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https://www.readbyqxmd.com/read/28732025/hand-factor-ablation-causes-defective-left-ventricular-chamber-development-and-compromised-adult-cardiac-function
#1
Joshua W Vincentz, Kevin P Toolan, Wenjun Zhang, Anthony B Firulli
Coordinated cardiomyocyte growth, differentiation, and morphogenesis are essential for heart formation. We demonstrate that the bHLH transcription factors Hand1 and Hand2 play critical regulatory roles for left ventricle (LV) cardiomyocyte proliferation and morphogenesis. Using an LV-specific Cre allele (Hand1LV-Cre), we ablate Hand1-lineage cardiomyocytes, revealing that DTA-mediated cardiomyocyte death results in a hypoplastic LV by E10.5. Once Hand1-linage cells are removed from the LV, and Hand1 expression is switched off, embryonic hearts recover by E16...
July 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28731465/pr-set7-deficiency-limits-uterine-epithelial-population-growth-hampering-postnatal-gland-formation-in-mice
#2
Tongtong Cui, Bo He, Shuangbo Kong, Chan Zhou, Hangxiao Zhang, Zhangli Ni, Haili Bao, Jingtao Qiu, Qiliang Xin, Danny Reinberg, John P Lydon, Jinhua Lu, Haibin Wang
Formation of secretary endometrial glands in the uterus known as adenogenesis is a typical process of branching morphogenesis involving dynamic epithelial growth and differentiation. Unsuccessful adenogenesis often leads to female infertility. However, it remains largely unexplored so far regarding the epigenetic machinery governing normal endometrial gland formation. Here, we demonstrated that PR-Set7, an epigenetic regulator for H4K20me1 modification, was extensively expressed in the postnatal uteri, and its conditional deletion resulted in a complete lack of endometrial glands and infertility in mice...
July 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28730707/establishment-and-characterization-of-a-novel-murine-model-of-pancreatic-cancer-cachexia
#3
Katherine A Michaelis, Xinxia Zhu, Kevin G Burfeind, Stephanie M Krasnow, Peter R Levasseur, Terry K Morgan, Daniel L Marks
BACKGROUND: Cachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) is one of the most important conditions associated with cachexia, with >80% of PDAC patients suffering from the condition. To establish the cardinal features of a murine model of PDAC-associated cachexia, we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRAS(G12D) P53(R172H) Pdx-Cre(+/+) (KPC) mouse...
July 20, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28729419/the-exocyst-is-required-for-photoreceptor-ciliogenesis-and-retinal-development
#4
Glenn P Lobo, Diana Fulmer, Lilong Guo, Xiaofeng Zuo, Yujing Dang, Seok-Hyung Kim, Yanhui Su, Kola George, Elisabeth Obert, Ben Fogelgren, Deepak Nihalani, Russell A Norris, Bärbel Rohrer, Joshua H Lipschutz
We previously have shown that the highly-conserved eight-protein exocyst trafficking complex is required for ciliogenesis in kidney tubule cells. We hypothesized here that ciliogenic programs are conserved across organs and species. To determine if renal primary ciliogenic programs are conserved in the eye, and to characterize the function and mechanisms by which the exocyst regulates eye development in zebrafish, we focused on exoc5, a central component of the exocyst complex, by analyzing both exoc5 zebrafish mutants, and photoreceptor-specific Exoc5 knockout mice...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28729389/severe-energy-deficit-up-regulates-leptin-receptors-leptin-signaling-and-ptp1b-in-human-skeletal-muscle
#5
Ismael Perez-Suarez, Jesus Gustavo Ponce-Gonzalez, Jaime de La Calle-Herrero, Jose Losa-Reyna, Marcos Martin-Rincon, David Morales-Alamo, Alfredo Santana, Hans-Christer Holmberg, Jose A L Calbet
In obesity, leptin receptors (OBR) and leptin signaling in skeletal muscle are down-regulated. To determine whether OBR and leptin signaling are up-regulated with a severe energy deficit fifteen overweight men were assessed before (PRE), after 4 days of caloric restriction (3.2 Kcal/kg BW/day) in combination with prolonged exercise (CRE) (8h walking + 45min single-arm cranking/day) to induce an energy deficit of ~5500 Kcal/d, and following 3 days of control diet (isoenergetic) and reduced exercise (CD). During CRE, the diet consisted solely of whey protein (n=8) or sucrose (n=7) (0...
July 20, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28729363/brg1-brahma-related-gene-1-promotes-endothelial-mrtf-transcription-to-establish-embryonic-capillary-integrity
#6
Matthew T Menendez, E-Ching Ong, Brian T Shepherd, Vijay Muthukumar, Robert Silasi-Mansat, Florea Lupu, Courtney T Griffin
OBJECTIVE: The chromatin remodeling enzyme BRG1 (brahma-related gene 1) transcriptionally regulates target genes important for early blood vessel development and primitive hematopoiesis. However, because Brg1 deletion in vascular progenitor cells results in lethal anemia by embryonic day 10.5 (E10.5), roles for BRG1 in embryonic vascular development after midgestation are unknown. In this study, we sought to determine whether endothelial cell BRG1 regulates genes important for vascular development or maintenance later in embryonic development...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28729032/a-novel-model-of-autosomal-recessive-polycystic-kidney-questions-the-role-of-the-fibrocystin-c-terminus-in-disease-mechanism
#7
Patricia Outeda, Luis Menezes, Erum A Hartung, Stacey Bridges, Fang Zhou, Xianjun Zhu, Hangxue Xu, Qiong Huang, Qin Yao, Feng Qian, Gregory G Germino, Terry Watnick
Autosomal recessive polycystic kidney disease (OMIM 263200) is a serious condition of the kidney and liver caused by mutations in a single gene, PKHD1. This gene encodes fibrocystin/polyductin (FPC, PD1), a large protein shown by in vitro studies to undergo Notch-like processing. Its cytoplasmic tail, reported to include a ciliary targeting sequence, a nuclear localization signal, and a polycystin-2 binding domain, is thought to traffic to the nucleus after cleavage. We now report a novel mouse line with a triple HA-epitope "knocked-in" to the C-terminus along with lox P sites flanking exon 67, which encodes most of the C-terminus (Pkhd1(Flox67HA))...
July 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28727705/activation-of-the-rage-stat3-pathway-in-the-dorsal-root-ganglion-contributes-to-the-persistent-pain-hypersensitivity-induced-by-lumbar-disc-herniation
#8
Xin-Sheng Zhang, Xiao Li, Hai-Jie Luo, Zhu-Xi Huang, Cui-Cui Liu, Qing Wan, Shu-Wei Xu, Shao-Ling Wu, Song-Jian Ke, Chao Ma
BACKGROUND: Clinically, chronic low back pain and sciatica associated with lumbar disc herniation (LDH) is a common musculoskeletal disorder. Due to the unawareness of detailed mechanisms, it is difficult to get an effective therapy. OBJECTIVE: The aim of the present study was to identify the role of the RAGE/STAT3 pathway in the dorsal root ganglion (DRG) on the formation and development of persistent pain hypersensitivity induced by LDH. STUDY DESIGN: Controlled animal study...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28727685/erbb4-signaling-in-dopaminergic-axonal-projections-increases-extracellular-dopamine-levels-and-regulates-spatial-working-memory-behaviors
#9
M Skirzewski, I Karavanova, A Shamir, L Erben, J Garcia-Olivares, J H Shin, D Vullhorst, V A Alvarez, S G Amara, A Buonanno
Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction. To date, most ErbB4 studies have focused on GABAergic interneurons in the hippocampus and neocortex, particularly fast-spiking parvalbumin-positive (PV+) basket cells. However, NRG has also been shown to modulate DA levels, suggesting a role for ErbB4 signaling in dopaminergic neuron function...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28726785/jun-is-important-for-ocular-hypertension-induced-retinal-ganglion-cell-degeneration
#10
Stephanie B Syc-Mazurek, Kimberly A Fernandes, Richard T Libby
Ocular hypertension, a major risk factor for glaucoma, is thought to trigger glaucomatous neurodegeneration through injury to retinal ganglion cell (RGC) axons. The molecular signaling pathway leading from ocular hypertension to RGC degeneration, however, is not well defined. JNK signaling, a component of the mitogen-activated protein kinase (MAPK) family, and its canonical target, the transcription factor JUN, have been shown to regulate neurodegeneration in many different systems. JUN is expressed after glaucoma-relevant injuries and Jun deficiency protects RGCs after mechanical injury to the optic nerve...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726143/endoscopic-management-of-post-laparoscopic-sleeve-gastrectomy-stenosis
#11
Valérie Deslauriers, Amélie Beauchamp, Fabio Garofalo, Henri Atlas, Ronald Denis, Pierre Garneau, Radu Pescarus
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is the most popular bariatric surgery worldwide. Gastric sleeve stenosis is the most common postoperative complication, occurring in up to 3.9% of the cases. Current treatment options include endoscopic treatments, such as dilatations and stent placement as well as surgical revisions such as laparoscopic Roux-en-Y gastric bypass (LRYGB), wedge gastrectomy or seromyotomy. METHODS: A retrospective analysis of our prospectively collected therapeutical endoscopy database was performed between January 2014 and February 2017...
July 19, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28725186/foxb1-regulates-negatively-the-proliferation-of-oligodendrocyte-progenitors
#12
Yuanfeng Zhang, Elti Hoxha, Tianyu Zhao, Xunlei Zhou, Gonzalo Alvarez-Bolado
Oligodendrocyte precursor cells (OPC), neurons and astrocytes share a neural progenitor cell (NPC) in the early ventricular zone (VZ) of the embryonic neuroepithelium. Both switch to produce either of the three cell types and the generation of the right number of them undergo complex genetic regulation. The components of these regulatory cascades vary between brain regions giving rise to the unique morphological and functional heterogeneity of this organ. Forkhead b1 (Foxb1) is a transcription factor gene expressed by NPCs in specific regions of the embryonic neuroepithelium...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28724963/midnolin-is-a-novel-regulator-of-parkin-expression-and-is-associated-with-parkinson-s-disease
#13
Yutaro Obara, Toru Imai, Hidenori Sato, Yuji Takeda, Takeo Kato, Kuniaki Ishii
Midnolin (MIDN) was first discovered in embryonic stem cells, but its physiological and pathological roles are, to date, poorly understood. In the present study, we therefore examined the role of MIDN in detail. We found that in PC12 cells, a model of neuronal cells, MIDN localized primarily to the nucleus and intracellular membranes. Nerve growth factor promoted MIDN gene expression, which was attenuated by specific inhibitors of extracellular signal-regulated kinases 1/2 and 5. MIDN-deficient PC12 cells created using CRISPR/Cas9 technology displayed significantly impaired neurite outgrowth...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724545/magnetic-resonance-spectroscopy-in-preterm-infants-association-with-neurodevelopmental-outcomes
#14
Reina Hyodo, Yoshiaki Sato, Miharu Ito, Yuichiro Sugiyama, Chikako Ogawa, Hisashi Kawai, Toshiki Nakane, Akiko Saito, Akihiro Hirakawa, Hiroyuki Kidokoro, Jun Natsume, Masahiro Hayakawa
OBJECTIVE: To compare magnetic resonance spectroscopy (MRS) metabolite ratios in preterm infants at term-equivalent age with those in term infants and to evaluate the association between MRS metabolites and neurodevelopmental outcomes at 18 months corrected age in preterm infants. DESIGN: We studied infants born at a gestational age <37 weeks and weighing <1500 g during 2009-2013 using MRS at term-equivalent age. Infants with major brain abnormalities were excluded...
July 19, 2017: Archives of Disease in Childhood. Fetal and Neonatal Edition
https://www.readbyqxmd.com/read/28722693/ikk-nf-%C3%AE%C2%BAb-dependent-satellite-glia-activation-induces-spinal-cord-microglia-activation-and-neuropathic-pain-after-nerve-injury
#15
Hyoungsub Lim, Hyunkyoung Lee, Kyungchul Noh, Sung Joong Lee
Increasing evidence indicates that both microglia and satellite glial cell (SGC) activation play causal roles in neuropathic pain development after peripheral nerve injury; however, the activation mechanisms and their contribution to neuropathic pain remain elusive. To address this issue, we generated Ikkβ conditional knockout mice (Cnp-Cre/Ikkβ; cIkkβ) in which IKK/NF-κB-dependent proinflammatory SGC activation was abrogated. In these mice, nerve injury-induced spinal cord microglia activation and pain hypersensitivity were significantly attenuated compared to those in control mice...
May 30, 2017: Pain
https://www.readbyqxmd.com/read/28722653/directing-visceral-white-adipocyte-precursors-to-a-thermogenic-adipocyte-fate-improves-insulin-sensitivity-in-obese-mice
#16
Chelsea Hepler, Mengle Shao, Jonathan Y Xia, Alexandra L Ghaben, Mackenzie J Pearson, Lavanya Vishvanath, Ankit X Sharma, Thomas S Morley, William L Holland, Rana K Gupta
Visceral adiposity confers significant risk for developing metabolic disease in obesity whereas preferential expansion of subcutaneous white adipose tissue (WAT) appears protective. Unlike subcutaneous WAT, visceral WAT is resistant to adopting a protective thermogenic phenotype characterized by the accumulation of Ucp1(+) beige/BRITE adipocytes (termed "browning"). In this study, we investigated the physiological consequences of browning murine visceral WAT by selective genetic ablation of Zfp423, a transcriptional suppressor of the adipocyte thermogenic program...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28720858/gsk-3%C3%AE-deletion-in-dentate-gyrus-excitatory-neuron-impairs-synaptic-plasticity-and-memory
#17
Enjie Liu, Ao-Ji Xie, Qiuzhi Zhou, Mengzhu Li, Shujuan Zhang, Shihong Li, Weijin Wang, Xiaochuan Wang, Qun Wang, Jian-Zhi Wang
Increasing evidence suggests that glycogen synthase kinase-3β (GSK-3β) plays a crucial role in neurodegenerative/psychiatric disorders, while pan-neural knockout of GSK-3β also shows detrimental effects. Currently, the function of GSK-3β in specific type of neurons is elusive. Here, we infused AAV-CaMKII-Cre-2A-eGFP into GSK-3β(lox/lox) mice to selectively delete the kinase in excitatory neurons of hippocampal dentate gyrus (DG), and studied the effects on cognitive/psychiatric behaviors and the molecular mechanisms...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719590/pericyte-expressed-tie2-controls-angiogenesis-and-vessel-maturation
#18
Martin Teichert, Laura Milde, Annegret Holm, Laura Stanicek, Nicolas Gengenbacher, Soniya Savant, Tina Ruckdeschel, Zulfiyya Hasanov, Kshitij Srivastava, Junhao Hu, Stella Hertel, Arne Bartol, Katharina Schlereth, Hellmut G Augustin
The Tie receptors with their Angiopoietin ligands act as regulators of angiogenesis and vessel maturation. Tie2 exerts its functions through its supposed endothelial-specific expression. Yet, Tie2 is also expressed at lower levels by pericytes and it has not been unravelled through which mechanisms pericyte Angiopoietin/Tie signalling affects angiogenesis. Here we show that human and murine pericytes express functional Tie2 receptor. Silencing of Tie2 in pericytes results in a pro-migratory phenotype. Pericyte Tie2 controls sprouting angiogenesis in in vitro sprouting and in vivo spheroid assays...
July 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28717030/intestinal-epithelial-ecto-5-nucleotidase-cd73-regulates-intestinal-colonization-and-infection-by-nontyphoidal-salmonella
#19
Daniel J Kao, Bejan J Saeedi, David Kitzenberg, Krista M Burney, Evgenia Dobrinskikh, Kayla D Battista, Andrés Vázquez-Torres, Sean P Colgan, Douglas J Kominsky
Ecto-5' -nucleotidase (CD73) is expressed abundantly on the apical surface of intestinal epithelial cells (IEC) and functions as the terminal enzyme in the generation of extracellular adenosine. Previous work has demonstrated that adenosine signaling in IECs results in a number of tissue-protective effects during inflammation; however, a rationale for its apical expression has been lacking. We hypothesized that the highly polarized expression of CD73 is indicative of an important role for extracellular adenosine as a mediator of host-microbe interactions...
July 17, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28716720/met-signaling-mediates-intestinal-crypt-villus-development-regeneration-and-adenoma-formation-and-is-promoted-by-stem-cell-cd44-isoforms
#20
Sander P J Joosten, Jurrit Zeilstra, Harmen van Andel, R Clinton Mijnals, Joost Zaunbrecher, Annet A M Duivenvoorden, Marc van de Wetering, Hans Clevers, Marcel Spaargaren, Steven T Pals
BACKGROUND & AIMS: Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor receptor (EGFR) signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET co-receptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice...
July 14, 2017: Gastroenterology
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