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Aug 1, 2016
Autonomic Testing in Women with Chronic Pelvic Pain.
[Medical College of Wisconsin; Case Western Reserve University] Researchers tested whether abnormal autonomic nervous system innervation of the bladder underlies IC (interstitial cystitis)/BPS (bladder pain syndrome) differently than other chronic pelvic pain. Some chronic pelvic pain types showed autonomic neuropathy and some show vagal withdrawal.
Jul 11, 2016
Human islets contain four distinct subtypes of β cells.
[Oregon Health and Science University; University of Pennsylvania School of Medicine] Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing β cells causes diabetes mellitus, a disease that harms millions. Until now, β cells were generally regarded as a single, homogenous cell population.
Jun 15, 2016
Antibiotics, birth mode, and diet shape microbiome maturation during early life.
[New York University Langone Medical Center] The intestinal “microbiota,” that is, the community of microbes inhabiting the human intestinal tract, undergoes many changes during the first 2 years of life. Bokulich et al. now show that this pattern of development is altered in children who are delivered by cesarean section, fed formula, or treated with antibiotics, compared to those babies who were born vaginally, breast-fed, or unexposed to antibiotics.
Jun 8, 2016
Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome.
[Yale University School of Medicine] Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota in rodents leads to activation of the parasympathetic nervous system, which, in turn, promotes increased glucose-stimulated insulin secretion, increased ghrelin secretion, hyperphagia, obesity and related sequelae.
Jun 7, 2016
Maternal diet quality in pregnancy and neonatal adiposity: the Healthy Start Study.
[Colorado School of Public Health; University of Colorado School of Medicine] Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass [%FM]) at birth by increasing the FM component of neonatal body composition.
Jun 7, 2016
Genetic Coding Variant in GPR65, alters Lysosomal ph and Links Lysosomal Dysfunction with Colitis Risk.
[The Broad Institute of MIT and Harvard; Monash University] Although numerous polymorphisms have been associated with inflammatory bowel disease (IBD), identifying the function of these genetic factors has proved challenging. Here we identified a role for nine genes in IBD susceptibility loci in antibacterial autophagy and characterized a role for one of these genes, GPR65, in maintaining lysosome function.
May 27, 2016
Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease.
[California Institute of Technology] Inflammatory bowel disease (IBD) is associated with risk variants in the human genome and dysbiosis of the gut microbiome, though unifying principles for these findings remain largely undescribed. The human commensal Bacteroides fragilis delivers immunomodulatory molecules to immune cells via secretion of outer membrane vesicles (OMVs).
May 10, 2016
Generation of stem cell-derived β-cells from patients with type 1 diabetes.
[Washington University School of Medicine; Harvard University; Case Western Reserve University School of Medicine] We recently reported the scalable in vitro production of functional stem cell-derived β-cells (SC-β cells). Here we extend this approach to generate the first SC-β cells from type 1 diabetic patients (T1D). β-cells are destroyed during T1D disease progression, making it difficult to extensively study them in the past.
May 2, 2016
Persistent metabolic adaptation 6 years after "The Biggest Loser" competition.
[National Institute of Diabetes and Digestive and Kidney Diseases] Researchers measured long-term changes in resting metabolic rate (RMR) and body composition in participants of “The Biggest Loser” competition. Body composition was measured by dual energy X-ray absorptiometry, and RMR was determined by indirect calorimetry at baseline, at the end of the 30-week competition and 6 years later.
Apr 27, 2016
ZP2 peptide beads select human sperm in vitro, decoy mouse sperm in vivo, and provide reversible contraception.
[National Institute of Diabetes and Digestive and Kidney Diseases; University of Murcia, Murcia, Spain] The zona pellucida, a matrix that surrounds ovulated eggs, is the site of sperm recognition and binding, which precede sperm penetration and fertilization. Avella et al. identified a peptide from the zona pellucida called ZP2, which the authors attached to agarose beads to facilitate infertility treatment or, conversely, contraception.
Apr 21, 2016
Asprosin, a Fasting-Induced Glucogenic Protein Hormone.
[Baylor College of Medicine] Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin.
Apr 1, 2016
First in human clinical trial of ultrasonic propulsion of kidney stones.
[University of Washington; Indiana University] Ultrasonic propulsion is a new technology using focused ultrasound energy applied transcutaneously to reposition kidney stones. We report what are to our knowledge the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones.
Mar 18, 2016
The nutrient sensor OGT in PVN neurons regulates feeding.
[Johns Hopkins University School of Medicine; National Institute on Drug Abuse] Overeating and obesity are rapidly becoming worldwide problems. Normally, mice do not overeat—they balance their caloric intake with their caloric needs. Lagerlöf et al. deleted an enzyme called O-GlcNAc transferase (OGT) from a subset of neurons in the mouse hypothalamus (see the Perspective by Schwartz). After the loss of OGT, the animals began to overeat and rapidly gained weight.
Mar 10, 2016
Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors.
[Johns Hopkins University School of Medicine] This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from deceased donors.
Mar 7, 2016
A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance.
[University of Pennsylvania; Harvard Medical School] Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear. Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species, a process that requires blood-borne lipids to initially traverse the blood vessel wall.
Feb 19, 2016
Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children.
[Washington University] As we come to appreciate how our microbial communities (microbiota) assemble following birth, there is an opportunity to determine how this facet of our developmental biology relates to the healthy or impaired growth of infants and children. Childhood undernutrition is a devastating global health problem whose long-term sequelae, including stunting, neurodevelopmental abnormalities, and immune dysfunction, remain largely refractory to current therapeutic interventions.
Feb 4, 2016
Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 diabetes: The DCCT/EDIC Study 30-Year Follow-up.
[Case-Western Reserve University; George Washington University; University of California San Diego] Early initiation of intensive diabetes therapy aimed at achieving near-normal glycemia reduces the early development of vascular complications in type 1 diabetes. We now assess whether intensive therapy compared with conventional therapy during the Diabetes Control and Complications Trial (DCCT) affected the incidence of cardiovascular disease over 30 years of follow-up.
Feb 1, 2016
Proton pump inhibitor use and the risk of chronic kidney disease.
[Johns Hopkins University; Yale University] Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide and have been linked to acute interstitial nephritis. Less is known about the association between PPI use and chronic kidney disease (CKD).
Jan 29, 2016
Airway acidification initiates host defense abnormalities in cystic fibrosis mice.
[University of Iowa] Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid.
Jan 25, 2016
Long-term glycemic control using polymer-encapsulated human stem cell–derived beta cells in immune-competent mice.
[Massachusetts Institute of Technology; Harvard University] The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in individuals with diabetes. Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically, but these approaches are limited by the adverse effects of immunosuppressive therapy over the lifetime of the recipient and the limited supply of donor tissue.
Jan 25, 2016
Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates.
[Massachusetts Institute of Technology] The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate.
Jan 14, 2016
Weight loss and health status 3 years after bariatric surgery in adolescents.
[University of Cincinnati; University of Pittsburgh; Baylor College of Medicine; University of Buffalo; University of Alabama] Severe obesity affects 4.4 million children and adolescents in the United States, and few effective treatments are available. Particular concern has centered on health problems among severely obese adolescents and possible treatment with bariatric surgery.
Jan 13, 2016
Diet-induced extinctions in the gut microbiota compound over generations.
[Stanford University; Harvard University] The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including immune function and metabolism. The reduced diversity of the gut microbiota in Western populations compared to that in populations living traditional lifestyles presents the question of which factors have driven microbiota change during modernization.
Jan 8, 2016
Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake.
[National Institute of Diabetes and Digestive and Kidney Diseases] Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs.
Jan 4, 2016
G(q/11)alpha and G(s)alpha mediate distinct physiological responses to central melanocortins.
[National Institute of Diabetes and Digestive and Kidney Diseases] Activation of brain melanocortin 4 receptors (MC4Rs) leads to reduced food intake, increased energy expenditure, increased insulin sensitivity, and reduced linear growth. MC4R effects on energy expenditure and glucose metabolism are primarily mediated by the G protein Gsα in brain regions outside of the paraventricular nucleus of the hypothalamus (PVN).
Dec 29, 2015
Musclin is an activity-stimulated myokine that enhances physical endurance.
[University of Iowa] Exercise remains the most effective way to promote physical and metabolic wellbeing, but molecular mechanisms underlying exercise tolerance and its plasticity are only partially understood. In this study we identify musclin—a peptide with high homology to natriuretic peptides (NP)—as an exercise-responsive myokine that acts to enhance exercise capacity in mice.
Nov 11, 2015
Tissue-engineered microvasculature to reperfuse isolated renal glomeruli.
[Yale University] Kidney transplantation is often the most effective therapy for end-stage renal disease, but there are not enough donor organs to meet the rising demand. Tissue engineering of kidneys is a potential solution to this organ shortage. Achieving microvascular perfusion has been a major barrier to engineering tissues beyond thin muscularized sheets such as the bladder wall.
Nov 3, 2015
Altered brain responses in subjects with irritable bowel syndrome during cued and uncued pain expectation.
[University of California, Los Angeles] A majority of the subjects with irritable bowel syndrome (IBS) show increased behavioral and brain responses to expected and delivered aversive visceral stimuli during controlled rectal balloon distension, and during palpation of the sigmoid colon. We aimed to determine if altered brain responses to cued and uncued pain expectation are also seen in the context of a noxious somatic pain stimulus applied to the same dermatome as the sigmoid colon.