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https://www.readbyqxmd.com/read/29054881/ablation-of-tfr1-in-purkinje-cells-inhibits-mglu1-trafficking-and-impairs-motor-coordination-but-not-autistic-like-behaviors
#1
Jia-Huan Zhou, Xin-Tai Wang, Liang Zhou, Lin Zhou, Fang-Xiao Xu, Li-Da Su, Hao Wang, Fan Jia, Fu-Qiang Xu, Gui-Quan Chen, Chris De Zeeuw, Ying Shen
Group 1 metabotropic glutamate receptors (mGlu1/5) are critical to synapse formation and participate in synaptic long-term potentiation (LTP) and long-term depression (LTD) in the brain. mGlu1/5 signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases, but underlying mechanisms for its modulation are not clear. Here, we report that transferrin receptor 1 (TFR1), a trans-membrane protein of clathrin complex, modulates the trafficking of mGlu1 in cerebellar Purkinje cells (PCs) from male mice...
October 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29054843/contribution-of-extra-cardiac-cells-in-murine-heart-valves-is-age-dependent
#2
Lindsey J Anstine, Tori E Horne, Edwin M Horwitz, Joy Lincoln
BACKGROUND: Heart valves are dynamic structures that open and close over 100 000 times a day to maintain unidirectional blood flow during the cardiac cycle. Function is largely achieved by highly organized layers of extracellular matrix that provide the necessary biomechanical properties. Homeostasis of valve extracellular matrix is mediated by valve endothelial and interstitial cell populations, and although the embryonic origins of these cells are known, it is not clear how they are maintained after birth...
October 20, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29054088/the-interactions-among-organophosphate-pesticide-exposure-oxidative-stress-and-genetic-polymorphisms-of-dopamine-receptor-d4-increase-the-risk-of-attention-deficit-hyperactivity-disorder-in-children
#3
Chia-Huang Chang, Ching-Jung Yu, Jung-Chieh Du, Hsien-Chih Chiou, Hsin-Chang Chen, Winnie Yang, Ming-Yi Chung, Ying-Sheue Chen, Betau Hwang, I-Fang Mao, Mei-Lien Chen
OBJECTIVE: The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. METHODS: This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified...
October 17, 2017: Environmental Research
https://www.readbyqxmd.com/read/29052235/establishment-of-a-markerless-multiple-gene-deletion-method-based-on-cre-loxp-mutant-system-for-bacillus-pumilus
#4
Zheng-Bing Guan, Kai-Qiang Wang, Yan Shui, Xiang-Ru Liao
In this study, we established a Cre/loxP mutant recombination system (Cre/lox71-66 system) for markerless gene deletion to facilitate our follow-up rational genetic engineering to the strain Bacillus pumilus W3. This modified method uses two mutant loxP sites, which after recombination creates a double-mutant loxP site that is poorly recognized by Cre recombinase, facilitating multiple gene deletions in a single genetic background. Two selected genes, cotA and sigF, were continuously knocked out and verified at different levels using this method...
October 20, 2017: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/29051279/expansion-of-epor-negative-macrophages-besides-erythroblasts-by-elevated-epor-signaling-in-erythrocytosis-mouse-models
#5
Jieyu Wang, Yoshihiro Hayashi, Asumi Yokota, Zefeng Xu, Yue Zhang, Rui Huang, Xiaomei Yan, Hongyun Liu, Liping Ma, Mohammad Azam, James P Bridges, Jose A Cancelas, Theodosia A Kalfa, Xiuli An, Zhijian Xiao, Gang Huang
Activated EPO receptor (EPOR) signaling causes erythrocytosis. The important role of macrophages for the erythroid expansion and differentiation process has been reported, both in baseline and stress erythropoiesis. However, the significance of EPOR signaling for regulation of macrophages contributing to erythropoiesis has not been fully understood. Here we show that EPOR signaling activation quickly expands both erythrocytes and macrophages in vivo in mouse models of primary and secondary erythrocytosis. To mimic the chimeric condition and expansion of the disease clone in the polycythemia vera patients, we combined Cre-inducible Jak2V617F/+ allele with LysM-Cre allele which expresses in mature myeloid cells and some of the HSC/Ps (LysM-Cre;Jak2V617F/+ mice)...
October 19, 2017: Haematologica
https://www.readbyqxmd.com/read/29051265/regulation-of-notch-signaling-by-rab7-and-rab8-requires-carboxyl-methylation-by-icmt
#6
Helen Court, Ian M Ahearn, Marc Amoyel, Erika A Bach, Mark R Philips
Isoprenylcysteine carboxyl methyltransferase (ICMT) methylesterifies C-terminal prenylcysteine residues of CaaX proteins and some RAB GTPases. Deficiency of either ICMT or NOTCH1 accelerates pancreatic neoplasia in Pdx1-Cre;LSL-Kras(G12D) mice, suggesting that ICMT is required for NOTCH signaling. We used Drosophila melanogaster wing vein and scutellar bristle development to screen Rab proteins predicted to be substrates for ICMT (ste14 in flies). We identified Rab7 and Rab8 as ICMT substrates that when silenced phenocopy ste14 deficiency...
October 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29050937/integrated-expression-profiling-of-potassium-channels-identifys-kcnn4-as-a-prognostic-biomarker-of-pancreatic-cancer
#7
Shuheng Jiang, Lili Zhu, Jianyu Yang, Lipeng Hu, Jianren Gu, Xin Xing, Yongwei Sun, Zhigang Zhang
Dysregulated potassium (K(+)) channels have previously been shown to promote the development and progression of many types of cancers. Meanwhile, K(+) channels are particularly important in regulating the endocrine and exocrine functions of pancreas. However, the expression pattern and prognostic significance of K(+) channels in pancreatic ductal adenocarcinoma (PDAC) remain unknown. In this study, by screening a GEO dataset containing 36 microdissected PDAC and matching normal pancreatic tissue samples, four differentially expressed K(+) channels (KCNJ5, KCNJ16, KCNN4 and KCNK1) were identified in PDAC...
October 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29049388/an-inducible-mouse-model-of-podocin-mutation-related-nephrotic-syndrome
#8
Mansoureh Tabatabaeifar, Tanja Wlodkowski, Ivana Simic, Helga Denc, Geraldine Mollet, Stefanie Weber, John Julius Moyers, Barbara Brühl, Michael Joseph Randles, Rachel Lennon, Corinne Antignac, Franz Schaefer
Mutations in the NPHS2 gene, encoding podocin, cause hereditary nephrotic syndrome. The most common podocin mutation, R138Q, is associated with early disease onset and rapid progression to end-stage renal disease. Knock-in mice carrying a R140Q mutation, the mouse analogue of human R138Q, show developmental arrest of podocytes and lethal renal failure at neonatal age. Here we created a conditional podocin knock-in model named NPHS2 R140Q/-, using a tamoxifen-inducible Cre recombinase, which permits to study the effects of the mutation in postnatal life...
2017: PloS One
https://www.readbyqxmd.com/read/29047390/roles-of-bccip-deficiency-in-mammary-tumorigenesis
#9
Roberto Droz-Rosario, Huimei Lu, Jingmei Liu, Ning-Ang Liu, Shridar Ganesan, Bing Xia, Bruce G Haffty, Zhiyuan Shen
BACKGROUND: Dysregulated DNA repair and cell proliferation controls are essential driving forces in mammary tumorigenesis. BCCIP was originally identified as a BRCA2 and CDKN1A interacting protein that has been implicated in maintenance of genomic stability, cell cycle regulation, and microtubule dynamics. The aims of this study were to determine whether BCCIP deficiency contributes to mammary tumorigenesis, especially for a subset of breast cancers with 53BP1 abnormality, and to reveal the mechanistic implications of BCCIP in breast cancer interventions...
October 18, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29046360/a-erk-rsk-mediated-negative-feedback-loop-regulates-m-csf-evoked-pi3k-akt-activation-in-macrophages
#10
Lijun Wang, Caterina Iorio, Kevin Yan, Howard Yang, Sunao Takeshita, Sumin Kang, Benjamin G Neel, Wentian Yang
Activation of the RAS/ERK and its downstream signaling components is essential for growth factor-induced cell survival, proliferation, and differentiation. The Src homology-2 domain containing protein tyrosine phosphatase 2 (SHP2), encoded by protein tyrosine phosphatase, non-receptor type 11 (Ptpn11), is a positive mediator required for most, if not all, receptor tyrosine kinase-evoked RAS/ERK activation, but differentially regulates the PI3K/AKT signaling cascade in various cellular contexts. The precise mechanisms underlying the differential effects of SHP2 deficiency on the PI3K pathway remain unclear...
October 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29046274/genetic-depletion-or-hyperresponsiveness-of-natural-killer-cells-do-not-affect-atherosclerosis-development
#11
Wared Nour Eldine, Jeremie Joffre, Kazem Zibara, Andreas Giraud, Bruno Esposito, Lynda Zeboudj, José Vilar, Megumi Terada, Patrick Bruneval, Eric Vivier, Hafid Ait-Oufella, Ziad Mallat, Sophie Ugolini, Alain Tedgui
Rationale: Chronic inflammation is central in the development of atherosclerosis. Both innate and adaptive immunity are involved. Although several studies have evaluated the functions of NK cells in experimental animal models of atherosclerosis, it is not yet clear whether NK cells behave as protective or pro-atherogenic effectors. One of the main caveats of previous studies was the lack of specificity in targeting loss- or gain-of-function of NK cells. Objective: We used two selective genetic approaches to investigate the role of NK cells in atherosclerosis: 1) Ncr1i(Cre/+)R26(lsl-DTA/+) mice in which NK cells were depleted, 2) Noé mice in which NK cells are hyperresponsive...
October 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/29045046/a-novel-mouse-cre-driver-line-targeting-perilipin-2-expressing-cells-in-the-neonatal-lung
#12
Aglaia Ntokou, Marten Szibor, José Alberto Rodríguez-Castillo, Jennifer Quantius, Susanne Herold, Elie El Agha, Saverio Bellusci, Isabelle Salwig, Thomas Braun, Robert Voswinckel, Werner Seeger, Rory E Morty, Katrin Ahlbrecht
Pulmonary diseases such as chronic obstructive pulmonary disease, lung fibrosis, and bronchopulmonary dysplasia are characterized by the destruction or malformation of the alveolar regions of the lung. The underlying pathomechanisms at play are an area of intense interest since these mechanisms may reveal pathways suitable for interventions to drive reparative processes. Lipid-laden fibroblasts (lipofibroblasts) express the Perilipin 2 (Plin2) gene-product, PLIN2, commonly called adipose-differentiation related protein (ADRP) These cells are also thought to play a role in alveolarization and repair after injury to the alveolus...
October 16, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/29044226/bone-marrow-transplant-induced-alterations-in-notch-signaling-promote-pathologic-th17-responses-to-%C3%AE-herpesvirus-infection
#13
S J Gurczynski, X Zhou, M Flaherty, C A Wilke, B B Moore
Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects...
October 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29042623/the-protein-phosphatase-1-regulator-nipp1-is-essential-for-mammalian-spermatogenesis
#14
Mónica Ferreira, Shannah Boens, Claudia Winkler, Kathelijne Szekér, Iris Verbinnen, Aleyde Van Eynde, Margarida Fardilha, Mathieu Bollen
NIPP1 is one of the major nuclear interactors of protein phosphatase PP1. The deletion of NIPP1 in mice is early embryonic lethal, which has precluded functional studies in adult tissues. Hence, we have generated an inducible NIPP1 knockout model using a tamoxifen-inducible Cre recombinase transgene. The inactivation of the NIPP1 encoding alleles (Ppp1r8) in adult mice occurred very efficiently in testis and resulted in a gradual loss of germ cells, culminating in a Sertoli-cell only phenotype. Before the overt development of this phenotype Ppp1r8 (-/-) testis showed a decreased proliferation and survival capacity of cells of the spermatogenic lineage...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042322/activation-of-parvalbumin-neurons-in-the-rostro-dorsal-sector-of-the-thalamic-reticular-nucleus-promotes-sensitivity-to-pain-in-mice
#15
Jing Liu, Meng-Qi Zhang, Xu Wu, Michael Lazarus, Yoan Cherasse, Mao-Yun Yuan, Zhi-Li Huang, Rui-Xi Li
The calcium-binding protein, parvalbumin (PV), is highly expressed in thalamic reticular nucleus (TRN) GABAergic neurons, which receive input from the cerebral cortex and thalamus and send inhibitory output to the thalamic relay nucleus. Previous studies suggest that the TRN is involved in pain regulation as an important relay nucleus of the ascending pain pathway. However, little is known about its functional role in pain regulation and interconnectivity. In our study, the role of rostro-dorsal sector of TRN (TRNrd) PV-positive neurons in pain regulation was studied using chemogenetics based on designer receptors exclusively activated by designer drugs (DREADD)...
October 14, 2017: Neuroscience
https://www.readbyqxmd.com/read/29039729/antimicrobial-activity-of-ceftolozane-tazobactam-tested-against-enterobacteriaceae-and-pseudomonas-aeruginosa-with-various-resistance-patterns-isolated-in-u-s-hospitals-2013-2016-as-part-of-the-surveillance-program-program-to-assess-ceftolozane-tazobactam-susceptibility
#16
Dee Shortridge, Michael A Pfaller, Mariana Castanheira, Robert K Flamm
This study evaluated the in vitro activity of ceftolozane-tazobactam and comparator agents tested against Enterobacteriaceae and Pseudomonas aeruginosa isolates from hospitalized patients in the United States. Ceftolozane-tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor. A total of 18,960 organisms (15,223 Enterobacteriaceae and 3,737 P. aeruginosa) were consecutively collected from 32 medical centers located in all nine U.S. census divisions from 2013 to 2016...
October 17, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29039455/cell-penetrating-peptides-and-their-utility-in-genome-function-modifications-review
#17
Maciej Gagat, Wioletta Zielińska, Alina Grzanka
For almost 30 years, studies have confirmed the effectiveness of cell-penetrating peptides (CPPs) in the facilitation of the intracellular delivery of various cargo molecules, including RNA, DNA, plasmids, proteins or nanoparticles, under in vitro and in vivo conditions. The cellular uptake of CPPs occurs via energy-dependent, as well as -independent mechanisms. In this relatively new direction of research, studies have attempted to introduce genome modification systems into cells by CPPs. Cellular uptake of CPPs carrying either covalently bound or electrostatically conjugated cargo, has several advantages over viral delivery systems, as it does not lead to any significant cytotoxicity or immunogenicity, and simultaneously it is more efficient than other non-viral systems...
October 4, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29038558/prokineticin-receptor-1-dependent-paracrine-and-autocrine-pathways-control-cardiac-tcf21-fibroblast-progenitor-cell-transformation-into-adipocytes-and-vascular-cells
#18
Rehana Qureshi, Michel Kindo, Himanshu Arora, Mounia Boulberdaa, Marja Steenman, Canan G Nebigil
Cardiac fat tissue volume and vascular dysfunction are strongly associated, accounting for overall body mass. Despite its pathophysiological significance, the origin and autocrine/paracrine pathways that regulate cardiac fat tissue and vascular network formation are unclear. We hypothesize that adipocytes and vasculogenic cells in adult mice hearts may share a common cardiac cells that could transform into adipocytes or vascular lineages, depending on the paracrine and autocrine stimuli. In this study utilizing transgenic mice overexpressing prokineticin receptor (PKR1) in cardiomyocytes, and tcf21ERT-cre(TM)-derived cardiac fibroblast progenitor (CFP)-specific PKR1 knockout mice (PKR1 (tcf-/-)), as well as FACS-isolated CFPs, we showed that adipogenesis and vasculogenesis share a common CFPs originating from the tcf21(+) epithelial lineage...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038439/analysis-of-nkx3-1-cre-driven-erk5-deletion-reveals-a-profound-spinal-deformity-which-is-linked-to-increased-osteoclast-activity
#19
Carolyn J Loveridge, Rob J van 't Hof, Gemma Charlesworth, Ayala King, Ee Hong Tan, Lorraine Rose, Anna Daroszewska, Amanda Prior, Imran Ahmad, Michelle Welsh, Ernest J Mui, Catriona Ford, Mark Salji, Owen Sansom, Karen Blyth, Hing Y Leung
Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate. While grossly normal at birth, we observed an unexpected phenotype of spinal protrusion in Nkx3.1:Cre;Erk5 (fl/fl) (Erk5 (fl/fl)) mice by ~6-8 weeks of age. X-ray, histological and micro CT (µCT) analyses showed that 100% of male and female Erk5 (fl/fl) mice had a severely deformed curved thoracic spine, with an associated loss of trabecular bone volume...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038309/deletion-of-protein-kinase-d1-in-pancreatic-beta-cells-impairs-insulin-secretion-in-high-fat-fed-mice
#20
Valérie Bergeron, Julien Ghislain, Kevin Vivot, Natalia Tamarina, Louis H Philipson, Jens Fielitz, Vincent Poitout
Beta-cell adaptation to insulin resistance is necessary to maintain glucose homeostasis in obesity. Failure of this mechanism is a hallmark of type 2 diabetes (T2D). Hence, factors controlling functional beta-cell compensation are potentially important targets for the treatment of T2D. Protein kinase D1 (PKD1) integrates diverse signals in the beta cell and plays a critical role in the control of insulin secretion. However, the role of beta-cell PKD1 in glucose homeostasis in vivo is essentially unknown. Using beta-cell specific, inducible PKD1 knock-out mice (βPKD1KO), we examined the role of beta-cell PKD1 under basal conditions and during high-fat feeding...
October 16, 2017: Diabetes
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