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https://www.readbyqxmd.com/read/28441528/phosphorylation-of-neurog3-links-endocrine-differentiation-to-the-cell-cycle-in-pancreatic-progenitors
#1
Nicole A J Krentz, Dennis van Hoof, Zhongmei Li, Akie Watanabe, Mei Tang, Cuilan Nian, Michael S German, Francis C Lynn
During pancreatic development, proliferating pancreatic progenitors activate the proendocrine transcription factor neurogenin 3 (NEUROG3), exit the cell cycle, and differentiate into islet cells. The mechanisms that direct robust NEUROG3 expression within a subset of progenitor cells control the size of the endocrine population. Here we demonstrate that NEUROG3 is phosphorylated within the nucleus on serine 183, which catalyzes its hyperphosphorylation and proteosomal degradation. During progression through the progenitor cell cycle, NEUROG3 phosphorylation is driven by the actions of cyclin-dependent kinases 2 and 4/6 at G1/S cell-cycle checkpoint...
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28440542/menstrual-and-reproductive-factors-and-lung-cancer-risk-a-pooled-analysis-from-the-international-lung-cancer-consortium-ilcco
#2
Soumaya Ben Khedher, Monica Neri, Alexandra Papadopoulos, David C Christiani, Nancy Diao, Curtis C Harris, Susan Olivo-Marston, Ann G Schwartz, Michele Cote, Anita Koushik, Jack Siemiatycki, Maria Teresa Landi, Rayjean J Hung, John McLaughlin, Eric J Duell, Angeline S Andrew, Irene Orlow, Bernard J Park, Hermann Brenner, Kai-Uwe Saum, Angela C Pesatori, Isabelle Stücker
Many clinical features of lung cancer are different in women and men. Sex steroid hormones exert effects in non-reproductive organs, such as the lungs. The association between menstrual and childbearing factors and the risk of lung cancer among women is still debated. We performed a pooled analysis of eight studies contributing to the International Lung Cancer Consortium (ILCCO; 4,386 cases and 4,177 controls). Pooled associations between menstrual or reproductive factors and lung cancer were estimated using multivariable unconditional logistic regression...
April 25, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28438193/pathos-a-decision-support-system-for-reporting-high-throughput-sequencing-of-cancers-in-clinical-diagnostic-laboratories
#3
Kenneth D Doig, Andrew Fellowes, Anthony H Bell, Andrei Seleznev, David Ma, Jason Ellul, Jason Li, Maria A Doyle, Ella R Thompson, Amit Kumar, Luis Lara, Ravikiran Vedururu, Gareth Reid, Thomas Conway, Anthony T Papenfuss, Stephen B Fox
BACKGROUND: The increasing affordability of DNA sequencing has allowed it to be widely deployed in pathology laboratories. However, this has exposed many issues with the analysis and reporting of variants for clinical diagnostic use. Implementing a high-throughput sequencing (NGS) clinical reporting system requires a diverse combination of capabilities, statistical methods to identify variants, global variant databases, a validated bioinformatics pipeline, an auditable laboratory workflow, reproducible clinical assays and quality control monitoring throughout...
April 24, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28437869/risk-modeling-of-interdependent-complex-systems-of-systems-theory-and-practice
#4
Yacov Y Haimes
The emergence of the complexity characterizing our systems of systems (SoS) requires a reevaluation of the way we model, assess, manage, communicate, and analyze the risk thereto. Current models for risk analysis of emergent complex SoS are insufficient because too often they rely on the same risk functions and models used for single systems. These models commonly fail to incorporate the complexity derived from the networks of interdependencies and interconnectedness (I-I) characterizing SoS. There is a need to reevaluate currently practiced risk analysis to respond to this reality by examining, and thus comprehending, what makes emergent SoS complex...
April 24, 2017: Risk Analysis: An Official Publication of the Society for Risk Analysis
https://www.readbyqxmd.com/read/28436566/atrial-fibrillation-originating-from-superior-vena-cava-with-atrial-flutter-electrocardiogram-pattern
#5
Hung-Kai Huang, Shih-Lin Chang, Yenn-Jiang Lin, Li-Wei Lo, Yu-Feng Hu, Fa-Po Chung, Yen-Chang Huang, Chung-Hsing Lin, Chao-Shun Chan, Hung-Yu Chang, Chin-Yu Lin, Yao-Ting Chang, Ching-Hui Huang, Shih-Ann Chen
BACKGROUNDS: Substrate property is related to the genesis and maintenance of atrial fibrillation (AF). The aim of the study was to investigate the impact of substrate property on the electrocardiogram (ECG) in patients with AF originating from the superior vena cava (SVC). METHODS AND RESULTS: Seventy-six patients with AF originating from SVC underwent catheter ablation were included from 2004 to 2013. Of these patients, 16 had a presentation of atrial flutter (AFL)-pattern ECG during AF (group 1), and 60 patients did not (group 2)...
April 24, 2017: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/28436491/extratropical-forcing-triggered-the-2015-madden-julian-oscillation-el-ni%C3%A3-o-event
#6
Chi-Cherng Hong, Huang-Hsiung Hsu, Wan-Ling Tseng, Ming-Ying Lee, Chun-Hoe Chow, Li-Chiang Jiang
In this paper, we report the triggering effect of extratropical perturbation on the onset of an atypical Madden-Julian Oscillation (MJO) and onset of the 2015-16 El Niño in March 2015. The MJO exhibited several unique characteristics: the effect of extratropical forcing, atypical genesis location and timing in the equatorial western Pacific, and the extremity of amplitudes in many aspects. The southward-penetrating northerly associated with the extratropical disturbances in the extratropical western North Pacific contributed to triggering the deep convection and westerly wind burst (WWB) and onset of the MJO over the anomalously warm tropical western Pacific in early March...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436171/sex-and-regional-differences-in-rabbit-right-ventricular-l-type-calcium-current-levels-and-mathematical-modeling-of-arrhythmia-vulnerability
#7
Zane M Kalik, Joshua L Mike, Cassandra Slipski, Moriah Wright, Jozsi Z Jalics, Mark D Womble
Previous studies have shown that adult rabbit left ventricular myocytes exhibit sex and regional differences in L-type calcium current (ICa-L ) levels that contribute to increased susceptibility to arrhythmogenic early afterdepolarizations (EADs). We used patch clamp recordings from isolated adult male and female rabbit right ventricular myocytes to determine apex-base differences in ICa-L density, and mathematical modeling to examine ICa-L contribution to EAD formation. Current density measured at 0 mV in female base myocytes was 67% higher than male base myocytes and 55% higher than female apex myocytes...
April 24, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28432635/role-of-inflammation-in-heart-failure
#8
REVIEW
Lily F Shirazi, Joe Bissett, Francesco Romeo, Jawahar L Mehta
PURPOSE OF REVIEW: This paper aims to discuss the interactions between inflammatory cytokines, immune cells, and heart failure (HF). The association of heart failure with inflammation has led to multiple studies on anti-inflammatory agents in acute and chronic heart failure. RECENT FINDINGS: Recent findings have implicated leukocytes subclasses and multiple inflammatory mediators in the progression of heart failure and cardiovascular disease. Studies have discovered further details on the interaction between immune cells-particularly macrophages and lymphocytes-and inflammation...
June 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28432313/multiple-clinical-characteristics-separate-med12-mutation-positive-and-negative-uterine-leiomyomas
#9
Hanna-Riikka Heinonen, Annukka Pasanen, Oskari Heikinheimo, Tomas Tanskanen, Kimmo Palin, Jaana Tolvanen, Pia Vahteristo, Jari Sjöberg, Esa Pitkänen, Ralf Bützow, Netta Mäkinen, Lauri A Aaltonen
Up to 86% of uterine leiomyomas harbour somatic mutations in mediator complex subunit 12 (MED12). These mutations have been associated with conventional histology, smaller tumour size, and larger number of tumours within the uterus. Prior studies, with limited sample sizes, have failed to detect associations between other clinical features and MED12 mutations. Here, we prospectively collected 763 uterine leiomyomas and the corresponding normal myometrial tissue from 244 hysterectomy patients, recorded tumour characteristics, collected clinical data from medical records, and screened the tissue samples for MED12 mutations to assess potential associations between clinical variables and mutation status...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427841/localized-shape-abnormalities-in-the-thalamus-and-pallidum-are-associated-with-secondarily-generalized-seizures-in-mesial-temporal-lobe-epilepsy
#10
Linglin Yang, Hong Li, Lujia Zhu, Xinfeng Yu, Bo Jin, Cong Chen, Shan Wang, Meiping Ding, Minming Zhang, Zhong Chen, Shuang Wang
Mesial temporal lobe epilepsy (mTLE) is a common type of drug-resistant epilepsy and secondarily generalized tonic-clonic seizures (sGTCS) have devastating consequences for patients' safety and quality of life. To probe the mechanism underlying the genesis of sGTCS, we investigated the structural differences between patients with and without sGTCS in a cohort of mTLE with radiologically defined unilateral hippocampal sclerosis. We performed voxel-based morphometric analysis of cortex and vertex-wise shape analysis of subcortical structures (the basal ganglia and thalamus) on MRI of 39 patients (21 with and 18 without sGTCS)...
April 17, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28427147/brca1-controls-the-cell-division-axis-and-governs-ploidy-and-phenotype-in-human-mammary-cells
#11
Zhengcheng He, Nagarajan Kannan, Oksana Nemirovsky, Helen Chen, Marisa Connell, Brian Taylor, Jihong Jiang, Linda M Pilarski, Markus C Fleisch, Dieter Niederacher, Miguel Angel Pujana, Connie J Eaves, Christopher A Maxwell
BRCA1 deficiency may perturb the differentiation hierarchy present in the normal mammary gland and is associated with the genesis of breast cancers that are genomically unstable and typically display a basal-like transcriptome. Oriented cell division is a mechanism known to regulate cell fates and to restrict tumor formation. We now show that the cell division axis is altered following shRNA-mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated normal human mammary cells with graded consequences in progeny cells that include aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective loss of cells with luminal features...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#12
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28424631/mechanisms-underlying-the-emergence-of-post-acidosis-arrhythmia-at-the-tissue-level-a-theoretical-study
#13
Jieyun Bai, Renli Yin, Kuanquan Wang, Henggui Zhang
Acidosis has complex electrophysiological effects, which are associated with a high recurrence of ventricular arrhythmias. Through multi-scale cardiac computer modeling, this study investigated the mechanisms underlying the emergence of post-acidosis arrhythmia at the tissue level. In simulations, ten Tusscher-Panfilov ventricular model was modified to incorporate various data on acidosis-induced alterations of cellular electrophysiology and intercellular electrical coupling. The single cell models were incorporated into multicellular one-dimensional (1D) fiber and 2D sheet tissue models...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28424479/wnt-%C3%AE-catenin-signaling-pathway-a-major-player-in-the-injury-induced-fibrosis-and-dysfunction-of-the-external-anal-sphincter
#14
M Raj Rajasekaran, Sadhana Kanoo, Johnny Fu, Valmik Bhargava, Ravinder K Mittal
Wnt-β catenin is an important signaling pathway in the genesis of fibrosis in many organ systems. Our goal was to examine the role of Wnt pathway in the external anal sphincter (EAS) injury-related fibrosis and muscle dysfunction. New Zealand White female rabbits were subjected to surgical EAS myotomy and administered local injections of either a Wnt antagonist (sFRP-2; daily for 7 days) or saline. Anal canal pressure and EAS length-tension (L-T) were measured for 15 weeks after which the animals were sacrificed...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423456/progesterone-resistance-in-endometriosis-origins-consequences-and-interventions
#15
Bansari G Patel, Martin Rudnicki, Jie Yu, Yimin Shu, Robert N Taylor
Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis...
April 19, 2017: Acta Obstetricia et Gynecologica Scandinavica
https://www.readbyqxmd.com/read/28420962/dysregulation-of-rna-binding-protein-aggregation-in-neurodegenerative-disorders
#16
REVIEW
Brandon Maziuk, Heather I Ballance, Benjamin Wolozin
The unique biology of RNA binding proteins is altering our view of the genesis of protein misfolding diseases. These proteins use aggregation of low complexity domains (LCDs) as a means to regulate the localization and utilization of RNA by forming RNA granules, such as stress granules, transport granules and P-bodies. The reliance on reversible aggregation as a mechanism for biological regulation renders this family of proteins highly vulnerable to promoting diseases of protein misfolding. Mutations in RNA binding proteins are associated with many neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28418912/human-microrna-expression-in-sporadic-and-fap-associated-desmoid-tumors-and-correlation-with-beta-catenin-mutations
#17
Aldo Cavallini, Maria Teresa Rotelli, Catia Lippolis, Domenico Piscitelli, Rosa Digennaro, Claudia Covelli, Nicola Carella, Matteo Accetturo, Donato Francesco Altomare
Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with β-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. microRNAs (miRNAs) are involved in many human carcinogenesis.The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls...
March 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418331/collagen-iv-and-basement-membrane-at-the-evolutionary-dawn-of-metazoan-tissues
#18
Aaron L Fidler, Carl E Darris, Sergei V Chetyrkin, Vadim K Pedchenko, Sergei P Boudko, Kyle L Brown, W Gray Jerome, Julie K Hudson, Antonis Rokas, Billy G Hudson
The role of the cellular microenvironment in enabling metazoan tissue genesis remains obscure. Ctenophora has recently emerged as one of the earliest-branching extant animal phyla, providing a unique opportunity to explore the evolutionary role of the cellular microenvironment in tissue genesis. Here, we characterized the extracellular matrix (ECM), with a focus on collagen IV and its variant, spongin short-chain collagens, of non-bilaterian animal phyla. We identified basement membrane (BM) and collagen IV in Ctenophora, and show that the structural and genomic features of collagen IV are homologous to those of non-bilaterian animal phyla and Bilateria...
April 18, 2017: ELife
https://www.readbyqxmd.com/read/28417261/neutrophil-infiltration-and-matrix-metalloproteinase-9-in-lacunar-infarction
#19
Wolfgang Walz, Francisco S Cayabyab
We use the modified pial vessel disruption rat model to elucidate the cellular and molecular mechanisms of cavitation as it plays a role in lacunar infarction. Here we discuss the similarities between the genesis of pulmonary cavitation in various animal models and lacunar infarction in the cerebral cortex of rats. Both pathological processes involve the creation of a cavity surrounded by fibroblasts or reactive astrocytes. A crucial step in both, the lung and the cerebral cortex, appears to be the migration of neutrophils across the endothelial barrier into the parenchyma...
April 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28415888/bioengineered-gold-nanoparticles-targeted-to-mesenchymal-cells-from-patients-with-bronchiolitis-obliterans-syndrome-does-not-rise-the-inflammatory-response-and-can-be-safely-inhaled-by-rodents
#20
Emanuela Cova, Simona Inghilleri, Laura Pandolfi, Monica Morosini, Sara Magni, Miriam Colombo, Davide Piloni, Chiara Finetti, Gabriele Ceccarelli, Laura Benedetti, Maria Gabriella Cusella, Manuela Agozzino, Fabio Corsi, Raffaele Allevi, Simona Mrakic-Sposta, Sarah Moretti, Simona De Gregori, Davide Prosperi, Federica Meloni
The use of gold nanoparticles as drug delivery system represents a promising issue for diseases without effective pharmacological treatment due to insufficient local drug accumulation and excessive systemic toxicity. Bronchiolitis obliterans syndrome (BOS) represents about 70% of cases of chronic lung allograft dysfunction, the main challenge to long term lung transplantation. It is believed that due to repeated insults to epithelial bronchiolar cells local inflammatory response creates a milieu that favours epithelial mesenchymal transition and activation of local mesenchymal cells leading to airway fibro-obliteration...
April 18, 2017: Nanotoxicology
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