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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.
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 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.
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.
Nov 1, 2015
Matrix-assisted transplantation of functional beige adipose tissue.
[University of California, Berkeley; École Polytechnique Fédérale de Lausanne, Switzerland] Novel, clinically relevant, approaches to shift energy balance are urgently needed to combat metabolic disorders such as obesity and diabetes. One promising approach has been the expansion of brown adipose tissues that express uncoupling protein (UCP) 1 and thus can uncouple mitochondrial respiration from ATP synthesis.
Sep 16, 2015
BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis.
[Harvard Medial School] Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human BCL11A, subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for erythroid BCL11A expression.
Aug 31, 2015
Functional footprinting of regulatory DNA
Regulatory regions harbor multiple transcription factor (TF) recognition sites; however, the contribution of individual sites to regulatory function remains challenging to define. We describe an approach that exploits the error-prone nature of genome editing-induced double-strand break repair to map functional elements within regulatory DNA at nucleotide resolution.
Jul 2, 2015
Genetic Variation Determines PPARγ Function and Anti-diabetic Drug Response In Vivo
SNPs affecting disease risk often reside in non-coding genomic regions. Here, we show that SNPs are highly enriched at mouse strain-selective adipose tissue binding sites for PPARγ, a nuclear receptor for anti-diabetic drugs. Many such SNPs alter binding motifs for PPARγ or cooperating factors and functionally regulate nearby genes whose expression is strain selective and imbalanced in heterozygous F1 mice.
Jul 1, 2015
Hypoactivity following perturbed estrogen signaling in the medial amygdala
Activation of estrogen receptor α (ERα) in the brain prevents obesity as the result of increased energy expenditure and decreased food intake. While ERα is present on several neural populations, it is not clear how different regions of the brain mediate the weight-regulating effects of ERα activation.
Jun 22, 2015
Estrogen receptor–α in medial amygdala neurons regulates body weight
Estrogens play critical roles in the regulation of energy homeostasis. Depletion of endogenous estrogens in female rodents, via ovariectomy (OVX), causes increased body weight and hyperadiposity (1,2). 17β-estradiol replacement can prevent obesity in OVX female animals (1).
May 6, 2015
Identification of a plant isoflavonoid that causes biliary atresia
Biliary atresia (BA) is a rapidly progressive and destructive fibrotic disorder of unknown etiology affecting the extrahepatic biliary tree of neonates. Epidemiological studies suggest that an environmental factor, such as a virus or toxin, is the cause of the disease, although none have been definitively established.
Mar 5, 2015
Hypothalamic POMC neurons promote cannabinoid-induced feeding
Hypothalamic pro-opiomelanocortin (POMC) neurons promote satiety. Cannabinoid receptor 1 (CB1R) is critical for the central regulation of food intake. Here we test whether CB1R-controlled feeding in sated mice is paralleled by decreased activity of POMC neurons.
Feb 26, 2015
Sensory detection of food rapidly modulates arcuate feeding circuits
Hunger is controlled by specialized neural circuits that translate homeostatic needs into motivated behaviors. These circuits are under chronic control by circulating signals of nutritional state, but their rapid dynamics on the timescale of behavior remain unknown.