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https://www.readbyqxmd.com/read/28098199/optogenetic-modulation-of-urinary-bladder-contraction-for-lower-urinary-tract-dysfunction
#1
Jae Hong Park, Jin Ki Hong, Ja Yun Jang, Jieun An, Kyu-Sung Lee, Tong Mook Kang, Hyun Joon Shin, Jun-Kyo Francis Suh
As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096470/dampened-amphetamine-stimulated-behavior-and-altered-dopamine-transporter-function-in-the-absence-of-brain-gdnf
#2
Jaakko Kopra, Anne Panhelainen, Sara Af Bjerkén, Lauriina Porokuokka, Kärt Varendi, Soophie Olfat, Heidi Montonen, T Petteri Piepponen, Mart Saarma, Jaan-Olle Andressoo
: Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases including drug addiction and Parkinson's disease. Because of its well-established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been extensively studied in various disorders with disturbed dopamine homeostasis. The outcomes from pre-clinical and clinical studies vary, however, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function...
January 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28096418/multi-institute-analysis-of-carbapenem-resistance-reveals-remarkable-diversity-unexplained-mechanisms-and-limited-clonal-outbreaks
#3
Gustavo C Cerqueira, Ashlee M Earl, Christoph M Ernst, Yonatan H Grad, John P Dekker, Michael Feldgarden, Sinéad B Chapman, João L Reis-Cunha, Terrance P Shea, Sarah Young, Qiandong Zeng, Mary L Delaney, Diane Kim, Ellena M Peterson, Thomas F O'Brien, Mary Jane Ferraro, David C Hooper, Susan S Huang, James E Kirby, Andrew B Onderdonk, Bruce W Birren, Deborah T Hung, Lisa A Cosimi, Jennifer R Wortman, Cheryl I Murphy, William P Hanage
Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28092668/upregulation-of-ret-induces-perineurial-invasion-of-pancreatic-adenocarcinoma
#4
M Amit, S Na'ara, L Leider-Trejo, Y Binenbaum, N Kulish, E Fridman, A Shabtai-Orbach, R J Wong, Z Gil
Tumor spread along nerves, a phenomenon known as perineurial invasion, is common in various cancers including pancreatic ductal adenocarcinoma (PDAC). Neural invasion is associated with poor outcome, yet its mechanism remains unclear. Using the transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we investigated the mechanism of neural invasion in PDAC. To detect tissue-specific factors that influence neural invasion by cancer cells, we characterized the perineurial microenvironment using a series of bone marrow transplantation (BMT) experiments in transgenic mice expressing single mutations in the Cx3cr1, GDNF and CCR2 genes...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28090567/the-rna-polymerase-iii-subunit-polr3b-is-required-for-the-maintenance-of-small-intestinal-crypts-in-mice
#5
Julia Kieckhaefer, Sabina Lukovac, Diana Z Ye, Dolim Lee, Danielle J Beetler, Michael Pack, Klaus H Kaestner
BACKGROUND & AIMS: The continuously self-renewing mammalian intestinal epithelium, with high cellular turnover, depends on adequate protein synthesis for its proliferative capacity. RNA polymerase III activity is closely related to cellular growth and proliferation. Here, we studied the role of Polr3b, a large RNA polymerase III subunit, in the mammalian intestinal epithelium. METHODS: We derived mice with an intestinal epithelium-specific hypomorphic mutation of the Polr3b gene, using VillinCre-mediated gene ablation...
November 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28090143/acute-exercise-regulates-adipogenic-gene-expression-in-white-adipose-tissue
#6
Y Shen, H Zhou, W Jin, H J Lee
White adipose tissue expansion is associated with both hypertrophy and hyperplasia of adipocytes. Exercise training results in adipocyte hypotrophy by activating lipolysis, but it is poorly understood whether exercise regulates adipogenesis by altering adipogenic gene expression. The purpose of this study was to evaluate the effect of a single bout of swimming exercise on adipogenic gene expression in white adipose tissue (WAT). Male C57BL/6J mice were divided into two groups: a sedentary control group and a 120-minute swimming exercise group...
December 2016: Biology of Sport
https://www.readbyqxmd.com/read/28089339/discovery-of-a-murine-model-of-clinical-pah-mission-impossible
#7
REVIEW
Zhiyu Dai, You-Yang Zhao
Pulmonary arterial hypertension (PAH) is a lung vascular disease characterized with a progressive increase of pulmonary vascular resistance and obliterative pulmonary vascular remodeling resulting in right heart failure and premature death. In this brief review, we document the recent advances in identifying genetically modified murine models of PH, with a focus on the recent discovery of the mouse model of Tie2 Cre-mediated deletion of prolyl hydroxylase 2, which exhibits progressive obliterative vascular remodeling, severe PAH, and right heart failure, thus recapitulating many of the features of clinical PAH...
December 15, 2016: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28088462/activation-of-the-hypoxia-inducible-factor-1-alpha-subunit-pathway-in-steatotic-liver-contributes-to-formation-of-cholesterol-gallstones
#8
Yoichiro Asai, Tetsuya Yamada, Sohei Tsukita, Kei Takahashi, Masamitsu Maekawa, Midori Honma, Masanori Ikeda, Keigo Murakami, Yuichiro Munakata, Yuta Shirai, Shinjiro Kodama, Takashi Sugisawa, Yumiko Chiba, Yasuteru Kondo, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Junta Imai, Yasuhiro Nakamura, Hiroaki Yamaguchi, Kozo Tanaka, Hironobu Sasano, Nariyasu Mano, Yoshiyuki Ueno, Tooru Shimosegawa, Hideki Katagiri
BACKGROUND AND AIMS: Hypoxia inducible factor 1 alpha subunit (HIF1A) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with non-alcoholic fatty liver disease (NAFLD). NAFLD increases risk for cholesterol gallstone disease by unclear mechanisms. We studied the relationship between HIF1A and gallstone formation associated with liver steatosis. METHODS: We performed studies with mice with inducible disruption of Hif1a in hepatocytes, via a Cre adenoviral vector (iH-HIFKO mice), and mice without disruption of Hif1a (control mice)...
January 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28078648/generation-of-a-floxed-allele-of-the-mouse-microrna-200-clusters
#9
Hongyan Ren, Cong Tao, Kui Li, Yanzhen Bi, Xinmin Zheng
MicroRNA-8 and its target gene, u-shaped (ush), regulate body size in Drosophila. As the mouse homolog of the Drosophila miR-8, whether the miR-200 family has similar functions and how they perform their regulatory roles in body size control is unknown. In order to discover the biological function of the miR-200s in vivo, we generated mice lacking the miR-200b/200a/429 gene cluster using the Cre/loxp system. miR-200b/200a/429 null mutant mice were viable, fertile, and showed normal development.
January 11, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28077718/integrin-linked-kinase-ilk-deletion-disrupts-oligodendrocyte-development-by-altering-cell-cycle
#10
Rashad Hussain, Wendy B Macklin
: During development, oligodendrocytes are initially specified, after which oligodendrocyte precursor cells (OPCs) migrate and proliferate before differentiating into myelinating cells. Lineage-specific programming of oligodendrocytes results from sensing environmental cues through membrane-bound receptors and related intracellular signaling molecules. Integrin-linked kinase (ILK) is an important protein that is expressed at the inner margins of the plasma membrane and can mediate some of these signals...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077715/excitatory-hindbrain-forebrain-communication-is-required-for-cisplatin-induced-anorexia-and-weight-loss
#11
Amber L Alhadeff, Ruby A Holland, Huiyuan Zheng, Linda Rinaman, Harvey J Grill, Bart C De Jonghe
: Cisplatin chemotherapy is commonly used to treat cancer despite severe energy balance side effects. In rats, cisplatin activates nucleus tractus solitarius (NTS) projections to the lateral parabrachial nucleus (lPBN) and calcitonin-gene related peptide (CGRP) projections from the lPBN to the central nucleus of the amygdala (CeA). We demonstrated previously that CeA glutamate receptor signaling mediates cisplatin-induced anorexia and body weight loss. Here, we used neuroanatomical tracing, immunofluorescence, and confocal imaging to demonstrate that virtually all NTS→lPBN and lPBN→CeA CGRP projections coexpress vesicular glutamate transporter 2 (VGLUT2), providing evidence that excitatory projections mediate cisplatin-induced energy balance dysregulation...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077706/connexin-mediated-signaling-in-nonsensory-cells-is-crucial-for-the-development-of-sensory-inner-hair-cells-in-the-mouse-cochlea
#12
Stuart L Johnson, Federico Ceriani, Oliver Houston, Roman Polishchuk, Elena Polishchuk, Giulia Crispino, Veronica Zorzi, Fabio Mammano, Walter Marcotti
: Mutations in the genes encoding for gap junction proteins connexin 26 (Cx26) and connexin 30 (Cx30) have been linked to syndromic and nonsyndromic hearing loss in mice and humans. The release of ATP from connexin hemichannels in cochlear nonsensory cells has been proposed to be the main trigger for action potential activity in immature sensory inner hair cells (IHCs), which is crucial for the refinement of the developing auditory circuitry. Using connexin knock-out mice, we show that IHCs fire spontaneous action potentials even in the absence of ATP-dependent intercellular Ca(2+) signaling in the nonsensory cells...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077701/a-comparison-of-eleven-phenotypic-assays-for-the-accurate-detection-of-carbapenemase-producing-enterobacteriaceae
#13
Pranita D Tamma, Belita N A Opene, Andrew Gluck, Krizia K Chambers, Karen C Carroll, Patricia J Simner
BACKGROUND: Early identification of carbapenemase-producing Enterobacteriaceae (CPE) is essential to prevent their dissemination within healthcare settings. Our objective was to evaluate the accuracy of 11 phenotypic assays for the detection of CPE. METHODS: Two collections of carbapenem-resistant Enterobacteriaceae (CRE) isolates were evaluated including 191 retrospective isolates (122 CP-CRE and 69 non-CP isolates) as well as 45 prospective clinical isolates (15 CP-CRE and 30 non-CP-CRE) obtained over a 3-month period...
January 11, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#14
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28076846/effect-of-trp53-gene-deficiency-on-brain-injury-after-neonatal-hypoxia-ischemia
#15
Ana A Baburamani, Kristina S Sobotka, Regina Vontell, Carina Mallard, Veena G Supramaniam, Claire Thornton, Henrik Hagberg
Hypoxia-ischemia (HI) can result in permanent life-long injuries such as motor and cognitive deficits. In response to cellular stressors such as hypoxia, tumor suppressor protein p53 is activated, potently initiating apoptosis and promoting Bax-dependent mitochondrial outer membrane permeabilization. The aim of this study was to investigate the effect of Trp53 genetic inhibition on injury development in the immature brain following HI. HI (50 min or 60 min) was induced at postnatal day 9 (PND9) in Trp53 heterozygote (het) and wild type (WT) mice...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28074441/activation-of-parvalbumin-positive-neurons-in-both-retina-and-primary-visual-cortex-improves-the-feature-selectivity-of-primary-visual-cortex-neurons
#16
Jinggang Duan, Hang Fu, Jiayi Zhang
Several recent studies using either viral or transgenic mouse models have shown different results on whether the activation of parvalbumin-positive (PV(+)) neurons expressing channelrhodopsin-2 (ChR2) in the primary visual cortex (V1) improves the orientation- and direction-selectivity of V1 neurons. Although this discrepancy was thoroughly discussed in a follow-up communication, the issue of using different models to express ChR2 in V1 was not mentioned. We found that ChR2 was expressed in retinal ganglion cells (RGCs) and V1 neurons in ChR2(fl/+); PV-Cre mice...
January 10, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28074253/c-abl-inhibition-mitigates-diet-induced-obesity-through-improving-insulin-sensitivity-of-subcutaneous-fat-in-mice
#17
Rong Wu, Jian-Guang Sun, Ji-Qiu Wang, Binhua Li, Qingsong Liu, Guang Ning, Wanzhu Jin, Zengqiang Yuan
AIMS/HYPOTHESIS: High-energy diets are among the main causes of the global epidemic of metabolic disorders, including obesity and type 2 diabetes. The mechanisms of high-energy-diet-induced metabolic disorders are complex and largely unknown. The non-receptor tyrosine kinase c-Abl plays an important role in adipogenesis in vitro but its role in vivo in the regulation of metabolism is still elusive. Hence, we sought to address the role of c-Abl in diet-induced obesity and obesity-associated insulin resistance...
January 10, 2017: Diabetologia
https://www.readbyqxmd.com/read/28073895/evaluation-of-genotypic-and-phenotypic-methods-to-detect-carbapenemase-production-in-gram-negative-bacilli
#18
Allison R McMullen, Melanie L Yarbrough, Meghan A Wallace, Angela Shupe, Carey-Ann D Burnham
BACKGROUND: Carbapenemase-producing gram-negative bacteria (CP-GNB) are an urgent and expanding public health threat. Rapid and accurate identification of these organisms facilitates infection prevention efforts in healthcare facilities. The objective of our study was to evaluate methods to detect and identify CP-GNB. METHODS: We examined 189 carbapenem-resistant GNB (CR-GNB), including Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii complex, using 3 different methods: 2 methods to screen isolates of GNB for carbapenemase production [the carbapenem inactivation method (CIM) and 2 chromogenic agars] and a molecular method (Cepheid GeneXpert Carba-R) to identify the mechanism of carbapenem resistance and the associated resistance genes (blaKPC, blaNDM, blaIMP, blaOXA-48-like, and blaVIM)...
January 10, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28072604/epigenetic-upregulation-of-cxcl12-expression-mediates-anti-tubulin-chemotherapeutics-induced-neuropathic-pain
#19
Ting Xu, Xiao-Long Zhang, Han-Dong Ou-Yang, Zhen-Yu Li, Cui-Cui Liu, Zhen-Zhen Huang, Jing Xu, Jia-You Wei, Bi-Lin Nie, Chao Ma, Shao-Ling Wu, Wen-Jun Xin
Clinically, Microtubule-targeted agents-induced neuropathic pain hampers chemotherapeutics for cancer patients. Here, we found that application of paclitaxel or vincristine increased the protein and mRNA expression of CXCL12, and frequency and amplitude of miniature excitatory post synaptic currents (mEPSCs) in spinal dorsal horn neurons. Spinal local application of CXCL12 induced the long-term potentiation (LTP) of nociceptive synaptic transmission and increased the amplitude of mEPSCs. Inhibition of CXCL12 by using the transgenic mice (CXCL12) or neutralizing antibody or siRNA ameliorated the mEPSCs enhancement and mechanical allodynia...
January 7, 2017: Pain
https://www.readbyqxmd.com/read/28071976/precise-flexible-and-affordable-gene-stacking-for-crop-improvement
#20
Weiqiang Chen, David W Ow
Addendum to: Hou L, Yau YY, Wei J, Han Z, Dong Z, Ow DW. An open-source system for in planta gene stacking by Bxb1 and Cre recombinases. Mol Plant, 2014; 7(12):1756-1765. doi:10.1093/mp/ssu107; Li R, Han Z, Hou L, Kaur G, Yin Q, Ow DW. Method for Biolistic Site-Specific Integration in Plants Catalyzed by Bxb1 Integrase. In: Murata M, editor. Chromosome and Genomic Engineering in Plants: Methods and Protocols, Methods in Molecular Biology. 2016; p.15-30; and Chen W, Ow DW. Protocol for In Vitro Stacked Molecules Compatible with In Vivo Recombinase-Mediated Gene Stacking...
January 10, 2017: Bioengineered
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