphocytes have been correlated to a high incidence of infection in poorly controlled diabetes. This study aimed to determine whether altered voltage-dependent anion channel (VDAC)-hexokinase (HK) association contributes to the increase in apoptosis. Mouse peripheral blood lymphocytes (PBL) exposed to high glucose (Glc)/palmitic acid (PA) were used as the in vitro model, which was compared with PBL isolated from alloxan-induced diabetic mice (in vivo model). Our results showed a significant increase in apoptosis as indicated by the apoptotic index, caspase-3 activity, mitochondrial membrane potential and ultrastructural study. HK and glucose-6-phosphate dehydrogenase (G6PDH) activities were markedly reduced with a profound increase in glucose-6-phosphate level. Co-immunoprecipitation confirms HK interaction with VDAC, an outer mitochondrial membrane protein. Inhibited glycolytic enzyme, i.e. HK and reduced HK-VDAC interaction in our study could contribute to increased apoptosis in lymphocytes exposed to high Glc/PA. Targeting HK-VDAC interaction may therefore provide therapeutic potential for the treatment of diabetes-associated infection.
Three-Dimensional Localization Algorithm Based on Improved A* and DV-Hop Algorithms in Wireless Sensor Network

In the traditional wireless sensor networks (WSNs) localization algorithm based on the Internet of Things (IoT), the distance vector hop (DV-Hop) localization algorithm has the disadvantages of large deviation and low accuracy in three-dimensional (3D) space. Based on the 3DDV-Hop algorithm and combined with the idea of A* algorithm, this paper proposes a wireless sensor network node location algorithm (MA*-3DDV-Hop) that integrates the improved A* algorithm and the 3DDV-Hop algorithm. In MA*-3DDV-Hop, firstly, the hop-count value of nodes is optimized and the error of average distance per hop is corrected. Then, the multi-objective optimization non dominated sorting genetic algorithm (NSGA-II) is adopted to optimize the coordinates locally. After selection, crossover, mutation, the Pareto optimal solution is obtained, which overcomes the problems of premature convergence and poor convergence of existing algorithms. Moreover, it reduces the error of coordinate calculation and raises the localization accuracy of wireless sensor network nodes. For three different multi-peak random scenes, simulation results show that MA*-3DDV-Hop algorithm has better robustness and higher localization accuracy than the 3DDV-Hop, PSO-3DDV-Hop, GA-3DDV-Hop, and N2-3DDV-Hop.
Mutation Maker, An Open Source Oligo Design Platform for Protein Engineering

Protein engineering is the discipline of developing useful proteins for applications in research, therapeutic and industrial processes by modification of naturally occurring proteins or by invention of de novo proteins. Modern protein engineering relies on the ability to rapidly generate and screen diverse libraries of mutant proteins. However, design of mutant libraries is typically hampered by scale and complexity, necessitating development of advanced automation and optimization tools that can improve efficiency and accuracy. At present, automated library design tools are functionally limited or not freely available. To address these issues, we developed Mutation Maker, an open source mutagenic oligo design software for large-scale protein engineering experiments. Mutation Maker is not only specifically tailored to multi-site random and directed mutagenesis protocols, but also pioneers bespoke mutagenic oligo design for de novo gene synthesis workflows. Enabled by a novel bundle of orchestrated heuristics, optimization, constraint-satisfaction and backtracking algorithms, Mutation Maker offers a versatile toolbox for gene diversification design at industrial scale. Supported by in-silico simulations and compelling experimental validation data, Mutation Maker oligos produce diverse gene libraries at high success rates irrespective of genes or vectors used. Finally, Mutation Maker was created as an extensible platform on the notion that directed evolution techniques will continue to evolve and revolutionize current and future-oriented applications.
Student outcomes for interprofessional education in student led clinics: A rapid review

ABSTRACT Student-led clinics provide a unique opportunity for interprofessional education as part of the education of future allied health professionals. A rapid review was conducted to determine the benefits to allied health students participating in interprofessional education in student-led clinics. Studies were included if they took place within a student-led clinic, reported on outcomes for students and where the clinic involved interprofessional education for students from either two or more allied health professions, or one allied health and one nursing student. Results were analyzed using a descriptive qualitative approach. Five themes were identified: (a) understanding of own role and scope of practice; (b) understanding of the role and scope of practice of other professions; (c) individual benefits to the students; (d) impact on patient-centered care; and (c) understanding of how to work in an interprofessional team. These benefits indicate that student-led clinics are a suitable setting for the delivery of interprofessional education to allied health students. More research is needed that considers the long-term impact on these student outcomes following students’ entry into the healthcare profession, as well as on the impact of specific components of the interprofessional education models on student outcomes.
Morphology Control of Films Formed by Atmospheric-Pressure Chemical Vapor Deposition Using Tetraethylorthosilicate/Ozone System

The effects of the reaction time of gas-phase intermediates, t r, initial concentrations of TEOS (C TEOSin) and O3 (C O3in), and O3 concentration on a substrate C O3s, on film formation by atmospheric-pressure chemical vapor deposition using tetraethylorthosilicate (TEOS) and ozone ( O3) were experimentally investigated. These four deposition parameters were altered by varying the merge position of TEOS/He and O3/O2 mixtures and the substrate position in the reactor. The structure of the intermediates was estimated from the chemical analysis of nanometer-sized particles generated during the film formation. The flow shape, the substrate dependence, and the chemical structure of films depended mainly on C TEOSin and C O3in, but were independent of C O3s. The parameter t r had little effect on the flow shape and substrate dependence. The intermediates that led to the formation of films with excellent flow shape and a small amount of water contained a large amount of carbon.
The Comparative Analysis of Carboxylic Acid Composition of Four Iris Species from Ukraine

The present article reports results of analysis of carboxylic acids in leaves of Iris species from Ukraine using a gas chromatography (GC) method with mass spectrometric (MS) detection (GC/MS). Carboxylic acids play significant roles in contemporary society as evidenced by multiple applications in fields of medicine, agriculture, pharmacy, food, and other industries. Study of natural plant products as a source of organic acids is of particular interest. Carboxylic acid composition of leaves of Iris hungarica Waldst. & Kit. , Iris germanica L. , Iris pallida Lam. , and Iris variegate L. was studied for the first time applying GC/MS method. The mass spectrums of compounds were matched with NIST and WILEY Libraries. The GC/MS analysis revealed the presence of 26 common acids in the plant raw materials studied. The short‐chain carboxylic acids, such as citric (1337.5–12364.4 mg/kg), malic (50.8–4558.0 mg/kg) and oxalic (1199.0–3435.2 mg/kg) acids were contained in significantly high quantity in all samples. Ferulic, p‐coumaric and vanillic acids were the most abundant among phenolic acids. α‐Linolenic acid was dominant in the leaves of I. germanica (869.5 mg/kg), I. pallida (753.3 mg/kg), and I. variegate (250.3 mg/kg) among polyunsaturated fatty acids, however, linoleic acid prevailed in the plant raw material of I. hungarica (1150.7 mg/kg). Since the leaves of Iris species studied contain carboxylic acids with diverse pharmacological activity, extracts of these raw materials are perspective for development food supplements and medicines.
Comprehensive Gene Expression Analyses of Immunohistochemically Defined Subgroups of Muscle-Invasive Urinary Bladder Urothelial Carcinoma

A number of urinary bladder urothelial carcinoma (UB UC) mRNA-based classification systems have been reported. It also has been observed that treatment response and prognosis are different for each molecular subtype. In this study, cytokeratin (CK)5/6 and CK20 immunohistochemistry (IHC) were performed, and IHC-based subgroup classification was applied. UB UC was classified into CK5/6 single-positive (SP), CK20 SP, double-positive (DP) and double-negative (DN) subgroups, and transcriptional analysis was performed. The results of gene ontology (GO) terms and functional analysis using differentially expressed genes indicate that, CK5/6 SP and DP subgroups were enriched in cell migration, immune activation, interleukin 6-Janus kinase-signal transducer and activator of transcription 3 (IL6-JAK-STAT3) signaling pathway and tumor necrosis factor-α signaling via the nuclear factor-κB (NF-κB) signaling pathway signature gene. In addition, compared with the other subgroups, the DN subgroup showed inhibited cell movement, cell migration, and cell activation. Furthermore, in survival analysis, the CK5/6 SP subgroup was significantly associated with poor progression-free survival (p = 0.008). The results of our study indicate that the CK5/6 positive subgroup exhibited high gene expression signature related to aggressive behavior and exhibited worse clinical outcome.
Development of an Isobaric Transfer Viscometer Operating up to 140 MPa. Application to a Methane + Decane System

A falling body viscometer with electromagnetic detection and operating at pressures up to 140 MPa and temperatures up to 120 °C has been developed in order to measure the dynamic viscosity of fluids with a low viscosity (i.e. methane) and which are not single phase at normal pressure. The isobaric transfer procedure from an additional cell to the measuring cell is described. The calibration procedure is also explained, and the measurements on the binary methane + decane (xmethane = 0.3124) are presented (65 experimental data).
Characterizing Bilingual Effects on Cognition: The Search for Meaningful Individual Differences

A debate over the past decade has focused on the so-called bilingual advantage—the idea that bilingual and multilingual individuals have enhanced domain-general executive functions, relative to monolinguals, due to competition-induced monitoring of both processing and representation from the task-irrelevant language(s). In this commentary, we consider a recent study by Pot, Keijzer, and de Bot (2018), which focused on the relationship between individual differences in language usage and performance on an executive function task among multilingual older adults. We discuss their approach and findings in light of a more general movement towards embracing complexity in this domain of research, including individuals’ sociocultural context and position in the lifespan. The field increasingly considers interactions between bilingualism/multilingualism and cognition, employing measures of language use well beyond the early dichotomous perspectives on language background. Moreover, new measures of bilingualism and analytical approaches are helping researchers interrogate the complexities of specific processing issues. Indeed, our review of the bilingualism/multilingualism literature confirms the increased appreciation researchers have for the range of factors—beyond whether someone speaks one, two, or more languages—that impact specific cognitive processes. Here, we highlight some of the most salient of these, and incorporate suggestions for a way forward that likewise encompasses neural perspectives on the topic.
Mesenchymal stem cell attachment to peptide density gradients on porous silicon generated by electrografting

Chemical gradients of ethyl‐6‐bromohexanoate (EBH) were generated over porous silicon (pSi) substrates via electrochemical attachment. Immobilised ester moieties were hydrolysed and activated to produce a gradient of functional carboxylic acid groups. After subsequent immobilisation of cyclic RGD (cRGD), the surfaces were used to screen the extent of rat mesenchymal stem cell (MSC) attachment. Mapping of surface chemistry was carried out by means of infrared microscopy and X‐ray photoelectron spectroscopy (XPS). MSC culture studies showed that short‐term cell attachment responded to the cRGD density present on the gradient surface.
Associations of Residential Brownness and Greenness with Fasting Glucose in Young Healthy Adults Living in the Desert

Evolutionary psychology theories propose that contact with green, natural environments may benefit physical health, but little comparable evidence exists for brown, natural environments, such as the desert. In this study, we examined the association between “brownness” and “greenness” with fasting glucose among young residents of El Paso, Texas. We defined brownness as the surface not covered by vegetation or impervious land within Euclidian buffers around participants’ homes. Fasting glucose along with demographic and behavioral data were obtained from the Nurse Engagement and Wellness Study (n = 517). We found that residential proximity to brownness was not associated with fasting glucose when modeled independently. In contrast, we found that residential greenness was associated with decreased levels of fasting glucose, despite the relatively low levels of greenness within the predominantly desert environment of El Paso. A difference between the top and bottom greenness exposure quartiles within a 250 m buffer was associated with a 3.5 mg/dL decrease in fasting glucose levels (95% confidence interval: −6.2, −0.8). Our results suggest that within the understudied context of the desert, green vegetation may be health promoting to a degree that is similar to other, non-desert locations in the world that have higher baselines levels of green.
GADD45β Regulates Hepatic Gluconeogenesis via Modulating the Protein Stability of FoxO1

Increased hepatic gluconeogenesis is one of the main contributors to the development of type 2 diabetes. Recently, it has been reported that growth arrest and DNA damage-inducible 45 beta (GADD45β) is induced under both fasting and high-fat diet (HFD) conditions that stimulate hepatic gluconeogenesis. Here, this study aimed to establish the molecular mechanisms underlying the novel role of GADD45β in hepatic gluconeogenesis. Both whole-body knockout (KO) mice and adenovirus-mediated knockdown (KD) mice of GADD45β exhibited decreased hepatic gluconeogenic gene expression concomitant with reduced blood glucose levels under fasting and HFD conditions, but showed a more pronounced effect in GADD45β KD mice. Further, in primary hepatocytes, GADD45β KD reduced glucose output, whereas GADD45β overexpression increased it. Mechanistically, GADD45β did not affect Akt-mediated forkhead box protein O1 (FoxO1) phosphorylation and forskolin-induced cAMP response element-binding protein (CREB) phosphorylation. Rather it increased FoxO1 transcriptional activity via enhanced protein stability of FoxO1. Further, GADD45β colocalized and physically interacted with FoxO1. Additionally, GADD45β deficiency potentiated insulin-mediated suppression of hepatic gluconeogenic genes, and it were impeded by the restoration of GADD45β expression. Our finding demonstrates GADD45β as a novel and essential regulator of hepatic gluconeogenesis. It will provide a deeper understanding of the FoxO1-mediated gluconeogenesis.