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https://www.readbyqxmd.com/read/29668112/pharmacogenetic-manipulation-of-the-nucleus-accumbens-alters-binge-like-alcohol-drinking-in-mice
#1
Kush Purohit, Puja K Parekh, Joseph Kern, Ryan W Logan, Zheng Liu, Yanhua Huang, Colleen A McClung, John C Crabbe, Angela R Ozburn
BACKGROUND: Chronic alcohol intake leads to long-lasting changes in reward- and stress-related neuronal circuitry. The nucleus accumbens (NAc) is an integral component of this circuitry. Here, we investigate the effects of DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) on neuronal activity in the NAc and binge-like drinking. METHODS: C57BL/6J mice were stereotaxically injected with AAV2 hSyn-HA hM3Dq, -hM4Di, or -eGFP bilaterally into NAc [core + shell, core or shell]...
April 18, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29668046/black-cohosh-extracts-and-powders-induce-micronuclei-a-biomarker-of-genetic-damage-in-human-cells
#2
Stephanie L Smith-Roe, Carol D Swartz, Kim G Shepard, Steven M Bryce, Stephen D Dertinger, Suramya Waidyanatha, Grace E Kissling, Scott S Auerbach, Kristine L Witt
Black cohosh extract (BCE) is a widely used dietary supplement marketed to women to alleviate symptoms of gynecological ailments, yet its toxicity has not been well characterized. The National Toxicology Program (NTP) previously reported significant increases in micronucleated erythrocytes in peripheral blood of female Wistar Han rats and B6C3F1/N mice administered 15-1,000 mg BCE/kg/day by gavage for 90 days. These animals also developed a dose-dependent nonregenerative macrocytic anemia characterized by clinical changes consistent with megaloblastic anemia...
April 18, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29668043/folate-deficiency-increases-chromosomal-damage-and-mutations-in-hematopoietic-cells-in-the-transgenic-mutamouse-model
#3
Danielle P LeBlanc, Nathalie A Behan, Jason M O'Brien, Francesco Marchetti, Amanda J MacFarlane
Folate deficiency causes megaloblastic anemia and neural tube defects, and is also associated with some cancers. In vitro, folate deficiency increases mutation frequency and genome instability, as well as exacerbates the mutagenic potential of known environmental mutagens. Conversely, it remains unclear whether or not elevated folic acid (FA) intakes are beneficial or detrimental to the induction of DNA mutations and by proxy human health. We used the MutaMouse transgenic model to examine the in vivo effects of FA deficient, control, and supplemented diets on somatic DNA mutant frequency (MF) and genome instability in hematopoietic cells...
April 18, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29667931/ave0991-a-nonpeptide-analogue-of-ang-1-7-attenuates-aging-related-neuroinflammation
#4
Teng Jiang, Liu-Jun Xue, Yang Yang, Qing-Guang Wang, Xiao Xue, Zhou Ou, Qing Gao, Jian-Quan Shi, Liang Wu, Ying-Dong Zhang
During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7)...
April 17, 2018: Aging
https://www.readbyqxmd.com/read/29667914/inactivation-of-map3k7-in-foxd1-expressing-cells-results-in-loss-of-mesangial-pdgfr%C3%AE-and-juvenile-kidney-scarring
#5
Michele J Karolak, Justin A Guay, Leif Oxburgh
Transforming growth factor beta (TGFβ) plays a central role in renal scarring, controlling extracellular matrix deposition by interstitial cells and mesangial cells. TGFβ signals through Smad and mitogen activated protein kinase (MAPK) pathways. To understand the role of MAPK in interstitial and mesangial cells, we genetically inactivated TGFβ-activated kinase 1 (Map3k7) using Foxd1+/cre. Embryonic kidney development was unperturbed in mutants, but spontaneous scarring of the kidney ensued during the first postnatal week, with retention of embryonic nephrogenic rests and accumulation of collagen IV in the mesangium...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29667913/ubiquitin-c-terminal-hydrolase-l1-deletion-is-associated-with-urinary-%C3%AE-klotho-deficiency-and-perturbed-phosphate-homeostasis
#6
Naomi C Boisvert, Chet E Holterman, Alexey Gutsol, Josee Coulombe, Wanling Pan, R Todd Alexander, Douglas A Gray, Chris R Kennedy
Loss of ubiquitin C-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme required for neuronal function, led to hyperphosphatemia accompanied by phosphaturia in mice, while calcium homeostasis remained intact. We therefore investigated the mechanisms underlying the phosphate imbalance in Uchl1-/- mice. Interestingly, phosphaturia was not a result of lower renal brush border membrane sodium-phosphate cotransporter expression as sodium-phosphate cotransporter 2a and 2c expression levels were similar to wild type levels...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29667912/renoprotective-impact-of-estrogen-receptor-%C3%AE-and-its-splice-variants-in-female-mice-with-type-1-diabetes
#7
Debra L Irsik, Melissa Jill Romero-Aleshire, Erin M Chavez, Rachel W Fallet, Heddwen L Brooks, Pamela K Carmines, Pascale H Lane
Estrogen has been implicated in the regulation of growth and immune function in the kidney, which expresses the full-length estrogen receptor α (ERα66), its ERα splice variants, and estrogen receptor β (ERβ). Thus, we hypothesized that these splice variants may inhibit glomerular enlargement that occurs early in type 1 diabetes (T1D). T1D was induced by streptozotocin (STZ) injection in 8-12 wk-old female mice lacking ERα66 (ERα66KO) or all ERα variants (αERKO), and their wild-type (WT) littermates...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29667911/experimental-heat-stress-nephropathy-and-liver-injury-are-improved-by-allopurinol
#8
Carlos A Roncal-Jimenez, Yuka Sato, Tamara Milagres, Ana Andres-Hernando, Gabriela E Garcia, Petter Bjornstad, Jaime Butler-Dawson, Cecilia Sorensen, Lee Newman, Lyndsay Krisher, Magdalena Madero, Jason Glaser, Ramon Garcia-Trabannino, Emmanuel Jarquin-Romero, Zhilin Song, Thomas Jensen, Masanari Kuwabara, Bernardo Rodriguez-Iturbe, Laura-Gabriela Sanchez-Lozada, Miguel A Lanaspa, Richard J Johnson
BACKGROUND: An epidemic of chronic kidney disease (CKD) has been observed in Central America among workers in the sugarcane fields. One hypothesis is that the CKD may be caused by recurrent heat stress and dehydration, and potentially by hyperuricemia. Accordingly, we developed a murine model of kidney injury associated with recurrent heat stress. In the current experiment, we tested whether treatment with allopurinol (a xanthine oxidase inhibitor that reduces serum urate) provides renal protection against recurrent heat stress and dehydration...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29667910/role-of-wnk4-and-kidney-specific-wnk1-in-mediating-the-effect-of-high-dietary-k-intake-on-romk-channel-in-the-distal-convoluted-tubule
#9
Peng Wu, Zhong-Xiuzi Gao, Xiao-Tong Su, David H Ellison, Juliette Hadchouel, Jacques Teulon, Wen-Hui Wang
With-no-lysine kinase 4 (WNK4) and kidney-Specific (KS)-WNK1 regulate ROMK (Kir1.1) channels in a variety of cell models. We now explore the role of WNK4 and KS-WNK1 in regulating ROMK in the native distal convoluted tubule (DCT)/connecting tubule (CNT) by measuring TPNQ (ROMK inhibitor)-sensitive K+ currents with whole-cell recording. TPNQ-sensitive K+ currents in DCT2/CNT of KS-WNK1-/- and WNK4-/- mice were significantly smaller than that of WT mice. In contrast, the basolateral K+ channels (a Kir4.1/5.1 heterotetramer) in the DCT were not inhibited...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29667908/the-macula-densa-prorenin-receptor-is-essential-in-renin-release-and-blood-pressure-control
#10
Anne D M Riquier-Brison, Arnold Sipos, Ágnes Prókai, Sarah L Vargas, Ildiko Toma, Elliott J Meer, Karie G Villanueva, Jennifer C M Chen, Georgina Gyarmati, Christopher Yih, Elaine Tang, Bahram Nadim, Sujith Pendekanti, Ingrid M Garrelds, Genevieve Nguyen, A H Jan Danser, Janos Peti-Peterdi
The prorenin receptor (PRR) was originally proposed to be a member of the renin-angiotensin system (RAS), however recent work questioned their association. The present paper describes a functional link between the PRR and RAS in the renal juxtaglomerular apparatus (JGA), a classic anatomical site of the RAS. PRR expression was found in the sensory cells of the JGA, the macula densa (MD), and immunohistochemistry localized PRR to the MD basolateral cell membrane in mouse, rat, and human kidneys. MD cell PRR activation led to MAP kinase ERK1/2 signaling and stimulation of PGE2 release, the classic pathway of MD-mediated renin release...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29667749/effect-of-lysm-macrophage-depletion-on-lung-pathology-in-mice-with-chronic-bronchitis
#11
Yogesh Saini, Brandon W Lewis, Dongfang Yu, Hong Dang, Alessandra Livraghi-Butrico, Fabio Del Piero, Wanda K O'Neal, Richard C Boucher
Macrophages (MΦ) are key sentinels of respiratory exposure to inhaled environmental stimuli. In normal "healthy" tissues, MΦ are believed to be a dormant cell type that, upon exposure to stress-causing stimuli, may get activated to exhibit pro- or anti-inflammatory roles. To test whether stress present in chronic bronchitic (CB) airways triggers MΦ to manifest protective or detrimental responses, the DTA+ (LysM-regulated Diphtheria Toxin A expressing) strain with partial MΦ-deficiency was crossed with the Scnn1b-Tg mouse model of CB and the progenies were studied at 4-5 weeks of age...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29667742/genetic-association-and-expression-analyses-of-the-phosphatidylinositol-4-phosphate-5-kinase-pip5k1c-gene-in-alcohol-use-disorder-relevance-for-pain-signaling-and-alcohol-use
#12
Ji Soo Lee, Jill L Sorcher, Allison D Rosen, Ruslan Damadzic, Hui Sun, Melanie Schwandt, Markus Heilig, John Kelly, Kelsey L Mauro, Audrey Luo, Daniel Rosoff, Christine Muench, Jeesun Jung, Zachary A Kaminsky, Falk W Lohoff
BACKGROUND: The gene encoding Phosphatidylinositol-4-Phosphate 5-Kinase (PIP5K1C) has been recently implicated in pain regulation. Interestingly, a recent cross-tissue and cross-phenotypic epigenetic analysis identified the same gene in alcohol use disorder (AUD). Given the high comorbidity between AUD and chronic pain, we hypothesized that genetic variation in PIP5K1C might contribute to susceptibility to AUD. METHODS: We conducted a case-control association study of genetic variants in PIP5K1C...
April 18, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29667617/combination-of-stromal-vascular-fraction-and-ad-comp-ang1-gene-therapy-improves-long-term-therapeutic-efficacy-for-diabetes-induced-erectile-dysfunction
#13
Guo-Nan Yin, Lin Wang, Xiang-Nan Lin, Lei Shi, Zhen-Lin Gao, Feng-Chan Han, Ping Li, Yin-Chuan Jin, Jun-Kyu Suh, Ji-Kan Ryu, Xiong Wang, Hai-Rong Jin
Men with diabetic erectile dysfunction (ED) respond poorly to the currently available oral phosphodiesterase-5 inhibitors. Therefore, functional therapies for diabetic ED are needed. Stromal vascular fraction (SVF) and the adenovirus-mediated cartilage oligomeric matrix angiopoietin-1 (Ad-COMP-Ang1) gene are known to play critical roles in penile erection. We previously reported that SVF and Ad-COMP-Ang1 have only a short-term effect in restoring erectile function. Further improvements to ED therapy are needed for long-lasting effects...
April 17, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29667487/pre-colonization-with-the-commensal-fungus-candida-albicans-reduces-murine-susceptibility-to-clostridium-difficile-infection
#14
Laura Markey, Lamyaa Shaban, Erin R Green, Katherine P Lemon, Joan Mecsas, Carol A Kumamoto
Clostridium difficile is a major nosocomial pathogen responsible for close to half a million infections and 27,000 deaths annually in the U.S. Preceding antibiotic treatment is a major risk factor for C. difficile infection (CDI) leading to recognition that commensal microbes play a key role in resistance to CDI. Current antibiotic treatment of CDI is only partially successful due to a high rate of relapse. As a result, there is interest in understanding the effects of microbes on CDI susceptibility to support treatment of patients with probiotic microbes or entire microbial communities (e...
April 18, 2018: Gut Microbes
https://www.readbyqxmd.com/read/29667369/fully-automated-production-and-characterization-of-64cu-and-proof-of-principle-small-animal-pet-imaging-using-64cu-labelled-ca-xii-targeting-6a10-fab
#15
Luise Fiedler, Markus Kellner, Rosel Oos, Guido Böning, Sibylle Ziegler, Peter Bartenstein, Reinhard Zeidler, Franz Josef Gildehaus, Simon Lindner
64Cu is a cyclotron-produced radionuclide which offers, due to its characteristic decay scheme the possibility to combine PET investigations with radiotherapy. We evaluated the Alceo sys-tem from Comecer SpA to automatically produce 64Cu for radiolabelling purposes. We established a 64Cu production routine with high yields and radionuclide purity in combination with excellent operator radiation protection. The carbonic anhydrase XII targeting 6A10 antibody fab fragment was successfully radiolabelled with the produced 64Cu and proof of principle small animal PET experiments on mice bearing glioma xenografts were performed...
April 18, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29667364/heritability-of-body-size-in-the-polar-bears-of-western-hudson-bay
#16
René M Malenfant, Corey S Davis, Evan S Richardson, Nicholas J Lunn, David W Coltman
Among polar bears (Ursus maritimus), fitness is dependent on body size through males' abilities to win mates, females' abilities to provide for their young, and all bears' abilities to survive increasingly longer fasting periods caused by climate change. In the Western Hudson Bay subpopulation (near Churchill, Manitoba, Canada), polar bears have declined in body size and condition, but nothing is known about the genetic underpinnings of body size variation, which may be subject to natural selection. Here, we combine a 4449-individual pedigree and an array of 5433 single-nucleotide polymorphisms (SNPs) to provide the first quantitative genetics study of polar bears...
April 18, 2018: Molecular Ecology Resources
https://www.readbyqxmd.com/read/29667304/inhibition-of-alpha7-nicotinic-receptors-in-the-ventral-hippocampus-selectively-attenuates-reinstatement-of-morphine-conditioned-place-preference-and-associated-changes-in-ampa-receptor-binding
#17
Victoria L Wright, Polymnia Georgiou, Alexis Bailey, David J Heal, Christopher P Bailey, Susan Wonnacott
Recurrent relapse is a major problem in treating opiate addiction. Pavlovian conditioning plays a role in recurrent relapse whereby exposure to cues learned during drug intake can precipitate relapse to drug taking. α7 nicotinic acetylcholine receptors (nAChRs) have been implicated in attentional aspects of cognition and mechanisms of learning and memory. In this study we have investigated the role of α7 nAChRs in morphine-conditioned place preference (morphine-CPP). CPP provides a model of associative learning that is pertinent to associative aspects of drug dependence...
April 17, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29667248/establishment-of-a-radiotelemetric-recording-technique-in-mice-to-investigate-gastric-slow-waves-modulatory-role-of-putative-neurotransmitter-systems
#18
Huichuan Wang, Zengbing Lu, Yuen Hang Liu, Yayi Sun, Longlong Tu, Man P Ngan, Chi-Kong Yeung, John A Rudd
NEW FINDINGS: What is the central question of this study? Gastric slow waves originating from interstitial cells of Cajal-smooth muscle syncytium are usually studied in culture or in tissue segments, but no studies have made recording of slow waves from conscious freely moving mice. Can radiotelemetry be used to record slow waves, and do they respond predictably to drug treatment? What is the main finding and its importance? Radiotelemetry may be used to record slow waves from conscious freely moving mice permitting an examination of drug action in vivo, which is critical to drug discovery projects characterizing drugs and metabolites on gastrointestinal function...
April 18, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29667227/effects-of-knockout-of-the-receptor-for-advanced-glycation-end-products-on-bone-mineral-density-and-synovitis-in-mice-with-intra-articular-fractures
#19
Dongrim Seol, Yuki Tochigi, Ashley M Bogner, Ino Song, Douglas C Fredericks, Gail L Kurriger, Sonja M Smith, Jessica E Goetz, Joseph A Buckwalter, James A Martin
Our group employed the mouse closed intra-articular fracture (IAF) model to test the hypothesis that the innate immune system plays a role in initiating synovitis and post-traumatic osteoarthritis (PTOA) in fractured joints. A transgenic strategy featuring knockout of the receptor for advanced glycation end-products (RAGE -/- ) was pursued. The 42 and 84 mJ impacts used to create fractures were in the range previously reported to cause PTOA at 60 days post-fracture. MicroCT (µCT) was used to assess fracture patterns and epiphyseal and metaphyseal bone loss at 30 and 60 days post-fracture...
April 17, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29667177/adverse-placental-effects-of-valproic-acid-studies-in-perfused-human-placentas
#20
Miriam Rubinchik-Stern, Miriam Shmuel, Jacob Bar, Michal Kovo, Sara Eyal
OBJECTIVE: In utero exposure to valproic acid (VPA) has been associated with worse pregnancy outcomes compared to all other antiepileptic drugs. We have previously shown that VPA alters the expression of placental transporters for hormones and nutrients in vitro and in pregnant mice. Here, our aim was to characterize the effects of short exposure to VPA on the expression of carriers for compounds essential for fetal development in human placentas ex vivo, under controlled conditions...
April 17, 2018: Epilepsia
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