Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis.

During infection, dengue virus (DENV) and Zika virus (ZIKV), two (ortho)flaviviruses of public health concern worldwide, induce alterations of mitochondria morphology to favor viral replication, suggesting a viral co-opting of mitochondria functions. Here, we performed an extensive transmission electron microscopy-based quantitative analysis to demonstrate that both DENV and ZIKV alter endoplasmic reticulum-mitochondria contact sites (ERMC). This correlated at the molecular level with an impairment of ERMC tethering protein complexes located at the surface of both organelles.

How many do we need? Meeting the challenges of studying the microbiome of a cryptic insect in an orchard.

The minimal sampling effort required to report the microbiome composition of insect surveyed in natural environment is often based on empirical or logistical constraints. This question was addressed with the white pine cone beetle, (Schwarz), a devastating insect pest of seed orchards. It attacks and stop the growth of the cones within which it will spend its life, on the ground.

Brain penetration of peripheral extracellular vesicles from Alzheimer's patients and induction of microglia activation.

Alzheimer's disease (AD) is an age-related neurodegenerative pathology. Brain-derived extracellular vesicles (EVs) have been demonstrated to be implicated in AD pathogenesis by facilitating the propagation of Tau, amyloid-β and inflammatory cytokines. However, the impact of peripheral EVs (pEVs) in AD pathogenesis remains poorly investigated.

Immunomodulatory properties of extracellular vesicles containing the Spike protein of SARS-CoV-2.

Extracellular vesicles released by the protozoan parasite display immunomodulatory properties towards mammalian immune cells. In this study, we have evaluated the potential of extracellular vesicles derived from the non-pathogenic protozoan towards the development of a vaccine adjuvant. As a proof of concept, we expressed in a codon-optimized SARS-CoV-2 Spike protein fused to the secreted acid phosphatase signal peptide in the N-terminal and to a 6×-His stretch in the C-terminal.

TGFβ1 Restores Energy Homeostasis of Human Trophoblast Cells Under Hyperglycemia In Vitro by Inducing PPARγ Expression, AMPK Activation, and HIF1α Degradation.

Elevated glucose levels at the fetal-maternal interface are associated with placental trophoblast dysfunction and increased incidence of pregnancy complications. Trophoblast cells predominantly utilize glucose as an energy source, metabolizing it through glycolysis in the cytoplasm and oxidative respiration in the mitochondria to produce ATP. The TGFβ1/SMAD2 signaling pathway and the transcription factors PPARγ, HIF1α, and AMPK are key regulators of cell metabolism and are known to play critical roles in extravillous trophoblast cell differentiation and function.

Pharmacological characterization of cannabidiol as a negative allosteric modulator of the 5-HT receptor.

Promising clinical evidence suggests that psychedelic compounds, like lysergic acid diethylamide (LSD), have therapeutic value for treatment of psychiatric disorders. However, they often produce hallucinations and dissociative states, likely mediated by the serotonin (5-HT) receptor 5-HT, raising challenges regarding therapeutic scalability. Given the reported antipsychotic effects of cannabidiol (CBD) and its promiscuous binding at many receptors, we assessed whether CBD could modulate 5-HT signalling.

Intrinsic Muscle Stem Cell Dysfunction Contributes to Impaired Regeneration in the mdx Mouse.

Background: Duchenne muscular dystrophy (DMD) is a devastating disease characterized by progressive muscle wasting that leads to diminished lifespan. In addition to the inherent weakness of dystrophin-deficient muscle, the dysfunction of resident muscle stem cells (MuSC) significantly contributes to disease progression.

Methods: Using the mdx mouse model of DMD, we performed an in-depth characterization of disease progression and MuSC function in dystrophin-deficient skeletal muscle using immunohistology, isometric force measurements, transcriptomic analysis and transplantation assays.

HSP60 controls mitochondrial ATP generation for optimal virus-specific IL-21-producing CD4 and cytotoxic CD8 memory T cell responses.

We have shown that virus-specific CD4 and CD8 memory T cells (TM) induce autophagy after T cell receptor (TCR) engagement to provide free glutamine and fatty acids, including in people living with HIV-1 (PLWH). These nutrients fuel mitochondrial ATP generation through glutaminolysis and fatty acid oxidation (FAO) pathways, to fulfill the bioenergetic demands for optimal IL-21 and cytotoxic molecule production in CD4 and CD8 cells, respectively. Here, we expand our knowledge on how the metabolic events that occur in the mitochondria of virus-specific TM down-stream of the autophagy are regulated.

Repurposing Drugs and Synergistic Combinations as Potential Therapies for Inhibiting SARS-CoV-2 and Coronavirus Replication.

Drug repurposing can serve an important role in rapidly discovering medicament options for emerging microbial pandemics. In this study, a pragmatic approach is demonstrated for screening and testing drug combinations as potential broad-spectrum therapies against SARS-CoV-2 and other betacoronaviruses. Rapid cell-based phenotypic small molecule screens were executed using related common-cold-causing HCoV-OC43 betacoronavirus to identify replication inhibitors from a library of drugs approved by regulatory agencies for other indications.

Core-Shell Bottlebrush Polymers: Unmatched Delivery of Small Active Compounds Deep Into Tissues.

The chemical structure of a delivery nanovehicle plays a pivotal role in determining the efficiency of drug delivery within the body. Leveraging the unique architecture of bottlebrush (BB) polymers-characterized by variations in backbone length, grafting density, and self-assembly morphology-offers a novel approach to understanding the influence of structural properties on biological behavior. In this study, developed a drug delivery system based on core-shell BB polymers synthesized using a "grafting-from" strategy.

A zebrafish-based in vivo model of Zika virus infection unveils alterations of the glutamatergic neuronal development and NS4A as a key viral determinant of neuropathogenesis.

Infection of pregnant women by Zika virus (ZIKV) is associated with severe neurodevelopmental defects in newborns through poorly defined mechanisms. Here, we established a zebrafish in vivo model of ZIKV infection to circumvent limitations of existing mammalian models. Leveraging the unique tractability of this system, we gained unprecedented access to the ZIKV-infected brain at early developmental stages.

Exploring the potential of plasma and adipose mesenchymal stem cell-derived extracellular vesicles as novel platforms for neuroinflammation therapy.

Persistent reactive oxygen species (ROS) and neuroinflammation contribute to the onset and progression of neurodegenerative diseases, underscoring the need for targeted therapeutic strategies to mitigate these effects. Extracellular vesicles (EVs) show promise in drug delivery due to their biocompatibility, ability to cross biological barriers, and specific interactions with cell and tissue receptors. In this study, we demonstrated that human plasma-derived EVs (pEVs) exhibit higher brain-targeting specificity, while adipose-derived mesenchymal stem cells EVs (ADMSC-EVs) offer regenerative and immunomodulatory properties.

Exposure to brominated flame retardants and through lactation delays the development of DMBA-induced mammary cancer: potential effects on subtypes?

Introduction: Brominated flame retardants (BFRs) are chemical compounds used to reduce the flammability of various products; some BFRs exhibit endocrine-disrupting properties and can leach into the environment leading to human and wildlife exposure. The mammary gland has specific vulnerability windows during which it is more sensitive to the effects of endocrine disrupting compounds (EDCs), such as the life, puberty and pregnancy. Our previous studies revealed precocious mammary gland development, disruptions in junctional proteins, and altered proliferation-apoptosis balance during puberty in rats exposed to BFRs and through lactation.

Epidemiology of Tomato Brown Rugose Fruit Virus (ToBRFV) in Commercial Greenhouses.

The tomato brown rugose fruit virus (ToBRFV) poses a considerable threat to tomato production worldwide. Substantial experimental evidence supports the role of infected seeds as a contamination route, but the epidemiologic portrait of the virus has received less attention. This study reports the first survey of ToBRFV prevalence in commercial greenhouses.

Phosphorylation on serine 72 modulates Rab7A palmitoylation and retromer recruitment.

Rab7A has a key role in regulating membrane trafficking at late endosomes. By interacting with several different effectors, this small GTPase controls late endosome mobility, orchestrates fusion events between late endosomes and lysosomes, and participates in the formation of and regulates the fusion between autophagosomes and lysosomes. Rab7A is also responsible for the spatiotemporal recruitment of retromer, which is required for the endosome-to-trans-Golgi network retrieval of cargo receptors such as sortilin (SORT1) and CI-MPR (also known as IGF2R).

Phenotypic plasticity in bacterial elongation among closely related species.

Cell elongation is a fundamental component of the bacterial cell cycle and has been studied over many decades, in part owing to its mechanisms being a target of numerous antibiotic classes. While several distinct modes of cell elongation have been described, these studies have largely relied on a handful of model bacterial species. Therefore, we have a limited view of the diversity of cell elongation approaches that are employed by bacteria, and how these vary in response to evolutionary and environmental influences.

Zika virus remodels and hijacks IGF2BP2 ribonucleoprotein complex to promote viral replication organelle biogenesis.

Zika virus (ZIKV) infection causes significant human disease that, with no approved treatment or vaccine, constitutes a major public health concern. Its life cycle entirely relies on the cytoplasmic fate of the viral RNA genome (vRNA) through a fine-tuned equilibrium between vRNA translation, replication, and packaging into new virions, all within virus-induced replication organelles (vROs). In this study, with an RNA interference (RNAi) mini-screening and subsequent functional characterization, we have identified insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) as a new host dependency factor that regulates vRNA synthesis.

Systemic administration of a viral nanoparticle neoadjuvant prevents lung metastasis development through emergency myelopoiesis.

Cancer presents a significant public health concern, particularly in the context of metastatic disease. Surgical removal of primary tumors, while essential, can inadvertently heighten the risk of metastasis. Thus, there is a critical need for innovative neoadjuvant therapies capable of curtailing metastatic progression before or immediately following tumor resection.

Defects in meiosis I contribute to the genesis of androgenetic hydatidiform moles.

To identify novel genes responsible for recurrent hydatidiform moles (HMs), we performed exome sequencing on 75 unrelated patients who were negative for mutations in the known genes. We identified biallelic deleterious variants in 6 genes, FOXL2, MAJIN, KASH5, SYCP2, MEIOB, and HFM1, in patients with androgenetic HMs, including a familial case of 3 affected members. Five of these genes are essential for meiosis I, and their deficiencies lead to premature ovarian insufficiency.

In Vitro Assessment of the Neuroprotective Effects of Pomegranate ( L.) Polyphenols Against Tau Phosphorylation, Neuroinflammation, and Oxidative Stress.

Background: Oxidative stress and chronic inflammation, at both the systemic and the central level, are critical early events in atherosclerosis and Alzheimer's disease (AD).

Purpose: To investigate the oxidative stress-, inflammation-, and Tau-phosphorylation-lowering effects of pomegranate polyphenols (PPs) (punicalagin, ellagic acid, peel, and aril extracts).

Methods: We used flow cytometry to quantify the protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific marker (CD86 and CD163) expression in human microglia HMC3 cells.

Exposure to an environmentally representative mixture of polybrominated diphenyl ethers (PBDEs) alters zebrafish neuromuscular development.

Polybrominated diphenyl ethers (PBDEs) are a prevalent group of brominated flame retardants (BFRs) added to several products such as electronics, plastics, and textiles to reduce their flammability. They are reported as endocrine disruptors and neurodevelopmental toxicants that can accumulate in human and wildlife tissues, thus making their ability to leach out of products into the environment a great cause for concern. In this study, zebrafish (Danio rerio) embryos and larvae were exposed to a wide concentration range (1.

The bacterial strains JAM1 and GP59 of the species differ in their expression profiles of denitrification genes in oxic and anoxic cultures.

Background: Strain JAM1 and strain GP59 of the methylotrophic, bacterial species were isolated from a microbial community of the biofilm that developed in a fluidized-bed, methanol-fed, marine denitrification system. Despite of their common origin, both strains showed distinct physiological characters towards the dynamics of nitrate ( ) reduction. Strain JAM1 can reduce to nitrite ( ) but not to nitric oxide (NO) as it lacks a NO-forming reductase.

Rhizospheric miRNAs affect the plant microbiota.

Small ribonucleic acids (RNAs) have been shown to play important roles in cross-kingdom communication, notably in plant-pathogen relationships. Plant micro RNAs (miRNAs)-one class of small RNAs-were even shown to regulate gene expression in the gut microbiota. Plant miRNAs could also affect the rhizosphere microbiota.

Expert-based assessment of chemical and physical exposures, and organizational factors, in past agricultural jobs.

Background: Limited data document the spectrum of exposures in the agricultural environment. We describe here the wide range of chemical and physical agents, and organizational factors, encountered in agricultural jobs held in the past in Canada and abroad.

Methods: We used data from a population-based case-control study of prostate cancer including 3,925 male participants residing in Montreal, Canada in 2005-2012.