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https://www.readbyqxmd.com/read/28430966/decreased-thromboembolic-stroke-but-not-atherosclerosis-or-vascular-remodeling-in-mice-with-rock2-deficient-platelets
#1
Nikola Sladojevic, Goo Taeg Oh, Hyung-Hwan Kim, Lea M Beaulieu, Hervé Falet, Karol Kaminski, Jane E Freedman, James K Liao
Aims: Rho-associated coiled-coil containing kinase (ROCK)-2 is an important mediator of the actin cytoskeleton. Because changes in the actin cytoskeleton are critical for platelet function, we hypothesized that ROCK2 in platelets will play important role in thrombosis and can be potentially a target for therapeutic intervention in thromboembolic stroke. Methods and Results: We generated platelet-specific ROCK2-deficient mice (ROCK2 Plt-/- ) from conditional ROCK2 fl°x/fl°x and platelet factor (PF)-4-Cre transgenic mice...
April 14, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430962/ulk1-prevents-cardiac-dysfunction-in-obesity-through-autophagy-meditated-regulation-of-lipid-metabolism
#2
Minae An, Dong-Ryeol Ryu, Jang Won Park, Ji Ha Choi, Eun-Mi Park, Kyung Eun Lee, Minna Woo, Minsuk Kim
Aims: Autophagy is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Whereas many studies support the importance of autophagy in the mechanisms underlying obesity-related cardiac dysfunction, the role of autophagy in cardiac lipid metabolism remains unclear. In the heart, lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates accumulation of fatty acids to the heart through intravascular triglyceride (TG) hydrolysis...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28396503/correlation-of-meiotic-dsb-formation-and-transcription-initiation-around-fission-yeast-recombination-hotspots
#3
Shintaro Yamada, Mika Okamura, Arisa Oda, Hiroshi Murakami, Kunihiro Ohta, Takatomi Yamada
Meiotic homologous recombination, a critical event for ensuring faithful chromosome segregation and creating genetic diversity, is initiated by programed DNA double strand breaks (DSBs) formed at recombination hotspots. Meiotic DSB formation is likely to be influenced by other DNA-templated processes including transcription, but how DSB formation and transcription interact with each other has not been understood well. In this study, we used fission yeast to investigate a possible interplay of these two events...
April 10, 2017: Genetics
https://www.readbyqxmd.com/read/28394187/using-critical-realistic-evaluation-to-support-translation-of-research-into-clinical-practice
#4
Michelle C Swift, Marilyn Langevin, Alexander M Clark
A challenge that speech-language pathologists (SLPs) face is the translation of research into clinical practice. While randomised controlled trials (RCTs) are often touted as the "gold standard" of efficacy research, much valuable information is lost through the process; RCTs by nature are designed to wash out individual client factors and contexts that might influence the outcome in order to present the "true" impact of the intervention. However, in the area of behavioural interventions, the interaction of client factors and contexts with the treatment agent can substantially influence the outcome...
April 10, 2017: International Journal of Speech-language Pathology
https://www.readbyqxmd.com/read/28391161/the-mvmp-p4-promoter-is-a-host-cell-type-range-determinant-in-vivo
#5
Chen Meir, Michal Mincberg, Irina Rostovsky, Saar Tal, Ellen M Vollmers, Adi Levi, Peter Tattersall, Claytus Davis
The protoparvovirus early promoters, e.g. P4 of Minute Virus of Mice (MVM), play a critical role during infection. Initial P4 activity depends on the host transcription machinery only. Since this is cell-type dependent, it is hypothesized that P4 is a host cell-type range determinant. Yet host range determinants have mapped mostly to capsid, never P4. Here we test the hypothesis using the mouse embryo as a model system. Disruption of the CRE element of P4 drastically decreased infection levels without altering range...
April 6, 2017: Virology
https://www.readbyqxmd.com/read/28385723/fabp4-cre-mediated-sirt6-deletion-impairs-adipose-tissue-function-and-metabolic-homeostasis-in-mice
#6
Xiwen Xiong, Cuicui Zhang, Yang Zhang, Rui Fan, Xinlai Qian, Xiaocheng Charlie Dong
SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis, and anti-inflammation. However, its function in the adipose tissue is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient in Sirt6 using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouse Fabp4 or Adipoq gene promoter were chosen for this study. The Sirt6 knockout mice generated by the Fabp4-Cre line (Sirt6f/f:Fabp4-Cre) had a significant increase in both body weight and fat mass, and exhibited glucose intolerance and insulin resistance as compared with the control wildtype mice...
April 6, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28383552/experimental-atopic-dermatitis-depends-on-il-33r-signaling-via-myd88-in-dendritic-cells
#7
Changwei Li, Isabelle Maillet, Claire Mackowiak, Camille Viala, Franco Di Padova, Mei Li, Dieudonnée Togbe, Valérie Quesniaux, Yuping Lai, Bernhard Ryffel
Atopic dermatitis (AD) is a chronic Th2 type inflammatory skin disorder. Here we report that MyD88 signaling is crucial in the pathogenesis of experimental AD induced by vitamin D3 analog MC903. The clinical signs and inflammation caused by MC903 are drastically reduced in MyD88(-/-) mice with diminished eosinophil, neutrophil infiltration and Th2 cytokine expression. The biological effect of interleukin-1 (IL-1) family members relies on MyD88 signaling. We observed a strong upregulation of IL-1 family cytokine expression, including IL-1α, IL-1β, IL-33, IL-18, IL-36α, IL-36β, IL-36γ and IL-36Ra...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28375030/aminoglycosides-against-carbapenem-resistant-enterobacteriaceae-in-the-critically-ill-the-pitfalls-of-aminoglycoside-susceptibility
#8
Alexandre P Zavascki, Brandon O Klee, Jürgen B Bulitta
The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has brought aminoglycosides to the frontline since an aminoglycoside may be the only antimicrobial to which CRE isolates show in vitro susceptibility. The appropriateness of aminoglycoside-based therapies for severe infections by CRE is discussed considering the current breakpoints and recent pharmacokinetic (PK) studies in critically ill patients. Areas covered: Many aminoglycoside-susceptible CRE isolates present minimal inhibitory concentrations (MICs) at or slightly below the breakpoint of amikacin or gentamicin...
April 17, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28346409/the-metabolic-er-stress-sensor-ire1%C3%AE-suppresses-alternative-activation-of-macrophages-and-impairs-energy-expenditure-in-obesity
#9
Bo Shan, Xiaoxia Wang, Ying Wu, Chi Xu, Zhixiong Xia, Jianli Dai, Mengle Shao, Feng Zhao, Shengqi He, Liu Yang, Mingliang Zhang, Fajun Nan, Jia Li, Jianmiao Liu, Jianfeng Liu, Weiping Jia, Yifu Qiu, Baoliang Song, Jing-Dong J Han, Liangyou Rui, Sheng-Zhong Duan, Yong Liu
Obesity is associated with metabolic inflammation and endoplasmic reticulum (ER) stress, both of which promote metabolic disease progression. Adipose tissue macrophages (ATMs) are key players orchestrating metabolic inflammation, and ER stress enhances macrophage activation. However, whether ER stress pathways underlie ATM regulation of energy homeostasis remains unclear. Here, we identified inositol-requiring enzyme 1α (IRE1α) as a critical switch governing M1-M2 macrophage polarization and energy balance...
May 2017: Nature Immunology
https://www.readbyqxmd.com/read/28344005/mir-342-5p-regulates-neural-stem-cell-proliferation-and-differentiation-downstream-to-notch-signaling-in-mice
#10
Fang Gao, Yu-Fei Zhang, Zheng-Ping Zhang, Luo-An Fu, Xiu-Li Cao, Yi-Zhe Zhang, Chen-Jun Guo, Xian-Chun Yan, Qin-Chuan Yang, Yi-Yang Hu, Xiang-Hui Zhao, Ya-Zhou Wang, Sheng-Xi Wu, Gong Ju, Min-Hua Zheng, Hua Han
Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout (Rbp-j cKO) and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl), was negatively regulated by Notch signaling, probably through HES5...
April 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28326341/cdc42-is-crucial-for-facial-and-palatal-formation-during-craniofacial-development
#11
Mutsuko Oshima-Nakayama, Atsushi Yamada, Tamaki Kurosawa, Ryo Aizawa, Dai Suzuki, Yoshiro Saito, Hidetoshi Kassai, Yuki Sato, Matsuo Yamamoto, Tatsuo Shirota, Atsu Aiba, Koutaro Maki, Ryutaro Kamijo
Craniofacial deformities with multifactorial etiologies, such as cleft palate and facial dysmorphism, represent some of the most frequent congenital birth defects seen in humans. Their pathogeneses are often related to cranial neural crest (CNC) cells. During CNC cell migration, changes in cell shape and formation, as well as maintenance of subcellular structures, such as filopodia and lamellipodia, are dependent on the complex functions of Rho family small GTPases, which are regulators of actin cytoskeletal organization...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28306563/antimicrobial-resistant-gram-negative-infections-in-neonates-burden-of-disease-and-challenges-in-treatment
#12
Laura Folgori, Julia Bielicki, Paul T Heath, Mike Sharland
PURPOSE OF REVIEW: This review summarizes the main challenges of antimicrobial resistance (AMR) in the neonatal population with a special focus on multidrug-resistant (MDR) Gram-negative pathogens. RECENT FINDINGS: MDR-Gram-negative bacteria are a great concern in the neonatal population, with a worldwide rise in the reported incidence and with very limited therapeutic options. Extended-spectrum β-lactamase and carbapenem-resistant Enterobacteriaceae (CRE) have been reported as responsible for neonatal ICU outbreaks...
March 16, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28290551/epithelial-lt%C3%AE-r-signaling-controls-the-population-size-of-the-progenitors-of-medullary-thymic-epithelial-cells-in-neonatal-mice
#13
Weiwei Wu, Yaoyao Shi, Huan Xia, Qian Chai, Caiwei Jin, Boyang Ren, Mingzhao Zhu
The establishment of T cell central tolerance critically relies on the development and maintenance of the medullary thymic epithelial cells (mTECs). Disrupted signaling of lymphotoxin beta receptor (LTβR) results in dramatically reduced mTEC population. However, whether LTβR directly or indirectly control mTECs remains undetermined; how LTβR controls this process also remain unclear. In this study, by utilizing K14-Cre × Ltbr(fl/fl) conditional knockout (cKO) mice, we show that epithelial intrinsic LTβR was essential for the mTEC development postnatally...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284905/embryonic-mosaic-deletion-of-app-results-in-displaced-reelin-expressing-cells-in-the-cerebral-cortex
#14
D G Callahan, W M Taylor, M Tilearcio, T Cavanaugh, D J Selkoe, T L Young-Pearse
It is widely accepted that amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimer's disease. In addition, APP has been proposed to have functions in numerous biological processes including neuronal proliferation, differentiation, migration, axon guidance, and neurite outgrowth, as well as in synapse formation and function. However, germline knockout of APP yields relatively subtle phenotypes, and brain development appears grossly normal. This is thought to be due in part to functional compensation by APP family members and other type I transmembrane proteins...
March 8, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28277610/the-notch-ligand-jagged1-regulates-the-osteoblastic-lineage-by-maintaining-the-osteoprogenitor-pool
#15
Rialnat A Lawal, Xichao Zhou, Kaylind Batey, Corey M Hoffman, Mary A Georger, Freddy Radtke, Matthew J Hilton, Lianping Xing, Benjamin J Frisch, Laura M Calvi
Notch signaling is critical for osteoblastic differentiation; however, the specific contribution of individual Notch ligands is unknown. Parathyroid hormone (PTH) regulates the Notch ligand Jagged1 in osteoblastic cells. To determine if osteolineage Jagged1 contributes to bone homeostasis, selective deletion of Jagged1 in osteolineage cells was achieved through the presence of Prx1 promoter-driven Cre recombinase expression, targeting mesenchymal stem cells (MSCs) and their progeny (PJag1 mice). PJag1 mice were viable and fertile and did not exhibit any skeletal abnormalities at 2 weeks of age...
March 9, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28275162/leptin-signalling-in-agrp-neurons-modulates-puberty-onset-and-adult-fertility-in-mice
#16
Olivia K Egan, Megan A Inglis, Greg M Anderson
The hormone leptin indirectly communicates metabolic information to brain neurons that control reproduction, using GABAergic circuitry. Agouti-related peptide (AgRP) neurons in the arcuate nucleus are GABAergic, express leptin receptors (LepR) and are known to influence reproduction. This study tested whether leptin actions on AgRP neurons are required and sufficient for puberty onset and subsequent fertility. Firstly, Agrp-Cre and Lepr-flox mice were used to target deletion of LepR to AgRP neurons. AgRP-LepR knockout female mice exhibited mild obesity and adiposity as previously described, as well as a significant delay in the pubertal onset of estrous cycles compared to control animals...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28228267/nrf2-improves-leptin-and-insulin-resistance-provoked-by-hypothalamic-oxidative-stress
#17
Yoko Yagishita, Akira Uruno, Toshiaki Fukutomi, Ritsumi Saito, Daisuke Saigusa, Jingbo Pi, Akiyoshi Fukamizu, Fumihiro Sugiyama, Satoru Takahashi, Masayuki Yamamoto
The relationship between loss of hypothalamic function and onset of diabetes mellitus remains elusive. Therefore, we generated a targeted oxidative-stress murine model utilizing conditional knockout (KO) of selenocysteine-tRNA (Trsp) using rat-insulin-promoter-driven-Cre (RIP-Cre). These Trsp-KO (Trsp(RIP)KO) mice exhibit deletion of Trsp in both hypothalamic cells and pancreatic β cells, leading to increased hypothalamic oxidative stress and severe insulin resistance. Leptin signals are suppressed, and numbers of proopiomelanocortin-positive neurons in the hypothalamus are decreased...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28224202/germline-specific-dgcr8-knockout-in-zebrafish-using-a-back-approach
#18
Yun Liu, Zeyao Zhu, Idy H T Ho, Yujian Shi, Yuxin Xie, Jianzhen Li, Yong Zhang, Matthew T V Chan, Christopher H K Cheng
Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28223138/foxc1-and-foxc2-are-necessary-to-maintain-glomerular-podocytes
#19
Masaru Motojima, Tsutomu Kume, Taiji Matsusaka
Foxc1 and Foxc2 (Foxc1/2) are transcription factors involved in many biological processes. In adult kidneys, expression of Foxc1/2 is confined to the glomerular epithelial cells, i.e., podocytes. To bypass embryonic lethality of Foxc1/2 null mice, mice ubiquitously expressing inducible-Cre (ROSA26-CreER(T2)) or mice expressing Cre in podocytes (Nephrin-Cre) were mated with floxed-Foxc1 and floxed-Foxc2 mice. The CreER(T2) was activated in adult mice by administrations of tamoxifen. Eight weeks after tamoxifen treatment, ROSA26-CreER(T2); Foxc1(+/flox); Foxc2(flox/flox) mice developed microalbuminuria, while ROSA26-Cre ER(T2); Foxc1(flox/flox); Foxc2(+/flox) mice had no microalbuminuria...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28222099/morphological-study-of-tooth-development-in-podoplanin-deficient-mice
#20
Kenyo Takara, Naoki Maruo, Kyoko Oka, Chiaki Kaji, Yuji Hatakeyama, Naruhiko Sawa, Yukinari Kato, Junro Yamashita, Hiroshi Kojima, Yoshihiko Sawa
Podoplanin is a mucin-type highly O-glycosylated glycoprotein identified in several somatyic cells: podocytes, alveolar epithelial cells, lymphatic endothelial cells, lymph node stromal fibroblastic reticular cells, osteocytes, odontoblasts, mesothelial cells, glia cells, and others. It has been reported that podoplanin-RhoA interaction induces cytoskeleton relaxation and cell process stretching in fibroblastic cells and osteocytes, and that podoplanin plays a critical role in type I alveolar cell differentiation...
2017: PloS One
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