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https://www.readbyqxmd.com/read/29458024/spinal-cord-specific-deletion-of-the-glutamate-transporter-glt1-causes-motor-neuron-death-in-mice
#1
Kaori Sugiyama, Kohichi Tanaka
Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disorder characterized by the selective loss of motor neurons. The precise mechanisms that cause the selective death of motor neurons remain unclear, but a growing body of evidence suggests that glutamate-mediated excitotoxicity has been considered to play an important role in the mechanisms of motor neuron degeneration in ALS. Reductions in glutamate transporter GLT1 have been reported in animal models of ALS and the motor cortex and spinal cord of ALS patients...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453306/acute-pressor-response-to-psychosocial-stress-is-dependent-on-endothelium-derived-endothelin-1
#2
Brandon M Fox, Bryan K Becker, Analia S Loria, Kelly A Hyndman, Chunhua Jin, Hannah Clark, Robin Johns, Masashi Yanagisawa, David M Pollock, Jennifer S Pollock
BACKGROUND: Acute psychosocial stress provokes increases in circulating endothelin-1 (ET-1) levels in humans and animal models. However, key questions about the physiological function and cellular source of stress-induced ET-1 remain unanswered. We hypothesized that endothelium-derived ET-1 contributes to the acute pressor response to stress via activation of the endothelin A receptor. METHODS AND RESULTS: Adult male vascular endothelium-specific ET-1 knockout mice and control mice that were homozygous for the floxed allele were exposed to acute psychosocial stress in the form of cage switch stress (CSS), with blood pressure measured by telemetry...
February 16, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29452569/up-regulation-of-sftpb-expression-and-attenuation-of-acute-lung-injury-by-pulmonary-epithelial-cell-specific-nampt-knockdown
#3
Guangliang Bi, Lei Wu, Peixin Huang, Shamima Islam, Daniel P Heruth, Li Qin Zhang, Ding-You Li, Venkatesh Sampath, Weimin Huang, Brett A Simon, Ronald Blaine Easley, Shui Qing Ye
Although a deficiency of surfactant protein B (SFTPB) has been associated with lung injury, SFTPB expression has not yet been linked with nicotinamide phosphoribosyltransferase (NAMPT), a potential biomarker of acute lung injury (ALI). The effects of Nampt in the pulmonary epithelial cell on both SFTPB expression and lung inflammation were investigated in a LPS-induced ALI mouse model. Pulmonary epithelial cell-specific knockdown of Nampt gene expression, achieved by the crossing of Nampt gene exon 2 floxed mice with mice expressing epithelial-specific transgene Cre or by the use of epithelial-specific expression of anti-Nampt antibody cDNA, significantly attenuated LPS-induced ALI...
February 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29446202/conditional-deletion-of-cadherin-13-perturbs-golgi-cells-and-disrupts-social-and-cognitive-behaviors
#4
Martesa Tantra, Lanboling Guo, Jinsook Kim, Norliyana Zainolabidin, George J Augustine, Volker Eulenburg, Albert I Chen
Inhibitory interneurons mediate the gating of synaptic transmission and modulate the activities of neural circuits. Disruption of the function of inhibitory networks in the forebrain is linked to impairment of social and cognitive behaviors, but the involvement of inhibitory interneurons in the cerebellum has not been assessed. We found that Cadherin 13 (Cdh13), a gene implicated in autism spectrum disorder and attention-deficit hyperactivity disorder, is specifically expressed in Golgi cells within the cerebelluar cortex...
February 15, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29433384/region-specific-knock-out-reveals-distinct-roles-of-chromatin-modifiers-in-adult-neurogenic-niches
#5
Christopher T Rhodes, Giulia Zunino, Shu-Wei Angela Huang, Sandra M Cardona, Astrid E Cardona, Mitchel S Berger, Vance P Lemmon, Chin-Hsing Annie Lin
Histone methyltransferases (HMTs) are present in heterogeneous cell populations within the adult brain including neurogenic niches. Yet the question remains whether loss of HMTs and the resulting changes in histone methylation alter cell fate in a region-specific manner. We utilized stereotaxic injection of Cre recombinant protein into the adult neurogenic niches, the subventricular zone (SVZ) adjacent to the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus. We confirmed that Cre protein was enzymatically active in vivo and recombination events were restricted to the vicinity of injection areas...
February 13, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29419930/stat1-is-a-sex-specific-tumor-suppressor-in-colitis-associated-colorectal-cancer
#6
Ilija Crnčec, Madhura Modak, Claire Gordziel, Jasmin Svinka, Irene Scharf, Stefan Moritsch, Paulina Pathria, Michaela Schlederer, Lukas Kenner, Gerald Timelthaler, Mathias Müller, Birgit Strobl, Emilio Casanova, Editha Bayer, Thomas Mohr, Johannes Stöckl, Karlheinz Friedrich, Robert Eferl
The interferon-inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated sex-specific STAT1 functions in colitis and colitis-associated colorectal cancer (CRC) using mice with specific STAT1 deletion in intestinal epithelial cells (STAT1 ∆ IEC ). Male but not female STAT1 ∆ IEC mice were more resistant to DSS-induced colitis than sex-matched STAT1 flox/flox controls and displayed reduced intraepithelial infiltration of CD8 + TCRαβ + Granzyme B + T cells. Moreover, DSS treatment failed to induce expression of T cell-attracting chemokines in intestinal epithelial cells of male but not of female STAT1 ∆ IEC mice...
February 8, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29415989/sphingolipid-de-novo-biosynthesis-is-essential-for-intestine-cell-survival-and-barrier-function
#7
Zhiqiang Li, Inamul Kabir, Gladys Tietelman, Chongmin Huan, Jianglin Fan, Tilla Worgall, Xian-Cheng Jiang
Serine palmitoyltransferase (SPT) is the rate-limiting enzyme for sphingolipid biosynthesis. SPT has two major subunits, SPTLC1 and SPTLC2. We previously found that liver Sptlc2 deficiency in early life impairs the development of adherens junctions. Here, we investigated the role of Sptlc2 deficiency in intestine. We treated Sptlc2-Flox/villin-Cre-ERT2 mice with tamoxifen (days 1, 2, and 3) to ablate Sptlc2 specifically in the intestine. At day 6 after tamoxifen treatment, Sptlc2-deficient mice had significantly decreased body weight with concurrent diarrhea and rectal bleeding...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29415226/temporal-regulation-of-dendritic-spines-through-nrcam-semaphorin3f-receptor-signaling-in-developing-cortical-pyramidal-neurons
#8
Vishwa Mohan, Chelsea S Sullivan, Jiami Guo, Sarah D Wade, Samarpan Majumder, Amit Agarwal, Eva S Anton, Brenda S Temple, Patricia F Maness
Neuron-glial related cell adhesion molecule NrCAM is a newly identified negative regulator of spine density that genetically interacts with Semaphorin3F (Sema3F), and is implicated in autism spectrum disorders (ASD). To investigate a role for NrCAM in spine pruning during the critical adolescent period when networks are established, we generated novel conditional, inducible NrCAM mutant mice (Nex1Cre-ERT2: NrCAMflox/flox). We demonstrate that NrCAM functions cell autonomously during adolescence in pyramidal neurons to restrict spine density in the visual (V1) and medial frontal cortex (MFC)...
February 3, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29415061/a-cre-inducible-dux4-transgenic-mouse-model-for-investigating-facioscapulohumeral-muscular-dystrophy
#9
Takako Jones, Peter L Jones
The Double homeobox 4 (DUX4) gene is an important regulator of early human development and its aberrant expression is causal for facioscapulohumeral muscular dystrophy (FSHD). The DUX4-full length (DUX4-fl) mRNA splice isoform encodes a transcriptional activator; however, DUX4 and its unique DNA binding preferences are specific to old-world primates. Regardless, the somatic cytotoxicity caused by DUX4 expression is conserved when expressed in cells and animals ranging from fly to mouse. Thus, viable animal models based on DUX4-fl expression have been difficult to generate due in large part to overt developmental toxicity of low DUX4-fl expression from leaky transgenes...
2018: PloS One
https://www.readbyqxmd.com/read/29410383/concentrated-ambient-pm2-5-induced-inflammation-and-endothelial-dysfunction-in-a-murine-model-of-neural-ikk2-deficiency
#10
Minjie Chen, Xiaobo Qin, Lianglin Qiu, Sufang Chen, Huifen Zhou, Yanyi Xu, Ziying Hu, Yuhao Zhang, Qi Cao, Zhekang Ying
BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) is associated with cardiovascular mortality, but underlying pathophysiologic mechanisms are not fully understood. Hypothalamic inflammation, characterized by the activation of Inhibitor kappaB kinase 2/Nuclear factor kappaB (IKK2/NF-κB) signaling pathway, may play an important role in the pathogenesis of cardiovascular diseases. We recently demonstrated that hypothalamic inflammation is increased in mice exposed to concentrated ambient PM2...
February 5, 2018: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29408885/ezh2-does-not-mediate-retinal-ganglion-cell-homeostasis-or-their-susceptibility-to-injury
#11
Lin Cheng, Lucy J Wong, Naihong Yan, Richard C Han, Honghua Yu, Chenying Guo, Khulan Batsuuri, Aniket Zinzuwadia, Ryan Guan, Kin-Sang Cho, Dong Feng Chen
Epigenetic predisposition is thought to critically contribute to adult-onset disorders, such as retinal neurodegeneration. The histone methyltransferase, enhancer of zeste homolog 2 (Ezh2), is transiently expressed in the perinatal retina, particularly enriched in retinal ganglion cells (RGCs). We previously showed that embryonic deletion of Ezh2 from retinal progenitors led to progressive photoreceptor degeneration throughout life, demonstrating a role for embryonic predisposition of Ezh2-mediated repressive mark in maintaining the survival and function of photoreceptors in the adult...
2018: PloS One
https://www.readbyqxmd.com/read/29401593/mmp14-is-a-novel-target-of-pth-signaling-in-osteocytes-that-controls-resorption-by-regulating-soluble-rankl-production
#12
Jesus Delgado-Calle, Benjamin Hancock, Elive F Likine, Amy Y Sato, Kevin McAndrews, Carolina Sanudo, Angela Bruzzaniti, Jose A Riancho, James R Tonra, Teresita Bellido
Parathyroid hormone (PTH) affects the skeleton by acting on osteocytes (Ot) in bone through yet unclear mechanisms. We report that matrix metalloproteinase 14 (MMP14) expression/activity are increased in bones from mice with genetic constitutive activation (ca) of the PTH receptor 1 (PTH1R) in Ot (caPTH1ROt) and in bones from mice exposed to elevated PTH levels but not in mice lacking [conditional knockout (cKO)] the PTH1R in Ot (cKOPTH1ROt). Furthermore, PTH upregulates MMP14 in human bone cultures and in Ot-enriched bones from floxed control mice but not from cKOPTH1ROt mice...
January 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29398618/a-role-for-long-chain-acyl-coa-synthetase-4-acsl4-in-diet-induced-phospholipid-remodeling-and-obesity-associated-adipocyte-dysfunction
#13
Elizabeth A Killion, Andrew R Reeves, Mahmoud A El Azzouny, Qing-Wu Yan, Defne Surujon, John D Griffin, Thomas A Bowman, Chunyan Wang, Nirupa R Matthan, Eric L Klett, Dong Kong, John W Newman, Xianlin Han, Mi-Jeong Lee, Rosalind A Coleman, Andrew S Greenberg
OBJECTIVE: Regulation of fatty acid (FA) metabolism is central to adipocyte dysfunction during diet-induced obesity (DIO). Long-chain acyl-CoA synthetase-4 (ACSL4) has been hypothesized to modulate the metabolic fates of polyunsaturated FA (PUFA), including arachidonic acid (AA), but the in vivo actions of ACSL4 are unknown. The purpose of our studies was to determine the in vivo role of adipocyte ACSL4 in regulating obesity-associated adipocyte dysfunction. METHODS: We developed a novel mouse model with adipocyte-specific ablation of ACSL4 (Ad-KO) using loxP Cre recombinase technology...
January 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29396649/ghrelin-causes-a-decline-in-gaba-release-by-reducing-fatty-acid-oxidation-in-cortex
#14
Joan Francesc Mir, Sebastián Zagmutt, Mathieu P Lichtenstein, Judit García-Villoria, Minéia Weber, Ana Gracia, Gemma Fabriàs, Josefina Casas, Miguel López, Núria Casals, Antònia Ribes, Cristina Suñol, Laura Herrero, Dolors Serra
Lipid metabolism, specifically fatty acid oxidation (FAO) mediated by carnitine palmitoyltransferase (CPT) 1A, has been described to be an important actor of ghrelin action in hypothalamus. However, it is not known whether CPT1A and FAO mediate the effect of ghrelin on the cortex. Here, we show that ghrelin produces a differential effect on CPT1 activity and γ-aminobutyric acid (GABA) metabolism in the hypothalamus and cortex of mice. In the hypothalamus, ghrelin enhances CPT1A activity while GABA transaminase (GABAT) activity, a key enzyme in GABA shunt metabolism, is unaltered...
February 2, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29396144/mouse-macrophage-specific-knockout-of-sirt1-influences-macrophage-polarization-and-promotes-angiotensin-ii-induced-abdominal-aortic-aneurysm-formation
#15
Zhuqin Zhang, Jing Xu, Yue Liu, Tingting Wang, Jianfei Pei, Liqin Cheng, Delong Hao, Xiang Zhao, Hou-Zao Chen, De-Pei Liu
Abdominal aortic aneurysm (AAA) is a vascular degenerative disease. Macrophage polarization and the balance between classically activated macrophages (M1) and alternatively activated macrophages (M2) are crucial for AAA pathogenesis. The present study aims to investigate the roles of macrophage SIRT1 in AAA formation and macrophage polarization. We found that in mouse peritoneal macrophages, SIRT1 expression was decreased after M1 stimulation, but was enhanced after M2 stimulation. Results from SIRT1flox/flox mice and macrophage specific SIRT1 knockout mice with treatment of angiotensin II (Ang II) for 4 weeks showed that macrophage specific deficiency of SIRT1 increased the incidence of AAA and exacerbated the severity, including more severe aneurysm types, enlarged diameter of the aneurysm and increased degradation of elastin...
January 17, 2018: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/29384525/mtor-inhibitor-based-combination-therapies-for-pancreatic-cancer
#16
Zonera Hassan, Christian Schneeweis, Matthias Wirth, Christian Veltkamp, Zahra Dantes, Benedikt Feuerecker, Güralp O Ceyhan, Shirley K Knauer, Wilko Weichert, Roland M Schmid, Roland Stauber, Alexander Arlt, Oliver H Krämer, Roland Rad, Maximilian Reichert, Dieter Saur, Günter Schneider
BACKGROUND: Although the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification. METHODS: We used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance...
January 2, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29384270/cognitive-deficits-and-increases-in-creatine-precursors-in-a-brain-specific-knockout-of-the-creatine-transporter-gene-slc6a8
#17
Kenea C Udobi, Amanda N Kokenge, Emily R Hautman, Gabriela Ullio, Julie Coene, Michael T Williams, Charles V Vorhees, Aloïse Mabondzo, Matthew R Skelton
Creatine transporter (CrT; SLC6A8) deficiency (CTD) is an X-linked disorder characterized by severe cognitive deficits, impairments in language, and an absence of brain creatine (Cr). In a previous study, we generated floxed Slc6a8 (Slc6a8flox ) mice to create ubiquitous Slc6a8 knockout (Slc6a8-/y ) mice. Slc6a8-/y mice lacked whole body Cr and exhibited cognitive deficits. While Slc6a8-/y mice have a similar biochemical phenotype to CTD patients, they also showed a reduction in size and reductions in swim speed that may have contributed to the observed deficits...
January 31, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29381243/neural-crest-derived-cells-migrate-from-nerve-to-participate-in-achilles-tendon-remodeling
#18
Kang Xu, Xin Pan, Xuefeng Qiu, Dong Wang, Nianguo Dong, Li Yang, Song Li
During tendon injuries, nerve ingrowth is one of the earliest events of tendon repair and remodeling. Since peripheral neurons and associated cells are mostly derived from neural crest (NC) cells, we sought to investigate the role of NC-derived cells in tendon regeneration. Thus, we used Sox10-Cre/ROSA26-Flox-Red Fluorescent Protein (RFP) transgenic mice to trace these cells during tendon regeneration. After 4 weeks of Achilles tendon rupture, the injured tendon tissues were harvested for immunohistological analyses, cell isolation, and phenotype identification...
January 30, 2018: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/29379893/the-orphan-nuclear-receptor-liver-homolog-receptor-1-nr5a2-regulates-ovarian-granulosa-cell-proliferation
#19
Marie-Charlotte Meinsohn, Fanny Morin, Kalyne Bertolin, Raj Duggavathi, Kristina Schoonjans, Bruce D Murphy
In mouse ovaries, liver receptor homolog-1 [nuclear receptor subfamily 5, group A, member 2 (Nr5a2)] expression is restricted to granulosa cells. Mice with Nr5a2 depletion in this cell population fail to ovulate. To determine whether Nr5a2 is essential for granulosa cell proliferation during follicular maturation, we generated granulosa-specific conditional knockout mice (genotype Nr5a2 floxed Cre-recombinase driven by the anti-Müllerian type II receptor, hereafter cKO) with Nr5a2 depletion from primary follicles forward...
January 1, 2018: Journal of the Endocrine Society
https://www.readbyqxmd.com/read/29378301/connexin43-and-zonula-occludens-1-are-targets-of-akt-in-cardiomyocytes-that-correlate-with-cardiac-contractile-dysfunction-in-akt-deficient-hearts
#20
Sangmi Ock, Wang Soo Lee, Hyun Min Kim, Kyu-Sang Park, Young-Kook Kim, Hyun Kook, Woo Jin Park, Tae Jin Lee, E D Abel, Jaetaek Kim
While deletion of Akt1 results in a smaller heart size and Akt2-/- mice are mildly insulin resistant, Akt1-/-/Akt2-/- mice exhibit perinatal lethality, indicating a large degree of functional overlap between the isoforms of the serine/threonine kinase Akt. The present study aimed to determine the cooperative contribution of Akt1 and Akt2 on the structure and contractile function of adult hearts. To generate an inducible, cardiomyocyte-restricted Akt2 knockout (KO) model, Akt2flox/flox mice were crossed with tamoxifen-inducible MerCreMer transgenic (MCM) mice and germline Akt1-/- mice to generate the following genotypes:Akt1+/+; Akt2flox/flox (WT), Akt2flox/flox; α-MHC-MCM (iAkt2 KO), Akt1-/-, and Akt1-/-; Akt2flox/flox; α-MHC-MCM mice (Akt1-/-/iAkt2 KO)...
January 31, 2018: Biochimica et Biophysica Acta
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