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https://www.readbyqxmd.com/read/28431402/micrometastasis-of-endometriosis-to-distant-organs-in-a-murine-model
#1
Elham N Samani, Ramanaiah Mamillapalli, Fei Li, Levent Mutlu, Demetra Hufnagel, Graciela Krikun, Hugh S Taylor
Endometriosis is an inflammatory gynecological disorder among reproductive-aged women caused by the engraftment and proliferation of endometrial cells outside the uterus, most commonly in the pelvis. It is thought that the disease arises primarily from retrograde menstruation where cells from the endometrium travel through the fallopian tubes to the peritoneal cavity. However, migration of endometriosis-derived cells to distant organs outside of the peritoneal cavity have not been explored. In the present study, we developed and validated a mouse model of disseminated endometriosis using syngeneic DsRed endometrial tissue introduced into the peritoneum of immunocompetent mice...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431399/muc2-mucin-deficiency-alters-inflammatory-and-metabolic-pathways-in-the-mouse-intestinal-mucosa
#2
Selamawit Tadesse, Georgia Corner, Elena Dhima, Michele Houston, Chandan Guha, Leonard Augenlicht, Anna Velcich
The mucus layer in the intestine affects several aspects of intestinal biology, encompassing physical, chemical protection, immunomodulation and growth, thus contributing to homeostasis. Mice with genetic inactivation of the Muc2 gene, encoding the MUC2 mucin, the major protein component of mucus, exhibit altered intestinal homeostasis, which is strictly dependent on the habitat, likely due to differing complements of intestinal microbes. Our previous work established that Muc2 deficiency was linked to low chronic inflammation resulting in tumor development in the small, large intestine including the rectum...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431394/effect-of-salmonella-enterica-serovar-typhimurium-vnp20009-and-vnp20009-with-restored-chemotaxis-on-4t1-mouse-mammary-carcinoma-progression
#3
Sheryl L Coutermarsh-Ott, Katherine M Broadway, Birgit E Scharf, Irving C Allen
A variety of bacterial strains have been evaluated as bio-therapeutic and immunomodulatory agents to treat cancer. One such strain, Salmonella enterica serovar Typhimurium VNP20009, which is attenuated by a purine auxotrophic mutation and modified lipid A, is characterized in previous models as a safely administered, tumor colonizing agent. However, earlier work tended to use less aggressive cancer cell lines and immunocompromised animal models. Here, we investigated the safety and efficacy of VNP20009 in a highly malignant murine model of human breast cancer...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431315/effects-of-pm2-5-exposure-on-the-notch-signaling-pathway-and-immune-imbalance-in-chronic-obstructive-pulmonary-disease
#4
Xing-Yu Gu, Xu Chu, Xiao-Li Zeng, Hai-Rong Bao, Xiao-Ju Liu
Chronic Obstructive Pulmonary Disease (COPD) is associated with T lymphocytes subset (Th1/Th2, Th17/Treg) imbalance. Notch signaling pathway plays a key role in the development of the adaptive immunity. The immune disorder induced by fine particulate matter (PM2.5) is related to COPD. The aim of this study was to investigate the mechanism by which PM2.5 influences the Notch signaling pathway leading to worsening immune disorder and accelerating COPD development. A COPD mouse model was established by cigarette smoke exposure...
April 18, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28431308/hyperexcitability-of-inferior-colliculus-and-acoustic-startle-reflex-with-age-related-hearing-loss
#5
Binbin Xiong, Ana'am Alkharabsheh, Senthilvelan Manohar, Guang-Di Chen, Ning Yu, Xiaoming Zhao, Richard Salvi, Wei Sun
Chronic tinnitus and hyperacusis often develop with age-related hearing loss presumably due to aberrant neural activity in the central auditory system (CAS) induced by cochlear pathologies. However, the full spectrum of physiological changes that occur in the CAS as a result age-related hearing loss are still poorly understood. To address this issue, neurophysiological measures were obtained from the cochlea and the inferior colliculus (IC) of 2, 6 and 12 month old C57BL/6J mice, a mouse model for early age-related hearing loss...
March 27, 2017: Hearing Research
https://www.readbyqxmd.com/read/28431282/the-role-of-pharmacologic-modulation-of-autophagy-on-anal-cancer-development-in-an-hpv-mouse-model-of-carcinogenesis
#6
Brooks L Rademacher, Kristina A Matkowskyj, Louise M Meske, Alexis Romero, Hana Sleiman, Evie H Carchman
Autophagy is an intracellular, catabolic process that maintains cellular health. We examined the response of pharmacologic modulation of autophagy in an HPV mouse model of anal carcinogenesis. K14E6/E7 mice were treated with the topical carcinogen DMBA weekly and assessed for tumors over 20 weeks. Concurrently, they were given either chloroquine or BEZ235, to inhibit or induce autophagy, respectively. Time to tumor onset was examined. Immunofluorescence (IF) was performed for LC3β and p62 to examine autophagy...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28431251/tunable-expression-tools-enable-single-cell-strain-distinction-in-the-gut-microbiome
#7
Weston R Whitaker, Elizabeth Stanley Shepherd, Justin L Sonnenburg
Applying synthetic biology to engineer gut-resident microbes provides new avenues to investigate microbe-host interactions, perform diagnostics, and deliver therapeutics. Here, we describe a platform for engineering Bacteroides, the most abundant genus in the Western microbiota, which includes a process for high-throughput strain modification. We have identified a novel phage promoter and translational tuning strategy and achieved an unprecedented level of expression that enables imaging of fluorescent-protein-expressing Bacteroides stably colonizing the mouse gut...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431249/macrophages-facilitate-electrical-conduction-in-the-heart
#8
Maarten Hulsmans, Sebastian Clauss, Ling Xiao, Aaron D Aguirre, Kevin R King, Alan Hanley, William J Hucker, Eike M Wülfers, Gunnar Seemann, Gabriel Courties, Yoshiko Iwamoto, Yuan Sun, Andrej J Savol, Hendrik B Sager, Kory J Lavine, Gregory A Fishbein, Diane E Capen, Nicolas Da Silva, Lucile Miquerol, Hiroko Wakimoto, Christine E Seidman, Jonathan G Seidman, Ruslan I Sadreyev, Kamila Naxerova, Richard N Mitchell, Dennis Brown, Peter Libby, Ralph Weissleder, Filip K Swirski, Peter Kohl, Claudio Vinegoni, David J Milan, Patrick T Ellinor, Matthias Nahrendorf
Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431241/akt-pkb-signaling-navigating-the-network
#9
REVIEW
Brendan D Manning, Alex Toker
The Ser and Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of AKT, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431181/protective-effect-of-mesenchymal-stem-cells-against-the-development-of-intracranial-aneurysm-rupture-in-mice
#10
Atsushi Kuwabara, Jia Liu, Yoshinobu Kamio, Airan Liu, Michael T Lawton, Jae-Woo Lee, Tomoki Hashimoto
BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent stem or stromal cells found in multiple tissues. Intravenous MSC injections have been used to treat various diseases with an inflammatory component in animals and humans. Inflammation is emerging as a key component of pathophysiology of intracranial aneurysms. Modulation of inflammation by MSCs may affect sustained inflammatory processes that lead to aneurysmal rupture. OBJECTIVE: To assess the effect of MSCs on the development of aneurysm rupture using a mouse model...
April 19, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28431163/an-evaluation-of-the-human-relevance-of-the-lung-tumors-observed-in-female-mice-treated-with-permethrin-based-on-mode-of-action
#11
Tomoya Yamada, Miwa Kondo, Kaori Miyata, Keiko Ogata, Masahiko Kushida, Kayo Sumida, Satoshi Kawamura, Thomas G Osimitz, Brian G Lake, Samuel M Cohen
Permethrin increased the incidence of bronchiolo-alveolar adenomas in female mice but not male mice or female or male rats. Studies were conducted to determine whether permethrin has mitogenic activity in Club cells in mouse lung as the basis for the mode of action (MOA) for the lung adenoma induction. Several short term experiments focusing on time-course, dose-response, reversibility, sex difference, strain difference, and species difference were evaluated for Club cell proliferation and morphology. The findings demonstrated that permethrin slightly and continuously enhanced Club cell proliferation at tumor-associated dose levels in female mice, but did not increase proliferation in male mice or in female rats...
April 18, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28431112/long-term-survival-of-the-mouse-es-cell-derived-mast-cell-medmc-brc6-in-mast-cell-deficient-kitw-sh-w-sh-mice
#12
Shohei Shibagaki, Satoko Tahara-Hanaoka, Takashi Hiroyama, Yukio Nakamura, Akira Shibuya
Mast cells (MCs) play pivotal roles in allergic reactions and the host defense against microbial infection through the immunoglobulin E (IgE)-dependent and IgE-independent signaling pathways. MC lines that can be analyzed both in vitro and in vivo would be useful for the study of MC-dependent immune responses. Here we investigated the functional characteristics of a mouse ES cell-derived mast cell-like cell line, MEDMC-BRC6. The cell line expressed FcεRI and c-Kit and showed degranulation and production of inflammatory cytokines and chemokine, including TNF-α, IL-6 and MCP-1, upon crosslinking FcεRI with IgE...
April 18, 2017: International Immunology
https://www.readbyqxmd.com/read/28430959/expression-immunogenicity-and-variation-of-iron-regulated-surface-protein-a-from-bovine-isolates-of-staphylococcus-aureus
#13
N Misra, T F Wines, C L Knopp, M A McGuire, J K Tinker
Staphylococcus aureus iron-regulated surface protein A (IsdA) is a fibrinogen and fibronectin adhesin that also contributes to iron sequestration and resistance to innate immunity. IsdA is conserved in human isolates and has been investigated as a human vaccine candidate. Here we report the expression of isdA, the efficacy of anti-IsdA responses, and the existence of IsdA sequence variants from bovine Staphylococcus. Clinical staphylococci were obtained from U.S. dairy farms and assayed by PCR for the presence and expression of isdA...
April 19, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28430907/food-intake-affects-sperm-egg-fusion-through-the-gip-psg17-axis-in-mice
#14
Tatsunori Shimizu, Takehiro Sato, Katsushi Tsukiyama, Hiroki Fujita, Shunsuke Kato, Manabu Hoizumi, Hiromitsu Shirasawa, Takuma Narita, Yukihiro Terada, Yutaka Seino, Yuichiro Yamada
In addition to overeating, starvation also reduces fecundity in mammals. However, little is known about the molecular mechanisms linking food intake to fertility, especially in males. Gastric inhibitory polypeptide (GIP), which is released from intestinal K-cells after meal ingestion, stimulates insulin secretion from pancreatic β-cells through the action of incretin and has several extra-pancreatic effects. Here, we identified GIP receptor (Gipr) expression in mouse spermatids. Microarray analysis revealed that pregnancy-specific glycoprotein 17 (Psg17), a potential CD9-binding partner, was significantly decreased in GIP receptor-knockout (Gipr-/-) testes...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430903/co-storage-of-enteroendocrine-hormones-evaluated-at-the-cell-and-subcellular-levels-in-male-mice
#15
Linda J Fothergill, Brid Callaghan, Billie Hunne, David M Bravo, John B Furness
Recent studies reveal complex patterns of hormone co-expression within enteroendocrine cells (EEC), contrary to the traditional view that gut hormones are expressed individually in EEC. Moreover, different hormones have been found in separate subcellular vesicles. However, detailed analysis of relative expression of multiple hormones has not been made. Subcellular studies have been confined to peptide hormones, and have not included the indolamine, 5-HT, or the neuroendocrine protein, chromogranin A (CgA). In the present work, co-expression of 5-HT, CgA, secretin, CCK, ghrelin, and GLP-1 in mouse duodenum was quantified at a cellular and subcellular level by semi-automated cell counting and quantitative vesicle measurements...
April 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430892/anti-arrhythmic-potential-of-the-late-sodium-current-inhibitor-gs-458967-in-murine-scn5a-1798insd-and-human-scn5a-1795insd-ipsc-derived-cardiomyocytes
#16
Vincent Portero, Simona Casini, Maaike Hoekstra, Arie O Verkerk, Isabella Mengarelli, Luiz Belardinelli, Sridharan Rajamani, Arthur A M Wilde, Connie R Bezzina, Marieke W Veldkamp, Carol Ann Remme
AIM: Selective inhibition of cardiac late sodium current (INaL) is an emerging target in the treatment of ventricular arrhythmias. We investigated the electrophysiological effects of GS-458967 (GS967), a potent, selective inhibitor of INaL, in an overlap syndrome model of both gain and loss of sodium channel function, comprising cardiomyocytes derived from both human SCN5A-1795insD+/- induced pluripotent stem cells (hiPSC-CMs) and mice carrying the homologous mutation Scn5a-1798insD+/-...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430882/inhibition-of-the-cardiac-myocyte-mineralocorticoid-receptor-ameliorates-doxorubicin-induced-cardiotoxicity
#17
Achim Lother, Stella Bergemann, Jessica Kowalski, Michael Huck, Ralf Gilsbach, Christoph Bode, Lutz Hein
Aim: HASH(0x52d13d0) Anthracyclines such as doxorubicin are widely used in cancer therapy but their use is limited by cardiotoxicity. Up to date there is no established strategy for the prevention of anthracyclin-induced heart failure. In this study, we evaluated the role of the cardiac myocyte mineralocorticoid receptor (MR) during doxorubicin-induced cardiotoxicity. Methods and results: HASH(0x49e2408) A single high-dose or repetitive low-dose doxorubicin administration lead to markedly reduced left ventricular function in mice...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430879/role-of-phosphatase-and-tensin-homolog-pten-in-hypoxic-pulmonary-vasoconstriction
#18
Adrienn Krauszman, Tak Mak, Katalin Szaszi, Wolfgang M Kuebler
AIMS: Hypoxic pulmonary vasoconstriction (HPV) redistributes blood flow from poorly ventilated to better aerated areas in the lung, thereby optimizing ventilation-perfusion ratio (V/Q). Pulmonary artery smooth muscle cell (PASMC) contraction in response to hypoxia is triggered by Ca2+ influx via transient receptor potential canonical 6 (TRPC6) cation channels that have translocated to caveolae in the plasma membrane. Since phosphatase and tensin homolog (PTEN) was suggested to regulate TRPC6 in endothelial cells, we aimed to define its role in the hypoxic response of PASMCs and as a putative mediator of HPV...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#19
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430800/the-burden-of-trisomy-21-disrupts-the-proteostasis-network-in-down-syndrome
#20
Stefanos Aivazidis, Christina M Coughlan, Abhishek K Rauniyar, Hua Jiang, L Alexander Liggett, Kenneth N Maclean, James R Roede
Down syndrome (DS) is a genetic disorder caused by trisomy of chromosome 21. Abnormalities in chromosome number have the potential to lead to disruption of the proteostasis network (PN) and accumulation of misfolded proteins. DS individuals suffer from several comorbidities, and we hypothesized that disruption of proteostasis could contribute to the observed pathology and decreased cell viability in DS. Our results confirm the presence of a disrupted PN in DS, as several of its elements, including the unfolded protein response, chaperone system, and proteasomal degradation exhibited significant alterations compared to euploid controls in both cell and mouse models...
2017: PloS One
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