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https://www.readbyqxmd.com/read/28087824/neuropathology-of-sudep-role-of-inflammation-blood-brain-barrier-impairment-and-hypoxia
#1
Zuzanna Michalak, Dima Obari, Matthew Ellis, Maria Thom, Sanjay M Sisodiya
OBJECTIVE: To seek a neuropathologic signature of sudden unexpected death in epilepsy (SUDEP) in a postmortem cohort by use of immunohistochemistry for specific markers of inflammation, gliosis, acute neuronal injury due to hypoxia, and blood-brain barrier (BBB) disruption, enabling the generation of hypotheses about potential mechanisms of death in SUDEP. METHODS: Using immunohistochemistry, we investigated the expression of 6 markers (CD163, human leukocyte antigen-antigen D related, glial fibrillary acid protein, hypoxia-inducible factor-1α [HIF-1α], immunoglobulin G, and albumin) in the hippocampus, amygdala, and medulla in 58 postmortem cases: 28 SUDEP (definite and probable), 12 epilepsy controls, and 18 nonepileptic sudden death controls...
January 13, 2017: Neurology
https://www.readbyqxmd.com/read/28087713/functional-genomics-reveals-that-tumors-with-activating-phosphoinositide-3-kinase-mutations-are-dependent-on-accelerated-protein-turnover
#2
Teresa Davoli, Kristen E Mengwasser, Jingjing Duan, Ting Chen, Camilla Christensen, Eric C Wooten, Anthony N Anselmo, Mamie Z Li, Kwok-Kin Wong, Kristopher T Kahle, Stephen J Elledge
Activating mutations in the phosphoinositide 3-kinase (PI3K) signaling pathway are frequently identified in cancer. To identify pathways that support PI3K oncogenesis, we performed a genome-wide RNAi screen in isogenic cell lines harboring wild-type or mutant PIK3CA to search for PI3K synthetic-lethal (SL) genes. A combined analysis of these results with a meta-analysis of two other large-scale RNAi screening data sets in PI3K mutant cancer cell lines converged on ribosomal protein translation and proteasomal protein degradation as critical nononcogene dependencies for PI3K-driven tumors...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28086750/a-genome-wide-scan-for-genes-under-balancing-selection-in-drosophila-melanogaster
#3
Myriam Croze, Andreas Wollstein, Vedran Božičević, Daniel Živković, Wolfgang Stephan, Stephan Hutter
BACKGROUND: In the history of population genetics balancing selection has been considered as an important evolutionary force, yet until today little is known about its abundance and its effect on patterns of genetic diversity. Several well-known examples of balancing selection have been reported from humans, mice, plants, and parasites. However, only very few systematic studies have been carried out to detect genes under balancing selection. We performed a genome scan in Drosophila melanogaster to find signatures of balancing selection in a derived (European) and an ancestral (African) population...
January 13, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28079887/drp-1-is-required-for-bh3-mimetic-mediated-mitochondrial-fragmentation-and-apoptosis
#4
Mateus Milani, Dominic P Byrne, Georgia Greaves, Michael Butterworth, Gerald M Cohen, Patrick A Eyers, Shankar Varadarajan
The concept of using BH3 mimetics as anticancer agents has been substantiated by the efficacy of selective drugs, such as Navitoclax and Venetoclax, in treating BCL-2-dependent haematological malignancies. However, most solid tumours depend on MCL-1 for survival, which is highly amplified in multiple cancers and a major factor determining chemoresistance. Most MCL-1 inhibitors that have been generated so far, while demonstrating early promise in vitro, fail to exhibit specificity and potency in a cellular context...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28075543/prognostic-value-of-tissue-based-biomarker-signature-in-clear-cell-renal-cell-carcinoma
#5
Ahmed Q Haddad, Jun-Hang Luo, Laura-Maria Krabbe, Oussama Darwish, Bishoy Gayed, Ramy Youssef, Payal Kapur, Dinesh Rakheja, Yair Lotan, Arthur Sagalowsky, Vitaly Margulis
OBJECTIVE: To improve risk stratification for recurrence prognostication in localized clear cell renal cell carcinoma (ccRCC) patients. PATIENTS AND METHODS: 367 patients with non-metastatic ccRCC were included. The cohort was divided into a training and validation set. Using tissue microarrays, immunostaining was performed for 24 biomarkers representative of key pathways in ccRCC. Using LASSO Cox regression, we identified several markers which were used to construct a risk classifier for risk of disease recurrence...
January 11, 2017: BJU International
https://www.readbyqxmd.com/read/28074842/analysis-of-the-fgf-gene-family-provides-insights-into-aquatic-adaptation-in-cetaceans
#6
Kiwoong Nam, Kyeong Won Lee, Oksung Chung, Hyung-Soon Yim, Sun-Shin Cha, Sae-Won Lee, JeHoon Jun, Yun Sung Cho, Jong Bhak, João Pedro de Magalhães, Jung-Hyun Lee, Jae-Yeon Jeong
Cetacean body structure and physiology exhibit dramatic adaptations to their aquatic environment. Fibroblast growth factors (FGFs) are a family of essential factors that regulate animal development and physiology; however, their role in cetacean evolution is not clearly understood. Here, we sequenced the fin whale genome and analysed FGFs from 8 cetaceans. FGF22, a hair follicle-enriched gene, exhibited pseudogenization, indicating that the function of this gene is no longer necessary in cetaceans that have lost most of their body hair...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28074068/a-cpg-island-methylator-phenotype-in-acute-myeloid-leukemia-independent-of-idh-mutations-and-associated-with-a-favorable-outcome
#7
A D Kelly, H Kroeger, J Yamazaki, R Taby, F Neumann, S Yu, J T Lee, B Patel, Y Li, R He, S Liang, Y Lu, M Cesaroni, S A Pierce, S M Kornblau, C E Bueso-Ramos, F Ravandi, H M Kantarjian, J Jelinek, J-Pj Issa
Genetic changes are infrequent in acute myeloid leukemia (AML) compared to other malignancies and often involve epigenetic regulators, suggesting that an altered epigenome may underlie AML biology and outcomes. In 96 AML cases including 65 pilot samples selected for cured/not-cured, we found higher CpG island (CGI) promoter methylation in cured patients. Expanded genome-wide digital restriction enzyme analysis of methylation (DREAM) data revealed a CGI methylator phenotype independent of IDH1/2 mutations we term AML-CIMP (A-CIMP(+))...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28073760/better-diagnostic-signatures-from-rnaseq-data-through-use-of-auxiliary-co-data
#8
Putri W Novianti, Barbara C Snoek, Saskia M Wilting, Mark A van de Wiel
: Our aim is to improve omics based prediction and feature selection using multiple sources of auxiliary information: co-data. Adaptive group regularized ridge regression (GRridge) was proposed to achieve this by estimating additional group-based penalty parameters through an empirical Bayes method at a low computational cost. We illustrate the GRridge method and software on RNA sequencing data sets. The method boosts the performance of an ordinary ridge regression and outperforms other classifiers...
January 10, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28070858/exosome-and-microvesicle-enriched-fractions-isolated-from-mesenchymal-stem-cells-by-gradient-separation-showed-different-molecular-signatures-and-functions-on-renal-tubular-epithelial-cells
#9
Federica Collino, Margherita Pomatto, Stefania Bruno, Rafael Soares Lindoso, Marta Tapparo, Wen Sicheng, Peter Quesenberry, Giovanni Camussi
Several studies have suggested that extracellular vesicles (EVs) released from mesenchymal stem cells (MSCs) may mediate MSC paracrine action on kidney regeneration. This activity has been, at least in part, ascribed to the transfer of proteins/transcription factors and different RNA species. Information on the RNA/protein content of different MSC EV subpopulations and the correlation with their biological activity is currently incomplete. The aim of this study was to evaluate the molecular composition and the functional properties on renal target cells of MSC EV sub-populations separated by gradient floatation...
January 9, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28070274/cunningham-s-skinks-show-low-genetic-connectivity-and-signatures-of-divergent-selection-across-its-distribution
#10
Benjamin Y Ofori, Linda J Beaumont, Adam J Stow
Establishing corridors of connecting habitat has become a mainstay conservation strategy to maintain gene flow and facilitate climate-driven range shifts. Yet, little attention has been given to ascertaining the extent to which corridors will benefit philopatric species, which might exhibit localized adaptation. Measures of genetic connectivity and adaptive genetic variation across species' ranges can help fill this knowledge gap. Here, we characterized the spatial genetic structure of Cunningham's skink (Egernia cunninghami), a philopatric species distributed along Australia's Great Dividing Range, and assessed evidence of localized adaptation...
January 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28069095/deficits-in-social-cognition-an-unveiled-signature-of-multiple-sclerosis
#11
Moussa A Chalah, Samar S Ayache
BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system, representing the primary cause of non-traumatic disability in young adults. Cognitive dysfunction can affect patients at any time during the disease process and might alter the six core functional domains. Social cognition is a multi-component construct that includes the theory of mind, empathy and social perception of emotions from facial, bodily and vocal cues...
January 10, 2017: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/28068175/cpg-methylation-signature-predicts-recurrence-in-early-stage-hepatocellular-carcinoma-results-from-a-multicenter-study
#12
Jiliang Qiu, Baogang Peng, Yunqiang Tang, Yeben Qian, Pi Guo, Mengfeng Li, Junhang Luo, Bin Chen, Hui Tang, Canliang Lu, Muyan Cai, Zunfu Ke, Wei He, Yun Zheng, Dan Xie, Binkui Li, Yunfei Yuan
Purpose Early-stage hepatocellular carcinoma (E-HCC) is being diagnosed increasingly, and in one half of diagnosed patients, recurrence will develop. Thus, it is urgent to identify recurrence-related markers. We investigated the effectiveness of CpG methylation in predicting recurrence for patients with E-HCCs. Patients and Methods In total, 576 patients with E-HCC from four independent centers were sorted by three phases. In the discovery phase, 66 tumor samples were analyzed using the Illumina Methylation 450k Beadchip...
January 9, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28067953/complex-genetic-architecture-underlies-maize-tassel-domestication
#13
Guanghui Xu, Xufeng Wang, Cheng Huang, Dingyi Xu, Dan Li, Jinge Tian, Qiuyue Chen, Chenglong Wang, Yameng Liang, Yaoyao Wu, Xiaohong Yang, Feng Tian
Maize (Zea mays) tassels underwent profound morphological changes during maize domestication and improvement. Although a number of genes affecting maize inflorescence development have been identified, the genetic basis of the morphological changes in maize tassels since domestication is not well understood. Here, using a large population of 866 maize-teosinte BC2 S3 recombinant inbred lines genotyped using 19 838 single nucleotide polymorphism (SNP) markers, we performed high-resolution quantitative trait locus (QTL) mapping for five tassel morphological traits...
January 9, 2017: New Phytologist
https://www.readbyqxmd.com/read/28067418/genome-wide-selection-components-analysis-in-a-fish-with-male-pregnancy
#14
Sarah P Flanagan, Adam G Jones
A major goal of evolutionary biology is to identify the genome-level targets of natural and sexual selection. With the advent of next-generation sequencing, whole-genome selection components analysis provides a promising avenue in the search for loci affected by selection in nature. Here, we implement a genome-wide selection components analysis in the sex-role-reversed Gulf pipefish, Syngnathus scovelli. Our approach involves a double-digest restriction-site associated DNA sequencing (ddRAD-seq) technique, applied to adult females, non-pregnant males, pregnant males and their offspring...
January 9, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28067020/spatial-detection-of-outlier-loci-with-moran-eigenvector-maps-mem
#15
Helene H Wagner, Mariana Chávez-Pesqueira, Brenna R Forester
The spatial signature of micro-evolutionary processes structuring genetic variation may play an important role in the detection of loci under selection. However, the spatial location of samples hasn't yet been used to quantify this. Here, we present a new two-step method of spatial outlier detection at the individual and deme levels using the power spectrum of Moran eigenvector maps (MEM). The MEM power spectrum quantifies how the variation in a variable, such as the frequency of an allele at a SNP locus, is distributed across a range of spatial scales defined by MEM spatial eigenvectors...
January 9, 2017: Molecular Ecology Resources
https://www.readbyqxmd.com/read/28064023/identification-and-characterization-of-a-gamma-interferon-inducible-lysosomal-thiol-reductase-homolog-from-guinea-pig-cavia-porcellus-that-exhibits-thiol-reductase-activity-in-vitro
#16
Lei Ma, Fang Cao, Runze Tang, Jiaxin Zhang, Shuangquan Zhang
Gamma-interferon-inducible lysosomal thiol reductase (GILT) is a key enzyme in the antigen processing and presentation pathway whereby it reduces disulfide bonds at an acidic pH. In this study, a homolog of GILT from guinea pigs (designated gpGILT) was identified and characterized using bioinformatic methods and bioactivity assays. The open reading frame of gpGILT is 705bp in length and encodes 234 amino acids, with a putative molecular weight of about 25.85kDa. The structure of gpGILT is similar to those of humans and zebrafish, containing six introns and seven exons...
December 28, 2016: Research in Veterinary Science
https://www.readbyqxmd.com/read/28062797/targeted-proteomics-for-multiplexed-verification-of-markers-of-colorectal-tumorigenesis
#17
Anuli Christiana Uzozie, Nathalie Selevsek, Asa Wahlander, Paolo Nanni, Jonas Grossmann, Achim Weber, Federico Buffoli, Giancarlo Marra
Targeted proteomic methods can accelerate the verification of multiple tumor marker candidates in large series of patient samples. We utilized the targeted approach known as selected / multiple reaction monitoring (SRM/MRM) to verify potential protein markers of colorectal adenoma identified by our group in previous transcriptomic and quantitative shotgun proteomic studies of a large cohort of precancerous colorectal lesions. We developed SRM assays to reproducibly detect and quantify 25 (62.5%) of the 40 selected proteins in an independent series of precancerous and cancerous tissue samples (19 adenoma/normal mucosa pairs; 17 adenocarcinoma/normal mucosa pairs)...
January 4, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28061449/central-spindle-proteins-and-mitotic-kinesins-are-direct-transcriptional-targets-of-muvb-b-myb-and-foxm1-in-breast-cancer-cell-lines-and-are-potential-targets-for-therapy
#18
Patrick Wolter, Steffen Hanselmann, Grit Pattschull, Eva Schruf, Stefan Gaubatz
The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1), plays an essential role in cell cycle progression by regulating the transcription of genes required for mitosis and cytokinesis. In many tumors, B-MYB and FOXM1 are overexpressed as part of the proliferation signature. However, the transcriptional targets that are important for oncogenesis have not been identified. Given that mitotic kinesins are highly expressed in cancer cells and that selected kinesins have been reported as target genes of MMB-FOXM1, we sought to determine which mitotic kinesins are directly regulated by MMB-FOXM1...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060736/investigating-the-utility-of-human-melanoma-cell-lines-as-tumour-models
#19
Krista Marie Vincent, Lynne-Marie Postovit
Melanoma researchers utilize cell lines to model many tumour phenomena. It is thus important to understand similarities and differences between cell lines and the tumours that they represent, so that the optimal models can be chosen to answer specific research questions. Herein, we compared the transcriptomes of 42 melanoma cell lines to hundreds of tumours from The Cancer Genome Atlas and thousands of single melanoma cells. Tumour purity was accounted for using the ESTIMATE algorithm, so that differences likely resulting from non-tumour cells could be accounted for...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060510/coordination-dependent-spectroscopic-signatures-of-divalent-metal-ion-binding-to-carboxylate-head-groups-h2-and-he-tagged-vibrational-spectra-of-m-2-%C3%A2-rco2%C3%A2-m-mg-and-ca-r-cd3-cd2cd3-complexes
#20
Joseph W DePalma, Patrick J Kelleher, Laís C Tavares, Mark A Johnson
We explore the intramolecular distortions present in divalent metal ion-carboxylate ion pairs using vibrational spectroscopy of the cryogenically cooled, mass-selected species isolated in the gas phase. The spectral signatures of the C-O stretching modes are identified using the perdeutero isotopologues of the acetate and propionate anions in order to avoid congestion arising from the CH2 fundamentals. Both Ca(2+) and Mg(2+) are observed to bind in a symmetrical, so-called "bidentate" arrangement to the -CO2¯ group...
January 6, 2017: Journal of Physical Chemistry Letters
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