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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
#1
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...
March 27, 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
#2
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...
March 15, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28326341/cdc42-is-crucial-for-facial-and-palatal-formation-during-craniofacial-development
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28193684/an-agonist-of-the-protective-factor-sirt1-improves-functional-recovery-and-promotes-neuronal-survival-by-attenuating-inflammation-after-spinal-cord-injury
#13
Haihong Chen, Hao Ji, Ming Zhang, Zude Liu, Lifeng Lao, Chao Deng, Jianwei Chen, Guibin Zhong
Targeting posttraumatic inflammation is crucial for improving locomotor function. SIRT1 has been shown to play a critical role in disease processes such as hepatic inflammation, rheumatoid arthritis and acute lung inflammation by regulating inflammation. However, the role of SIRT1 in spinal cord injury (SCI) is unknown. We hypothesized that SIRT1 plays an important role in improving locomotor function after SCI by regulating neuroinflammation. In this study, we investigated the effect of SIRT1 in SCI using pharmacological intervention (SRT1720) and the Mx1-Cre/loxP recombination system to knock out target genes...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28193238/transient-ikk2-activation-in-astrocytes-initiates-selective-non-cell-autonomous-neurodegeneration
#14
Michael Lattke, Stephanie N Reichel, Alexander Magnutzki, Alireza Abaei, Volker Rasche, Paul Walther, Dinis P Calado, Boris Ferger, Thomas Wirth, Bernd Baumann
BACKGROUND: Neuroinflammation is associated with a wide range of neurodegenerative disorders, however the specific contribution to individual disease pathogenesis and selective neuronal cell death is not well understood. Inflammatory cerebellar ataxias are neurodegenerative diseases occurring in various autoimmune/inflammatory conditions, e.g. paraneoplastic syndromes. However, how inflammatory insults can cause selective cerebellar neurodegeneration in the context of these diseases remains open, and appropriate animal models are lacking...
February 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28182872/enhanced-critical-size-calvarial-bone-healing-by-ascs-engineered-with-cre-loxp-based-hybrid-baculovirus
#15
Shih-Chun Lo, Kuei-Chang Li, Yu-Han Chang, Mu-Nung Hsu, Li-Yu Sung, Truong Anh Vu, Yu-Chen Hu
Calvarial bone repair remains challenging for adults. Although adipose-derived stem cells (ASCs) hold promise to heal bone defects, use of ASCs for critical-size calvarial bone repair is ineffective. Stromal cell-derived factor 1 (SDF-1) is a chemokine capable of triggering stem cell migration. Although recombinant SDF-1 protein is co-delivered with other molecules including BMP-2 to facilitate calvarial bone repair, these approaches did not yield satisfactory healing. This study aimed to exploit a newly developed Cre/loxP-based hybrid baculovirus for efficient gene delivery and prolonged transgene expression in ASCs...
January 30, 2017: Biomaterials
https://www.readbyqxmd.com/read/28182733/pyruvate-dehydrogenase-kinase-1-is-essential-for-transplantable-mouse-bone-marrow-hematopoietic-stem-cell-and-progenitor-function
#16
Camilla Halvarsson, Pernilla Eliasson, Jan-Ingvar Jönsson
BACKGROUND: Accumulating evidence suggests that hypoxic areas in the bone marrow are crucial for maintenance of hematopoietic stem cells (HSCs) by supporting a quiescent state of cell cycle and regulating the transplantation capacity of long-term (LT)-HSCs. In addition, HSCs seem to express a metabolic profile of energy production away from mitochondrial oxidative phosphorylation in favor of glycolysis. At oxygen deprivation, hypoxia inducible factor 1α (HIF-1α) is known to induce glycolytic enzymes as well as suppressing mitochondrial energy production by inducing pyruvate dehydrogenase kinase 1 (Pdk1) in most cell types...
2017: PloS One
https://www.readbyqxmd.com/read/28167493/smad4-regulates-growth-plate-matrix-production-and-chondrocyte-polarity
#17
Amanda T Whitaker, Ellora Berthet, Andrea Cantu, Diana J Laird, Tamara Alliston
Smad4 is an intracellular effector of the TGFβ family that has been implicated in Myhre syndrome, a skeletal dysplasia characterized by short stature, brachydactyly and stiff joints. The TGFβ pathway also plays a critical role in the development, organization and proliferation of the growth plate, although the exact mechanisms remain unclear. Skeletal phenotypes in Myhre syndrome overlap with processes regulated by the TGFβ pathway, including organization and proliferation of the growth plate and polarity of the chondrocyte...
March 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28165624/myeloid-myd88-contributes-to-ethanol-induced-liver-injury-in-mice-linking-hepatocellular-death-to-inflammation
#18
Hao Zhou, Minja Yu, Sanjoy Roychowdhury, Carlos Sanz-Garcia, Katherine A Pollard, Megan R McMullen, Xiuli Liu, Xiaoxia Li, Laura E Nagy
BACKGROUND: Toll-like receptor 4 (TLR4) is critical for ethanol (EtOH)-induced liver injury. TLR4 signaling is mediated by 2 proximal adaptor molecules: myeloid differentiation primary response protein (MyD88) and TLR-domain-containing adaptor-inducing interferon-β (TRIF). Studies utilizing global knockouts of MyD88 and TRIF identified a predominant role for TRIF signaling in the progression of EtOH-induced liver injury. In contrast, IL-1 receptor, which signals solely via the MyD88 pathway, is also known to mediate EtOH-induced liver injury...
February 6, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28163952/unintended-targeting-of-dmp1-cre-reveals-a-critical-role-for-bmpr1a-signaling-in-the-gastrointestinal-mesenchyme-of-adult-mice
#19
Joohyun Lim, Joseph Burclaff, Guangxu He, Jason C Mills, Fanxin Long
Cre/loxP technology has been widely used to study cell type-specific functions of genes. Proper interpretation of such data critically depends on a clear understanding of the tissue specificity of Cre expression. The Dmp1-Cre mouse, expressing Cre from a 14-kb DNA fragment of the mouse Dmp1 gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using the Ai9 reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in 2-month-old mice, Dmp1-Cre targets not only osteocytes within the bone matrix but also osteoblasts on the bone surface and preosteoblasts at the metaphyseal chondro-osseous junction...
2017: Bone Research
https://www.readbyqxmd.com/read/28123942/fetal-development-of-subcutaneous-white-adipose-tissue-is-dependent-on-zfp423
#20
Mengle Shao, Chelsea Hepler, Lavanya Vishvanath, Karen A MacPherson, Napoleon C Busbuso, Rana K Gupta
OBJECTIVE: Zfp423 is a multi zinc-finger transcription factor expressed in preadipocytes and mature adipocytes in vivo. Our recent work has revealed a critical role for Zfp423 in maintaining the fate of white adipocytes in adult mice through suppression of the beige cell thermogenic gene program; loss of Zfp423 in mature adipocytes of adult mice results in a white-to-beige phenotypic switch. However, the exact requirements of Zfp423 in the fetal stages of early adipose development in vivo have not been clarified...
January 2017: Molecular Metabolism
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