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Systematic Comparison of Indicator and Pathogenic Viruses Using High-Throughput qPCR Identifies Pepper Mild Mottle Virus as a Robust Indicator of Virus Removal in Wastewater Treatment

The selection of appropriate viral indicators for evaluating wastewater treatment performance remains challenging because candidate markers have rarely been compared systematically within a unified analytical framework. Here, we collected influent and effluent samples monthly for one year from two wastewater treatment plants in Japan and conducted, to our knowledge, the first comprehensive comparison of 19 viral targets and one protozoan target using high-throughput quantitative PCR. Pepper...

bioRxiv 9d ago

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

Abstract BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1,2,3.

Nature 19h ago

SIRT7 regulates dosage compensation and safeguards the female X chromosome

Abstract Sirtuins are deacetylases implicated in stress responses and longevity in mammals1,2. Although their differential impact on disease for the two sexes has been noted3,4,5,6,7, the underlying reasons are unclear. Here, using Sirt7 as a model in mice, we examine the mechanisms leading to sex differences and find that Sirt7−/− female mice have decreased fitness throughout their lifespan.

Nature 19h ago

Living brain gene activity revealed noninvasively through programmable blood test

Living brain gene activity revealed noninvasively through programmable blood test Stephanie Baum Scientific Editor Robert Egan Associate Editor Cell function is determined by how DNA is expressed into proteins. That process includes two main steps—transcription, when messenger RNA (mRNA) makes copies of active genes; and translation, when mRNA guides protein assembly. Knowing which genes are active at any given moment would make it possible to track the body's response to factors in the...

Phys.org 8d ago

Minimal effective dose of telacebec administered orally in a murine model of leprosy

Leprosy treatment requires prolonged therapy with challenging patient follow-up. New regimens are needed to simplify current treatments. A recent clinical trial evaluating bedaquiline has shown promising results; however, to prevent the emergence of drug resistance, additional therapeutic options are required.

bioRxiv 5d ago

The intertwined fate: exploring the hepatitis C virus/Nrf1 crosstalk

Despite advances in knowledge and medicine, hepatitis C virus (HCV) infection remains a global challenge. The viral life cycle heavily depends on lipid metabolism; therefore, HCV infection is associated with profound changes in host lipid homeostasis. The transcription factor nuclear factor erythroid 2 related factor-1 (Nrf1) is one of the regulators maintaining this homeostasis.

bioRxiv 11d ago

Repurposing drugs to treat Amoebic Gill Disease in Atlantic Salmon

Neoparameoba perurans causes Amoebic Gill Disease (AGD), a major parasitic disease of marine-phase Atlantic salmon and rainbow trout worldwide. Treatment options are limited to freshwater baths, which are costly at scale and exhibit only limited long-term efficacy. N. perurans contains an obligate eukaryotic symbiont, Perkinsela-like organism (PLO).

bioRxiv 3d ago

PAD2 knockout reduces myelin protein aggregates, modulates neuroinflammation and protects motor neurons, axons and neuromuscular junction in a SOD1-ALS mouse model

Background: Dysregulated peptidyl deiminase 2 (PAD2) and aberrant protein citrullination (PC), a posttranslational modification (PTM), are involved in various inflammatory and neurodegenerative diseases. We previously showed in transgenic mice and postmortem human tissues that PC and PAD2 are altered in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by motor neurons loss, paralysis, and death. Herein, we investigated the role of PAD2 in ALS by PAD2 knockout in...

bioRxiv 7d ago

Bacteroides fragilis modulates gut microbiome community composition, frontal cortex gene expression, and fecal and frontal cortex metabolites in a mouse model of Alzheimers disease pathologies

Alzheimers disease (AD) is a neurodegenerative disease and the leading cause of dementia among elderly. Gut microbiome alterations precede pathogenesis and may affect disease outcomes. We evaluated the role of Bacteroides fragilis in triple transgenic mice modeling AD pathologies (3xTg-AD) and wild-type controls (WT).

bioRxiv 11d ago

SRC Knockdown Impairs Proliferation, Migration, and Invasion While Promoting Apoptosis in HTR8/SVneo Trophoblast Cells via Activation of the PI3K/Akt/Bcl-2 Signaling Pathway

SRC knockdown inhibits trophoblast cell proliferation, migration, and invasion while inducing apoptosis via activation of the PI3K/Akt/Bcl-2 signaling pathway. Trophoblast dysfunction is central to pregnancy disorders such as preeclampsia and miscarriage, yet the role of SRC, a non-receptor tyrosine kinase, in these cells remains poorly understood. This study aimed to elucidate the functional impact of SRC on trophoblast behavior and its underlying mechanism.

bioRxiv 9d ago