Impact of the Stress Response on Quaternary Ammonium Compound Disinfectant Susceptibility in Species.

The well-known problem of antibiotic resistance foreshadows a similar threat posed by microbial resistance to biocides such as disinfectants and antiseptics. These products are vital for infection control, yet their overuse during the COVID-19 pandemic has accelerated the development of resistant microorganisms. This study investigates the molecular mechanisms underlying disinfectant resistance in sp.

Suppression of Huntington's Disease Somatic Instability by Transcriptional Repression and Direct CAG Repeat Binding.

Huntington's disease (HD) arises from a CAG expansion in the () gene beyond a critical threshold. A major thrust of current HD therapeutic development is lowering levels of mutant mRNA (m) and protein (mHTT) with the aim of reducing the toxicity of these product(s). Human genetic data also support a key role for somatic instability (SI) in 's CAG repeat - whereby it lengthens with age in specific somatic cell types - as a key driver of age of motor dysfunction onset.

Hereditary spastic paraplegia with thin corpus callosum and SPG11 mutation: A neuropathological evaluation.

Hereditary spastic paraplegia (HSP) with thin corpus callosum can be due to a variety of genetic causes, the most common of which are biallelic variants in SPG11 (HSP11). Only six cases of neuropathologic examination of HSP11 have been reported. Here we present neuropathological findings in another case of HSP11 with novel mutation (homozygous c.

Differential Expression Analysis Reveals Possible New Quaternary Ammonium Compound Resistance Gene in Highly Resistant sp. HRI.

During the COVID-19 pandemic, the surge in disinfectant use emphasised their pivotal role in infection control. While the majority of antimicrobial resistance research focuses on antibiotics, resistance to biocides, which are present in disinfectants and sanitisers, is escalating. sp.

Global huntingtin knockout in adult mice leads to fatal neurodegeneration that spares the pancreas.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG tract in the huntingtin (HTT) gene, leading to toxic gains of function. HTT-lowering treatments are in clinical trials, but the risks imposed are unclear. Recent studies have reported on the consequences of widespread HTT loss in mice, where one group described early HTT loss leading to fatal pancreatitis, but later loss as benign.

Transcriptomic signature of bacteria exposed to benzalkonium chloride.

The COVID-19 pandemic has highlighted our reliance on biocides, the increasing prevalence of resistance to biocides is a risk to public health. Bacterial exposure to the biocide, benzalkonium chloride (BAC), resulted in a unique transcriptomic profile, characterised by both a short and long-term response. Differential gene expression was observed in four main areas: motility, membrane composition, proteostasis, and the stress response.

Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation.

Huntington's disease arises from a toxic gain of function in the () gene. As a result, many HTT-lowering therapies are being pursued in clinical studies, including those that reduce HTT RNA and protein expression in the liver. To investigate potential impacts, we characterized molecular, cellular, and metabolic impacts of chronic HTT lowering in mouse hepatocytes.

Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation.

Huntington's disease arises from a toxic gain of function in the ( ) gene. As a result, many HTT-lowering therapies are being pursued in clinical studies, including those that reduce HTT RNA and protein expression in the liver. To investigate potential impacts, we characterized molecular, cellular, and metabolic impacts of chronic HTT lowering in mouse hepatocytes.

The Hormetic Effect Observed for Benzalkonium Chloride and Didecyldimethylammonium Chloride in sp. HRI.

Hormesis, or the hormetic effect, is a dose- or concentration-dependent response characterised by growth stimulation at low concentrations and inhibition at high concentrations. The impact of sub-lethal levels of disinfectants on the growth of species is critical to understanding the increasing number of outbreaks caused by this pathogen in healthcare settings. sp.

Genomic Islands Identified in Highly Resistant sp. HRI: A Pathway to Discover New Disinfectant Resistance Elements.

Molecular insights into the mechanisms of resistance to disinfectants are severely limited, together with the roles of various mobile genetic elements. Genomic islands are a well-characterised molecular resistance element in antibiotic resistance, but it is unknown whether genomic islands play a role in disinfectant resistance. Through whole-genome sequencing and the bioinformatic analysis of sp.

Investigation into the Metabolism of Quaternary Ammonium Compound Disinfectants by Bacteria.

Since the start of the COVID-19 pandemic, our reliance on disinfectants and sanitizers and the use thereof has grown. While this may protect human health, it may be selecting for antimicrobial-resistant microorganisms, including those that are not only capable of growth in the presence of disinfectants but also thrive using this as an energy source. Furthermore, there is a growing concern in emerging nosocomial pathogens, which have shown resistance to antibiotics and disinfectants.

Genome Sequence of Resistant sp. Strain HRI, Isolated from a Bottle of Didecyldimethylammonium Chloride-Based Disinfectant.

Antimicrobial resistance is a significant issue, and it threatens the prevention and effective treatment of a range of bacterial infections. Here, we report the whole-genome sequence of the multidrug-resistant isolate sp. strain HRI.

Molecular basis of bacterial disinfectant resistance.

Antibiotic resistance could accelerate humanity towards an already fast-approaching post-antibiotic era, where disinfectants and effective biosecurity measures will be critically important to control microbial diseases. Disinfectant resistance has the potential to change our way of life from compromising food security to threatening our medical health systems. Resistance to antimicrobial agents occurs through either intrinsic or acquired resistance mechanisms.

Kynurenine inhibits autophagy and promotes senescence in aged bone marrow mesenchymal stem cells through the aryl hydrocarbon receptor pathway.

Osteoporosis is an age-related deterioration in bone health that is, at least in part, a stem cell disease. The different mechanisms and signaling pathways that change with age and contribute to the development of osteoporosis are being identified. One key upstream mechanism that appears to target a number of osteogenic pathways with age is kynurenine, a tryptophan metabolite and an endogenous Aryl hydrocarbon receptor (AhR) agonist.

Stromal cell-derived factor-1 as a potential therapeutic target for osteoarthritis and rheumatoid arthritis.

With age, joints become subject to chronic inflammatory processes that lead to degeneration of articular cartilage. Although multifactorial, cytokines have been shown to play a role in the pathogenesis of these chronic disease states. Stromal cell-derived factor 1 (SDF-1) is a chemokine that has been shown to be active in homeostatic mechanisms and developmental processes throughout the body, such as endochondral bone formation.

Stromal cell-derived factor-1 (CXCL12) and its role in bone and muscle biology.

Musculoskeletal disorders are the leading cause of disability worldwide; two of the most prevalent of which are osteoporosis and sarcopenia. Each affect millions in the aging population across the world and the associated morbidity and mortality contributes to billions of dollars in annual healthcare cost. Thus, it is important to better understand the underlying pathologic mechanisms of the disease process.

Regulation of outer-membrane proteins (OMPs) A and F, during -induced outer-membrane vesicle (OMV) biosynthesis.

Background: Gram-negative bacteria actively secrete outer membrane vesicles into the surrounding environment and these vesicles have been shown to play various physiological and protective roles such as carrying antibiotic-degrading enzymes and acting as decoys against host defences, therefore promoting the pathogenesis of the bacterium. It has been shown that avian pathogenic species can increase vesicle biosynthesis through the acquisition of the gene but the effect this has on the cell by scavenging outer-membrane associated proteins (OmpA, OmpF) into the vesicles during vesicle release have not yet been investigated.

Results: Relative quantitative real-time PCR data obtained from expressing and non-expressing cells showed that during induction, showed a nearly 2-fold down regulation relative to the non-expressing cells during the entire 24 hours, while was expressed at the same level as the non-expressing cells during the first 8 hours of expression.

Age-Dependent Oxidative Stress Elevates Arginase 1 and Uncoupled Nitric Oxide Synthesis in Skeletal Muscle of Aged Mice.

Aging is associated with reduced muscle mass (sarcopenia) and poor bone quality (osteoporosis), which together increase the incidence of falls and bone fractures. It is widely appreciated that aging triggers systemic oxidative stress, which can impair myoblast cell survival and differentiation. We previously reported that arginase plays an important role in oxidative stress-dependent bone loss.

Detection of virulence factors of South African Lactococcus garvieae isolated from rainbow trout, Oncorhynchus mykiss (Walbaum).

Lactococcus garvieae is a Gram-positive bacterium that causes mortalities in freshwater and marine fish worldwide and therefore results in severe economic losses in the aquaculture industry. Apart from the apparent integral role of the exopolysaccharide (EPS) capsule in pathogenesis, factors associated with virulence of this bacterium are poorly understood. However, recent studies have indicated that the ability of L.

Transcriptional regulatory networks underlying gene expression changes in Huntington's disease.

Transcriptional changes occur presymptomatically and throughout Huntington's disease (HD), motivating the study of transcriptional regulatory networks (TRNs) in HD We reconstructed a genome-scale model for the target genes of 718 transcription factors (TFs) in the mouse striatum by integrating a model of genomic binding sites with transcriptome profiling of striatal tissue from HD mouse models. We identified 48 differentially expressed TF-target gene modules associated with age- and CAG repeat length-dependent gene expression changes in CAG knock-in mouse striatum and replicated many of these associations in independent transcriptomic and proteomic datasets. Thirteen of 48 of these predicted TF-target gene modules were also differentially expressed in striatal tissue from human disease.

Early Detection of Apathetic Phenotypes in Huntington's Disease Knock-in Mice Using Open Source Tools.

Apathy is one of the most prevalent and progressive psychiatric symptoms in Huntington's disease (HD) patients. However, preclinical work in HD mouse models tends to focus on molecular and motor, rather than affective, phenotypes. Measuring behavior in mice often produces noisy data and requires large cohorts to detect phenotypic rescue with appropriate power.

Peripheral huntingtin silencing does not ameliorate central signs of disease in the B6.HttQ111/+ mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease whose predominant neuropathological signature is the selective loss of medium spiny neurons in the striatum. Despite this selective neuropathology, the mutant protein (huntingtin) is found in virtually every cell so far studied, and, consequently, phenotypes are observed in a wide range of organ systems both inside and outside the central nervous system. We, and others, have suggested that peripheral dysfunction could contribute to the rate of progression of striatal phenotypes of HD.