165 research outputs found
Species specific exome probes reveal new insights in positively selected genes in nonhuman primates
Nonhuman primates (NHP) are important biomedical animal models for the study of human disease. Of these, the most widely used models in biomedical research currently are from the genus Macaca. However, evolutionary genetic divergence between human and NHP species makes human-based probes inefficient for the capture of genomic regions of NHP for sequencing and study. Here we introduce a new method to resequence the exome of NHP species by a designed capture approach specifically targeted to the NHP, and demonstrate its superior performance on four NHP species or subspecies. Detailed investigation on biomedically relevant genes demonstrated superior capture by the new approach. We identified 28 genes that appeared to be pseudogenized and inactivated in macaque. Finally, we identified 187 genes showing strong evidence for positive selection across all branches of the primate phylogeny including many novel findings
The molecular basis of the genesis of basal tone in internal anal sphincter
Smooth muscle sphincters exhibit basal tone and control passage of contents through organs such as the gastrointestinal tract; loss of this tone leads to disorders such as faecal incontinence. However, the molecular mechanisms underlying this tone remain unknown. Here, we show that deletion of myosin light-chain kinases (MLCK) in the smooth muscle cells from internal anal sphincter (IAS-SMCs) abolishes basal tone, impairing defecation. Pharmacological regulation of ryanodine receptors (RyRs), L-type voltage-dependent Ca(2+) channels (VDCCs) or TMEM16A Ca(2+)-activated Cl(-) channels significantly changes global cytosolic Ca(2+) concentration ([Ca(2+)]i) and the tone. TMEM16A deletion in IAS-SMCs abolishes the effects of modulators for TMEM16A or VDCCs on a RyR-mediated rise in global [Ca(2+)]i and impairs the tone and defecation. Hence, MLCK activation in IAS-SMCs caused by a global rise in [Ca(2+)]i via a RyR-TMEM16A-VDCC signalling module sets the basal tone. Targeting this module may lead to new treatments for diseases like faecal incontinence
Increased susceptibility to metabolic syndrome in adult offspring of Angiotensin type 1 receptor autoantibody-positive rats.
Abstract Aims: Abnormal fetal and early postnatal growth is closely associated with adult-onset metabolic syndrome (MetS). However, the underlying etiological factors remain complex. The presence of the autoantibody against the angiotensin II type 1 receptor (AT1-Ab), a known risk factor for pre-eclampsia, may create a suboptimal intrauterine fetal environment. The current study investigated whether middle-aged offspring of AT1-Ab-positive mothers were prone to metabolic disorder development. Results: The AT1-Abs was detected in placental trophoblastic cells, capillary endothelium, and milk of pregnant rats actively immunized with the second extracellular loop of the AT1 receptor. AT1-Abs in newborn rats induced vasoconstriction, increased intracellular-free Ca(2+) in vitro, and was undetectable 7 weeks later. Immunized group offspring exhibited increased weight variability and insulin resistance at 40 weeks of age under a normal diet, evidenced by elevated fasting serum insulin and homeostasis model assessment score compared with the vehicle control. To further observe metabolic alterations, the offspring were given a high-sugar diet (containing 20% sucrose) 40-48 weeks postnatally. The fasting plasma glucose in immunized group offspring was markedly increased. Concomitantly, these offspring manifested increased visceral adipose tissue, increased fatty liver, increased triglycerides, decreased high-density lipoprotein cholesterol, and decreased adiponectin levels, indicative of MetS. Innovation: AT1-Abs could be transferred from mother to offspring via the placenta and milk. Moreover, offspring of an AT1-Ab-positive mother were more vulnerable to MetS development in middle age. Conclusion: AT1-Ab-positivity of mothers during pregnancy is a previously unrecognized silent risk factor for MetS development in their offspring. Antioxid. Redox Signal. 17, 733-743
Frequency and spectrum of mitochondrial 12S rRNA variants in 440 Han Chinese hearing impaired pediatric subjects from two otology clinics
Corrosion and in vitro cytocompatibility investigation on the designed Mg-Zn-Ag metallic glasses for biomedical application
Corrigendum: Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants
Implementation and performances of the IPbus protocol for the JUNO Large-PMT readout electronics
The Jiangmen Underground Neutrino Observatory (JUNO) is a large neutrino
detector currently under construction in China. Thanks to the tight
requirements on its optical and radio-purity properties, it will be able to
perform leading measurements detecting terrestrial and astrophysical neutrinos
in a wide energy range from tens of keV to hundreds of MeV. A key requirement
for the success of the experiment is an unprecedented 3% energy resolution,
guaranteed by its large active mass (20 kton) and the use of more than 20,000
20-inch photo-multiplier tubes (PMTs) acquired by high-speed, high-resolution
sampling electronics located very close to the PMTs. As the Front-End and
Read-Out electronics is expected to continuously run underwater for 30 years, a
reliable readout acquisition system capable of handling the timestamped data
stream coming from the Large-PMTs and permitting to simultaneously monitor and
operate remotely the inaccessible electronics had to be developed. In this
contribution, the firmware and hardware implementation of the IPbus based
readout protocol will be presented, together with the performances measured on
final modules during the mass production of the electronics
Mass testing of the JUNO experiment 20-inch PMTs readout electronics
The Jiangmen Underground Neutrino Observatory (JUNO) is a multi-purpose,
large size, liquid scintillator experiment under construction in China. JUNO
will perform leading measurements detecting neutrinos from different sources
(reactor, terrestrial and astrophysical neutrinos) covering a wide energy range
(from 200 keV to several GeV). This paper focuses on the design and development
of a test protocol for the 20-inch PMT underwater readout electronics,
performed in parallel to the mass production line. In a time period of about
ten months, a total number of 6950 electronic boards were tested with an
acceptance yield of 99.1%
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