Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function.

ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number of biological outputs includes control of tuberculosis in animal models. Here, we show that ATG5 associates with retromer's core components VPS26, VPS29, and VPS35 and modulates retromer function. Knockout of ATG5 blocked trafficking of a key glucose transporter sorted by the retromer, GLUT1, to the plasma membrane.

ATG9A facilitates the closure of mammalian autophagosomes.

Canonical autophagy captures within specialized double-membrane organelles, termed autophagosomes, an array of cytoplasmic components destined for lysosomal degradation. An autophagosome is completed when the growing phagophore undergoes ESCRT-dependent membrane closure, a prerequisite for its subsequent fusion with endolysosomal organelles and degradation of the sequestered cargo. ATG9A, a key integral membrane protein of the autophagy pathway, is best known for its role in the formation and expansion of phagophores.

The Role of ETNPPL in Dopaminergic Neuron Stability: Insights from Neuromelanin-Associated Protein Expression in Parkinson's Disease.

More than six million people worldwide are affected by Parkinson's disease (PD), a multifactorial disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Several immunohistochemical studies suggest that neuromelanin (NM), found in these neurons, plays a key role in their degeneration. In this study, twelve formalin-fixed, paraffin-embedded (FFPE) brain sections were analyzed, comprising six samples from PD patients and six from healthy controls.

Phylogenetic-informed graph deep learning to classify dynamic transmission clusters in infectious disease epidemics.

Motivation: In the midst of an outbreak, identification of groups of individuals that represent risk for transmission of the pathogen under investigation is critical to public health efforts. Dynamic transmission patterns within these clusters, whether it be the result of changes at the level of the virus (e.g.

Calcium signaling from damaged lysosomes induces cytoprotective stress granules.

Lysosomal damage induces stress granule (SG) formation. However, the importance of SGs in determining cell fate and the precise mechanisms that mediate SG formation in response to lysosomal damage remain unclear. Here, we describe a novel calcium-dependent pathway controlling SG formation, which promotes cell survival during lysosomal damage.

Inflammatory Prostatitis Plus IBS-D Subtype and Correlation with Immunomodulating Agent Imbalance in Seminal Plasma: Novel Combined Treatment.

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic DSF (De Simone formulation) in improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because the low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and DSF treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. Methods: We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria).

Forecasting dominance of SARS-CoV-2 lineages by anomaly detection using deep AutoEncoders.

The COVID-19 pandemic is marked by the successive emergence of new SARS-CoV-2 variants, lineages, and sublineages that outcompete earlier strains, largely due to factors like increased transmissibility and immune escape. We propose DeepAutoCoV, an unsupervised deep learning anomaly detection system, to predict future dominant lineages (FDLs). We define FDLs as viral (sub)lineages that will constitute >10% of all the viral sequences added to the GISAID, a public database supporting viral genetic sequence sharing, in a given week.

COVID-19 lineages in a minimally vaccinated island population: Genomic epidemiology of SARS-CoV-2 in Haiti.

We monitored SARS-CoV-2 variants in Haiti from 2020-2023. Despite Haitian COVID-19 travel restrictions and in the setting of a vaccination rate of 2.7%, the timing and lineage evolution of the Haiti epidemic mirrored what was occurring in the rest of the world.

Hepatic Proteomic Changes Associated with Liver Injury Caused by Alcohol Consumption in Mice.

Alcohol-associated liver disease (ALD) is a prevalent medical problem with limited effective treatment strategies. Although many biological processes contributing to ALD have been elucidated, a complete understanding of the underlying mechanisms is still lacking. The current study employed a proteomic approach to identify hepatic changes resulting from ethanol (EtOH) consumption and the genetic ablation of the formyl peptide receptor 2 (FPR2), a G-protein coupled receptor known to regulate multiple signaling pathways and biological processes, in a mouse model of ALD.

Temperature-dependent alterations in the proteome of the emergent fish pathogen Edwardsiella piscicida.

Edwardsiella piscicida is an emerging bacterial pathogen and the aetiological agent of edwardsiellosis among cultured and wild fish species globally. The increased frequency of outbreaks of this Gram-negative, facultative intracellular pathogen pose not only a threat to the aquaculture industry but also a possible foodborne/waterborne public health risk due to the ill-defined zoonotic potential. Thus, understanding the role of temperature on the virulence of this emerging pathogen is essential for comprehending the pathogenesis of piscine edwardsiellosis in the context of current warming trends associated with climate change, as well as providing insight into its zoonotic potential.

Novel insights on unraveling dynamics of transmission clusters in outbreaks using phylogeny-based methods.

Molecular data analysis is invaluable in understanding the overall behavior of a rapidly spreading virus population when epidemiological surveillance is problematic. It is also particularly beneficial in describing subgroups within the population, often identified as clades within a phylogenetic tree that represent individuals connected via direct transmission or transmission via differing risk factors in viral spread. However, transmission patterns or viral dynamics within these smaller groups should not be expected to exhibit homogeneous behavior over time.

The Triad of Sleep, Immunity, and Cancer: A Mediating Perspective.

The triadic interplay between sleep, immunity, and cancer represents a growing area of biomedical research with significant clinical implications. This review synthesizes the current knowledge on how sleep influences immune function, the immune system's role in cancer dynamics, and the direct connections between sleep patterns and cancer risk. After a comprehensive overview of the interrelationships among these three domains, the mechanisms of sleep in immune function are described, detailing how sleep regulates the immune system, the effects of sleep duration and quality on immune responses, and the underlying molecular and cellular mechanisms.

Transcriptome Study in Sicilian Patients with Autism Spectrum Disorder.

ASD is a complex condition primarily rooted in genetics, although influenced by environmental, prenatal, and perinatal risk factors, ultimately leading to genetic and epigenetic alterations. These mechanisms may manifest as inflammatory, oxidative stress, hypoxic, or ischemic damage. To elucidate potential variances in gene expression in ASD, a transcriptome analysis of peripheral blood mononuclear cells was conducted via RNA-seq on 12 ASD patients and 13 healthy controls, all of Sicilian ancestry to minimize environmental confounds.

CSF1R inhibition depletes brain macrophages and reduces brain virus burden in SIV-infected macaques.

Perivascular macrophages (PVMs) and, to a lesser degree, microglia are targets and reservoirs of HIV and simian immunodeficiency virus (SIV) in the brain. Previously, we demonstrated that colony-stimulating factor 1 receptor (CSF1R) in PVMs was upregulated and activated in chronically SIV-infected rhesus macaques with encephalitis, correlating with SIV infection of PVMs. Herein, we investigated the role of CSF1R in the brain during acute SIV infection using BLZ945, a brain-penetrant CSF1R kinase inhibitor.

Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function.

ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number of biological outputs includes control of tuberculosis in animal models. Here we show that ATG5 associates with retromer's core components VPS26, VPS29 and VPS35 and modulates retromer function. Knockout of ATG5 blocked trafficking of a key glucose transporter sorted by the retromer, GLUT1, to the plasma membrane.

The role of central neck dissection and adjuvant treatment in pT4aN0 laryngeal carcinoma treated with open partial horizontal laryngectomy.

Purpose: The study aimed to identify parameters that could predict oncological and functional outcomes in patients with pT4aN0 laryngeal squamous cell carcinoma (LSCC) who underwent open partial horizontal laryngectomy (OPHL). The role of paratracheal neck dissection (PTND) was analyzed as the primary outcome. Additionally, the study compared the outcomes of patients who underwent postoperative radio/chemotherapy (PORT/PORCT) with those who refused or did not adhere to adjuvant treatments.

Phylodynamic Insights into Global Emergence and Diversification of the Tomato Pathogen pv. .

The emergence of plant pathogens is often associated with waves of unique evolutionary and epidemiological events. pv. is one of the major pathogens causing bacterial spot disease of tomatoes.

Transcriptome Analysis in Patients With Muscle-invasive Bladder Cancer.

Background/aim: Bladder cancer (BC) is the most prevalent malignant tumor in the urinary tract, classified mainly into muscle-invasive BC (MIBC) and non-MIBC (NMIBC). Recent studies highlight the important role of changes in transcriptome activity in carcinogenesis, aiding in the identification of additional differentially regulated candidate genes, improving our understanding of the molecular basis of gene regulation in BC. This study aimed to evaluate the transcriptome of MIBC patients compared with normal subjects.

Investigation of Neuropsychological Dysfunction Among Recovered Nurses: The COVID-19.

Objective: This investigation aimed to compare the neuropsychological dysfunctions of coronavirus (COVID-19)-recovered nurses to those of healthy nurses.

Methodology: The present research method was descriptive and causal-comparative, in which the statistical population consisted of nurses with a history of COVID disease and working in the COVID department of public hospitals in Isfahan city. The available method selected 30 nurses with a history of illness and compared them with 30 other nurses from the same hospitals.

The balance between antiviral and antibacterial responses during infection is regulated by the ubiquitin ligase CBL.

As a first line of host defense, macrophages must be able to effectively sense and respond to diverse types of pathogens, and while a particular type of immune response may be beneficial in some circumstances, it can be detrimental in others. Upon infecting a macrophage, () induces proinflammatory cytokines that activate antibacterial responses. Surprisingly, also triggers antiviral responses that actually hinder the ability of macrophages to control infection.

Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions.

Unveiling the pathophysiology of restless legs syndrome through transcriptome analysis.

The aim of this study was to analyze signaling pathways associated with differentially expressed messenger RNAs in people with restless legs syndrome (RLS). Seventeen RLS patients and 18 controls were enrolled. Coding RNA expression profiling of 12,857 gene transcripts by next-generation sequencing was performed.

A mechanism that transduces lysosomal damage signals to stress granule formation for cell survival.

Lysosomal damage poses a significant threat to cell survival. Our previous work has reported that lysosomal damage induces stress granule (SG) formation. However, the importance of SG formation in determining cell fate and the precise mechanisms through which lysosomal damage triggers SG formation remains unclear.