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https://www.readbyqxmd.com/read/28750307/resilient-protein-co-expression-network-in-male-orbitofrontal-cortex-layer-2-3-during-human-aging
#1
Mohan Pabba, Enzo Scifo, Fenika Kapadia, Yuliya S Nikolova, Tianzhou Ma, Naguib Mechawar, George C Tseng, Etienne Sibille
The orbitofrontal cortex (OFC) is vulnerable to normal and pathologic aging. Currently, layer resolution large-scale proteomic studies describing "normal" age-related alterations at OFC are not available. Here, we performed a large-scale exploratory high-throughput mass spectrometry-based protein analysis on OFC layer 2/3 from 15 "young" (15-43 years) and 18 "old" (62-88 years) human male subjects. We detected 4193 proteins and identified 127 differentially expressed (DE) proteins (p-value ≤0.05; effect size >20%), including 65 up- and 62 downregulated proteins (e...
July 5, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28750277/familial-liability-to-psychosis-is-a-risk-factor-for-multimorbidity-in-people-with-psychotic-disorders-and-their-unaffected-siblings
#2
M A Islam, M F H Khan, P J Quee, H Snieder, E R van den Heuvel, R Bruggeman, B Z Alizadeh
BACKGROUND: Multimorbidity may impose an overwhelming burden on patients with psychosis and is affected by gender and age. Our aim is to study the independent role of familial liability to psychosis as a risk factor for multimorbidity. METHODS: We performed the study within the framework of the Genetic Risk and Outcome of Psychosis (GROUP) project. Overall, we compared 1024 psychotic patients, 994 unaffected siblings and 566 controls on the prevalence of 125 lifetime diseases, and 19 self-reported somatic complaints...
June 1, 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28750120/association-between-genomic-metrics-and-immune-infiltration-in-triple-negative-breast-cancer
#3
Thomas Karn, Tingting Jiang, Christos Hatzis, Nicole Sänger, Ahmed El-Balat, Achim Rody, Uwe Holtrich, Sven Becker, Giampaolo Bianchini, Lajos Pusztai
Importance: Why some triple-negative breast cancers (TNBCs) have high and others have low immune cell infiltration is unknown. Understanding how immune surveillance shapes the cancer genome could help in the selection of patients and the development of more effective immunotherapy strategies. Objective: To examine the association between genomic metrics and the extent of immune infiltration in TNBCs. Design, Setting, and Participants: This study, performed from June 1, 2015, through January 31, 2017, used DNA and RNA sequencing data and messenger RNA expression results from The Cancer Genome Atlas (TCGA) breast cancer data set (n = 1215) to calculate previously described immune metagene expression values and histologic lymphocyte counts to quantify immune infiltration and assign prognostic categories to TNBCs...
July 27, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28750086/gene-expression-and-metabolite-profiling-of-gibberellin-biosynthesis-during-induction-of-somatic-embryogenesis-in-medicago-truncatula-gaertn
#4
Rafał Igielski, Ewa Kępczyńska
Gibberellins (GAs) are involved in the regulation of numerous developmental processes in plants including zygotic embryogenesis, but their biosynthesis and role during somatic embryogenesis (SE) is mostly unknown. In this study we show that during three week- long induction phase, when cells of leaf explants from non-embryogenic genotype (M9) and embryogenic variant (M9-10a) were forming the callus, all the bioactive gibberellins from non-13-hydroxylation (GA4, GA7) and 13-hydroxylation (GA1, GA5, GA3, GA6) pathways were present, but the contents of only a few of them differed between the tested lines...
2017: PloS One
https://www.readbyqxmd.com/read/28750028/clinical-impact-of-a-targeted-next-generation-sequencing-gene-panel-for-autoinflammation-and-vasculitis
#5
Ebun Omoyinmi, Ariane Standing, Annette Keylock, Fiona Price-Kuehne, Sonia Melo Gomes, Dorota Rowczenio, Sira Nanthapisal, Thomas Cullup, Rodney Nyanhete, Emma Ashton, Claire Murphy, Megan Clarke, Helena Ahlfors, Lucy Jenkins, Kimberly Gilmour, Despina Eleftheriou, Helen J Lachmann, Philip N Hawkins, Nigel Klein, Paul A Brogan
BACKGROUND: Monogenic autoinflammatory diseases (AID) are a rapidly expanding group of genetically diverse but phenotypically overlapping systemic inflammatory disorders associated with dysregulated innate immunity. They cause significant morbidity, mortality and economic burden. Here, we aimed to develop and evaluate the clinical impact of a NGS targeted gene panel, the "Vasculitis and Inflammation Panel" (VIP) for AID and vasculitis. METHODS: The Agilent SureDesign tool was used to design 2 versions of VIP; VIP1 targeting 113 genes, and a later version, VIP2, targeting 166 genes...
2017: PloS One
https://www.readbyqxmd.com/read/28749946/genome-wide-association-analysis-identifies-genetic-correlates-of-immune-infiltrates-in-solid-tumors
#6
Nathan O Siemers, James L Holloway, Han Chang, Scott D Chasalow, Petra B Ross-MacDonald, Charles F Voliva, Joseph D Szustakowski
Therapeutic options for the treatment of an increasing variety of cancers have been expanded by the introduction of a new class of drugs, commonly referred to as checkpoint blocking agents, that target the host immune system to positively modulate anti-tumor immune response. Although efficacy of these agents has been linked to a pre-existing level of tumor immune infiltrate, it remains unclear why some patients exhibit deep and durable responses to these agents while others do not benefit. To examine the influence of tumor genetics on tumor immune state, we interrogated the relationship between somatic mutation and copy number alteration with infiltration levels of 7 immune cell types across 40 tumor cohorts in The Cancer Genome Atlas...
2017: PloS One
https://www.readbyqxmd.com/read/28748347/molecular-basis-of-pediatric-brain-tumors
#7
REVIEW
Alexia Klonou, Christina Piperi, Antonios N Gargalionis, Athanasios G Papavassiliou
Brain tumors emerge as the second commonest type of pediatric solid tumors following hematologic malignancies. Genomic profiling of low- and high-grade gliomas, ependymomas and medulloblastomas has revealed chromosomal abnormalities and specific gene mutations which have been associated with aberrant activation of crucial signal transduction pathways, including mitogen-activated protein kinase, mammalian target of rapamycin and retinoblastoma tumor suppressor signaling. Furthermore, pediatric high-grade gliomas are associated with chromatin remodeling defects and somatic histone gene mutations that affect prognosis...
July 26, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28748333/evaluation-of-motor-skills-in-children-with-rubinstein-taybi-syndrome
#8
Jean René Cazalets, Emma Bestaven, Emilie Doat, Marie Pierre Baudier, Cécile Gallot, Anouck Amestoy, Manuel Bouvard, Etienne Guillaud, Isabelle Guillain, Emelyne Grech, Julien Van-Gils, Patricia Fergelot, Sonia Fraisse, Emmanuelle Taupiac, Benoit Arveiler, Didier Lacombe
Rubinstein-Taybi syndrome (RTS) is a rare genetic disease that associates intellectual disability with somatic characteristics. We have conducted a study of the overall motor abilities of RTS participants. Static postural performance as well as gait parameters were somewhat decreased, although not significantly compared to typically developing (TD) participants. In contrast, the motor skills requiring a high level of visuomotor coordination were considerably degraded in RTS participants compared to TD participants...
July 26, 2017: Journal of Autism and Developmental Disorders
https://www.readbyqxmd.com/read/28748323/mechanisms-of-protein-homeostasis-proteostasis-maintain-stem-cell-identity-in-mammalian-pluripotent-stem-cells
#9
REVIEW
Alireza Noormohammadi, Giuseppe Calculli, Ricardo Gutierrez-Garcia, Amirabbas Khodakarami, Seda Koyuncu, David Vilchez
Protein homeostasis, or proteostasis, is essential for cell function, development, and organismal viability. The composition of the proteome is adjusted to the specific requirements of a particular cell type and status. Moreover, multiple metabolic and environmental conditions challenge the integrity of the proteome. To maintain the quality of the proteome, the proteostasis network monitors proteins from their synthesis through their degradation. Whereas somatic stem cells lose their ability to maintain proteostasis with age, immortal pluripotent stem cells exhibit a stringent proteostasis network associated with their biological function and intrinsic characteristics...
July 26, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28748301/the-aflatoxin-detoxifizyme-specific-expression-in-the-parotid-gland-of-transgenic-pigs
#10
An-Gang Lou, Jin-Shun Cai, Xue-Mei Zhang, Cheng-Dou Cui, Ying-Shu Piao, Li-Zeng Guan
Producing aflatoxin-detoxifizyme (ADTZ) in pigs to control the AFT contamination of pig feed is a new research strategy by transgenic technology. In this study, transgenic pigs specifically expressing ADTZ gene in the parotid gland were successfully produced by somatic cell nuclear transfer technology. The ADTZ activity in saliva of 6 transgenic pigs was found to be 7.11 ± 2.63 U/mL. The feeding trial with aflatoxin (AFT) results showed that there were significant difference about the serum biochemical index such as total protein (TP), albumin (ALB), globulin (GLB) contents and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity and AFT residues in serum and liver between the pigs in the test treatment (transgenic pigs) producing ADTZ and those in the positive control (P < 0...
July 26, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28748255/cellular-and-subcellular-localization-of-adp-ribosylation-factor-6-in-mouse-peripheral-tissues
#11
Osamu Katsumata, Momoko Mori, Yusuke Sawane, Tomoko Niimura, Akiko Ito, Hirotsugu Okamoto, Masahiro Fukaya, Hiroyuki Sakagami
ADP-ribosylation factor 6 (Arf6) is a small GTPase that regulates endosomal trafficking and actin cytoskeleton remodeling. In the present study, we comprehensively examined the cellular and subcellular localization of Arf6 in adult mouse peripheral tissues by immunofluorescence and immunoelectron microscopy using the heat-induced antigen retrieval method with Tris-EDTA buffer (pH 9.0). Marked immunolabeling of Arf6 was observed particularly in epithelial cells of several tissues including the esophagus, stomach, small and large intestines, trachea, kidney, epididymis, oviduct, and uterus...
July 26, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28747773/deciphering-mechanisms-of-acquired-t790m-mutation-after-egfr-inhibitors-for-nsclc-by-computational-simulations
#12
Bin Zou, Victor H F Lee, Lijiang Chen, Lichun Ma, Debby D Wang, Hong Yan
Metastatic non-small-cell lung cancer (NSCLC) with activating EGFR mutations responds very well to first and second generation tyrosine-kinase inhibitors (TKI) including gefitinib, erlotinib and afatinib. Unfortunately, drug resistance will eventually develop and about half of the cases are secondary to the emergence of acquired T790M somatic mutation. In this work, we prospectively recruited 68 patients with metastatic EGFR-mutated NSCLC who have developed progressive disease after first-line TKI with or without subsequent TKI and/or other systemic therapy...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747770/the-distribution-characteristics-and-applications-for-maternal-cells-on-chicken-egg-vitelline-membrane
#13
Quanlin Li, Wenbo Li, Xingzheng Li, Lulu Liu, Ying Zhang, Yuying Guo, Xia Chen, Guiyun Xu, Jiangxia Zheng
The major components of vitelline membrane (VM) are ovomucin, VM outer (VMO) I and VMO II. At present, the distribution pattern of maternal cells on the VM has not been described in detail. In this study, the existence and distribution characteristics of maternal cells on VM were observed. There were more than 3.2 × 10(5) somatic cells on VM, which were uneven distributed. The calcein AM/PI staining of the maternal cells on the VM showed that the cells' viability changed with the freshness of the eggs, and that the maternal cells gradually underwent apoptosis and became degraded...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747543/mutation-profile-based-methods-for-understanding-selection-forces-in-cancer-somatic-mutations-a-comparative-analysis
#14
Zhan Zhou, Yangyun Zou, Gangbiao Liu, Jingqi Zhou, Jingcheng Wu, Shimin Zhao, Zhixi Su, Xun Gu
Human genes exhibit different effects on fitness in cancer and normal cells. Here, we present an evolutionary approach to measure the selection pressure on human genes, using the well-known ratio of the nonsynonymous to synonymous substitution rate in both cancer genomes (CN/CS) and normal populations (pN/pS). A new mutation-profile-based method that adopts sample-specific mutation rate profiles instead of conventional substitution models was developed. We found that cancer-specific selection pressure is quite different from the selection pressure at the species and population levels...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747530/sequence-intrinsic-somatic-mutation-mechanisms-contribute-to-affinity-maturation-of-vrc01-class-hiv-1-broadly-neutralizing-antibodies
#15
Joyce K Hwang, Chong Wang, Zhou Du, Robin M Meyers, Thomas B Kepler, Donna Neuberg, Peter D Kwong, John R Mascola, M Gordon Joyce, Mattia Bonsignori, Barton F Haynes, Leng-Siew Yeap, Frederick W Alt
Variable regions of Ig chains provide the antigen recognition portion of B-cell receptors and derivative antibodies. Ig heavy-chain variable region exons are assembled developmentally from V, D, J gene segments. Each variable region contains three antigen-contacting complementarity-determining regions (CDRs), with CDR1 and CDR2 encoded by the V segment and CDR3 encoded by the V(D)J junction region. Antigen-stimulated germinal center (GC) B cells undergo somatic hypermutation (SHM) of V(D)J exons followed by selection for SHMs that increase antigen-binding affinity...
July 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28747472/disentangling-sources-of-variation-in-ssu-rdna-sequences-from-single-cell-analyses-of-ciliates-impact-of-copy-number-variation-and-experimental-error
#16
Chundi Wang, Tengteng Zhang, Yurui Wang, Laura A Katz, Feng Gao, Weibo Song
Small subunit ribosomal DNA (SSU rDNA) is widely used for phylogenetic inference, barcoding and other taxonomy-based analyses. Recent studies indicate that SSU rDNA of ciliates may have a high level of sequence variation within a single cell, which impacts the interpretation of rDNA-based surveys. However, sequence variation can come from a variety of sources including experimental errors, especially the mutations generated by DNA polymerase in PCR. In the present study, we explore the impact of four DNA polymerases on sequence variation and find that low-fidelity polymerases exaggerate the estimates of single-cell sequence variation...
July 26, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28747387/molecular-characteristics-of-the-kcnj5-mutated-aldosterone-producing-adenomas
#17
Masanori Murakami, Takanobu Yoshimoto, Kazuhiko Nakabayashi, Yujiro Nakano, Takahiro Fukaishi, Kyoichiro Tsuchiya, Isao Minami, Ryotaro Bouchi, Kohji Okamura, Yasuhisa Fujii, Koshi Hashimoto, Ken-Ichiro Hata, Kazunori Kihara, Yoshihiro Ogawa
The pathophysiology of aldosterone-producing adenomas (APAs) has been investigated via genetic approaches and the pathogenic significance of a series of somatic mutations, including KCNJ5, has been uncovered. However, how the mutational status of an APA is associated with its molecular characteristics, including its transcriptome and methylome, has not been fully understood. This study was undertaken to explore the molecular characteristics of APAs, specifically focusing on APAs with KCNJ5 mutations as opposed to those without KCNJ5 mutations, by comparing their transcriptome and methylome status...
July 26, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28746916/a-missense-mutation-in-tcn2-is-associated-with-decreased-risk-for-congenital-heart-defects-and-may-increase-cellular-uptake-of-vitamin-b12-via-megalin
#18
Peiqiang Li, Lijuan Huang, Yufang Zheng, Xuedong Pan, Rui Peng, Yueming Jiang, Richard H Finnell, Haijie Li, Bin Qiao, Hong-Yan Wang
Deregulation of folate and vitamin B12 (VB12) metabolism contributes to the risk of congenital heart defects (CHDs). Transcobalamin (TCN2) is essential for transporting VB12 from blood to cells as TCN2-bound VB12 (holo-TC) is the only form for somatic cellular uptake. In this study, we performed an association study between common polymorphisms in 46 one carbon metabolism genes and CHD in 412 CHDs and 213 controls. Only two significant association signals in coding regions were identified: FTCD c.1470C>T & TCN2 c...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28746783/cd73-expression-identifies-a-subset-of-igm-antigen-experienced-cells-with-memory-attributes-that-is-t-cell-and-cd40-signaling-dependent
#19
Lucas D'Souza, Sneh Lata Gupta, Vineeta Bal, Satyajit Rath, Anna George
B cell memory was long characterized as isotype-switched, somatically mutated and germinal center (GC)-derived. However, it is now clear that the memory pool is a complex mixture that includes unswitched and unmutated cells. Further, expression of CD73, CD80 and CD273 has allowed the categorization of B cell memory into multiple subsets, with combinatorial expression of the markers increasing with GC progression, isotype-switching and acquisition of somatic mutations. We have extended these findings to determine whether these markers can be used to identify IgM memory phenotypically as arising from T-dependent versus T-independent responses...
July 26, 2017: Immunology
https://www.readbyqxmd.com/read/28746660/somatic-maturation-and-the-relationship-between-bone-mineral-variables-and-types-of-sports-among-adolescents-cross-sectional-study
#20
Ricardo Ribeiro Agostinete, Igor Hideki Ito, Han Kemper, Carlos Marcelo Pastre, Mário Antônio Rodrigues-Júnior, Rafael Luiz-de-Marco, Rômulo Araújo Fernandes
CONTEXT AND OBJECTIVE: Peak height velocity (PHV) is an important maturational event during adolescence that affects skeleton size. The objective here was to compare bone variables in adolescents who practiced different types of sports, and to identify whether differences in bone variables attributed to sports practice were dependent on somatic maturation status. DESIGN AND SETTING: Cross-sectional study, São Paulo State University (UNESP). METHODS: The study was composed of 93 adolescents (12 to 16...
May 2017: São Paulo Medical Journal, Revista Paulista de Medicina
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