Quaternary ammonium compound exposure causes infertility by altering endocrine signaling and gametogenesis.

Quaternary ammonium compounds (QACs) are common substances utilized in cleaners, ophthalmic solutions, swimming pool treatments, cosmetics, and other consumer goods. Previous studies have shown that QAC exposure causes infertility in both male and female mice. Based on these studies, we hypothesized that oral QAC exposure negatively impacts male and female reproduction through changes in physiologic and endocrine mechanisms rather than direct toxicity to gametes.

Lack of pathogenic involvement of CCL4 and its receptor CCR5 in arthritogenic alphavirus disease.

Arthritogenic alphaviruses, including chikungunya virus (CHIKV), Mayaro virus (MAYV), Ross River virus (RRV), and O'nyong nyong virus (ONNV) are emerging and reemerging viruses that cause disease characterized by fever, rash, and incapacitating joint swelling. Alphavirus infection induces robust immune responses in infected hosts, leading to the upregulation of several cytokines and chemokines, including chemokine C ligand 4 (CCL4). CCL4 is a chemoattractant for immune cells such as T cells, natural killer cells, monocytes/macrophages, and dendritic cells, recruiting these cells to the site of infection, stimulating the release of proinflammatory mediators, and inducing T cell differentiation.

Forgotten Natural Products: Semisynthetic Development of Blasticidin S As an Antibiotic Lead.

Forgotten natural products offer value as antimicrobial scaffolds, providing diverse mechanisms of action that complement existing antibiotic classes. This study focuses on the derivatization of the cytotoxin blasticidin S, seeking to leverage its unique ribosome inhibition mechanism. Despite its complex zwitterionic properties, a selective protection and amidation strategy enabled the creation of a library of blasticidin S derivatives including the natural product P10.

Enhanced attenuation of chikungunya vaccines expressing antiviral cytokines.

Alphaviruses are vector-borne, medically relevant, positive-stranded RNA viruses that cause disease in animals and humans worldwide. Of this group, chikungunya virus (CHIKV) is the most significant human pathogen, responsible for generating millions of infections leading to severe febrile illness and debilitating chronic joint pain. Currently, there are limited treatments to protect against alphavirus disease; thus, there is a tremendous need to generate safe and effective vaccines.

One receptor, two worlds: MXRA8's alphavirus tango.

Mammalian MXRA8 functions as a receptor for chikungunya and other related alphaviruses. A recent study in Cell molecularly characterizes host-specific receptor usage, specifically showing avian MXRA8 acts as a receptor for several alphaviruses with avian reservoirs in an inverted manner relative to alphaviruses that use mammalian MXRA8 as a receptor.

Data Driven Computational Design and Experimental Validation of Drugs for Accelerated Mitigation of Pandemic-like Scenarios.

Emerging pathogens are a historic threat to public health and economic stability. Current trial-and-error approaches to identify new therapeutics are often ineffective due to their inefficient exploration of the enormous small molecule design space. Here, we present a data-driven computational framework composed of hybrid evolutionary algorithms for evolving functional groups on existing drugs to improve their binding affinity toward the main protease (M) of SARS-CoV-2.

Optimized protocol for mouse footpad immune cell isolation for single-cell RNA sequencing and flow cytometry.

Single-cell RNA sequencing (scRNA-seq) requires the preparation of a highly viable single-cell suspension to get reliable sequencing results. Here, we present a protocol for isolating mouse footpad leukocytes while maintaining high viability. We describe steps for footpad collection, enzymatic tissue dissociation, leukocyte isolation and purification, and cell fixation and preservation.

Expression of anti-chikungunya single-domain antibodies in transgenic reduces vector competence for chikungunya virus and Mayaro virus.

Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related alphaviruses that cause acute febrile illness accompanied by an incapacitating polyarthralgia that can persist for years following initial infection. In conjunction with sporadic outbreaks throughout the sub-tropical regions of the Americas, increased global travel to CHIKV- and MAYV-endemic areas has resulted in imported cases of MAYV, as well as imported cases and autochthonous transmission of CHIKV, within the United States and Europe. With increasing prevalence of CHIKV worldwide and MAYV throughout the Americas within the last decade, a heavy focus has been placed on control and prevention programs.

An in vitro workflow to create and modify infectious clones using replication cycle reaction.

Reverse genetics systems are critical tools in combating emerging viruses which enable a better understanding of the genetic mechanisms by which viruses cause disease. Traditional cloning approaches using bacteria are fraught with difficulties due to the bacterial toxicity of many viral sequences, resulting in unwanted mutations within the viral genome. Here, we describe a novel in vitro workflow that leverages gene synthesis and replication cycle reaction to produce a supercoiled infectious clone plasmid that is easy to distribute and manipulate.

Semisynthetic blasticidin S ester derivatives show enhanced antibiotic activity.

A rich potential source of new antibiotics are undeveloped natural product cytotoxins, provided they can be derivatized to restrict their activity to bacteria. In this work, we describe modification of one such candidate, the broad-spectrum, translation termination inhibitor, blasticidin S. By semisynthetically modifying blasticidin S, we produced a series of ester derivatives of this highly polar, zwitterionic compound in a single step.

Immune response to arbovirus infection in obesity.

Obesity is a global health problem that affects 650 million people worldwide and leads to diverse changes in host immunity. Individuals with obesity experience an increase in the size and the number of adipocytes, which function as an endocrine organ and release various adipocytokines such as leptin and adiponectin that exert wide ranging effects on other cells. In individuals with obesity, macrophages account for up to 40% of adipose tissue (AT) cells, three times more than in adipose tissue (10%) of healthy weight individuals and secrete several cytokines and chemokines such as interleukin (IL)-1β, chemokine C-C ligand (CCL)-2, IL-6, CCL5, and tumor necrosis factor (TNF)-α, leading to the development of inflammation.

Comparison of linear and volumetric criteria for the determination of therapeutic response in dogs with intracranial gliomas.

Background: Brain tumor therapeutic responses can be quantified from magnetic resonance images (MRI) using 1- (1D) and 2-dimensional (2D) linear and volumetric methods, but few studies in dogs compare these techniques.

Hypotheses: Linear methods will be obtained faster, but have less agreement than volumetric measurements. Therapeutic response agreement will be highest with the total T2W tumor volumetric (TTV) method.

A draft genome assembly for the eastern fox squirrel, Sciurus niger.

The eastern fox squirrel, Sciurus niger, exhibits marked geographic variation in size and coat color, is a model organism for studies of behavior and ecology, and a potential model for investigating physiological solutions to human porphyrias. We assembled a genome using Illumina HiSeq, PacBio SMRT, and Oxford Nanopore MinION sequencing platforms. Together, the sequencing data resulted in a draft genome of 2.

A selective sweep in the Spike gene has driven SARS-CoV-2 human adaptation.

The coronavirus disease 2019 (COVID-19) pandemic underscores the need to better understand animal-to-human transmission of coronaviruses and adaptive evolution within new hosts. We scanned more than 182,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes for selective sweep signatures and found a distinct footprint of positive selection located around a non-synonymous change (A1114G; T372A) within the spike protein receptor-binding domain (RBD), predicted to remove glycosylation and increase binding to human ACE2 (hACE2), the cellular receptor. This change is present in all human SARS-CoV-2 sequences but not in closely related viruses from bats and pangolins.

Noble Metal Organometallic Complexes Display Antiviral Activity against SARS-CoV-2.

SARS-CoV-2 emerged in 2019 as a devastating viral pathogen with no available preventative or treatment to control what led to the current global pandemic. The continued spread of the virus and increasing death toll necessitate the development of effective antiviral treatments to combat this virus. To this end, we evaluated a new class of organometallic complexes as potential antivirals.

Zurich Cementless Dual Mobility Cup for Canine Total Hip Prosthesis: Implant Characteristics and Surgical Outcome in 105 Cases.

Dislocation after total hip arthroplasty (THA) remains a troublesome complication, and a source of frustration for the owner and the surgeon. The dislocation rate of hip prostheses in dogs is reported to range from 4 to 15%, representing the most common short-term complication. This is especially true in large and giant breed dogs, usually requiring revision surgery.

Defective viral genomes from chikungunya virus are broad-spectrum antivirals and prevent virus dissemination in mosquitoes.

Defective viral genomes (DVGs) are truncated and/or rearranged viral genomes produced during virus replication. Described in many RNA virus families, some of them have interfering activity on their parental virus and/or strong immunostimulatory potential, and are being considered in antiviral approaches. Chikungunya virus (CHIKV) is an alphavirus transmitted by Aedes spp.

American Aedes japonicus japonicus, Culex pipiens pipiens, and Culex restuans mosquitoes have limited transmission capacity for a recent isolate of Usutu virus.

Usutu virus (USUV; Flavivirus) has caused massive die-offs in birds across Europe since the 1950s. Although rare, severe neurologic disease in humans has been reported. USUV is genetically related to West Nile virus (WNV) and shares an ecological niche, suggesting it could spread from Europe to the Americas.

Development and characterization of infectious clones of two strains of Usutu virus.

Usutu virus (USUV; genus Flavivirus; family Flaviviridae) is a mosquito-borne, positive-sense RNA virus that is currently causing significant die-offs in numerous bird species throughout Europe and has caused infections in humans. Currently, there are no molecular clones for USUV, hence, hindering studies on the pathogenesis and transmission of USUV. Here, we demonstrate the development and characterization of infectious clones for two modern strains of USUV isolated from Europe and Africa.

Chikungunya virus superinfection exclusion is mediated by a block in viral replication and does not rely on non-structural protein 2.

Superinfection exclusion (SIE) is a process by which a virally infected cell is protected from subsequent infection by the same or a closely related virus. By preventing cell coinfection, SIE favors preservation of genome integrity of a viral strain and limits its recombination potential with other viral genomes, thereby impacting viral evolution. Although described in virtually all viral families, the precise step(s) impacted by SIE during the viral life cycle have not been systematically explored.

Rolling circle amplification: A high fidelity and efficient alternative to plasmid preparation for the rescue of infectious clones.

Alphaviruses (genus Alphavirus; family Togaviridae) are a medically relevant family of viruses that include chikungunya virus and Mayaro virus. Infectious cDNA clones of these viruses are necessary molecular tools to understand viral biology. Traditionally, rescuing virus from an infectious cDNA clone requires propagating plasmids in bacteria, which can result in mutations in the viral genome due to bacterial toxicity or recombination and requires specialized equipment and knowledge to propagate the bacteria.