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https://www.readbyqxmd.com/read/29787037/effects-of-perinatal-exposure-to-dibutyltin-chloride-on-fat-and-glucose-metabolism-in-mice-and-molecular-mechanisms-in-vitro
#1
Raquel Chamorro-García, Bassem M Shoucri, Sigal Willner, Heidi Käch, Amanda Janesick, Bruce Blumberg
BACKGROUND: The organotin dibutyltin (DBT) is used in the manufacture of polyvinyl chloride (PVC) plastics, in construction materials, and in medical devices. Previous animal studies showed detrimental effects of DBT during in utero development at relatively high doses, but little was known about the effects of DBT exposure at environmentally relevant doses on endpoints such as obesity and metabolic disease. OBJECTIVES: We tested the potential obesogenic effects of DBT using in vitro and in vivo models...
May 2018: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29786878/dietary-omega-3-fatty-acids-differentially-impact-acute-ethanol-responsive-behaviors-and-ethanol-consumption-in-dba-2j-versus-c57bl-6j-mice
#2
Jennifer T Wolstenholme, M Scott Bowers, Alexander B Pais, A Christian Pais, Ryan S Poland, Justin L Poklis, Andrew G Davies, Jill C Bettinger
BACKGROUND: Complex interactions between environmental and genetic factors influence the risk for developing alcohol use disorder (AUD) in humans. To date, studies of the impact of environment on AUD risk have primarily focused on psychological characteristics or on the effects of developmental exposure to ethanol. We recently observed that modifying levels of the long-chain ω-3 (LC ω-3) fatty acid, eicosapentaenoic acid (EPA), alters acute physiological responses to ethanol in C. elegans...
May 22, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29786791/protocols-for-studies-on-tmprss2-erg-in-prostate-cancer
#3
Hubert Pakula, Douglas E Linn, Daniel R Schmidt, Marit Van Gorsel, Matthew G Vander Heiden, Zhe Li
TMPRSS2/ERG is the most common type of gene fusions found in human prostate cancer. There are two important features of TMPRSS2/ERG fusions. One is that these gene fusions lead to ectopic expression of ERG, an ETS family transcription factor, in prostate epithelial cells from the 5' control region of an androgen/estrogen dual-responsive gene, TMPRSS2; the other is that ~60% of these fusions are generated via intrachromosomal deletion of the interstitial region between TMPRSS2 and ERG. To recapitulate these important aspects of TMPRSS2/ERG fusions, we generated several TMPRSS2/ERG knockin mouse models based on the endogenous Tmprss2 locus...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786645/skeletal-muscle-micrornas-as-key-players-in-the-pathogenesis-of-amyotrophic-lateral-sclerosis
#4
REVIEW
Lorena Di Pietro, Wanda Lattanzi, Camilla Bernardini
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, for which, to date, no effective treatment to ameliorate the clinical manifestations is available. The long-standing view of ALS as affecting only motor neurons has been challenged by the finding that the skeletal muscle plays an active role in the disease pathogenesis and can be a valuable target for therapeutic strategies. In recent years, non-coding RNAs, including microRNAs, have emerged as important molecules that play key roles in several cellular mechanisms involved in the pathogenic mechanisms underlying various human conditions...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29785746/systematic-in-depth-proteomic-analysis-of-mitochondria-associated-endoplasmic-reticulum-membranes-mam-in-mouse-and-human-testes
#5
Xiaoli Wang, Yujiao Wen, Juan Dong, Congcong Cao, Shuiqiao Yuan
Mitochondria-associated endoplasmic reticulum membranes (MAMs) regulate important cellular functions including calcium signaling, bioenergetics, and apoptosis during neurodevelopment and carcinogenesis, but its function in male reproduction and spermatogenesis remains enigmatic because the field lacks a complete understanding of the proteome within testis MAMs. To better understand the biological processes and molecular functions of MAM in testes, here, we report a global mass spectrometry-based proteomic evaluation of the MAM obtained from human testes, mouse testes and brains, respectively...
May 21, 2018: Proteomics
https://www.readbyqxmd.com/read/29785486/radiation-induced-bystander-effect-in-large-japanese-field-mouse-apodemus-speciosus-embryonic-cells
#6
Kentaro Ariyoshi, Tomisato Miura, Kosuke Kasai, Nakata Akifumi, Yohei Fujishima, Mitsuaki A Yoshida
Although evidence suggests that ionizing radiation can induce the bystander effect (radiation-induced bystander effect: RIBE) in cultured cells or mouse models, it is unclear whether the effect occurs in cells of wild animals. We investigated medium-mediated bystander micronucleus (MN) formation and DNA damage in un-irradiated cells from a large Japanese field mouse (Apodemus speciosus). We isolated four clones of A. speciosus embryonic fibroblasts (A603-1, A603-2, A603-3, and A603-4) derived from the same mother, and examined their radiation sensitivity using the colony-forming assay...
May 22, 2018: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/29785143/pilot-study-of-the-antifibrotic-effects-of-the-multikinase-inhibitor-pacritinib-in-a-mouse-model-of-liver-fibrosis
#7
Suliman Al-Fayoumi, Taishi Hashiguchi, Yuka Shirakata, John Mascarenhas, Jack W Singer
Background: Fibrotic diseases result from an exuberant response to chronic inflammation. Myelofibrosis is the end result of inflammation in bone, caused by an inflammatory process triggered by production of abnormal myeloid cells driven by mutations affecting the JAK-STAT pathway. Inflammatory cytokine overproduction leads to increased mesenchymal cell proliferation, culminating in fibrosis. Although JAK2 inhibitors, such as the JAK1/2 inhibitor ruxolitinib and the JAK2/FLT3/CSF1R/IRAK1 inhibitor pacritinib suppress abnormal clone expansion in myelofibrosis, ruxolitinib does not appear to prevent or reverse bone-marrow fibrosis in most patients...
2018: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/29785139/blockage-of-store-operated-ca-2-entry-antagonizes-epstein-barr-virus-promoted-angiogenesis-by-inhibiting-ca-2-signaling-regulated-vegf-production-in-nasopharyngeal-carcinoma
#8
Jiaxiang Ye, Junqi Huang, Qian He, Weilin Zhao, Xiaoying Zhou, Zhe Zhang, Yongqiang Li, Jiazhang Wei, Jinyan Zhang
Background: Epstein-Barr virus (EBV) actively contributes to the pathological process of nasopharyngeal carcinoma (NPC) by enabling NPC cells to acquire various capacities required for their malignant biological actions. Our earlier works demonstrated that EBV-encoded latent membrane protein 1 (LMP1) enhanced vascular endothelial growth factor (VEGF)-mediated angiogenesis by boosting store-operated Ca2+ entry (SOCE) upon extracellular epidermal growth factor (EGF) stimulation. However, the antagonistic effects of SOCE blockage on EBV-promoted angiogenesis must be appropriately evaluated in vivo, and the global effect of EBV infection on the EGF-elicited cytosolic Ca2+ signaling, which regulates VEGF-mediated angiogenesis remains to be further clarified...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29785122/aloperine-executes-antitumor-effects-through-the-induction-of-apoptosis-and-cell-cycle-arrest-in-prostate-cancer-in-vitro-and-in-vivo
#9
Zhixin Ling, Han Guan, Zonghao You, Can Wang, Ling Hu, Lei Zhang, Yiduo Wang, Shuqiu Chen, Bin Xu, Ming Chen
Background: Prostate cancer (PCa) is one of the most common malignant diseases among male patients. Although androgen deprivation therapy remains the main treatment for PCa, most patients would inevitably progress to castration-resistant PCa, which is the main cause of cancer-related deaths. Thus, novel antitumor agents are urgently needed. Recent studies demonstrated that aloperine (ALO) as a natural alkaloid showed antitumor effects in other cancer types. However, the biological function and underlying mechanisms of ALO in PCa have not been investigated...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29785027/targeting-g-quadruplex-dna-as-cognitive-function-therapy-for-atr-x-syndrome
#10
Norifumi Shioda, Yasushi Yabuki, Kouya Yamaguchi, Misaki Onozato, Yue Li, Kenji Kurosawa, Hideyuki Tanabe, Nobuhiko Okamoto, Takumi Era, Hiroshi Sugiyama, Takahito Wada, Kohji Fukunaga
Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by mutations in ATRX, which encodes a chromatin-remodeling protein. Genome-wide analyses in mouse and human cells indicate that ATRX tends to bind to G-rich sequences with a high potential to form G-quadruplexes. Here, we report that Atrx mutation induces aberrant upregulation of Xlr3b expression in the mouse brain, an outcome associated with neuronal pathogenesis displayed by ATR-X model mice. We show that ATRX normally binds to G-quadruplexes in CpG islands of the imprinted Xlr3b gene, regulating its expression by recruiting DNA methyltransferases...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29785004/a-direct-tissue-grafting-approach-to-increasing-endogenous-brown-fat
#11
Nicole R Blumenfeld, Hwan June Kang, Anna Fenzl, Ziwei Song, Janice J Chung, Ranjodh Singh, Roshawn Johnson, Ayse Karakecili, Jun B Feranil, Ninna S Rossen, Vivian Zhang, Sahir Jaggi, Bret McCarty, Steven Bessler, Gary J Schwartz, Robert Grant, Judith Korner, Florian W Kiefer, Brian M Gillette, Samuel K Sia
There is widespread evidence that increasing functional mass of brown adipose tissue (BAT) via browning of white adipose tissue (WAT) could potentially counter obesity and diabetes. However, most current approaches focus on administration of pharmacological compounds which expose patients to highly undesirable side effects. Here, we describe a simple and direct tissue-grafting approach to increase BAT mass through ex vivo browning of subcutaneous WAT, followed by re-implantation into the host; this cell-therapy approach could potentially act synergistically with existing pharmacological approaches...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29784859/igg-responses-to-the-plasmodium-falciparum-antigen-var2csa-in-colombia-are-restricted-to-pregnancy-and-are-not-induced-by-exposure-to-p-vivax
#12
Mary Lopez-Perez, Mads Delbo Larsen, Rafael Bayarri-Olmos, Paulina Ampomah, Liz Stevenson, Myriam Arévalo-Herrera, Sócrates Herrera, Lars Hviid
Clinical immunity to malaria is associated with acquisition of IgG specific for members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family of clonally variant antigens on the surface of infected erythrocytes (IEs). The VAR2CSA subtype of PfEMP1 mediates IE binding in the placenta. VAR2CSA-specific IgG is normally acquired only after exposure to placental parasites. However, it was recently reported that men and children from Colombia often have high levels of functional VAR2CSA-specific IgG...
May 21, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29784808/hamartin-regulates-cessation-of-mouse-nephrogenesis-independently-of-mtor
#13
Oded Volovelsky, Thi Nguyen, Alison E Jarmas, Alexander N Combes, Sean B Wilson, Melissa H Little, David P Witte, Eric W Brunskill, Raphael Kopan
Nephrogenesis concludes by the 36th week of gestation in humans and by the third day of postnatal life in mice. Extending the nephrogenic period may reduce the onset of adult renal and cardiovascular disease associated with low nephron numbers. We conditionally deleted either Mtor or Tsc1 (coding for hamartin, an inhibitor of Mtor) in renal progenitor cells. Loss of one Mtor allele caused a reduction in nephron numbers; complete deletion led to severe paucity of glomeruli in the kidney resulting in early death after birth...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784789/ck1%C3%AE-%C3%AE%C2%B5-protein-kinase-primes-the-per2-circadian-phosphoswitch
#14
Rajesh Narasimamurthy, Sabrina R Hunt, Yining Lu, Jean-Michel Fustin, Hitoshi Okamura, Carrie L Partch, Daniel B Forger, Jae Kyoung Kim, David M Virshup
Multisite phosphorylation of the PERIOD 2 (PER2) protein is the key step that determines the period of the mammalian circadian clock. Previous studies concluded that an unidentified kinase is required to prime PER2 for subsequent phosphorylation by casein kinase 1 (CK1), an essential clock component that is conserved from algae to humans. These subsequent phosphorylations stabilize PER2, delay its degradation, and lengthen the period of the circadian clock. Here, we perform a comprehensive biochemical and biophysical analysis of mouse PER2 (mPER2) priming phosphorylation and demonstrate, surprisingly, that CK1δ/ε is indeed the priming kinase...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784673/formation-of-the-sacrum-requires-down-regulation-of-sonic-hedgehog-signaling-in-the-sacral-intervertebral-discs
#15
Raffaella Bonavita, Kathleen Vincent, Robert Pinelli, Chitra Lekha Dahia
In humans, the sacrum forms an important component of the pelvic arch, and it transfers the weight of the body to the lower limbs. The sacrum is formed by collapse of the intervertebral discs (IVDs) between the five sacral vertebrae during childhood, and their fusion to form a single bone. We show that collapse of the sacral discs in the mouse is associated with the down-regulation of sonic hedgehog (SHH) signaling in the nucleus pulposus (NP) of the disc, and many aspects of this phenotype can be reversed by experimental postnatal activation of HH signaling...
May 21, 2018: Biology Open
https://www.readbyqxmd.com/read/29784648/mouse-models-of-nesprin-related-diseases
#16
REVIEW
Can Zhou, Li Rao, Derek T Warren, Catherine M Shanahan, Qiuping Zhang
Nesprins (nuclear envelope spectrin repeat proteins) are a family of multi-isomeric scaffolding proteins. Nesprins form the LInker of Nucleoskeleton-and-Cytoskeleton (LINC) complex with SUN (Sad1p/UNC84) domain-containing proteins at the nuclear envelope, in association with lamin A/C and emerin, linking the nucleoskeleton to the cytoskeleton. The LINC complex serves as both a physical linker between the nuclear lamina and the cytoskeleton and a mechanosensor. The LINC complex has a broad range of functions and is involved in maintaining nuclear architecture, nuclear positioning and migration, and also modulating gene expression...
May 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29784639/tyrosine-kinase-inhibitor-induced-defects-in-dna-repair-sensitize-flt3-itd-positive-leukemia-cells-to-parp1-inhibitors
#17
Silvia Maifrede, Margaret Nieborowska-Skorska, Katherine Sullivan, Yashodhara Dasgupta, Paulina Podszywalow-Bartnicka, Bac Viet Le, Martyna Solecka, Zhaorui Lian, Elizaveta A Belyaeva, Alina Nersesyan, Marcin M Machnicki, Monika Toma, Nicolas Chatain, Malgorzata Rydzanicz, Huaqing Zhao, Jaroslav Jelinek, Katarzyna Piwocka, Tomasz Sliwinski, Tomasz Stoklosa, Rafal Ploski, Thomas Fischer, Stephen M Sykes, Steffen Koschmieder, Lars Bullinger, Peter Valent, Mariusz Wasik, Jian Huang, Tomasz Skorski
Mutations in the FMS-like tyrosine-kinase 3 (FLT3) such as internal tandem duplications (ITD) can be found in up to 23% of patients with acute myeloid leukemia (AML) and confer a poor prognosis. Current treatment options for FLT3(ITD)-positive AMLs include genotoxic therapy and FLT3 inhibitors (FLT3i), which are rarely curative. PARP1 inhibitors (PARP1i) have been successfully applied to induce synthetic lethality in tumors harboring BRCA1/2 mutations and displaying homologous recombination (HR) deficiency...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29784076/analgesic-efficacy-and-hematologic-effects-of-robenacoxib-in-mice
#18
Jennifer A Beninson, Jennifer L Lofgren, Patrick A Lester, Madeline M Hileman, Daniel J Berkowitz, Daniel D Myers
NSAID analgesics may confound models that require inflammation to mimic disease development in humans. This effect presents a challenge for veterinary staff and investigators, because surgery is often necessary to create mouse models of disease and NSAID are first-line analgesics used to treat postoperative pain. We evaluated robenacoxib, a NSAID highly selective for cyclooxygenase 2, in a carrageenan paw edema (CPE) assay and surgical model of venous thrombosis (VT). We generated a mouse-specific dose-response curve by using the CPE assay for robenacoxib doses of 3...
May 1, 2018: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/29784049/identification-and-therapeutic-modulation-of-a-pro-inflammatory-subset-of-disease-associated-microglia-in-alzheimer-s-disease
#19
Srikant Rangaraju, Eric B Dammer, Syed Ali Raza, Priyadharshini Rathakrishnan, Hailian Xiao, Tianwen Gao, Duc M Duong, Michael W Pennington, James J Lah, Nicholas T Seyfried, Allan I Levey
BACKGROUND: Disease-associated-microglia (DAM) represent transcriptionally-distinct and neurodegeneration-specific microglial profiles with unclear significance in Alzheimer's disease (AD). An understanding of heterogeneity within DAM and their key regulators may guide pre-clinical experimentation and drug discovery. METHODS: Weighted co-expression network analysis (WGCNA) was applied to existing microglial transcriptomic datasets from neuroinflammatory and neurodegenerative disease mouse models to identify modules of highly co-expressed genes...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29784015/induction-of-multiple-myeloma-cancer-stem-cell-apoptosis-using-conjugated-anti-abcg2-antibody-with-epirubicin-loaded-microbubbles
#20
Fangfang Shi, Miao Li, Jing Wang, Di Wu, Meng Pan, Mei Guo, Jun Dou
BACKGROUND: Multiple myeloma (MM) currently remains largely incurable. Cancer stem cells (CSCs) are believed to be responsible for drug resistance and eventual relapse. In this study, we exploited a novel agent to evaluate its inhibitory effect on MM CSCs. METHODS: Epirubicin (EPI)-loaded lipid microbubbles (MBs) conjugated with anti-ABCG2 monoclonal antibody (EPI-MBs + mAb) were developed and their effect on MM 138- CD34- CSCs isolated from human MM RPMI 8226 cell line plus ultrasound exposure in vitro and in vivo in a nonobese diabetic/severe combined immunodeficient mouse model were assessed...
May 21, 2018: Stem Cell Research & Therapy
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