Relationship between expression of ss 3-adrenoceptor mRNA in bladder mucosa and urodynamic findings in men with lower urinary tract symptoms

Aims To investigate the relationship between urinary bladder mucosal expression of beta 3-adrenoceptor (AR) mRNA and urodynamic findings in patients with lower urinary tract symptoms and benign prostatic obstruction (BPO). Methods During surgical prostate resection of 32 BPO patients, mucosal biopsies were collected and analyzed by reverse transcriptase polymerase chain reaction to determine the expression level of beta 3-AR mRNA. First desire to void (FDV) and strong desire to void (SDV), detrusor overactivity (DO), and bladder outlet obstruction (BOO) were measured pre-operatively. Patients with FDVs??201?ml and SDVs?>?301?ml were assigned to the large capacity group (n?=?13). The same patients with positive DO were also assigned to the DO+ group (n?=?11), and those with negative DO were assigned to the DO- group (n?=?21). Finally, patients whose position on the Schafer nomogram was greater than degree V were assigned to the severe BOO group (n?=?17), while those with less than degree IV were assigned to the mild BOO group (n?=?15). Results The expression level of beta 3-AR mRNA was similar in both bladder capacity groups and both DO groups. However, the expression level in the severe BOO group was significantly less than in the mild BOO group (P?=?0.043). Conclusions The expression of bladder mucosal beta 3-AR mRNA was significantly decreased in patients with severe BOO, suggesting that beta 3-ARs might be affected by the degree of BOO. Neurourol. Urodynam. 32: 8891, 2013. (c) 2012 Wiley Periodicals, Inc.ArticleNEUROUROLOGY AND URODYNAMICS. 32(1):88-91 (2013)journal articl

Mice deficient in the Shmt2 gene have mitochondrial respiration defects and are embryonic lethal

Accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for human aging and age-associated mitochondrial respiration defects. However, our previous findings suggested an alternative hypothesis of human aging—that epigenetic changes but not mutations regulate age-associated mitochondrial respiration defects, and that epigenetic downregulation of nuclear-coded genes responsible for mitochondrial translation [e.g., glycine C-acetyltransferase (GCAT), serine hydroxymethyltransferase 2 (SHMT2)] is related to age-associated respiration defects. To examine our hypothesis, here we generated mice deficient in Gcat or Shmt2 and investigated whether they have respiration defects and premature aging phenotypes. Gcat-deficient mice showed no macroscopic abnormalities including premature aging phenotypes for up to 9 months after birth. In contrast, Shmt2-deficient mice showed embryonic lethality after 13.5 days post coitum (dpc), and fibroblasts obtained from 12.5-dpc Shmt2-deficient embryos had respiration defects and retardation of cell growth. Because Shmt2 substantially controls production of N-formylmethionine-tRNA (fMet-tRNA) in mitochondria, its suppression would reduce mitochondrial translation, resulting in expression of the respiration defects in fibroblasts from Shmt2-deficient embryos. These findings support our hypothesis that age-associated respiration defects in fibroblasts of elderly humans are caused not by mtDNA mutations but by epigenetic regulation of nuclear genes including SHMT2

Palmitoylation of the canine histamine H2 receptor occurs at Cys305 and is important for cell surface targeting

AbstractTo determine the presence and functional role of the histamine H2 receptor (H2R) palmitoylation, a receptor with a Cys305 to Ala (A305 receptor) mutation was generated. Wild-type (WT) and A305 receptors were tagged at their N-termini with a hemagglutinin (HA) epitope. WT, but not A305, receptors incorporated [3H]palmitate by metabolic labeling, indicating that the H2R is palmitoylated at Cys305. Immunocytochemistry of WT and A305 receptors expressed in COS7 cells revealed WT receptors to be distributed at the plasma membrane, while the majority of A305 receptors were localized intracellularly with only a small portion being at the plasma membrane. However, the affinity of the A305 receptor for tiotidine was comparable to that of the WT receptor. In addition, when the amounts of cell surface receptors as determined by anti-HA antibody binding were equivalent, A305 receptors mediated production of more cAMP than WT receptors. Preincubation of COS7 cells expressing each receptor with 10−5 M histamine for 30 min reduced subsequent cAMP production in response to histamine via the receptors to similar extents, indicating that palmitoylation is not necessary for desensitization. In addition, cell surface A305 receptors were capable of being internalized from the cell surface at a rate and extent similar to those of WT receptors. Finally, CHO cell lines stably expressing either WT or A305 receptors were incubated with 10−5 M histamine for 1, 6, 12 and 24 h. Total amounts of WT and A305 receptors, as determined by tiotidine binding, were reduced by incubation, indicating downregulation. Downregulation of the A305 receptor was more extensive than that of the WT receptor. Thus, palmitoylation of the H2R might be important for targeting to the cell surface and stability

Computer-controlled closed-loop norepinephrine infusion system for automated control of mean arterial pressure in dogs under isoflurane-induced hypotension: a feasibility study

Introduction: Intra-operative hypotension is a common complication of surgery under general anesthesia in dogs and humans. Computer-controlled closed-loop infusion systems of norepinephrine (NE) have been developed and clinically applied for automated optimization of arterial pressure (AP) and prevention of intra-operative hypotension in humans. This study aimed to develop a simple computer-controlled closed-loop infusion system of NE for the automated control of the mean arterial pressure (MAP) in dogs with isoflurane-induced hypotension and to validate the control of MAP by the developed system. Methods: NE was administered via the cephalic vein, whereas MAP was measured invasively by placing a catheter in the dorsal pedal artery. The proportional-integral-derivative (PID) controller in the negative feedback loop of the developed system titrated the infusion rate of NE to maintain the MAP at the target value of 60 mmHg. The titration was updated every 2 s. The performance of the developed system was evaluated in six laboratory Beagle dogs under general anesthesia with isoflurane. Results: In the six dogs, when the concentration [median (interquartile range)] of inhaled isoflurane was increased from 1.5 (1.5-1.5)% to 4 (4-4)% without activating the system, the MAP was lowered from 95 (91-99) to 41 (37-42) mmHg. In contrast, when the concentration was increased from 1.5 (1.0-1.5)% to 4 (4-4.8)% for a 30-min period and the system was simultaneously activated, the MAP was temporarily lowered from 92 (89-95) to 47 (43-49) mmHg but recovered to 58 (57-58) mmHg owing to the system-controlled infusion of NE. If the acceptable target range for MAP was defined as target MAP ±5 mmHg (55 ≤ MAP ≤65 mmHg), the percentage of time wherein the MAP was maintained within the acceptable range was 96 (89-100)% in the six dogs during the second half of the 30-min period (from 15 to 30 min after system activation). The median performance error, median absolute performance error, wobble, and divergence were - 2.9 (-4.7 to 1.9)%, 2.9 (2.0-4.7)%, 1.3 (0.8-1.8)%, and - 0.24 (-0.34 to -0.11)%·min-1, respectively. No adverse events were observed during the study period, and all dogs were extubated uneventfully. Conclusion: This system was able to titrate the NE infusion rates in an accurate and stable manner to maintain the MAP within the predetermined target range in dogs with isoflurane-induced hypotension. This system can be a potential tool in daily clinical practice for the care of companion dogs

An Operating System Architecture for Future Information Appliances

Abstract. A software platform for developing future information appliances requires to satisfy various diverse requirements. The operating system architecture presented in this paper enhances the flexibility and dependability through virtualization techniques. The architecture allows a system to use multiple operating systems simultaneously, and to use multi-core processors in a flexible way. Also, dependability mechanisms in our architecture will avoid crashing or hanging a system as much as possible in order to improve the user experience when defects in the software are exposed. We present a brief overview of each component in the operating system architecture and some sample scenarios that illustrate the effectiveness of the architecture

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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection