Anesthesia can impact memory: Coverage from Fox News, Yahoo News, and Live Science on “Sustained increase in α5GABAA receptor function impairs memory after anesthesia,” by Agnieszka A. Zurek, Jieying Yu, and colleagues.
Hair disorders and tooth decay linked by keratin mutations: Coverage from NIH/NIAMS and Tech Times on "Hair keratin mutations in tooth enamel increase dental decay risk," by Olivier Duverger, Takahiro Ohara, and colleagues.
Ketogenesis prevents fatty liver disease in mice: Coverage from Diabetes.co.uk and SF Gate on "Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia," by David G. Cotter, Baris Ercal, and colleagues.
Preventing Type 2 diabetes mellitus using bile acids: Coverage from Diabetes.co.uk on "TGR5 reduces macrophage migration through mTOR-induced C/EBPβ differential translation," by Alessia Perino, Thijs Willem Hendrik Pols, and colleagues.
Rare genetic mutation eliminates the ability to sweat: Coverage from Newser.com on "Abolished InsP3R2 function inhibits sweat secretion in both humans and mice," by Joakim Klar, Chihiro Hisatsune, and colleagues.
Elevation of certain protein levels may be the reason MS strikes more women than men: Coverage from Discover Magazine (subscription) on "Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility," by Lillian Cruz-Orengo, Brian P. Daniels, and colleagues.
There are 3 major sweat-producing glands present in skin; eccrine, apocrine, and apoeccrine glands. Due to the high rate of secretion, eccrine sweating is a vital regulator of body temperature in response to thermal stress in humans; therefore, an inability to sweat (anhidrosis) results in heat intolerance that may cause impaired consciousness and death. Here, we have reported 5 members of a consanguineous family with generalized, isolated anhidrosis, but morphologically normal eccrine sweat glands. Whole-genome analysis identified the presence of a homozygous missense mutation in
Joakim Klar, Chihiro Hisatsune, Shahid M. Baig, Muhammad Tariq, Anna C.V. Johansson, Mahmood Rasool, Naveed Altaf Malik, Adam Ameur, Kotomi Sugiura, Lars Feuk, Katsuhiko Mikoshiba, Niklas Dahl
The bile acid–responsive G protein–coupled receptor TGR5 is involved in several metabolic processes, and recent studies suggest that TGR5 activation may promote pathways that are protective against diet-induced diabetes. Here, we investigated the role of macrophage-specific TGR5 signaling in protecting adipose tissue from inflammation and associated insulin resistance. Examination of adipose tissue from obese mice lacking macrophage
Alessia Perino, Thijs Willem Hendrik Pols, Mitsunori Nomura, Sokrates Stein, Roberto Pellicciari, Kristina Schoonjans
Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose of much of the fat that enters the liver, and dysfunction in this pathway could promote the development of NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine the role of ketogenesis in preventing diet-induced steatohepatitis. Antisense oligonucleotide–induced loss of HMGCS2 in chow-fed adult mice caused mild hyperglycemia, increased hepatic gluconeogenesis from pyruvate, and augmented production of hundreds of hepatic metabolites, a suite of which indicated activation of the de novo lipogenesis pathway. High-fat diet feeding of mice with insufficient ketogenesis resulted in extensive hepatocyte injury and inflammation, decreased glycemia, deranged hepatic TCA cycle intermediate concentrations, and impaired hepatic gluconeogenesis due to sequestration of free coenzyme A (CoASH). Supplementation of the CoASH precursors pantothenic acid and cysteine normalized TCA intermediates and gluconeogenesis in the livers of ketogenesis-insufficient animals. Together, these findings indicate that ketogenesis is a critical regulator of hepatic acyl-CoA metabolism, glucose metabolism, and TCA cycle function in the absorptive state and suggest that ketogenesis may modulate fatty liver disease.
David G. Cotter, Baris Ercal, Xiaojing Huang, Jamison M. Leid, D. André d’Avignon, Mark J. Graham, Dennis J. Dietzen, Elizabeth M. Brunt, Gary J. Patti, Peter A. Crawford
Tooth enamel is the hardest substance in the human body and has a unique combination of hardness and fracture toughness that protects teeth from dental caries, the most common chronic disease worldwide. In addition to a high mineral content, tooth enamel comprises organic material that is important for mechanical performance and influences the initiation and progression of caries; however, the protein composition of tooth enamel has not been fully characterized. Here, we determined that epithelial hair keratins, which are crucial for maintaining the integrity of the sheaths that support the hair shaft, are expressed in the enamel organ and are essential organic components of mature enamel. Using genetic and intraoral examination data from 386 children and 706 adults, we found that individuals harboring known hair disorder–associated polymorphisms in the gene encoding keratin 75 (KRT75), KRT75A161T and KRT75E337K, are prone to increased dental caries. Analysis of teeth from individuals carrying the KRT75A161T variant revealed an altered enamel structure and a marked reduction of enamel hardness, suggesting that a functional keratin network is required for the mechanical stability of tooth enamel. Taken together, our results identify a genetic locus that influences enamel structure and establish a connection between hair disorders and susceptibility to dental caries.
Olivier Duverger, Takahiro Ohara, John R. Shaffer, Danielle Donahue, Patricia Zerfas, Andrew Dullnig, Christopher Crecelius, Elia Beniash, Mary L. Marazita, Maria I. Morasso
Many patients who undergo general anesthesia and surgery experience cognitive dysfunction, particularly memory deficits that can persist for days to months. The mechanisms underlying this postoperative cognitive dysfunction in the adult brain remain poorly understood. Depression of brain function during anesthesia is attributed primarily to increased activity of γ-aminobutyric acid type A receptors (GABAARs), and it is assumed that once the anesthetic drug is eliminated, the activity of GABAARs rapidly returns to baseline and these receptors no longer impair memory. Here, using a murine model, we found that a single in vivo treatment with the injectable anesthetic etomidate increased a tonic inhibitory current generated by α5 subunit–containing GABAARs (α5GABAARs) and cell-surface expression of α5GABAARs for at least 1 week. The sustained increase in α5GABAAR activity impaired memory performance and synaptic plasticity in the hippocampus. Inhibition of α5GABAARs completely reversed the memory deficits after anesthesia. Similarly, the inhaled anesthetic isoflurane triggered a persistent increase in tonic current and cell-surface expression of α5GABAARs. Thus, α5GABAAR function does not return to baseline after the anesthetic is eliminated, suggesting a mechanism to account for persistent memory deficits after general anesthesia.
Agnieszka A. Zurek, Jieying Yu, Dian-Shi Wang, Sean C. Haffey, Erica M. Bridgwater, Antonello Penna, Irene Lecker, Gang Lei, Tom Chang, Eric W.R. Salter, Beverley A. Orser