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https://www.readbyqxmd.com/read/28710293/probing-gata-factor-function-in-mouse-leydig-cells-via-testicular-injection-of-adenoviral-vectors
#1
Gervette M Penny, Rebecca B Cochran, Marjut Pihlajoki, Antti Kyrönlahti, Anja Schrade, Merja Häkkinen, Jorma Toppari, Markku Heikinheimo, David B Wilson
Testicular Leydig cells produce androgens essential for proper male reproductive development and fertility. Here, we describe a new Leydig cell ablation model based on Cre/Lox recombination of mouse Gata4 and Gata6, two genes implicated in the transcriptional regulation of steroidogenesis. The testicular interstitium of adult Gata4(flox/flox);Gata6(flox/flox) mice was injected with adenoviral vectors encoding Cre + GFP (Ad-Cre-IRES-GFP) or GFP alone (Ad-GFP). The vectors efficiently and selectively transduced Leydig cells, as evidenced by GFP reporter expression...
July 14, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28699895/a-role-for-brg1-in-the-regulation-of-genes-required-for-development-of-the-lymphatic-system
#2
Ajeet Pratap Singh, Julie Foley, Arpit Tandon, Dhiral Phadke, H Karimi Kinyamu, Trevor K Archer
Lymphatic vasculature is an important part of the cardiovascular system with multiple functions, including regulation of the return of interstitial fluid (lymph) to the bloodstream, immune responses, and fat absorption. Consequently, lymphatic vasculature defects are involved in many pathological processes, including tumor metastasis and lymphedema. BRG1 is an important player in the developmental window when the lymphatic system is initiated. In the current study, we used tamoxifen inducible Rosa26CreERT2-BRG1floxed/floxed mice that allowed temporal analysis of the impact of BRG1 inactivation in the embryo...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28668388/fampk%C3%AE-1-deficiency-suppresses-brown-adipogenesis-in-favor-of-fibrogenesis-during-brown-adipose-tissue-development
#3
Junxing Zhao, Qiyuan Yang, Lupei Zhang, Xingwei Liang, Xiaofei Sun, Bo Wang, Yanting Chen, Meijun Zhu, Min Du
Brown adipose tissue (BAT) dissipates energy for thermogenesis which reduces or prevents obesity and metabolic dysfunction. AMP-activated protein kinase (AMPK) is a master regulator of energy metabolism and its activity is inhibited in the developing BAT due to obesity. We previously found that AMPK is required for brown fat development and thermogenic function, but the non-brown adipogenic differentiation of progenitor cells due to AMPKα1 deficiency has not been defined. We found that, in vivo, the thermogenic capacity and morphology of BAT were compromised due to AMPK deficiency, which was correlated with decreased progenitor density in BAT...
June 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28663252/glucose-transporter-3-potentiates-degranulation-and-is-required-for-platelet-activation
#4
Trevor P Fidler, Elizabeth Middleton, Jesse W Rowley, Luc H Boudreau, Robert A Campbell, Rhonda Souvenir, Trevor Funari, Nicolas Tessandier, Eric Boilard, Andrew S Weyrich, E Dale Abel
OBJECTIVE: On activation, platelets increase glucose uptake, glycolysis, and glucose oxidation and consume stored glycogen. This correlation between glucose metabolism and platelet function is not well understood and even less is known about the role of glucose metabolism on platelet function in vivo. For glucose to enter a cell, it must be transported through glucose transporters. Here we evaluate the contribution of GLUT3 (glucose transporter 3) to platelet function to better understand glucose metabolism in platelets...
June 29, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28660243/effects-of-selective-deletion-of-tyrosine-hydroxylase-from-kisspeptin-cells-on-puberty-and-reproduction-in-male-and-female-mice
#5
Shannon B Z Stephens, Melvin L Rouse, Kristen P Tolson, Reanna B Liaw, Ruby A Parra, Navi Chahal, Alexander S Kauffman
The neuropeptide kisspeptin, encoded by Kiss1, regulates reproduction by stimulating GnRH secretion. Kiss1-syntheizing neurons reside primarily in the hypothalamic anteroventral periventricular (AVPV/PeN) and arcuate (ARC) nuclei. AVPV/PeN Kiss1 neurons are sexually dimorphic, with females expressing more Kiss1 than males, and participate in estradiol (E2)-induced positive feedback control of GnRH secretion. In mice, most AVPV/PeN Kiss1 cells coexpress tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis (in this case, dopamine)...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28659288/overload-mediated-skeletal-muscle-hypertrophy-is-not-impaired-by-loss-of-myofiber-stat3
#6
Joaquín Pérez-Schindler, Mary Esparza, James McKendry, Leigh Breen, Andrew Philp, Simon Schenk
Although the signal pathways mediating muscle protein synthesis and degradation are well characterized, the transcriptional processes modulating skeletal muscle mass and adaptive growth are poorly understood. Recently, studies in mouse models of muscle wasting or acutely exercised human muscle have suggested a potential role for the transcription factor, signal transducer and activator of transcription 3 (STAT3), in adaptive growth. Hence, in the present study we sought to define the contribution of STAT3 to skeletal muscle adaptive growth...
June 28, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28657172/asic1a-in-neurons-is-critical-for-fear-related-behaviors
#7
R J Taugher, Y Lu, R Fan, A Ghobbeh, C J Kreple, F M Faraci, J A Wemmie
Acid-sensing ion channels (ASICs) have been implicated in fear-, addiction-, and depression-related behaviors in mice. While these effects have been attributed to ASIC1A in neurons, it has been reported that ASICs may also function in non-neuronal cells. To determine if ASIC1A in neurons is indeed required, we generated neuron-specific knockout mice with floxed Asic1a alleles disrupted by Cre recombinase driven by the neuron-specific synapsin I promoter (SynAsic1a KO mice). We confirmed that Cre expression occurred in neurons, but not all neurons, and not in non-neuronal cells including astrocytes...
June 28, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28657129/acetyl-coa-production-from-pyruvate-is-not-necessary-for-preservation-of-myelin
#8
Gustavo Della-Flora Nunes, Lauren Mueller, Nicholas Silvestri, Mulchand S Patel, Lawrence Wrabetz, M Laura Feltri, Yannick Poitelon
Oligodendrocytes and Schwann cells not only form myelin in the central and peripheral nervous system, but also provide metabolic and trophic support to the axons they ensheathe. Acetyl-CoA is potentially a key molecule in Schwann cells and oligodendrocytes because it is at the crossroads of cellular lipid biosynthesis and energy generation. The main route for acetyl-CoA production is the oxidation of pyruvate by the pyruvate dehydrogenase complex (PDC). PDC deficiency in humans results in neurodegeneration and developmental impairments in both white and gray matter structures...
June 28, 2017: Glia
https://www.readbyqxmd.com/read/28652279/pregabalin-for-the-prevention-of-oxaliplatin-induced-painful-neuropathy-a-randomized-double-blind-trial
#9
Daniel Ciampi de Andrade, Manoel Jacobsen Teixeira, Ricardo Galhardoni, Karine S L Ferreira, Paula Braz Mileno, Nathalia Scisci, Alexandra Zandonai, William G J Teixeira, Daniel F Saragiotto, Valquíria Silva, Irina Raicher, Rubens Gisbert Cury, Ricardo Macarenco, Carlos Otto Heise, Mario Wilson Iervolino Brotto, Alberto Andrade de Mello, Marcelo Zini Megale, Luiz Henrique Curti Dourado, Luciana Mendes Bahia, Antonia Lilian Rodrigues, Daniella Parravano, Julia Tizue Fukushima, Jean-Pascal Lefaucheur, Didier Bouhassira, Evandro Sobroza, Rachel P Richelmann, Paulo M Hoff, Fernanda Valério da Silva, Thais Chile, Camila S Dale, Daniela Nebuloni, Luiz Senna, Helena Brentani, Rosana L Pagano, Ângela M de Souza
LESSONS LEARNED: Pregabalin is a medication that can decrease neuronal hyperexcitability, relieve neuropathic pain, and reach stable plasma levels after a titration period of only a few days.Its use during oxaliplatin infusions was not able to decrease the incidence of chronic, oxalipaltin-related neuropathic pain, compared with placebo. BACKGROUND: Patients with colorectal cancer (CRC) receiving oxaliplatin (OXA) develop acute and chronic painful oxaliplatin-induced peripheral neuropathy (OXAIPN)...
June 26, 2017: Oncologist
https://www.readbyqxmd.com/read/28646022/nf1-hematopoietic-cells-accelerate-malignant-peripheral-nerve-sheath-tumor-development-without-altering-chemotherapy-response
#10
Rebecca D Dodd, Chang-Lung Lee, Tess Overton, Wesley Huang, William C Eward, Lixia Luo, Yan Ma, Davis R Ingram, Keila E Torres, Diana M Cardona, Alexander Lazar, David G Kirsch
Haploinsufficiency in the tumor suppressor NF1 contributes to the pathobiology of type 1 neurofibromatosis, but a related role has not been established in malignant peripheral nerve sheath tumors (MPNST) where NF1 mutations also occur. Patients with NF1-associated MPNST appear to have worse outcomes than patients with sporadic MPNST, but the mechanism underlying this correlation is not understood. To define the impact of stromal genetics on the biology of this malignancy, we developed unique mouse models that reflect the genetics of patient-associated MPNST...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28642969/diverse-metabolic-effects-of-o-glcnacylation-in-the-pancreas-but-limited-effects-in-insulin-sensitive-organs-in-mice
#11
Shogo Ida, Katsutaro Morino, Osamu Sekine, Natsuko Ohashi, Shinji Kume, Tokuhiro Chano, Kanako Iwasaki, Norio Harada, Nobuya Inagaki, Satoshi Ugi, Hiroshi Maegawa
AIMS/HYPOTHESIS: O-GlcNAcylation is characterised by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (OGT) and serves in sensing intracellular nutrients by modulating various cellular processes. Although it has been speculated that O-GlcNAcylation is associated with glucose metabolism, its exact role in whole body glucose metabolism has not been fully elucidated. Here, we investigated whether loss of O-GlcNAcylation globally and in specific organs affected glucose metabolism in mammals under physiological conditions...
June 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28637242/yap-and-wwtr1-regulate-the-expression-of-sex-determining-genes-in-sertoli-cells-but-their-inactivation-does-not-cause-sex-reversal
#12
Adrien Levasseur, Marilène Paquet, Derek Boerboom, Alexandre Boyer
Yes-associated protein (YAP) and WW containing transcription regulator 1 (WWTR1) are two functionally redundant transcriptional regulators that are downstream effectors of the Hippo signaling pathway, and that act as major regulators of cell growth and differentiation. To elucidate their role in Sertoli cells, primary Sertoli cell culture from Yapflox/flox; Wwtr1flox/flox animals were infected with a Cre recombinase-expressing adenovirus. Concomitant inactivation of Yap and Wwtr1 resulted in a decrease in the mRNA levels of the male sex differentiation genes Dhh, Dmrt1, Sox9 and Wt1, whereas those of genes involved in female differentiation (Wnt4, Rspo1 and Foxl2) were induced...
June 16, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28626064/monitoring-c3ar-expression-using-a-floxed-tdtomato-c3ar-reporter-knock-in-mouse
#13
Katharina M Quell, Christian M Karsten, Anna Kordowski, Larissa Nogueira Almeida, Daria Briukhovetska, Anna V Wiese, Jing Sun, Fanny Ender, Konstantina Antoniou, Torsten Schröder, Inken Schmudde, Johann L Berger, Peter König, Tillman Vollbrandt, Yves Laumonnier, Jörg Köhl
C3a exerts multiple biologic functions through activation of its cognate C3a receptor. C3(-/-) and C3aR(-/-) mice have been instrumental in defining important roles of the C3a/C3aR axis in the regulation of acute and chronic inflammatory diseases, including ischemia/reperfusion injury, allergic asthma, autoimmune nephritis, and rheumatoid arthritis. Surprisingly little is known about C3aR expression and function in immune and stromal cells. To close this gap, we generated a floxed tandem-dye Tomato (tdTomato)-C3aR reporter knock-in mouse, which we used to monitor C3aR expression in cells residing in the lung, airways, lamina propria (LP) of the small intestine, brain, visceral adipose tissue, bone marrow (BM), spleen, and the circulation...
June 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28621199/sciatic-nerve-regeneration-by-transplantation-of-in-vitro-differentiated-nucleus-pulposus-progenitor-cells
#14
Takayuki Ishii, Daisuke Sakai, Jordy Schol, Tomoko Nakai, Kaori Suyama, Masahiko Watanabe
AIM: To assess the applicability of mouse intervertebral disc-derived nucleus pulposus (NP) progenitor cells as a cell source for sciatic nerve regeneration. MATERIALS & METHODS: P0-Cre/Floxed-EGFP-transgenic mouse-derived NP progenitor cells were differentiated to Schwann-like cells in conventional induction medium. Schwann-like cells were subsequently transplanted into a mouse model of sciatic nerve transection, and nerve regeneration assessed by immunohistochemistry, electron microscopy and functional walking track analysis and heat stimulus reflex...
June 16, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28620387/notch-regulates-macrophage-mediated-inflammation-in-diabetic-wound-healing
#15
Andrew S Kimball, Amrita D Joshi, Anna E Boniakowski, Matthew Schaller, Jooho Chung, Ronald Allen, Jennifer Bermick, William F Carson, Peter K Henke, Ivan Maillard, Steve L Kunkel, Katherine A Gallagher
Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAML(floxed)Lyz2(Cre+) ) demonstrated delayed early healing (days 1-3) and wound macrophages had decreased inflammatory gene expression...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28620244/specific-ablation-of-mouse-fam20c-in-cells-expressing-type-i-collagen-leads-to-skeletal-defects-and-hypophosphatemia
#16
Peihong Liu, Su Ma, Hua Zhang, Chao Liu, Yongbo Lu, Li Chen, Chunlin Qin
FAM20C mutations in humans cause Raine syndrome and our previous studies showed that global inactivation of mouse Fam20C led to bone and dental defects. By crossbreeding 2.3  kb Col 1a1-Cre mice with Fam20C (flox/flox) mice, we created 2.3  kb Col 1a1-Cre;Fam20C (foxl/flox) (cKO) mice, in which Fam20C was inactivated in cells expressing Type I collagen. This study showed that the long bones of cKO mice were shorter and had a lower level of mineralization compared to the normal mice. The collagen fibrils in Fam20C-deficient bone were disorganized and thicker while the growth plate cartilage in cKO mice was disorganized and wider compared to the normal mice...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620068/x-box-binding-protein-1-dependent-plasma-cell-responses-limit-the-development-of-atherosclerosis
#17
Andrew P Sage, Meritxell Nus, Jayashree Bagchi Chakraborty, Dimitrios Tsiantoulas, Stephen A Newland, Alison J Finigan, Leanne Masters, Christoph J Binder, Ziad Mallat
Rationale: Diverse B cell responses and functions may be involved in atherosclerosis. Protective antibody responses, such as those against oxidized lipid epitopes, are thought to mainly derive from T cell-independent innate B cell subsets. In contrast, both pathogenic and protective roles have been associated with T cell-dependent antibodies and their importance in both humans and mouse models is still unclear. Objective: To specifically target antibody production by plasma cells and determine the impact on atherosclerotic plaque development in mice with and without CD4+ T cells...
June 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28615301/irf4-dependent-cd103-cd11b-dendritic-cells-and-the-intestinal-microbiome-regulate-monocyte-and-macrophage-activation-and-intestinal-peristalsis-in-postoperative-ileus
#18
Judith-Mira Pohl, Sebastian Gutweiler, Stephanie Thiebes, Julia K Volke, Ludger Klein-Hitpass, Denise Zwanziger, Matthias Gunzer, Steffen Jung, William W Agace, Christian Kurts, Daniel Robert Engel
OBJECTIVE: Postoperative ileus (POI), the most frequent complication after intestinal surgery, depends on dendritic cells (DCs) and macrophages. Here, we have investigated the mechanism that activates these cells and the contribution of the intestinal microbiota for POI induction. DESIGN: POI was induced by manipulating the intestine of mice, which selectively lack DCs, monocytes or macrophages. The disease severity in the small and large intestine was analysed by determining the distribution of orally applied fluorescein isothiocyanate-dextran and by measuring the excretion time of a retrogradely inserted glass ball...
June 14, 2017: Gut
https://www.readbyqxmd.com/read/28611114/notch1-deficiency-in-postnatal-neural-progenitor-cells-in-the-dentate-gyrus-leads-to-emotional-and-cognitive-impairment
#19
Shufang Feng, Tianyao Shi, Jiangxia Qiu, Haihong Yang, Yan Wu, Wenxia Zhou, Wei Wang, Haitao Wu
It is well known that Notch1 signaling plays a crucial role in embryonic neural development and adult neurogenesis. The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in hippocampal mature neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus...
June 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28608929/high-grade-serous-carcinomas-arise-in-the-mouse-oviduct-via-defects-linked-to-the-human-disease
#20
Yali Zhai, Rong Wu, Rork Kuick, Michael S Sessine, Stephanie Schulman, Megan Green, Eric R Fearon, Kathleen R Cho
Recent studies suggest that the most common and lethal type of "ovarian" cancer, high-grade serous carcinoma (HGSC), usually arises from epithelium on the fallopian tube fimbriae, and not from the ovarian surface epithelium (OSE). We have developed Ovgp1-iCreER(T2) mice in which the Ovgp1 promoter controls expression of tamoxifen (TAM)-regulated Cre recombinase in oviductal epithelium - the murine equivalent of human fallopian tube epithelium (FTE). We employed Ovgp1-iCreER(T2) mice to show that FTE-specific inactivation of several different combinations of tumour suppressor genes recurrently mutated in human HGSCs - namely Brca1, Trp53, Rb1, and Nf1 - results in serous tubal intraepithelial carcinomas (STICs) that progress to HGSC or carcinosarcoma, and to widely metastatic disease in a subset of mice...
June 13, 2017: Journal of Pathology
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