Loss of OcaB Prevents Age-Induced Fat Accretion and Insulin Resistance by Altering B-Lymphocyte Transition and Promoting Energy Expenditure.

The current demographic shift toward an aging population has led to a robust increase in the prevalence of age-associated metabolic disorders. Recent studies have demonstrated that the etiology of obesity-related insulin resistance that develops with aging differs from that induced by high-calorie diets. Whereas the role of adaptive immunity in changes in energy metabolism driven by nutritional challenges has recently gained attention, its impact on aging remains mostly unknown.

Three-body correlations and conditional forces in suspensions of active hard disks.

Self-propelled Brownian particles show rich out-of-equilibrium physics, for instance, the motility-induced phase separation (MIPS). While decades of studying the structure of liquids have established a deep understanding of passive systems, not much is known about correlations in active suspensions. In this work we derive an approximate analytic theory for three-body correlations and forces in systems of active Brownian disks starting from the many-body Smoluchowski equation.

Inactivation of Plasmepsins 2 and 3 Sensitizes Plasmodium falciparum to the Antimalarial Drug Piperaquine.

Dihydroartemisinin-piperaquine (DHA-PPQ), the current frontline artemisinin combination therapy used to treat malaria in multiple Southeast Asian countries, is now increasingly failing in Cambodia, where artemisinin resistance is nearly fixed, which suggests that PPQ resistance has emerged and is spreading rapidly in the Greater Mekong Subregion. Recent reports have shown that amplification of the genes encoding plasmepsins 2 and 3 is a molecular marker of PPQ resistance; however, whether these enzymes play a role in the mechanism of resistance is currently unknown. We show here that inactivating the genes encoding plasmepsin 2 or 3 individually in reference strain 3D7 results in hypersusceptibility to PPQ.

From the day they are born: a qualitative study exploring violence against children with disabilities in West Africa.

Background: Despite the building evidence on violence against children globally, almost nothing is known about the violence children with disabilities in low and middle-income countries (LMICs) experience. The prevalence of violence against children with disabilities can be expected to be higher in LMICs where there are greater stigmas associated with having a child with a disability, less resources for families who have children with disabilities, and wider acceptance of the use of corporal punishment to discipline children. This study explores violence experienced by children with disabilities based on data collected from four countries in West Africa- Guinea, Niger, Sierra Leone, and Togo.

Evidence that the Protein Sortilin Potentially Acts as an Escorter for the Trafficking of the Rhoptry-Associated Membrane Antigen to the Rhoptries.

The rhoptry organelle is critical for the invasion of an erythrocyte by the malaria parasite . Despite their critical roles, the mechanisms behind their biogenesis are still poorly defined. Our earlier work had suggested that the interaction between the glycosylphosphatidylinositol (GPI)-anchored rhoptry-associated membrane antigen (RAMA) and the soluble rhoptry-associated protein 1 was involved in the transport of the latter from the Golgi apparatus to the rhoptry.

Determination of point of zero charge of natural organic materials.

This study evaluates different methods to determine points of zero charge (PZCs) on five organic materials, namely maple sawdust, wood ash, peat moss, compost, and brown algae, used for the passive treatment of contaminated neutral drainage effluents. The PZC provides important information about metal sorption mechanisms. Three methods were used: (1) the salt addition method, measuring the PZC; (2) the zeta potential method, measuring the isoelectric point (IEP); (3) the ion adsorption method, measuring the point of zero net charge (PZNC).

Epigenetic profiling of growth plate chondrocytes sheds insight into regulatory genetic variation influencing height.

GWAS have identified hundreds of height-associated loci. However, determining causal mechanisms is challenging, especially since height-relevant tissues (e.g.

Rainbow trout exposed to benzo[a]pyrene yields conserved microRNA binding sites in DNA methyltransferases across 500 million years of evolution.

The objective of this study was to examine the regulation of DNA methylation following acute (24 h) and prolonged (14 d) exposure to low (1 ng/L) and high (10 ng/L) benzo[a]pyrene. However, with the recent release of the rainbow trout genome, we were able to conduct a more detailed analysis regarding the regulation of the enzymes involved in DNA methylation; DNA methyltransferases (DNMTs). Bioinformatic approaches were used to identify candidate microRNA (miRNA) that potentially bind to the DNMT1 and DNMT3a 3'UTR.

Impact of a non-restrictive satiating diet on anthropometrics, satiety responsiveness and eating behaviour traits in obese men displaying a high or a low satiety phenotype.

The aim of this study was to evaluate the impact of a non-restrictive satiating diet in men displaying various degrees of satiety efficiency. In all, sixty-nine obese men aged 41·5 (sd 5·7) years were randomly assigned to a control (10-15, 55-60 and 30 % energy as protein, carbohydrate and lipid, respectively; n 34) or satiating (20-25, 45-50 and 30-35 % energy as protein, carbohydrate and lipid, respectively; n 35) diet for 16 weeks, and were classified as having a low (LSP) or high (HSP) satiety phenotype. Both diets were consumed ad libitum.

A map of the subcellular distribution of phosphoinositides in the erythrocytic cycle of the malaria parasite Plasmodium falciparum.

Despite representing a small percentage of the cellular lipids of eukaryotic cells, phosphoinositides (PIPs) are critical in various processes such as intracellular trafficking and signal transduction. Central to their various functions is the differential distribution of PIP species to specific membrane compartments through the actions of kinases, phosphatases and lipases. Despite their importance in the malaria parasite lifecycle, the subcellular distribution of most PIP species in this organism is still unknown.

Functional characterization of the Ucp1-associated oxidative phenotype of human epicardial adipose tissue.

Brown fat presence and metabolic activity has been associated with lower body mass index, higher insulin sensitivity and better cardiometabolic profile in humans. We, and others, have previously reported the presence of Ucp1, a marker of brown adipocytes, in human epicardial adipose tissue (eAT). Characterization of the metabolic activity and associated physiological relevance of Ucp1 within eAT, however, is still awaited.

Substantial Variability Across Individuals in the Vascular and Nutrigenomic Response to an Acute Intake of Curcumin: A Randomized Controlled Trial.

Scope: Curcumin exerts biological activities of interest in cardiovascular prevention. However, its vascular protective effect is still poorly investigated in humans. The present study aims to assess vascular effect of an acute intake of curcumin and its nutrigenomic impact in circulating immune cells.

Characterization of a putative Plasmodium falciparum SAC1 phosphoinositide-phosphatase homologue potentially required for survival during the asexual erythrocytic stages.

Despite marked reductions in morbidity and mortality in the last ten years, malaria still takes a tremendous toll on human populations throughout tropical and sub-tropical regions of the world. The absence of an effective vaccine and resistance to most antimalarial drugs available demonstrate the urgent need for new intervention strategies. Phosphoinositides are a class of lipids with critical roles in numerous processes and their specific subcellular distribution, generated through the action of kinases and phosphatases, define organelle identity in a wide range of eukaryotic cells.

Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study.

Background: Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar.

Methods: The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable.

Fatty Acid Metabolic Remodeling During Type 2 Diabetes Remission After Bariatric Surgery.

Hypertrophic remodeling of white adipose tissues is associated with overexposure of lean organs to circulating triglycerides (TGs) and nonesterified fatty acids (NEFAs), ultimately leading to insulin resistance. Bariatric surgery promotes type 2 diabetes (T2D) remission through a succession of weight loss-dependent and -independent mechanisms. However, the longitudinal contribution of adipocyte size reduction and fatty acid metabolic handling remain unknown.

Selective HIF-1 Regulation under Nonhypoxic Conditions by the p42/p44 MAP Kinase Inhibitor PD184161.

Hypoxia-inducible factor-1 (HIF-1) is a key gene regulator for cellular adaptation to low oxygen. In addition to hypoxia, several nonhypoxic stimuli, including hormones and growth factors, are essential for cell-specific HIF-1 regulation. Our studies have highlighted angiotensin II (AngII), a vasoactive hormone, as a potent HIF-1 activator in vascular smooth muscle cells (VSMC).

Biliopancreatic diversion with duodenal switch leads to better postprandial glucose level and beta cell function than sleeve gastrectomy in individuals with type 2 diabetes very early after surgery.

Objective: The aim of this study was to compare the short-term effect of sleeve gastrectomy (SG) and biliopancreatic diversion with duodenal switch (DS) in order to determine if exclusion of the upper gastrointestinal tract confers greater metabolic improvement, independent of weight loss.

Methods: Standard meals were administered before and on day 3 and 4 after SG to assess insulin sensitivity, β-cell function and gastrointestinal hormone responses in matched normoglycemic (NG) and type 2 diabetes (T2D) participants. A third group of matched T2D participants who underwent DS with the same meal test administered prior to and 3days after surgery was also recruited.

Effects of Bariatric Surgery on Energy Homeostasis.

Bariatric surgery represents the most efficient therapy for severe obesity. It reduces the size of fat stores or the amount of body fat gain. The bariatric surgery procedures currently used include Roux-en-Y gastric bypass and sleeve gastrectomy, which are the most commonly performed procedures.

Emerging Signaling Pathway in Arcuate Feeding-Related Neurons: Role of the Acbd7.

The understanding of the mechanisms whereby energy balance is regulated is essential to the unraveling of the pathophysiology of obesity. In the last three decades, focus was put on the metabolic role played by the hypothalamic neurons expressing proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART) and the neurons co-localizing agouti-related peptide (AgRP), neuropeptide Y (NPY), and gamma-aminobutyric acid (GABA). These neurons are part of the leptin-melanocortin pathway, whose role is key in energy balance regulation.

A data-driven structural model of hSSB1 (NABP2/OBFC2B) self-oligomerization.

The maintenance of genome stability depends on the ability of the cell to repair DNA efficiently. Single-stranded DNA binding proteins (SSBs) play an important role in DNA processing events such as replication, recombination and repair. While the role of human single-stranded DNA binding protein 1 (hSSB1/NABP2/OBFC2B) in the repair of double-stranded breaks has been well established, we have recently shown that it is also essential for the base excision repair (BER) pathway following oxidative DNA damage.

hSSB1 associates with and promotes stability of the BLM helicase.

Background: Maintenance of genome stability is critical in human cells. Mutations in or loss of genome stability pathways can lead to a number of pathologies including cancer. hSSB1 is a critical DNA repair protein functioning in the repair and signalling of stalled DNA replication forks, double strand DNA breaks and oxidised DNA lesions.

Nucleolar caspase-2: Protecting us from DNA damage.

Caspase-2 triggers apoptosis, but how it is activated by different stimuli is unclear. In this issue, Ando et al. (2017.

Expression of CDCA3 Is a Prognostic Biomarker and Potential Therapeutic Target in Non-Small Cell Lung Cancer.

Introduction: NSCLC is the leading cause for cancer-related deaths worldwide. New therapeutic targets are needed, as development of resistance to current treatment, such as platinum-based chemotherapy, is inevitable. The purpose of this study was to determine the functional relevance and therapeutic potential of cell division cycle associated 3 protein (CDCA3) in NSCLC.

Loss of hepatic DEPTOR alters the metabolic transition to fasting.

Objective: The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions into distinct protein complexes (mTORC1 and mTORC2) that regulates growth and metabolism. DEP-domain containing mTOR-interacting protein (DEPTOR) is part of these complexes and is known to reduce their activity. Whether DEPTOR loss affects metabolism and organismal growth has never been tested.