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Rinat Sultanov, Olga Lebedeva, Georgij Arapidi, Maria Lagarkova, Sergei Kiselev
The genetic reprogramming technology allows generation of induced pluripotent stem cells (iPSCs) from somatic cells (Takahashi and Yamanaka, 2006) [1]. iPSCs have the ability to self-renew, and to differentiate into any type of somatic cells, and are considered as a promising tool for drug development, disease modeling, and regenerative medicine. The reprogramming factors (oct4, sox2, klf4, c-myc) can be delivered to the cell nucleus either by vectors integrating into the genome (lentiviruses, retroviruses) or by non-integrative methods (e...
April 2018: Data in Brief
Chang Xu
Detection of somatic mutations holds great potential in cancer treatment and has been a very active research field in the past few years, especially since the breakthrough of the next-generation sequencing technology. A collection of variant calling pipelines have been developed with different underlying models, filters, input data requirements, and targeted applications. This review aims to enumerate these unique features of the state-of-the-art variant callers, in the hope to provide a practical guide for selecting the appropriate pipeline for specific applications...
2018: Computational and Structural Biotechnology Journal
Dominique Lombardo, Françoise Silvy, Isabelle Crenon, Emmanuelle Martinez, Aurélie Collignon, Evelyne Beraud, Eric Mas
Pancreatic adenocarcinomas and diabetes mellitus are responsible for the deaths of around two million people each year worldwide. Patients with chronic pancreatitis do not die directly of this disease, except where the pathology is hereditary. Much current literature supports the involvement of bile salt-dependent lipase (BSDL), also known as carboxyl ester lipase (CEL), in the pathophysiology of these pancreatic diseases. The purpose of this review is to shed light on connections between chronic pancreatitis, diabetes, and pancreatic adenocarcinomas by gaining an insight into BSDL and its variants...
February 23, 2018: Oncotarget
Andrew S Fister, Lena Landherr, Siela N Maximova, Mark J Guiltinan
Theobroma cacao , the source of cocoa, suffers significant losses to a variety of pathogens resulting in reduced incomes for millions of farmers in developing countries. Development of disease resistant cacao varieties is an essential strategy to combat this threat, but is limited by sources of genetic resistance and the slow generation time of this tropical tree crop. In this study, we present the first application of genome editing technology in cacao, using Agrobacterium-mediated transient transformation to introduce CRISPR/Cas9 components into cacao leaves and cotyledon cells...
2018: Frontiers in Plant Science
Liang-Qing Dong, Yang Shi, Li-Jie Ma, Liu-Xiao Yang, Xiao-Ying Wang, Shu Zhang, Zhi-Chao Wang, Meng Duan, Zhao Zhang, Long-Zi Liu, Bo-Hao Zheng, Zhen-Bin Ding, Ai-Wu Ke, Da-Ming Gao, Ke Yuan, Jian Zhou, Jia Fan, Ruibin Xi, Qiang Gao
BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (ICC) is the second-most lethal primary liver cancer. Little is known about intratumoral heterogeneity (ITH) and its impact on ICC progression. We aim to investigate its ITH in hope of helping develop new therapeutic strategies. METHODS: We obtained 69 spatially distinct regions from 6 operable ICCs. Patient-derived primary cancer cells (PDPCs) were established for each region, followed by whole-exome sequencing(WES) and multi-level validation...
March 15, 2018: Journal of Hepatology
Daniel J Merk, Jasmin Ohli, Natalie D Merk, Venu Thatikonda, Sorana Morrissy, Melanie Schoof, Susanne N Schmid, Luke Harrison, Severin Filser, Julia Ahlfeld, Serap Erkek, Kaamini Raithatha, Thomas Andreska, Marc Weißhaar, Michael Launspach, Julia E Neumann, Mehdi Shakarami, Dennis Plenker, Marco A Marra, Yisu Li, Andrew J Mungall, Richard A Moore, Yussanne Ma, Steven J M Jones, Beat Lutz, Birgit Ertl-Wagner, Andrea Rossi, Rabea Wagener, Reiner Siebert, Andreas Jung, Charles G Eberhart, Boleslaw Lach, Michael Sendtner, Stefan M Pfister, Michael D Taylor, Lukas Chavez, Marcel Kool, Ulrich Schüller
Recurrent mutations in chromatin modifiers are specifically prevalent in adolescent or adult patients with Sonic hedgehog-associated medulloblastoma (SHH MB). Here, we report that mutations in the acetyltransferase CREBBP have opposing effects during the development of the cerebellum, the primary site of origin of SHH MB. Our data reveal that loss of Crebbp in cerebellar granule neuron progenitors (GNPs) during embryonic development of mice compromises GNP development, in part by downregulation of brain-derived neurotrophic factor (Bdnf)...
March 9, 2018: Developmental Cell
Janne Mikkonen, Heta Moustgaard, Hanna Remes, Pekka Martikainen
OBJECTIVES: To quantify how large a part of educational dropout is due to adverse childhood health conditions and to estimate the risk of dropout across various physical and mental health conditions. STUDY DESIGN: A registry-based cohort study was conducted on a 20% random sample of Finns born in 1988-1995 (n = 101 284) followed for school dropout at ages 17 and 21. Four broad groups of health conditions (any, somatic, mental, and injury) and 25 specific health conditions were assessed from inpatient and outpatient care records at ages 10-16 years...
March 14, 2018: Journal of Pediatrics
Michael J Ziller, Juan A Ortega, Katharina A Quinlan, David P Santos, Hongcang Gu, Eric J Martin, Christina Galonska, Ramona Pop, Susanne Maidl, Alba Di Pardo, Mei Huang, Herbert Y Meltzer, Andreas Gnirke, C J Heckman, Alexander Meissner, Evangelos Kiskinis
The somatic DNA methylation (DNAme) landscape is established early in development but remains highly dynamic within focal regions that overlap with gene regulatory elements. The significance of these dynamic changes, particularly in the central nervous system, remains unresolved. Here, we utilize a powerful human embryonic stem cell differentiation model for the generation of motor neurons (MNs) in combination with genetic mutations in the de novo DNAme machinery. We quantitatively dissect the role of DNAme in directing somatic cell fate with high-resolution genome-wide bisulfite-, bulk-, and single-cell-RNA sequencing...
March 14, 2018: Cell Stem Cell
Akane Yamamichi, Fumiharu Ohka, Kosuke Aoki, Hiromichi Suzuki, Akira Kato, Masaki Hirano, Kazuya Motomura, Kuniaki Tanahashi, Lushun Chalise, Sachi Maeda, Toshihiko Wakabayashi, Yukinari Kato, Atsushi Natsume
The IDH-mutant and 1p/19q co-deletion (1p19q codel) provides significant diagnostic and prognostic value in lower-grade gliomas. As ATRX mutation and 1p19q codel are mutually exclusive, ATRX immunohistochemistry (IHC) may substitute for 1p19q codel, but this has not been comprehensively examined. In the current study, we performed ATRX-IHC in 78 gliomas whose ATRX statuses were comprehensively determined by whole exome sequencing. Among the 60 IHC-positive and 18 IHC-negative cases, 86.7 and 77.8% were ATRX-wildtype and ATRX-mutant, respectively...
March 17, 2018: Brain Tumor Pathology
Samantha K Wall, Olga Wellnitz, Rupert M Bruckmaier, Daniel Schwarz
Intramammary infections induce the initiation of the inflammatory response, resulting in an increase in somatic cell count (SCC) in milk. The SCC includes several different types of cells but does not differentiate between them. On the contrary, the new differential somatic cell count (DSCC) parameter allows for the differentiation between 2 groups of cells: polymorphonuclear neutrophils (PMN) and lymphocytes versus macrophages. Therefore, the aim of this paper was to describe the changes of both DSCC and SCC during mastitis induced by cell wall components from typical mastitis-causing pathogens [lipopolysaccharide (LPS), Escherichia coli; lipoteichoic acid (LTA), Staphylococcus aureus] known to trigger different severities of mastitis...
March 14, 2018: Journal of Dairy Science
Ricardo C Chebel, Luís G D Mendonça, Pietro S Baruselli
The objectives of the current study were to determine the association between body condition score change during the dry period (ΔBCS) and postpartum health and reproductive and productive performance of Holstein cows. Data from 16,104 lactations from 9,950 parous cows from 2 dairies located in the San Joaquin Valley of California were used. Within dairy, cows were scored for body condition at dry off and parturition by the same herd workers, who were trained by veterinarians from the Veterinary Medicine Teaching and Research Center of the University of California Davis...
March 14, 2018: Journal of Dairy Science
Irena Mladenovic, Jelena Krunic, Gordana Supic, Ruzica Kozomara, Dejan Bokonjic, Nikola Stojanovic, Zvonko Magic
INTRODUCTION: The purpose of this study was to evaluate the associations of variability in pulp sensitivity with sex, psychosocial variables, the gene that encodes for the enzyme catechol-O-methyltransferase (COMT), and chronic painful conditions (temporomandibular disorders [TMDs]). METHODS: The study was composed of 97 subjects (68 women and 29 men aged 20-44 years). The electric (electric pulp tester) and cold (refrigerant spray) stimuli were performed on mandibular lateral incisors...
March 14, 2018: Journal of Endodontics
Xin-Yu Yao, Jing-Dong Zhou, Jing Yang, Wei Zhang, Ji-Chun Ma, Xiang-Mei Wen, Dong-Ming Yao, Zi-Jun Xu, De-Hong Wu, Pin-Fang He, Jun Qian, Jiang Lin
BACKGROUND: Somatic mutations in SETBP1 gene have recently been detected in hematologic malignancies. The present study aimed to explore the frequency and clinical correlations of SETBP1 mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: In this study, we used high-resolution melting analysis (HRMA) to detect the SETBP1 mutations in a cohort of 363 patients with AML or MDS. RESULTS: A total of 1...
March 7, 2018: Pathology, Research and Practice
Julia Brenmoehl, Daniela Ohde, Elisa Wirthgen, Andreas Hoeflich
Cytokines are required for normal growth and development of the mammary gland and TGF-β prominently represents an established effector of apoptosis, e.g., during involution of the mammary gland. By the control of intracellular signaling pathways, including JAK/STAT, MAPK, PI-3K, and NF-κB, cytokines efficiently regulate cell proliferation and inflammation in the breast. Therefore, cytokines are discussed also in a context of malignant mammary growth. As a group of tissue hormones produced by somatic cells or by cells from the immune system, cytokines are defined by their immunomodulatory potential...
January 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
Antonio Cano-Vindel, Roger Muñoz-Navarro, Leonardo Adrián Medrano, Paloma Ruiz-Rodríguez, César González-Blanch, María Dolores Gómez-Castillo, Antonio Capafons, Fernando Chacón, Francisco Santolaya
BACKGROUND: The Patient Health Questionnaire-4 (PHQ-4) is an ultra-brief self-report consisting of a 2-item depression scale (PHQ-2) and a 2-item anxiety scale (GAD-2). The aim of the present study is to determine the psychometric properties of a computerized version of the PHQ-4 used to detect emotional disorders (anxiety and depression) in the primary care setting. METHOD: A total of 1052 patients with suspected anxiety, depression, or somatic symptoms were recruited from 28 primary care centres participating in the PsicAP trial and completed the full version of the computerized PHQ...
February 16, 2018: Journal of Affective Disorders
Buğra Çetin, Hüseyin Güleç, Hayal Ergin Toktaş, Özgür Ulutaş, Seda Güleç Yılmaz, Turgay İsbir
We aimed to investigate the changes in the objective and subjective sleep variables during painful episodes of fibromyalgia and post-episode period, and to evaluate the impact of the sleep variables on the current clinical, psychological, and immunologic parameters. Thirty-one consecutive patients who were referred to the Erenköy Physical Therapy and Rehabilitation Polyclinic with a diagnosis of fibromyalgia were evaluated before and in the sixth week of the acute pain treatment. The sleep variables were measured by polysomnography, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale...
March 3, 2018: Psychiatry Research
Peipei Lin, Yingwan Luo, Shuanghong Zhu, Dominic Maggio, Haiyang Yang, Chao Hu, Jinghan Wang, Hua Zhang, Yanling Ren, Xinping Zhou, Chen Mei, Liya Ma, Weilai Xu, Li Ye, Zhengping Zhuang, Jie Jin, Hongyan Tong
PURPOSE: The myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by the presence of somatically mutated hematopoietic stem cells (HSCs) that increase the risk of progression to secondary acute myeloid leukemia (sAML). Mutations in isocitrate dehydrogenase (IDHmut ) are thought to correlate with the increased production of the oncogenic protein 2-hydroxyglutarate (2-HG) in AML. The aim of this study was to examine whether serum 2-HG has utility as a prognostic biomarker, and whether elevated 2-HG levels are predictive of IDH mutations in patients with MDS...
March 16, 2018: Journal of Cancer Research and Clinical Oncology
Asti Jackson, Roger L Papke, M Imad Damaj
RATIONALE: Recent preclinical data has implicated the α7 nicotinic acetylcholine receptor (nAChR) as a target in modulating nicotine reward. However, the role of the channel properties of the α7 nAChR in nicotine withdrawal is unknown. OBJECTIVES: This study aimed to investigate the impact of α7 nAChR pharmacological modulation on mecamylamine-precipitated nicotine withdrawal behaviors in mice by using positive allosteric modulators (PAMs). METHODS: The effect of the orthosteric α7 nAChR full agonist PNU282987 (1, 3, 9 mg/kg, s...
March 16, 2018: Psychopharmacology
Kristina Laugesen, Lisbeth Munksgård Baggesen, Sigrún Alba Jóhannesdóttir Schmidt, M Maria Glymour, Mathias Lasgaard, Arnold Milstein, Henrik Toft Sørensen, Nancy E Adler, Vera Ehrenstein
Social isolation is associated with increased mortality. Meta-analytic results, however, indicate heterogeneity in effect sizes. We aimed to provide new evidence to the association between social isolation and mortality by conducting a population-based cohort study. We reconstructed the Berkman and Syme's social network index (SNI), which combines four components of social networks (partnership, interaction with family/friends, religious activities, and membership in organizations/clubs) into an index, ranging from 0/1 (most socially isolated) to 4 (least socially isolated)...
March 16, 2018: Scientific Reports
Yu-Han Su, Elham Rastegri, Shih-Han Kao, Chun-Min Lai, Kun-Yang Lin, Hung-Yu Liao, Mu-Hsiang Wang, Hwei-Jan Hsu
Diet is an important regulator of stem cell homeostasis, however, the underlying mechanisms of this regulation are not fully known. Here, we report that insulin signaling mediates dietary maintenance of Drosophila ovarian germline stem cells (GSCs) by promoting the extension of niche escort cell (EC) membranes to wrap around GSCs. This wrapping may facilitate the delivery of BMP stemness factors from ECs in the niche to GSCs. In addition to the effects on GSCs, insulin signaling-mediated regulation of EC number and protrusions controls the division and growth of GSC progeny...
March 16, 2018: Development
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