APE1 is a master regulator of the ATR-/ATM-mediated DNA damage response.

To maintain genomic integrity, cells have evolved several conserved DNA damage response (DDR) pathways in response to DNA damage and stress conditions. Apurinic/apyrimidinic endonuclease 1 (APE1) exhibits AP endonuclease, 3'-5' exonuclease, 3'-phosphodiesterase, and 3'-exoribonuclease activities and plays critical roles in the DNA repair and redox regulation of transcription. However, it remains unclear whether and how APE1 is involved in DDR pathways.

Implementation of the Mind Youth Questionnaire (MY-Q) for routine health-related quality of life screening of adolescents with type 1 diabetes in a large tertiary care center.

Objectives: Prevalence of diabetes distress and mental health comorbidities among adolescents with type 1 diabetes (T1D) is high. Despite recommendations for routine psychosocial risk assessment, there is little guidance for their implementation. This study aims to describe the implementation and baseline outcomes of the Mind Youth Questionnaire (MY-Q), a validated psychosocial screening tool for health-related quality of life (QoL) including mood, among adolescents living with T1D.

Association of Fructosamine Levels With Glycemic Management in Children With Type 1 Diabetes as Determined by Continuous Glucose Monitoring: Results From the CGM TIME Trial.

Objective: Our aim in this study was to determine the correlation between serum fructosamine and average blood glucose, as measured by continuous glucose monitoring (CGM) in children with type 1 diabetes.

Methods: Ninety-seven blood samples were collected from 70 participants in the Timing of Initiation of continuous glucose Monitoring in Established pediatric diabetes (CGM TIME) Trial. Each eligible participant had 3 weeks of CGM data with at least 60% CGM adherence before blood collection.

cGAS Mediates the Inflammatory Responses of Human Microglial Cells to Genotoxic DNA Damage.

Genomic instability is a key driving force for the development and progression of many age-related neurodegenerative diseases and central nervous system (CNS) cancers. Recently, the cytosolic DNA sensor, cyclic GMP-AMP synthase (cGAS), has been shown to detect and respond to self-DNA accumulation resulting from DNA damaging insults in peripheral cell types. cGAS has been shown to be important in the responses of microglia to DNA viruses and amyloid beta, and we have reported that it underlies the responses of human microglia to exogenous DNA.

NET4 and RabG3 link actin to the tonoplast and facilitate cytoskeletal remodelling during stomatal immunity.

Members of the NETWORKED (NET) family are involved in actin-membrane interactions. Here we show that two members of the NET family, NET4A and NET4B, are essential for normal guard cell actin reorganization, which is a process critical for stomatal closure in plant immunity. NET4 proteins interact with F-actin and with members of the Rab7 GTPase RABG3 family through two distinct domains, allowing for simultaneous localization to actin filaments and the tonoplast.

Implementation and evaluation of a longitudinal diabetes educational programme for adolescents.

Introduction: International guidelines recommend educational programmes to expand diabetes knowledge and self-efficacy in youth. To address these recommendations within a paediatric diabetes clinic, we conducted a three-phase quality improvement project aimed at improving adolescents' confidence in diabetes self-management skills.

Methods: In phase 1, the Diabetes Learning Centre (DLC), an educational programme for adolescents with type 1 diabetes (T1D) ages 13-17 years, was developed and implemented.

An Intervention of Four Weeks of Time-Restricted Eating (16/8) in Male Long-Distance Runners Does Not Affect Cardiometabolic Risk Factors.

Timing of nutrient intake for athletes may affect exercise performance and cardiometabolic factors. Our objective was to examine the effect of time-restricted eating (TRE) on cardiometabolic health. Using a cross-over study design, 15 endurance-trained male runners were randomized to either a normal dietary pattern (ND) first (12 h eating/fasting times) followed by time-restricted eating (TRE) pattern (16 h fast; 8 h eating) or the reverse, with a 4-week washout period between interventions.

NPC Structure in Model Organisms: Transmission Electron Microscopy and Immunogold Labeling Using High-Pressure Freezing/Freeze Substitution of Yeast, Worms, and Plants.

The nuclear pore complex (NPC) is a large elaborate structure embedded within the nuclear envelope, and intimately linked to the cytoskeleton, nucleoskeleton, and chromatin. Many different cargoes pass through its central channel and along the membrane at its periphery. The NPC is dismantled and reassembly, fully or partially, every cell cycle.

Satiety Associated with Calorie Restriction and Time-Restricted Feeding: Peripheral Hormones.

Calorie restriction (CR) is a common approach to inducing negative energy balance. Recently, time-restricted feeding (TRF), which involves consuming food within specific time windows during a 24-h day, has become popular owing to its relative ease of practice and potential to aid in achieving and maintaining a negative energy balance. TRF can be implemented intentionally with CR, or TRF might induce CR simply because of the time restriction.

The Omega-3 Index Response to an 8 Week Randomized Intervention Containing Three Fatty Fish Meals Per Week Is Influenced by Adiposity in Overweight to Obese Women.

Background: The Dietary Guidelines for Americans (DGA) recommends consuming ~225 g/wk of a variety of seafood providing >1.75 g/wk of long-chain omega-3 fatty acids to reduce cardiovascular disease risk, however individual responses to treatment vary.

Objective: This study had three main objectives.

Satiety Associated with Calorie Restriction and Time-Restricted Feeding: Central Neuroendocrine Integration.

This review focuses on summarizing current knowledge on how time-restricted feeding (TRF) and continuous caloric restriction (CR) affect central neuroendocrine systems involved in regulating satiety. Several interconnected regions of the hypothalamus, brainstem, and cortical areas of the brain are involved in the regulation of satiety. Following CR and TRF, the increase in hunger and reduction in satiety signals of the melanocortin system [neuropeptide Y (NPY), proopiomelanocortin (POMC), and agouti-related peptide (AgRP)] appear similar between CR and TRF protocols, as do the dopaminergic responses in the mesocorticolimbic circuit.

Four Weeks of 16/8 Time Restrictive Feeding in Endurance Trained Male Runners Decreases Fat Mass, without Affecting Exercise Performance.

Background: Time restricted Feeding (TRF) is a dietary pattern utilized by endurance athletes, but there is insufficient data regarding its effects on performance and metabolism in this population. The purpose of this investigation was to examine the effects of a 16/8 TRF dietary pattern on exercise performance in trained male endurance runners.

Methods: A 4-week randomized crossover intervention was used to compare an 8-h TRF to a 12-h normal diet (ND) feeding window.

STING nuclear partners contribute to innate immune signaling responses.

STimulator of INterferon Genes (STING) is an adaptor for cytoplasmic DNA sensing by cGAMP/cGAS that helps trigger innate immune responses (IIRs). Although STING is mostly localized in the ER, we find a separate inner nuclear membrane pool of STING that increases mobility and redistributes to the outer nuclear membrane upon IIR stimulation by transfected dsDNA or dsRNA mimic poly(I:C). Immunoprecipitation of STING from isolated nuclear envelopes coupled with mass spectrometry revealed a distinct nuclear envelope-STING proteome consisting of known nuclear membrane proteins and enriched in DNA- and RNA-binding proteins.

Motivational Stage at Continuous Glucose Monitoring (CGM) Initiation in Pediatric Type 1 Diabetes Is Associated With Current Glycemic Control but Does Not Predict Future CGM Adherence or Glycemic Control.

Objectives: The Timing of Initiation of Continuous Glucose Monitoring in Established Pediatric Diabetes (CGM TIME) Trial is a multicenter, randomized controlled trial in children with type 1 diabetes, comparing simultaneous pump and CGM with CGM initiation 6 months later (Paradigm, Veo, Enlite Sensor, Medtronic Canada). This study addresses the ability of SOCRATES (Stages Of Change Readiness And Treatment Eagerness Scale) to classify children and parents into distinct motivational stages and identify the stages' association with glycated hemoglobin (A1C) at trial entry and outcomes 6 months after CGM initiation.

Methods: Ninety-eight of 99 eligible children 10 to 18 years of age and 137 of 141 eligible parents completed SOCRATES at trial entry and 6 months later.

BBLN-1 is essential for intermediate filament organization and apical membrane morphology.

Epithelial tubes are essential components of metazoan organ systems that control the flow of fluids and the exchange of materials between body compartments and the outside environment. The size and shape of the central lumen confer important characteristics to tubular organs and need to be carefully controlled. Here, we identify the small coiled-coil protein BBLN-1 as a regulator of lumen morphology in the C.

Fear of hypoglycemia in children with type 1 diabetes and their parents: Effect of pump therapy and continuous glucose monitoring with option of low glucose suspend in the CGM TIME trial.

To determine if pump therapy with continuous glucose monitoring offering low glucose suspend (LGS) decreases fear of hypoglycemia among children with type 1 diabetes and their parents. The CGM TIME trial is a multicenter randomized controlled trial that enrolled 144 children with type 1 diabetes for at least 1 year (mean duration 3.4 ± 3.

Timing of CGM initiation in pediatric diabetes: The CGM TIME Trial.

Objective: To determine whether timing of CGM initiation offering low glucose suspend (LGS) affects CGM adherence in children and youth starting insulin pump therapy.

Methods: A 5-site RCT of pump-naïve subjects (aged 5-18 years) with type 1 diabetes (T1D) for at least 1 year compared simultaneous pump and CGM initiation offering LGS vs standard pump therapy with CGM initiation delayed for 6 months. Primary outcome was CGM adherence (hours per 28 days) (MiniMed™ Paradigm™ Veo™ system; CareLink Pro™ software) over 6 months after CGM initiation.

Bioflavonoids cause DNA double-strand breaks and chromosomal translocations through topoisomerase II-dependent and -independent mechanisms.

Bioflavonoids have a similar chemical structure to etoposide, the well-characterized topoisomerase II (Top2) poison, and evidence shows that they also induce DNA double-strand breaks (DSBs) and promote genome rearrangements. The purpose of this study was to determine the kinetics of bioflavonoid-induced DSB appearance and repair, and their dependence on Top2. Cells were exposed to bioflavonoids individually or in combination in the presence or absence of the Top2 catalytic inhibitor dexrazoxane.

Intestinal intermediate filament polypeptides in C. elegans: Common and isotype-specific contributions to intestinal ultrastructure and function.

The abundance and diversity of intermediate filaments (IFs) in the C. elegans intestine indicate important contributions to intestinal function and organismal wellbeing. Fluorescent IF reporters localize below the actin-rich brush border and are highly enriched in the lumen-enveloping endotube, which is attached to the C.

APE1 senses DNA single-strand breaks for repair and signaling.

DNA single-strand breaks (SSBs) represent the most abundant type of DNA damage. Unrepaired SSBs impair DNA replication and transcription, leading to cancer and neurodegenerative disorders. Although PARP1 and XRCC1 are implicated in the SSB repair pathway, it remains unclear how SSB repair and SSB signaling pathways are coordinated and regulated.

Plant AtEH/Pan1 proteins drive autophagosome formation at ER-PM contact sites with actin and endocytic machinery.

The Arabidopsis EH proteins (AtEH1/Pan1 and AtEH2/Pan1) are components of the endocytic TPLATE complex (TPC) which is essential for endocytosis. Both proteins are homologues of the yeast ARP2/3 complex activator, Pan1p. Here, we show that these proteins are also involved in actin cytoskeleton regulated autophagy.

Host Vesicle Fusion Protein VAPB Contributes to the Nuclear Egress Stage of Herpes Simplex Virus Type-1 (HSV-1) Replication.

The primary envelopment/de-envelopment of Herpes viruses during nuclear exit is poorly understood. In Herpes simplex virus type-1 (HSV-1), proteins pUL31 and pUL34 are critical, while pUS3 and some others contribute; however, efficient membrane fusion may require additional host proteins. We postulated that vesicle fusion proteins present in the nuclear envelope might facilitate primary envelopment and/or de-envelopment fusion with the outer nuclear membrane.

The intestinal intermediate filament network responds to and protects against microbial insults and toxins.

The enrichment of intermediate filaments in the apical cytoplasm of intestinal cells is evolutionarily conserved, forming a sheath that is anchored to apical junctions and positioned below the microvillar brush border, which suggests a protective intracellular barrier function. To test this, we used , the intestinal cells of which are endowed with a particularly dense intermediate filament-rich layer that is referred to as the endotube. We found alterations in endotube structure and intermediate filament expression upon infection with nematicidal or treatment with its major pore-forming toxin crystal protein Cry5B.

Bioflavonoids promote stable translocations between MLL-AF9 breakpoint cluster regions independent of normal chromosomal context: Model system to screen environmental risks.

Infant acute leukemias are aggressive and characterized by rapid onset after birth. The majority harbor translocations involving the MLL gene with AF9 as one of its most common fusion partners. MLL and AF9 loci contain breakpoint cluster regions (bcrs) with sequences hypothesized to be targets of topoisomerase II inhibitors that promote translocation formation.