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https://www.readbyqxmd.com/read/28432873/conditional-deletion-of-bmal1-accentuates-microvascular-and-macrovascular-injury
#1
Ashay D Bhatwadekar, Eleni Beli, Diao Yanpeng, Jonathan Chen, Qianyi Luo, Alpha Alex, Sergio Caballero, James M Dominguez, Tatiana E Salazar, Julia V Busik, Mark S Segal, Maria B Grant
The brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (BMAL)-1 constitutes a major transcriptional regulator of the circadian clock. Here, we explored the impact of conditional deletion of Bmal1 in endothelium and hematopoietic cells in murine models of microvascular and macrovascular injury. We used two models of Bmal1(fx/fx);Tek-Cre mice, a retinal ischemia/reperfusion model and a neointimal hyperplasia model of the femoral artery. Eyes were enumerated for acellular capillaries and were stained for oxidative damage markers using nitrotyrosine immunohistochemistry...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28430802/the-quality-changes-in-fresh-frozen-plasma-of-the-blood-donors-at-high-altitude
#2
Zongkui Wang, Hua Liu, Miaomiao Dou, Xi Du, Jijun Hu, Na Su, Ya Wang, Rong Zhang, Changqing Li
OBJECTIVE: According to the international guidelines, fresh frozen plasma (FFP) is unanimously used to treat coagulation disorders. The quality of FFP is critical for the clinical transfusion. Till now, few studies have integratedly evaluated the differences of FFP from blood donors at between high altitude (HA) and low altitude (LA). Besides, there were no special quality standards for HA FFP in China. MATERIALS AND METHODS: Up to 41 HA (Lhasa, 3700 m) and 46 LA (Chengdu, 500 m) blood donors were included in our study to estimate the differences of FFP from HA and LA blood donors...
2017: PloS One
https://www.readbyqxmd.com/read/28401808/associations-between-volume-changes-and-spatial-dose-metrics-for-the-urinary-bladder-during-local-versus-pelvic-irradiation-for-prostate-cancer
#3
Oscar Casares-Magaz, Vitali Moiseenko, Austin Hopper, Niclas Johan Pettersson, Maria Thor, Rick Knopp, Joseph O Deasy, Ludvig Paul Muren, John Einck
BACKGROUND: Inter-fractional variation in urinary bladder volumes during the course of radiotherapy (RT) for prostate cancer causes deviations between planned and delivered doses. This study compared planned versus daily cone-beam CT (CBCT)-based spatial bladder dose distributions, for prostate cancer patients receiving local prostate treatment (local treatment) versus prostate including pelvic lymph node irradiation (pelvic treatment). MATERIAL AND METHODS: Twenty-seven patients (N = 15 local treatment; N = 12 pelvic treatment) were treated using daily image-guided RT (1...
April 12, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28400758/leptospira-infection-interferes-with-the-prothrombinase-complex-assembly-during-experimental-leptospirosis
#4
Monica L Vieira, Sonia A de Andrade, Zenaide M Morais, Silvio A Vasconcellos, Maria Lucia Z Dagli, Ana Lucia T O Nascimento
Leptospirosis is a worldwide zoonotic and neglected infectious disease of human and veterinary concern, caused by pathogenic Leptospira species. Although bleeding is a common symptom of severe leptospirosis, the cause of hemorrhage is not completely understood. In severe infections, modulation of hemostasis by pathogens is an important virulence mechanism, and hemostatic impairments such as coagulation/fibrinolysis dysfunction are frequently observed. Here, we analyze the coagulation status of experimentally infected hamsters in an attempt to determine coagulation interferences and the origin of leptospirosis hemorrhagic symptomatology...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28388885/the-influence-of-actin-depolymerization-induced-by-cytochalasin-d-and-mechanical-stretch-on-interleukin-8-expression-and-jnk-phosphorylation-levels-in-human-retinal-pigment-epithelial-cells
#5
Meng Gao, Shen Wu, Jing Ji, JingXue Zhang, Qian Liu, YanKun Yue, Lu Liu, XinXin Liu, Wu Liu
BACKGROUND: This study explores the role of actin cytoskeleton depolymerization induced by Cytochalasin D and mechanical stretch on the interleukin-8 (IL-8) expression and c-jun N-terminal kinase (JNK) phosphorylation levels in human retinal pigment epithelial (RPE) cells. METHODS: A Flexcell FX-5000 Tension system was used to apply cyclic stretch to cultured human RPE cells (ARPE-19) at 0.33 Hz with 20% elongation for 0 h, 6 h or 24 h. The cells were stretched alone or pre-treated with Cytochalasin D...
April 7, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/28387741/effects-of-low-molecular-weight-fucoidan-and-high-stability-fucoxanthin-on-glucose-homeostasis-lipid-metabolism-and-liver-function-in-a-mouse-model-of-type-ii-diabetes
#6
Hong-Ting Victor Lin, Yu-Chi Tsou, Yu-Ting Chen, Wen-Jung Lu, Pai-An Hwang
The combined effects of low-molecular-weight fucoidan (LMF) and fucoxanthin (Fx) in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism...
April 7, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28381574/defining-a-novel-role-for-the-coxsackie-and-adenovirus-receptor-in-human-adenovirus-serotype-5-transduction-in-vitro-in-the-presence-of-mouse-serum
#7
Estrella Lopez-Gordo, Andor Doszpoly, Margaret R Duffy, Lynda Coughlan, Angela C Bradshaw, Katie M White, Laura Denby, Stuart A Nicklin, Andrew H Baker
Human adenoviral serotype 5 (HAdV-5) vectors have predominantly hepatic tropism when delivered intravascularly, resulting in immune activation and toxicity. Coagulation FX binding to HAdV-5 mediates liver transduction and provides protection from virion neutralisation in mice. FX is dispensable for liver transduction in mice lacking IgM antibodies or complement, suggesting alternative transduction pathways exist. To identify novel factor(s) mediating HAdV-5 FX-independent entry, we investigated HAdV-5 transduction in vitro in the presence of serum from immunocompetent C57BL/6 or immunocompromised mice lacking IgM antibodies (Rag 2(-/-) and NSG)...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28357617/interaction-of-various-types-of-photosystem-i-complexes-with-exogenous-electron-acceptors
#8
Anastasia A Petrova, Baina K Boskhomdzhieva, Georgy E Milanovsky, Olga A Koksharova, Mahir D Mamedov, Dmitry A Cherepanov, Alexey Yu Semenov
Interaction of photosystem I (PS I) complexes from cyanobacteria Synechocystis sp. PCC 6803 containing various quinones in the A1-site (phylloquinone PhQ in the wild-type strain (WT), and plastoquinone PQ or 2,3-dichloronaphthoquinone Cl 2 NQ in the menB deletion strain) and different numbers of Fe4S4 clusters (intact WT and FX-core complexes depleted of FA/FB centers) with external acceptors has been studied. The efficiency of interaction was estimated by measuring the light-induced absorption changes at 820 nm due to the reduction of the special pair of chlorophylls (P700(+)) by an external acceptor(s)...
March 29, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28347456/long-term-release-of-fluoride-from-fissure-sealants-in-vitro-study
#9
Piotr Kosior, Maciej Dobrzyński, Mariusz Korczyński, Katarzyna Herman, Agnieszka Czajczyńska-Waszkiewicz, Małgorzata Kowalczyk-Zając, Dagmara Piesiak-Pańczyszyn, Katarzyna Fita, Maciej Janeczek
The intensity of the cariostatic activity of fluoride ions can be attributed to their multidirectional influence on the caries process. They are an irreplaceable factor that helps sustain mineral balance of dental tissues, simultaneously demonstrating antibacterial properties. As a consequence, many manufacturers of fissure sealants include fluoride ions in their products. The aim of this in vitro study was to determine long-term fluoride release from four fissure sealants (Conseal F, Fissurit FX, Delton Fs+, Admira Seal)...
May 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28333212/structural-history-of-human-srgap2-proteins
#10
Michael Sporny, Julia Guez-Haddad, Annett Kreusch, Sivan Shakartzi, Avi Neznansky, Alice Cross, Michail N Isupov, Britta Qualmann, Michael M Kessels, Yarden Opatowsky
In the development of the human brain, human-specific genes are considered to play key roles, conferring its unique advantages and vulnerabilities. At the time of Homo lineage divergence from Australopithecus, SRGAP2C gradually emerged through a process of serial duplications and mutagenesis from ancestral SRGAP2A (3.4-2.4 Ma). Remarkably, ectopic expression of SRGAP2C endows cultured mouse brain cells, with human-like characteristics, specifically, increased dendritic spine length and density. To understand the molecular mechanisms underlying this change in neuronal morphology, we determined the structure of SRGAP2A and studied the interplay between SRGAP2A and SRGAP2C...
February 21, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28333010/quantitative-assessment-of-breast-cosmetic-outcome-after-whole-breast-irradiation
#11
Jay P Reddy, Xiudong Lei, Sheng-Cheng Huang, Krista M Nicklaus, Michelle C Fingeret, Simona F Shaitelman, Kelly K Hunt, Thomas A Buchholz, Fatima Merchant, Mia K Markey, Benjamin D Smith
PURPOSE: To measure, by quantitative analysis of digital photographs, breast cosmetic outcome within the setting of a randomized trial of conventionally fractionated (CF) and hypofractionated (HF) whole-breast irradiation (WBI), to identify how quantitative cosmesis metrics were associated with patient- and physician-reported cosmesis and whether they differed by treatment arm. METHODS AND MATERIALS: From 2011 to 2014, 287 women aged ≥40 with ductal carcinoma in situ or early invasive breast cancer were randomized to HF-WBI (42...
April 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28329674/%C3%AE-arrestin2-couples-metabotropic-glutamate-receptor-5-to-neuronal-protein-synthesis-and-is-a-potential-target-to-treat-fragile-x
#12
Laura J Stoppel, Benjamin D Auerbach, Rebecca K Senter, Anthony R Preza, Robert J Lefkowitz, Mark F Bear
Synaptic protein synthesis is essential for modification of the brain by experience and is aberrant in several genetically defined disorders, notably fragile X (FX), a heritable cause of autism and intellectual disability. Neural activity directs local protein synthesis via activation of metabotropic glutamate receptor 5 (mGlu5), yet how mGlu5 couples to the intracellular signaling pathways that regulate mRNA translation is poorly understood. Here, we provide evidence that β-arrestin2 mediates mGlu5-stimulated protein synthesis in the hippocampus and show that genetic reduction of β-arrestin2 corrects aberrant synaptic plasticity and cognition in the Fmr1(-/y) mouse model of FX...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28324062/gene-hormone-therapy-interaction-and-fracture-risk-in-postmenopausal-women
#13
Youjin Wang, Jean Wactawski-Wende, Lara E Sucheston-Campbell, Leah Preus, Kathleen M Hovey, Jing Nie, Rebecca D Jackson, Samuel K Handelman, Rami Nassir, Carolyn J Crandall, Heather M Ochs-Balcom
Context: Evidence supports a protective effect of menopausal hormone therapy (HT) on bone. However, whether genetic susceptibility modifies the association of HT and fracture risk is not sufficiently explored. Objective: The objective was to test an interaction between genetic susceptibility and HT on fracture risk. Design: We constructed two weighted genetic risk scores (GRSs) based on 16 fracture-associated variants (Fx-GRS) and 50 bone mineral density (BMD) variants (BMD-GRS)...
March 6, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28314295/development-and-applicability-of-integrative-tumor-response-assays-for-metastatic-colorectal-cancer
#14
Yong Sik Yoon, Chan Wook Kim, Seon Ae Roh, Dong Hyung Cho, Tae Won Kim, Moon Bo Kim, Jin Cheon Kim
AIM: The present study investigated how well the results of integrative tumor-response assay (ITRA) compared to those of clinical response to chemotherapy in patients with metastatic colorectal cancer (CRC). PATIENTS AND METHODS: A total of 129 patients with metastatic CRC were prospectively enrolled. ITRA consisted of two sequential histoculture drug-response assays (HDRAs). First-stage HDRAs were performed using 5-fluorouracil with leucovorin and oxaliplatin (FX), or with irinotecan (FR)...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28306345/a-retrospective-study-on-non-drug-related-poisoning-in-the-community-among-children-from-south-india
#15
Debasis Das Adhikari, Saibal Das, Blessed Winston A, Kaysina Vazhudhi, Aniket Kumar, Margaret Shanthi Fx, Indira Agarwal
OBJECTIVES: This retrospective study was performed to determine the incidence, demographic distribution, types and outcomes across various non-drug related poisonings among children attending a tertiary care center in south India. METHODS: All children from 0-16 years who presented to the Paediatric Emergency Department, Christian Medical College, Vellore with non-drug related poisoning from October 2004 to September 2013 were included. RESULTS: Out of the total 997 cases of poisoning, 629 (63...
April 2017: Hospital Practice (Minneapolis)
https://www.readbyqxmd.com/read/28302935/factor-x-deficiency-with-heterozygous-mutations-of-novel-p-g435s-and-known-p-g244r-in-a-patient-presenting-with-severe-umbilical-hemorrhage
#16
Yoko Matsuo, Tatsuki Mizuochi, Miho Mitsuo, Shinichiro Nakagawa, Shuichi Ozono, Koichiro Ueda, Yoko Sogabe, Ritsuko Seki, Kenji Soejima, Takashi Okamura, Yushiro Yamashita
A 10-day-old male patient was referred to our hospital with severe umbilical bleeding. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were prominently prolonged. Plasma coagulation factor X (FX) activity and antigen levels were 1% and 0.6%, respectively. A DNA sequence analysis of his leukocytes revealed a compound heterozygous state; known Gly244 to Arg (p.G244R) in exon 6 and a novel mutation of Gly 435 to Ser (p.G435S) in exon 8. A pedigree analysis showed that p.G244R originated from the paternal side, while p...
March 15, 2017: Kurume Medical Journal
https://www.readbyqxmd.com/read/28301083/age-specific-autistic-like-behaviors-in-heterozygous-fmr1-ko-female-mice
#17
Manon Gauducheau, Valerie Lemaire-Mayo, Francesca R D'Amato, Diego Oddi, Wim E Crusio, Susanna Pietropaolo
Fragile X syndrome (FXS) is a major developmental disorder and the most frequent monogenic cause of autism. Surprisingly, most existing studies on the Fmr1-KO mouse model for FXS have focused on males, although FX women, who are mostly heterozygous for the Fmr1 mutation, are known to exhibit several behavioral deficits, including autistic-like features. Furthermore, most animal research has been carried out on adults only; so that little is known about the age progression of the behavioral phenotype of Fmr1 mutants, which is a crucial issue to optimize the impact of therapeutic interventions...
March 16, 2017: Autism Research: Official Journal of the International Society for Autism Research
https://www.readbyqxmd.com/read/28294941/natural-haplotypes-of-flm-non-coding-sequences-fine-tune-flowering-time-in-ambient-spring-temperatures-in-arabidopsis
#18
Ulrich Lutz, Thomas Nussbaumer, Manuel Spannagl, Julia Diener, Klaus Fx Mayer, Claus Schwechheimer
Cool ambient temperatures are major cues determining flowering time in spring. The mechanisms promoting or delaying flowering in response to ambient temperature changes are only beginning to be understood. In Arabidopsis thaliana, FLOWERING LOCUS M (FLM) regulates flowering in the ambient temperature range and FLM is transcribed and alternatively spliced in a temperature-dependent manner. We identify polymorphic promoter and intronic sequences required for FLM expression and splicing. In transgenic experiments covering 69% of the available sequence variation in two distinct sites, we show that variation in the abundance of the FLM-ß splice form strictly correlate (R(2) = 0...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28294526/phase-1-dose-escalating-study-of-the-safety-pharmacokinetics-and-pharmacodynamics-of-activated-factor-x-i-16l
#19
Dana Parsons-Rich, Fei Hua, Gang Li, Constantino Kantaridis, Debra D Pittman, Steven Arkin
BACKGROUND: FXa(I16L) (PF-05230907) is a zymogen-like variant of activated coagulation factor X (FXa). It exhibits enhanced resistance to inactivation by endogenous inhibitors compared with wild-type FXa and restores hemostatic activity in nonclinical models of various bleeding conditions. OBJECTIVES: To evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of FXa(I16L) , a phase 1, first-in-human, dose escalation clinical trial in healthy adult volunteers was conducted METHODS: Participants were assigned to 1 of 6 ascending single-dose cohorts (0...
March 14, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28288667/dual-inhibition-of-thrombin-and-activated-factor-x-attenuates-disseminated-intravascular-coagulation-and-protects-organ-function-in-a-baboon-model-of-severe-gram-negative-sepsis
#20
Herbert Schöchl, Martijn van Griensven, Stefan Heitmeier, Volker Laux, Ulrike Kipman, Jan Roodt, Soheyl Bahrami, Heinz Redl
BACKGROUND: Inhibition of procoagulant pathways may improve outcome in sepsis. We examined whether a dual short-acting thrombin (factor II) and factor X (FX)a inhibitor (SATI) ameliorates sepsis-induced disseminated intravascular coagulation (DIC) and is organ-protective. METHODS: Escherichia coli were infused for 2 h in 22 anesthetized baboons. The control (CO) group (n = 8) received sterile isotonic solution only. In the treatment groups, SATI was administered starting 15 minutes after the end of the bacterial exposure...
March 13, 2017: Critical Care: the Official Journal of the Critical Care Forum
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