PNKP safeguards stalled replication forks from nuclease-dependent degradation during replication stress.

Uncontrolled degradation and collapse of stalled replication forks (RFs) are primary sources of genomic instability, yet the molecular mechanisms for protecting forks from degradation/collapse remain to be fully elaborated. Here, we show that polynucleotide kinase-phosphatase (PNKP) localizes at stalled forks and protects stalled forks from excessive degradation. The loss of PNKP results in nucleolytic degradation of nascent DNA at stalled RFs.

The Role of Probiotics in Modulating Myocardial Infarction and Depression-like Symptoms: A Study on Sex-Specific Responses.

Background/objectives: This study explores the effects of two probiotics, R0052 and R0175, on myocardial infarction (MI) and associated depression-like behaviours, with a focus on sex differences.

Methods: MI was induced in adult male and female rats by occluding the left anterior coronary artery for 30 min, followed by 24 h of reperfusion. Probiotics were administered via drinking water for at least two weeks before ischemia.

Docetaxel-Induced Cell Death Is Regulated by a Fatty Acid-Binding Protein 12-Slug-Survivin Pathway in Prostate Cancer Cells.

Chemotherapy is an important treatment option for advanced prostate cancer, especially for metastatic prostate cancer (PCa). Resistance to first-line chemotherapeutic drugs such as docetaxel often accompanies prostate cancer progression. Attempts to overcome resistance to docetaxel by combining docetaxel with other biological agents have been mostly unsuccessful.

Overcoming retinoic acid resistance in HER2-enriched breast cancers: role of MYC.

HER2-enriched (HER2) breast cancers express high levels of the growth-promoting HER2 protein. Although these cancers are treated with the HER2-targeted drug, trastuzumab, resistance to treatment is common. Retinoic acid (RA) is an anti-cancer agent that has been successfully used for the treatment of leukemia and holds promise for the treatment of solid cancers, including breast cancer.

The practice of Daylight Saving Time in Canada: Its suitability with respect to sleep and circadian rhythms.

Daylight Saving Time (DST) is the practice of setting the clocks one hour forward from Standard Time (ST) in the spring and back again to ST in the fall. This commentary discusses the impact of bi-annual time changes on sleep and circadian rhythms and suggests avenues to minimize negative outcomes on the well-being of Canadian citizens. Ideally, ST should be close to solar time, meaning that daylight is equally distributed before and after noon time, i.

The Signature Biobank: A longitudinal biopsychosocial repository of psychiatric emergency patients.

The Signature Biobank is a longitudinal repository of biospecimen, psychological, sociodemographic, and diagnostic data that was created in 2012. The Signature Consortium represents a group of approximately one hundred Quebec-based transdisciplinary clinicians and research scientists with various expertise in the field of psychiatry. The objective of the Signature Biobank is to investigate the multi-faceted underpinnings of psychiatric disorders among patients in crisis.

Role of DDX1 in the oxidative response of ataxia telangiectasia patient-derived fibroblasts.

Ataxia Telangiectasia (A-T) is an inherited autosomal recessive disorder characterized by cerebellar neurodegeneration, radiosensitivity, immunodeficiency and a high incidence of lymphomas. A-T is caused by mutations in the ATM gene. While loss of ATM function in DNA repair explains some aspects of A-T pathophysiology such as radiosensitivity and cancer predisposition, other A-T features such as neurodegeneration imply additional roles for ATM outside the nucleus.

[Assessments of sleepiness in adolescents: A key tool for better intervene in mental health].

Objectives Daytime sleepiness in adolescents has negative impacts on physical, cognitive, and emotional health, with direct or indirect consequences on their mental health. This review aims to describe specialized tools assessing daytime sleepiness in adolescents so that mental health professionals can screen for a variety of sleep disorders, from the rarest ones, such as narcolepsy, to the most common ones, such as sleep-wake cycle delay in adolescents. Method Articles were selected in Medline (https://pubmed.

An eHealth Program for Insomnia in Children With Neurodevelopmental Disorders (Better Nights, Better Days): Protocol for an Economic Evaluation of a Randomized Controlled Trial.

Background: Children with neurodevelopmental disorders have a high risk of sleep disturbances, with insomnia being the most common sleep disorder (ie, chronic and frequent difficulties with going and staying asleep). Insomnia adversely affects the well-being of these children and their caregivers. Pediatric sleep experts recommend behavioral interventions as the first-line treatment option for children.

Stationary-to-migratory transition in glioblastoma stem-like cells driven by a fatty acid-binding protein 7-RXRα neurogenic pathway.

Background: Glioblastoma (GBM) stem-like cells (GSCs) are crucial drivers of treatment resistance and tumor recurrence. While the concept of "migrating" cancer stem cells was proposed a decade ago, the roles and underlying mechanisms of the heterogeneous populations of GSCs remain poorly defined.

Methods: Cell migration using GBM cell lines and patient-derived GSCs was examined using Transwell inserts and the scratch assay.

Radiation-Induced Cellular Senescence Reduces Susceptibility of Glioblastoma Cells to Oncolytic Vaccinia Virus.

Glioblastoma (GBM) is a malignant brain cancer refractory to the current standard of care, prompting an extensive search for novel strategies to improve outcomes. One approach under investigation is oncolytic virus (OV) therapy in combination with radiotherapy. In addition to the direct cytocidal effects of radiotherapy, radiation induces cellular senescence in GBM cells.

Radiation combined with oncolytic vaccinia virus provides pronounced antitumor efficacy and induces immune protection in an aggressive glioblastoma model.

Glioblastoma (GB) is a malignant and immune-suppressed brain cancer that remains incurable despite the current standard of care. Radiotherapy is a mainstay of GB treatment, however invasive cancer cells outside the irradiated field and radioresistance preclude complete eradication of GB cells. Oncolytic virus therapy harnesses tumor-selective viruses to spread through and destroy tumors while stimulating antitumor immune responses, and thus has potential for use following radiotherapy.

RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma.

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. The standard treatment achieves a median overall survival for GBM patients of only 15 months. Hence, novel therapies based on an increased understanding of the mechanistic underpinnings of GBM are desperately needed.

Habitual sleep and intraindividual variability of sleep in gifted children: an actigraphy study.

Study Objectives: Giftedness is a multidimensional condition. It is increasingly put forward that gifted children (GC) could be a population at high risk for sleep problems. The current study investigated GC and typically developing children for their habitual sleep, night-to-night sleep variability, and parental reports of child sleep.

Association between sleep and problematic behaviours in gifted children: a polysomnographic study.

Neurological uniqueness, maladaptive behaviours, as well as atypical sleep patterns are reported to be defining characteristics of giftedness, but this has received little empirical support. We studied the polysomnography recorded sleep of gifted and typically-developing children together with features of maladaptive behaviours. The association of sleep macrostructure and sleep instability with maladaptive behaviours was also investigated in gifted children.

Implementation of a mailed faecal immunochemical test programme for colorectal cancer screening among Veterans.

Background: Screening for colorectal cancer (CRC) with faecal immunochemical test (FIT) is effective at reducing CRC mortality. Unfortunately, the COVID-19 pandemic has been associated with deferred care, especially screening for CRC.

Aim: We sought to develop a mailed FIT programme (MFP) to increase CRC screening and make recommendations for adoption across the Veterans Health Administration (VHA) and for other large healthcare systems.

Dysbiotic microbiota contributes to the extent of acute myocardial infarction in rats.

Increasing evidence suggests that the intestinal microbiota composition could play a role in specific pathologies such as hypertension, obesity and diabetes. This study aims to demonstrate that the intestinal microbiota modulated by a diet creating dysbiosis increased the size of the myocardial infarction and that probiotics could attenuate this effect. To do this, microbiota transplants from rats fed a dysbiotic or non-dysbiotic diet in the presence or absence of probiotics were performed for 10 days on rats whose microbiota had been previously suppressed by antibiotic therapy.

[Sleepiness among adolescents: etiology and multiple consequences].

Over the past century a dramatic decline in sleep duration among adolescents, such as more than one hour of sleep loss per night, has been reported. A debt in sleep duration could lead to sleep deprivation, a major risk factor associated with daytime sleepiness. Sleepiness refers to the inability to maintain an adequate level of alertness during the day which may result in more or less being able to control falling asleep at inappropriate times.

Lipid phosphate phosphatase-2 promotes tumor growth through increased c-Myc expression.

LPP2 is one of three enzymes in the lipid phosphate phosphatase family (LPP1-3) that dephosphorylate extracellular and intracellular bioactive lipid phosphates and pyrophosphates. LPP2 increases cell growth and LPP2 expression is elevated in a variety of malignancies, implying that LPP2 is a pro-tumorigenic factor. LPP2 expression in human breast tumors and normal breast tissue was measured by qPCR.

DDX1 vesicles control calcium-dependent mitochondrial activity in mouse embryos.

The DEAD box protein DDX1, previously associated with 3'-end RNA processing and DNA repair, forms large aggregates in the cytoplasm of early mouse embryos. Ddx1 knockout causes stalling of embryos at the 2-4 cell stages. Here, we identify a DDX1-containing membrane-bound calcium-containing organelle with a nucleic acid core.

DEAD box 1 (DDX1) protein binds to and protects cytoplasmic stress response mRNAs in cells exposed to oxidative stress.

The integrated stress response is a network of highly orchestrated pathways activated when cells are exposed to environmental stressors. While global repression of translation is a well-recognized hallmark of the integrated stress response, less is known about the regulation of mRNA stability during stress. DEAD box proteins are a family of RNA unwinding/remodeling enzymes involved in every aspect of RNA metabolism.

Sleep Instability Correlates with Attentional Impairment in Boys with Attention Deficit Hyperactivity Disorder.

Theoretical models of sleep and attention deficit hyperactivity disorder (ADHD) suggest that symptoms of ADHD are associated with daytime sleepiness, but it has received little support. The present study aimed at testing an alternative model involving the association of attentional instability with sleep instability, i.e.