Refined methodology for quantifying virulence using .

Larvae of (the greater wax moth) are being increasingly used as a model to study microbial pathogenesis. In this model, bacterial virulence is typically measured by determining the 50% lethal dose (LD) of a bacterial strain or mutant. The use of to study pathogenesis, however, is challenging because of the extreme sensitivity of larvae to this bacterium.

BTK regulates microglial function and neuroinflammation in human stem cell models and mouse models of multiple sclerosis.

Neuroinflammation in the central nervous system (CNS), driven largely by resident phagocytes, has been proposed as a significant contributor to disability accumulation in multiple sclerosis (MS) but has not been addressed therapeutically. Bruton's tyrosine kinase (BTK) is expressed in both B-lymphocytes and innate immune cells, including microglia, where its role is poorly understood. BTK inhibition may provide therapeutic benefit within the CNS by targeting adaptive and innate immunity-mediated disease progression in MS.

Taxonomic characterization of sp. nov., a novel species discovered from a commercially purchased antibiotic.

In an attempt to identify novel bacterial species, microbiologists have examined a wide range of environmental niches. We describe the serendipitous discovery of a novel gram-negative bacterial species from a different type of extreme niche: a purchased vial of antibiotic. The vial of antibiotic hygromycin B was found to be factory contaminated with a bacterial species, which we designate sp.

Bruton tyrosine kinase inhibitors for multiple sclerosis.

Current therapies for multiple sclerosis (MS) reduce both relapses and relapse-associated worsening of disability, which is assumed to be mainly associated with transient infiltration of peripheral immune cells into the central nervous system (CNS). However, approved therapies are less effective at slowing disability accumulation in patients with MS, in part owing to their lack of relevant effects on CNS-compartmentalized inflammation, which has been proposed to drive disability. Bruton tyrosine kinase (BTK) is an intracellular signalling molecule involved in the regulation of maturation, survival, migration and activation of B cells and microglia.

Glucose assimilation rate determines the partition of flux at pyruvate between lactic acid and ethanol in Saccharomyces cerevisiae.

Engineered Saccharomyces cerevisiae expressing a lactic acid dehydrogenase can metabolize pyruvate into lactic acid. However, three pyruvate decarboxylase (PDC) isozymes drive most carbon flux toward ethanol rather than lactic acid. Deletion of endogenous PDCs will eliminate ethanol production, but the resulting strain suffers from C auxotrophy and struggles to complete a fermentation.

Trends in valorization of highly-toxic lignocellulosic biomass derived-compounds via engineered microbes.

Lignocellulosic biomass-derived fuels, chemicals, and materials are promising sustainable solutions to replace the current petroleum-based production. The direct microbial conversion of thermos-chemically pretreated lignocellulosic biomass is hampered by the presence of highly toxic chemical compounds. Also, thermo-catalytic upgrading of lignocellulosic biomass generates wastewater that contains heterogeneous toxic chemicals, a mixture of unutilized carbon.

Idiopathic Pulmonary Comorbidities and Mechanisms.

Idiopathic pulmonary fibrosis (IPF) is a disease with an unknown etiology mainly characterized by a progressive decline of lung function due to the scarring of the tissue deep in the lungs. The overall survival after diagnosis remains low between 3 and 5 years. IPF is a heterogeneous disease and much progress has been made in the past decade in understanding the disease mechanisms that contributed to the development of two new drugs, pirfenidone and nintedanib, which improved the therapeutic management of the disease.

Teriflunomide Inhibits JCPyV Infection and Spread in Glial Cells and Choroid Plexus Epithelial Cells.

Several classes of immunomodulators are used for treating relapsing-remitting multiple sclerosis (RRMS). Most of these disease-modifying therapies, except teriflunomide, carry the risk of progressive multifocal leukoencephalopathy (PML), a severely debilitating, often fatal virus-induced demyelinating disease. Because teriflunomide has been shown to have antiviral activity against DNA viruses, we investigated whether treatment of cells with teriflunomide inhibits infection and spread of JC polyomavirus (JCPyV), the causative agent of PML.

Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial.

Background: Tolebrutinib is an oral, CNS-penetrant, irreversible inhibitor of Bruton's tyrosine kinase, an enzyme expressed in B lymphocytes and myeloid cells including microglia, which are major drivers of inflammation in multiple sclerosis. We aimed to determine the dose-response relationship between tolebrutinib and the reduction in new active brain MRI lesions in patients with relapsing multiple sclerosis.

Methods: We did a 16-week, phase 2b, randomised, double-blind, placebo-controlled, crossover, dose-finding trial at 40 centres (academic sites, specialty clinics, and general neurology centres) in ten countries in Europe and North America.

First report of cultured from the lungs of a patient with pneumonia.

A man in his 50s with neutropenic fever and multifocal lung opacities was diagnosed with a viral pneumonia. A small number of bacteria grown from bronchoalveolar lavage fluid collected during a repeat bronchoscopy were initially identified as by VITEK-2 and mass spectrometry platforms. Whole-genome sequencing, however, subsequently demonstrated that the bacteria were , representing the first known case of cultured from human lungs.

Effect of Teriflunomide on Cells From Patients With Human T-cell Lymphotropic Virus Type 1-Associated Neurologic Disease.

Objective: To test the hypothesis that teriflunomide can reduce ex vivo spontaneous proliferation of peripheral blood mononuclear cells (PBMCs) from patients with human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

Methods: PBMCs from patients with HAM/TSP were cultured in the presence and absence of teriflunomide and assessed for cell viability, lymphocyte proliferation, activation markers, HTLV-1 and HTLV-1 messenger ribonucleic acid (mRNA) expression, and HTLV-1 Tax protein expression.

Results: In culture, teriflunomide did not affect cell viability.

Radiosynthesis of a Bruton's tyrosine kinase inhibitor, [ C]Tolebrutinib, via palladium-NiXantphos-mediated carbonylation.

Bruton's tyrosine kinase (BTK) is a key component in the B-cell receptor signaling pathway and is consequently a target for in vivo imaging of B-cell malignancies as well as in multiple sclerosis (MS) with positron emission tomography (PET). A recent Phase 2b study with Sanofi's BTK inhibitor, Tolebrutinib (also known as [a.k.

Effects of a Virtual Pointer on Trainees' Cognitive Load and Communication Efficiency in Surgical Training.

We investigated the cognitive load effect of a trainer providing surgical instruction by pointing/drawing over laparoscopic video to a trainee. Results showed that while cognitive load is higher overall with the use of the instructional system, there is a decrease by the second experience of being instructed by the Virtual Pointer. Further analysis showed that trainees were more likely to perform the surgical task and watch/listen to the trainer's instruction at the same time when the instructional system was used.

Functional relevance of the multi-drug transporter abcg2 on teriflunomide therapy in an animal model of multiple sclerosis.

Background: The multi-drug resistance transporter ABCG2, a member of the ATP-binding cassette (ABC) transporter family, mediates the efflux of different immunotherapeutics used in multiple sclerosis (MS), e.g., teriflunomide (teri), cladribine, and mitoxantrone, across cell membranes and organelles.

Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator.

Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high levels of glucose. Flux through GK is also responsible for reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can activate GK could provide a therapeutic benefit.

An extra copy of the β-glucosidase gene improved the cellobiose fermentation capability of an engineered strain.

In a previously engineered recombinant, the cellobiose fermentation rate was significantly lower than the glucose fermentation rate. Thus, we implemented a genome-wide perturbation library to find gene targets for improving the cellobiose fermentation capability of the yeast strain. Unexpectedly, we discovered a transformant that contained an additional β-glucosidase gene (-), possibly through homologous recombination between the plasmids.

Deletion of JEN1 and ADY2 reduces lactic acid yield from an engineered Saccharomyces cerevisiae, in xylose medium, expressing a heterologous lactate dehydrogenase.

Microorganisms have evolved to produce specific end products for many reasons, including maintaining redox balance between NAD+ and NADH. The yeast Saccharomyces cerevisiae, for example, produces ethanol as a primary end product from glucose for the regeneration of NAD+. Engineered S.

Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects.

Interference with immune cell proliferation represents a successful treatment strategy in T cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis (MS). One prominent example is pharmacological inhibition of dihydroorotate dehydrogenase (DHODH), which mediates de novo pyrimidine synthesis in actively proliferating T and B lymphocytes. Within the TERIDYNAMIC clinical study, we observed that the DHODH inhibitor teriflunomide caused selective changes in T cell subset composition and T cell receptor repertoire diversity in patients with relapsing-remitting MS (RRMS).

Biochemical and histopathological evaluation of AlO nanomaterials in kidney of Wistar rats.

The present study was conducted to evaluate the response of kidneys in Wistar rats following long-term exposure to AlO nanomaterials (NMs). To achieve this objective, AlO of three different sizes (30 nm, 40 nm and bulk) was orally administered for 28 days to 9 groups of 10 Wistar rats each at the dose of 500, 1000 and 2000 mg/kg/rat. A tenth group of 10 rats received distilled water and served as control.

Expression of Gre2p improves tolerance of engineered xylose-fermenting Saccharomyces cerevisiae to glycolaldehyde under xylose metabolism.

Engineered S. cerevisiae employing the xylose reductase pathway enables efficient xylose valorization to fuels and chemicals. However, toxicity of thermochemically pretreated biomass hydrolysate on S.

Direct conversion of cellulose into ethanol and ethyl-β-d-glucoside via engineered Saccharomyces cerevisiae.

Simultaneous saccharification and fermentation (SSF) of cellulose via engineered Saccharomyces cerevisiae is a sustainable solution to valorize cellulose into fuels and chemicals. In this study, we demonstrate the feasibility of direct conversion of cellulose into ethanol and a biodegradable surfactant, ethyl-β-d-glucoside, via an engineered yeast strain (i.e.

Racial Disparities and Preventive Measures to Renal Cell Carcinoma.

Kidney cancer ranks among the top 10 cancers in the United States. Although it affects both male and female populations, it is more common in males. The prevalence rate of renal cell carcinoma (RCC), which represents about 85% of kidney cancers, has been increasing gradually in many developed countries.

A virtual pointer to support the adoption of professional vision in laparoscopic training.

Purpose: To assess a virtual pointer in supporting surgical trainees' development of professional vision in laparoscopic surgery.

Methods: We developed a virtual pointing and telestration system utilizing the Microsoft Kinect movement sensor as an overlay for any imagine system. Training with the application was compared to a standard condition, i.

Evaluation of the Learning Curve When Transitioning From Posterolateral to Direct Anterior Hip Arthroplasty: A Consecutive Series of 1000 Cases.

Background: The direct anterior approach (DAA) for primary hip replacement has been gaining more attention and widespread use in recent years. There are a number of published studies evaluating the learning curve when a surgeon changes technique; these studies typically look at complications during the initial cases. This study examines procedure and total operating room (OR) time along with all complications for a surgeon transitioning from the posterolateral approach (PA) to DAA.