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https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#1
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of SCD1 in regulation of liver T-ICs and sorafenib resistance...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28647061/vesicle-fusion-mediated-by-solanesol-anchored-dna
#2
Kristina M Flavier, Steven G Boxer
Fusion between two lipid bilayers is one of the central processes in cell biology, playing a key role in endocytosis, exocytosis, and vesicle transport. We have previously developed a model system that uses the hybridization of complementary DNA strands to model the formation of the SNARE four-helix bundle that mediates synaptic vesicle fusion and used it to study vesicle fusion to a tethered lipid bilayer. Using single vesicle assays, 70% of observed fusion events in the DNA-lipid system are arrested at the hemifusion stage, whereas only 5% eventually go to full fusion...
June 21, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28646485/findings-from-the-harvard-medical-school-cambridge-integrated-clerkship-a-year-long-longitudinal-psychiatry-experience
#3
Elisa Cheng, David Hirsh, Elizabeth Gaufberg, Todd Griswold, J Wesley Boyd
OBJECTIVE: The Harvard Medical School Cambridge Integrated Clerkship is a longitudinal integrated clerkship that has provided an alternative clinical model for medical education in psychiatry since its inception in 2004. This study was undertaken in an effort to better understand the student experience of the Cambridge Integrated Clerkship and how it may have impacted students' perceptions of and interest in psychiatry, as well as performance. METHODS: Qualitative surveys were sent via e-mail to the first 11 student cohorts who had completed the Cambridge Integrated Clerkship (from 2004 to 2014) and for whom we had e-mail addresses (N = 100), and the free-text responses were coded thematically...
June 23, 2017: Academic Psychiatry
https://www.readbyqxmd.com/read/28646338/chemotherapy-induced-gastrointestinal-toxicity-is-associated-with-changes-in-serum-and-urine-metabolome-and-fecal-microbiota-in-male-sprague-dawley-rats
#4
Richard A Forsgård, Vannina G Marrachelli, Katri Korpela, Rafael Frias, Maria Carmen Collado, Riitta Korpela, Daniel Monleon, Thomas Spillmann, Pia Österlund
PURPOSE: Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT...
June 23, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28646194/magnetic-resonance-imaging-of-fetal-persistent-left-superior-vena-cava
#5
Su-Zhen Dong, Ming Zhu
This study aimed to evaluate the diagnostic accuracy of fetal magnetic resonance imaging (MRI) for persistent left superior vena cava (LSVC). Prenatal echocardiography (echo) and/or ultrasound (US) and MRI data for 49 fetuses with persistent LSVC, confirmed via postnatal diagnoses between January 2010 and October 2015, were retrospectively reviewed. All prenatal MRI was performed at 1.5 T. Imaging sequences included steady-state free-precession (SSFP), single-shot turbo spin echo (SSTSE), and other sequences...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646079/identification-of-flavin-containing-monooxygenase-5-fmo5-as-a-regulator-of-glucose-homeostasis-and-a-potential-sensor-of-gut-bacteria
#6
Flora Scott, Sandra G Gonzalez Malagon, Brett A O'Brien, Diede Fennema, Sunil Veeravalli, Clarissa R Coveney, Ian R Phillips, Elizabeth A Shephard
We have previously identified flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing. The aim of the present study was to investigate the role of FMO5 in glucose homeostasis and the impact of diet and gut flora on the phenotype of mice in which the Fmo5 gene has been disrupted (Fmo5(-/-) mice). In comparison with wild-type (WT) counterparts, Fmo5(-/-) mice are resistant to age-related changes in glucose homeostasis and maintain the higher glucose tolerance and insulin sensitivity characteristic of young animals...
June 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28645512/the-rna-seq-analysis-suggests-a-potential-multi-component-complement-system-in-oyster-crassostrea-gigas
#7
Lingling Wang, Huan Zhang, Leilei Wang, Daoxiang Zhang, Zhao Lv, Zhaoqun Liu, Weilin Wang, Zhi Zhou, Limei Qiu, Hao Wang, Jun Li, Linsheng Song
The complement system is one of the major effector mechanisms of immune system, playing essential roles in both the innate and adaptive immune responses. In the present study, the counterparts of vertebrate complement components were identified by screening the sequenced genome of Crassostrea gigas, resulting in the identification of 792 gene models containing complement-related domains. The transcriptome of haemocytes at 6, 12 and 24 h post lipopolysaccharides (LPS) stimulation showed differential expression of 77 C1q domain containing proteins, 53 C-type lectins and 42 fibrinogen-related proteins...
June 20, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28645247/the-correlation-between-poor-prognosis-and-increased-yes-associated-protein-1-expression-in-keratin-19-expressing-hepatocellular-carcinomas-and-cholangiocarcinomas
#8
KyuHo Lee, Kyoung-Bun Lee, Hae Yoen Jung, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh, Ja-June Jang
BACKGROUND: The Hippo pathway plays a vital role in liver regeneration and development by determining cellular lineage and regulating cell proliferation and apoptosis. In this study, we aimed to assess the role of the Hippo pathway in hepatic carcinogenesis and morphogenesis by examining Yes-associated protein 1 (YAP1) expression in the spectrum of hepatic carcinomas based on cellular lineage. METHODS: We examined 913 primary hepatic carcinomas, including hepatocellular carcinomas (HCCs), combined hepatocellular and cholangiocarcinomas (cHC-CCAs), intrahepatic cholangiocarcinomas (IHCCAs) and perihilar extrahepatic bile duct carcinomas (EHBCAs)...
June 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28645089/drug-resistance-mechanism-of-l10f-l10f-n88s-and-l90m-mutations-in-crf01_ae-hiv-1-protease-molecular-dynamics-simulations-and-binding-free-energy-calculations
#9
C S Vasavi, Ramasamy Tamizhselvi, Punnagai Munusami
HIV-1 protease plays a crucial role in viral replication and maturation, which makes it one of the most attractive targets for anti-retroviral therapy. The majority of HIV infections in developing countries are due to non-B subtype. Subtype AE is spreading rapidly and infecting huge population worldwide. The mutations in the active site of subtype AE directly impair the interactions with the inhibitor. The non-active site mutations influence the binding of the inhibitor indirectly and their resistance mechanism is not well understood...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28644884/ligand-induced-rapid-skeletal-muscle-atrophy-in-hsa-fv2e-perk-transgenic-mice
#10
Masato Miyake, Masashi Kuroda, Hiroshi Kiyonari, Kenji Takehana, Satoshi Hisanaga, Masatoshi Morimoto, Jun Zhang, Miho Oyadomari, Hiroshi Sakaue, Seiichi Oyadomari
BACKGROUND: Formation of 43S and 48S preinitiation complexes plays an important role in muscle protein synthesis. There is no muscle-wasting mouse model caused by a repressed 43S preinitiation complex assembly. OBJECTIVE: The aim of the present study was to develop a convenient mouse model of skeletal muscle wasting with repressed 43S preinitiation complex assembly. MATERIAL AND METHODS: A ligand-activatable PERK derivative Fv2E-PERK causes the phosphorylation of eukaryotic initiation factor 2α (eIF2α), which inhibits 43S preinitiation complex assembly...
2017: PloS One
https://www.readbyqxmd.com/read/28644580/a-free-ride-an-analysis-of-the-association-of-casino-bus-tours-and-problem-gambling-among-older-adults
#11
Mark van der Maas, Robert E Mann, Flora I Matheson, Nigel E Turner, Hayley A Hamilton, John McCready
BACKGROUND AND AIMS: Little research has examined the relationship between incentives used by gambling venues to attract customers and the experience of gambling related harm. Organized and subsidized bus tours are a common example of such incentives. The aim of this study was to examine whether bus tour patronage was associated with increased odds of problem gambling among older adults. This study also compared rates of bus tour use by sociodemographic characteristics and gambling behaviours...
June 23, 2017: Addiction
https://www.readbyqxmd.com/read/28643762/serum-butyrylcholinesterase-and-zinc-in-breast-cancer
#12
Rupesh Kumar, Sairoz Razab, Krishnananda Prabhu, Satadru Ray, Bhanu Prakash
CONTEXT: Even though, a large number of serological, molecular markers have been proposed for breast cancer screening, most of them lack specificity, sensitivity, prognostic value, and cost effectiveness. Butyrylcholinesterase (BChE) and its genes are aberrantly expressed in a variety of human cancers. It has-been linked to tumorigenesis, cell proliferation, and cell differentiation. Zinc (Zn) is a cofactor for superoxide dismutase, an enzyme that protects cellular components against free radical-induced damage and carcinogenesis...
April 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28643343/alpha-beta-hydrolases-a-unique-structural-motif-coordinates-catalytic-acid-residue-in-40-protein-fold-families
#13
Polytimi S Dimitriou, Alexander Denesyuk, Seiji Takahashi, Satoshi Yamashita, Mark S Johnson, Toru Nakayama, Konstantin Denessiouk
The alpha/beta-hydrolases (ABH) are a family of acid-base-nucleophile catalytic triad enzymes with a common fold, but using a wide variety of substrates, having different pH optima, catalyzing unique catalytic reactions and often showing improved chemical and thermo stability. The ABH enzymes are prime targets for protein engineering. Here, we have classified active sites from 51 representative members of 40 structural ABH fold families into eight distinct conserved geometries. We demonstrate the occurrence of a common structural motif, the catalytic acid zone, at the catalytic triad acid turn...
June 23, 2017: Proteins
https://www.readbyqxmd.com/read/28643196/genetic-variants-in-cell-death-pathway-genes-and-hbv-related-hepatocellular-carcinoma-among-a-chinese-han-population
#14
Fei Liu, Fuqiang Li, Limei Luo, Hanteng Yang, Yonggang Wei, Wentao Wang, Lvnan Yan, Tianfu Wen, Jiayin Yang, Bo Li
Cell death pathway plays an important role in apoptosis, and corruption of this signaling pathway has been shown to participate in carcinogenesis. We aimed at determining whether genetic variants in CASP8, CASP10 and CFLAR influence the development and clinical outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A hospital-based case-control study, including 600 HCC cases and 600 HBsAg positive controls without HCC, was conducted to assess the relationship between 11 tagging SNPs in CASP8, CASP10 and CFLAR and HBV-related HCC risk and prognosis in a Chinese Han population...
June 22, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28642436/metalloprotein-entatic-control-of-ligand-metal-bonds-quantified-by-ultrafast-x-ray-spectroscopy
#15
Michael W Mara, Ryan G Hadt, Marco Eli Reinhard, Thomas Kroll, Hyeongtaek Lim, Robert W Hartsock, Roberto Alonso-Mori, Matthieu Chollet, James M Glownia, Silke Nelson, Dimosthenis Sokaras, Kristjan Kunnus, Keith O Hodgson, Britt Hedman, Uwe Bergmann, Kelly J Gaffney, Edward I Solomon
The multifunctional protein cytochrome c (cyt c) plays key roles in electron transport and apoptosis, switching function by modulating bonding between a heme iron and the sulfur in a methionine residue. This Fe-S(Met) bond is too weak to persist in the absence of protein constraints. We ruptured the bond in ferrous cyt c using an optical laser pulse and monitored the bond reformation within the protein active site using ultrafast x-ray pulses from an x-ray free-electron laser, determining that the Fe-S(Met) bond enthalpy is ~4 kcal/mol stronger than in the absence of protein constraints...
June 23, 2017: Science
https://www.readbyqxmd.com/read/28641950/cholinergic-signaling-plasticity-maintains-viscerosensory-responses-during-aspiculuris-tetraptera-infection-in-mice-small-intestine
#16
Egina C Villalobos-Hernández, Carlos Barajas-López, Elizabeth A Martínez-Salazar, Roberto C Salgado-Delgado, Marcela Miranda-Morales
Intestinal parasites alter gastrointestinal (GI) functions like the cholinergic function. Aspiculuris tetraptera is a pinworm frequently observed in laboratory facilities, which infests the mice cecum and proximal colon. However, little is known about the impact of this infection on the GI sensitivity. Here, we investigated possible changes in spontaneous mesenteric nerve activity and on the mechanosensitivity function of worm-free regions of naturally infected mice with A. tetraptera. Infection increased the basal firing of mesenteric afferent nerves in jejunum...
June 3, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28641620/-role-of-microparticles-derived-from-acute-promyelocytic-leukemia-cells-in-coagulopathy
#17
Ying-Mei Zhang, Bo Chen, Long-Yue Wu, Jin-Xiao Hou, Jin-Yue Fu
OBJECTIVE: To evaluate the role of microparticle (MP) derived from acute promyelocytic leukemia (APL) cells and tissue factor (TF) carried by the MP in hypercoagulable state, and the effect of treatment with cytotoxic chemotherapy/differentiating agents on procoagulant activity (PCA) of these MP. METHODS: Bone marrow mononuclear cells (BMMNC) were extracted from 5 APL patients and 5 sex- and age- matched patients with iron deficiency anemia as controls. The cells were cultured in vitro for 48 h, then MP-rich culture medium and MP-free culture medium were harvested and MP was further obtained from certain volume of MP-rich culture medium...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641605/state-dependent-parasitism-by-a-facultative-parasite-of-fruit-flies
#18
Lien T Luong, Taylor Brophy, Emily Stolz, Solomon J Chan
Parasites can evolve phenotypically plastic strategies for transmission such that a single genotype can give rise to a range of phenotypes depending on the environmental condition. State-dependent plasticity in particular can arise from individual differences in the parasite's internal state or the condition of the host. Facultative parasites serve as ideal model systems for investigating state-dependent plasticity because individuals can exhibit two life history strategies (free-living or parasitic) depending on the environment...
June 23, 2017: Parasitology
https://www.readbyqxmd.com/read/28641562/structural-characterization-of-amyloid-%C3%AE-17-42-dimer-by-potential-of-mean-force-analysis-insights-from-molecular-dynamics-simulations
#19
Mary Dutta, Rajkalyan Chutia, Venkata Satish Kumar Mattaparthi
Recent experiments with Amyloid β1-42 peptide have indicated that the initial dimerization of Aβ1-42 monomers to form amyloid dimers stand out as a key event in the generation of toxic oligomers. However, the structural characterization of Aβ1-42 dimer at the atomistic level and the dimerization mechanism by which Aβ1-42 peptides co-aggregate still remains not clear. In the present study, the process of Aβ17-42 peptide dimerization which is known to play an important role in the plaque formation was evaluated in terms of potential of mean force, which provided free energies along the reaction coordinates...
June 20, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28641547/recent-advances-on-the-role-of-micrornas-in-both-insulin-resistance-and-cancer
#20
Adele Vivacqua, Paola De Marco, Antonino Belfiore, Marcello Maggiolini
BACKGROUND: Insulin resistance is a pathological condition characterized by the failure of target cells to uptake and metabolizes glucose in response to insulin. In particular, the elevated concentrations of glucose, insulin and free insulin growth factor-1, which result from insulin resistance, may generate a pro-inflammatory and pro-tumorigenic state. These alterations may underlie the increased risk to develop various types of cancer as well as the worse cancer prognosis observed in obese and diabetic patients...
June 22, 2017: Current Pharmaceutical Design
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