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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
#1
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
#2
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
#3
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
#4
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
#5
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...
February 6, 2017: Biology Open
https://www.readbyqxmd.com/read/28165624/myeloid-myd88-contributes-to-ethanol-induced-liver-injury-in-mice-linking-hepatocellular-death-to-inflammation
#6
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-induced liver injury. TLR4 signaling is mediated by two proximal adaptor molecules: myeloid differentiation primary-response protein (MyD88) and TLR-domain-containing adapter-inducing interferon-β (TRIF). Studies utilizing global knock-outs of MyD88 and TRIF identified a predominant role for TRIF signaling in the progression of ethanol-induced liver injury. In contrast, IL1 receptor, which signals solely via the MyD88 pathway, is also known to mediate ethanol-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
#7
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
#8
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
https://www.readbyqxmd.com/read/28120642/a-novel-mouse-model-of-conditional-irak-m-deficiency-in-myeloid-cells-application-in-lung-pseudomonas-aeruginosa-infection
#9
Di Jiang, Jennifer Matsuda, Reena Berman, Niccolette Schaefer, Connor Stevenson, James Gross, Bicheng Zhang, Amelia Sanchez, Liwu Li, Hong Wei Chu
Myeloid cells such as macrophages are critical to innate defense against infection. IL-1 receptor-associated kinase M (IRAK-M) is a negative regulator of TLR signaling during bacterial infection, but the role of myeloid cell IRAK-M in bacterial infection is unclear. Our goal was to generate a novel conditional knockout mouse model to define the role of myeloid cell IRAK-M during bacterial infection. Myeloid cell-specific IRAK-M knockout mice were generated by crossing IRAK-M floxed mice with LysM-Cre knock-in mice...
February 2017: Innate Immunity
https://www.readbyqxmd.com/read/28119060/conditional-knockout-of-fgf13-in-murine-hearts-increases-arrhythmia-susceptibility-and-reveals-novel-ion-channel-modulatory-roles
#10
Xiangchong Wang, He Tang, Eric Q Wei, Zhihua Wang, Jing Yang, Rong Yang, Sheng Wang, Yongjian Zhang, Geoffrey S Pitt, Hailin Zhang, Chuan Wang
The intracellular fibroblast growth factors (iFGF/FHFs) bind directly to cardiac voltage gated Na(+) channels, and modulate their function. Mutations that affect iFGF/FHF-Na(+) channel interaction are associated with arrhythmia syndromes. Although suspected to modulate other ionic currents, such as Ca(2+) channels based on acute knockdown experiments in isolated cardiomyocytes, the in vivo consequences of iFGF/FHF gene ablation on cardiac electrical activity are still unknown. We generated inducible, cardiomyocyte-restricted Fgf13 knockout mice to determine the resultant effects of Fgf13 gene ablation...
January 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28104803/microrna-processing-enzymes-are-essential-for-survival-and-function-of-mature-retinal-pigmented-epithelial-cells-in-mice
#11
Thomas R Sundermeier, Sanae Sakami, Bhubanananda Sahu, Scott J Howell, Songqi Gao, Zhiqian Dong, Marcin Golczak, Akiko Maeda, Krzysztof Palczewski
Age-related macular degeneration (AMD) is a major cause of irreversible vision loss. The neovascular or "wet" form of AMD can be treated to a varying degree with anti-angiogenic drugs, but geographic atrophy (GA) is an advanced stage of the more prevalent "dry" form of AMD for which there is no effective treatment. Development of GA has been linked to loss of the microRNA (miRNA)-processing enzyme DICER1 in the mature retinal pigmented epithelium (RPE). This loss results in the accumulation of toxic transcripts of Alu transposable elements which activate the NLRP3 inflammasome and additional downstream pathways that compromise the integrity and function of the RPE...
January 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28065741/essential-roles-for-cdx-in-murine-primitive-hematopoiesis
#12
Travis Brooke-Bisschop, Joanne G A Savory, Tanya Foley, Randy Ringuette, David Lohnes
The Cdx transcription factors play essential roles in primitive hematopoiesis in the zebrafish where they exert their effects, in part, through regulation of hox genes. Defects in hematopoiesis have also been reported in Cdx mutant murine embryonic stem cell models, however, to date no mouse model reflecting the zebrafish Cdx mutant hematopoietic phenotype has been described. This is likely due, in part, to functional redundancy among Cdx members and the early lethality of Cdx2 null mutants. To circumvent these limitations, we used Cre-mediated conditional deletion to assess the impact of concomitant loss of Cdx1 and Cdx2 on murine primitive hematopoiesis...
February 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28062693/pu-1-regulates-ig-light-chain-transcription-and-rearrangement-in-pre-b-cells-during-b-cell-development
#13
Carolina R Batista, Stephen K H Li, Li S Xu, Lauren A Solomon, Rodney P DeKoter
B cell development and Ig rearrangement are governed by cell type- and developmental stage-specific transcription factors. PU.1 and Spi-B are E26-transformation-specific transcription factors that are critical for B cell differentiation. To determine whether PU.1 and Spi-B are required for B cell development in the bone marrow, Spi1 (encoding PU.1) was conditionally deleted in B cells by Cre recombinase under control of the Mb1 gene in Spib (encoding Spi-B)-deficient mice. Combined deletion of Spi1 and Spib resulted in a lack of mature B cells in the spleen and a block in B cell development in the bone marrow at the small pre-B cell stage...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28057770/neuroendocrine-integration-of-nutritional-signals-on-reproduction
#14
Maggie Corr Evans, Greg Anderson
Reproductive function in mammals is energetically costly and therefore tightly regulated by nutritional status. To enable this integration of metabolic and reproductive function, information regarding peripheral nutritional status must be relayed centrally to the gonadotropin-releasing hormone (GnRH) neurons that drive reproductive function. The metabolically relevant hormones leptin, insulin and ghrelin have been identified as key mediators of this 'metabolic control of fertility'. However, the neural circuitry through which they act to exert their control over GnRH drive remains incompletely understood...
January 5, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28049832/forkhead-box-a2-foxa2-is-essential-for-uterine-function-and-fertility
#15
Andrew M Kelleher, Wang Peng, James K Pru, Cindy A Pru, Francesco J DeMayo, Thomas E Spencer
Establishment of pregnancy is a critical event, and failure of embryo implantation and stromal decidualization in the uterus contribute to significant numbers of pregnancy losses in women. Glands of the uterus are essential for establishment of pregnancy in mice and likely in humans. Forkhead box a2 (FOXA2) is a transcription factor expressed specifically in the glands of the uterus and is a critical regulator of postnatal uterine gland differentiation in mice. In this study, we conditionally deleted FOXA2 in the adult mouse uterus using the lactotransferrin Cre (Ltf-Cre) model and in the neonatal mouse uterus using the progesterone receptor Cre (Pgr-Cre) model...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28039555/disruption-of-non-anchored-cell-wall-protein-ncw-1-promotes-cellulase-production-by-increasing-cellobiose-uptake-in-neurospora-crassa
#16
Liangcai Lin, Yong Chen, Jingen Li, Shanshan Wang, Wenliang Sun, Chaoguang Tian
OBJECTIVES: To elucidate the mechanism of cellulase signal transduction in filamentous fungi including the components of the cellulase induction pathway. RESULTS: Neurospora crassa ncw-1 encodes a non-anchored cell wall protein. The absence of ncw-1 increased cellulase gene expression and this is not due to relieving carbon catabolite repression mediated by the cre-1 pathway. A mutant lacking genes encoding both three major β-glucosidase enzymes and NCW-1 (Δ3βGΔncw-1) was constructed...
December 30, 2016: Biotechnology Letters
https://www.readbyqxmd.com/read/28039362/defining-the-temporal-course-of-murine-neurofibromatosis-1-optic-gliomagenesis-reveals-a-therapeutic-window-to-attenuate-retinal-dysfunction
#17
Joseph A Toonen, Yu Ma, David H Gutmann
BACKGROUND: Optic gliomas arising in the neurofibromatosis type 1 (NF1) cancer predisposition syndrome cause reduced visual acuity in 30%-50% of affected children. Since human specimens are rare, genetically engineered mouse (GEM) models have been successfully employed for preclinical therapeutic discovery and validation. However, the sequence of cellular and molecular events that culminate in retinal dysfunction and vision loss has not been fully defined relevant to potential neuroprotective treatment strategies...
December 29, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/28039299/hyperactivation-of-the-nlrp3-inflammasome-in-myeloid-cells-leads-to-severe-organ-damage-in-experimental-lupus
#18
Ailing Lu, Hua Li, Junling Niu, Shuxian Wu, Guang Xue, Xiaomin Yao, Qiuhong Guo, Nianhong Wan, Paride Abliz, Guiwen Yang, Liguo An, Guangxun Meng
Systemic lupus erythematosus (SLE) is an autoimmune syndrome associated with severe organ damage resulting from the activation of immune cells. Recently, a role for caspase-1 in murine lupus was described, indicating an involvement of inflammasomes in the development of SLE. Among multiple inflammasomes identified, the NLRP3 inflammasome was connected to diverse diseases, including autoimmune encephalomyelitis. However, the function of NLRP3 in SLE development remains elusive. In this study, we explored the role of NLRP3 in the development of SLE using the pristane-induced experimental lupus model...
December 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28003412/dicer-maintains-the-identity-and-function-of-proprioceptive-sensory-neurons
#19
Sean Michael O'Toole, Monica M Ferrer, Jennifer Mekonnen, Haihan Zhang, Yasuyuki Shima, David R Ladle, Sacha B Nelson
Neuronal cell identity is established during development and must be maintained throughout an animal's life (Fishell and Heintz 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris and Hobert 2014). Post-transcriptional regulation also plays an important role in neuronal differentiation (Bian and Sun 2011), but its role in maintaining cell identity is less established. To better understand how post-transcriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory neuron class, with well established properties that distinguish them from other neurons in the ganglion...
December 21, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27998825/hematopoietic-arginase-1-deficiency-results-in-decreased-leukocytosis-and-increased-foam-cell-formation-but-does-not-affect-atherosclerosis
#20
Baoyan Ren, Erik Van Kampen, Theo J C Van Berkel, Sheena M Cruickshank, Miranda Van Eck
BACKGROUND AND AIMS: Arginase1 (Arg1), an M2 macrophage marker, plays a critical role in a number of immunological functions in macrophages, which are the main cell type facilitating atherosclerotic lesion development. Arg1 uses the substrate l-arginine to create l-ornithine, a precursor molecule required for collagen formation and vascular smooth muscle cell differentiation. By reducing l-arginine availability, Arg1 limits the production of nitric oxide (NO), a pro-atherogenic factor in macrophages...
January 2017: Atherosclerosis
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