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https://www.readbyqxmd.com/read/28431018/disulfide-bonds-enable-accelerated-protein-evolution
#1
Felix Feyertag, David Alvarez-Ponce
The different proteins of any proteome evolve at enormously different rates. What factors contribute to this variability, and to what extent, is still a largely open question. We hypothesized that disulfide bonds, by increasing protein stability, should make proteins' structures relatively independent of their amino acid sequences, thus acting as buffers of deleterious mutations and enabling accelerated sequence evolution. In agreement with this hypothesis, we observed that membrane proteins with disulfide bonds evolved 88% faster than those without disulfide bonds, and that extracellular proteins with disulfide bonds evolved 49% faster than those without disulfide bonds...
April 18, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28430657/microrna-signatures-predict-prognosis-of-patients-with-glioblastoma-multiforme-through-the-cancer-genome-atlas
#2
Ying Yuan, Hua Zhang, Xuexia Liu, Zhongming Lu, Guojun Li, Meixia Lu, Xiaofeng Tao
MicroRNAs (miRNAs) play major roles in various biological processes and have been implicated in the pathogenesis and malignant progression of glioblastoma multiforme (GBM). The aim of this study was to assess the predictive values of miRNAs for overall survival (OS) of patients with GBM. MiRNA expression profiles and clinical information of 563 GBM patients were obtained from the Cancer Genome Atlas. The most significantly altered miRNAs were identified and miRNA expression profiles were performed, through principal component analysis, the least absolute shrinkage and selection operator method...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428190/in-vivo-detection-of-egfrviii-in-glioblastoma-via-perfusion-magnetic-resonance-imaging-signature-consistent-with-deep-peritumoral-infiltration-the-%C3%AF-index
#3
Spyridon Bakas, Hamed Akbari, Jared Pisapia, Maria Martinez-Lage, Martin Rozycki, Saima Rathore, Nadia Dahmane, Donald M O'Rourke, Christos Davatzikos
<br />The epidermal growth factor receptor variant III (EGFRvIII) mutation has been considered a driver mutation and therapeutic target in glioblastoma, the most common and aggressive brain cancer. Currently, detecting EGFRvIII requires postoperative tissue analyses, which are ex vivo and unable to capture the tumor's spatial heterogeneity. Considering the increasing evidence of in vivo imaging signatures capturing molecular characteristics of cancer, this study aims to detect EGFRvIII in primary glioblastoma non-invasively, using routine clinically-acquired imaging...
April 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28426719/transcriptome-of-interstitial-cells-of-cajal-reveals-unique-and-selective-gene-signatures
#4
Moon Young Lee, Se Eun Ha, Chanjae Park, Paul J Park, Robert Fuchs, Lai Wei, Brian G Jorgensen, Doug Redelman, Sean M Ward, Kenton M Sanders, Seungil Ro
Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI) smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes...
2017: PloS One
https://www.readbyqxmd.com/read/28425970/aneurysm-specific-mir-221-and-mir-146a-participates-in-human-thoracic-and-abdominal-aortic-aneurysms
#5
Premakumari Venkatesh, Julie Phillippi, Sasanka Chukkapalli, Mercedes Rivera-Kweh, Irina Velsko, Thomas Gleason, Paul VanRyzin, Seyed Hossein Aalaei-Andabili, Ravi Kiran Ghanta, Thomas Beaver, Edward Kar Leung Chan, Lakshmyya Kesavalu
Altered microRNA expression is implicated in cardiovascular diseases. Our objective was to determine microRNA signatures in thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs) compared with control non-aneurysmal aortic specimens. We evaluated the expression of fifteen selected microRNA in human TAA and AAA operative specimens compared to controls. We observed significant upregulation of miR-221 and downregulation of miR-1 and -133 in TAA specimens. In contrast, upregulation of miR-146a and downregulation of miR-145 and -331-3p were found only for AAA specimens...
April 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28425754/immunotherapy-and-targeted-therapy-in-brain-metastases-emerging-options-in-precision-medicine
#6
Tyler Lazaro, Priscilla K Brastianos
Brain metastases (BM) continue to represent an unmet clinical need in oncology. Immunotherapy and targeted therapy hold great promise in the treatment of BM. Emerging data are confirming the activity of these agents in patients with BM. Genomic studies have confirmed that clinically actionable mutations are present in BM and they can be used in clinical studies to link targeted therapies with their genetic targets. Furthermore, as molecular signatures associated with sensitivity and resistance to immunotherapies are developed, we will better be able to select BM patients who will most benefit from these therapies...
April 2017: CNS Oncology
https://www.readbyqxmd.com/read/28425584/changes-in-ciap2-survivin-and-bimel-expression-characterize-the-switch-from-autophagy-to-apoptosis-in-prolonged-starvation
#7
A Hay-Koren, S Bialik, V Levin-Salomon, A Kimchi
BACKGROUND: Autophagy is a catabolic process involving the engulfment of cytoplasmic content within autophagosomes followed by their delivery to lysosomes. This process is a survival mechanism, enabling cells to cope with nutrient deprivation by degradation and recycling of macromolecules. Yet during continued stress such as prolonged starvation, a switch from autophagy to apoptosis is often detected. OBJECTIVE: In this work, we characterized the temporal dynamics of the transition from autophagy towards apoptosis with the aim of elucidating the molecular mechanism regulating the switch from survival autophagy to apoptotic cell death...
May 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28424429/the-volatile-molecule-signature-of-four-mycobacteria-species
#8
Theodore Mellors, Christiaan Rees, Wendy Wieland-Alter, C Fordham von Reyn, Jane E Hill
Mycobacteria are the leading cause of death from infectious disease worldwide and limitations in current diagnostics are hampering control efforts. In recent years, the use of small volatile molecules as diagnostic biomarkers for mycobacteria has shown promise for use in the rapid analysis of in vitro cultures as well as ex vivo diagnosis using breath or sputum. In this study, 18 strains from four mycobacteria species (Mycobacterium avium, M. bovis BCG, M. intracellulare and M. xenopi) were analyzed for the first time using two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS)...
April 20, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/28424085/the-within-host-population-dynamics-of-mycobacterium-tuberculosis-vary-with-treatment-efficacy
#9
Andrej Trauner, Qingyun Liu, Laura E Via, Xin Liu, Xianglin Ruan, Lili Liang, Huimin Shi, Ying Chen, Ziling Wang, Ruixia Liang, Wei Zhang, Wang Wei, Jingcai Gao, Gang Sun, Daniela Brites, Kathleen England, Guolong Zhang, Sebastien Gagneux, Clifton E Barry, Qian Gao
BACKGROUND: Combination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We address this question by studying the population dynamics of Mycobacterium tuberculosis within tuberculosis patients undergoing treatment with different combinations of antibiotics...
April 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28423967/identifying-selectively-important-amino-acid-positions-associated-with-alternative-habitat-environments-in-fish-mitochondrial-genomes
#10
Jun Hong Xia, Hong Lian Li, Yong Zhang, Zi Ning Meng, Hao Ran Lin
Fish species inhabitating seawater (SW) or freshwater (FW) habitats have to develop genetic adaptations to alternative environment factors, especially salinity. Functional consequences of the protein variations associated with habitat environments in fish mitochondrial genomes have not yet received much attention. We analyzed 829 complete fish mitochondrial genomes and compared the amino acid differences of 13 mitochondrial protein families between FW and SW fish groups. We identified 47 specificity determining sites (SDS) that associated with FW or SW environments from 12 mitochondrial protein families...
April 19, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/28423875/adaptive-selection-at-agouti-gene-inferred-breed-specific-selection-signature-within-the-indigenous-goat-populations
#11
Hafiz Ishfaq Ahmad, Guiqiong Liu, Xunping Jiang, Chenhui Liu, Xu Fangzheng, Yuqing Chong, Nabeel Ijaz, Huang Huarong
Objective: The aim of this study was to calculate selection signatures at possible loci leading to population differentiation, as well as pattern of selection of agouti gene within the local goat breeds and its correlation among other animal species to reveal molecular evolution. Methods: The high Fst outlier method corresponding to Fst distribution was used to identify the loci subject to positive selection. According to the empirical distribution of Fst estimates, we selected the SNPs having high Fst outlier corresponded to the upper 1% of the distribution as the loci under selection...
April 19, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28422780/understanding-the-gut-microbiota-in-inflammatory-and-functional-gastrointestinal-diseases
#12
Johanna Sundin, Lena Öhman, Magnus Simren
OBJECTIVE: During the last decade experimental and observational studies have shown that patients with Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS) may have an altered intestinal microbial composition compared to healthy subjects. However, no uniform microbial signature has as yet been detected for either IBD or IBS. This review summarizes the current knowledge of microbial dysbiosis, and its potential relationship to the pathophysiology in IBD and IBS. METHODS: A selective review was conducted to summarize the current knowledge of gut microbiota in the pathophysiology of IBD and IBS...
April 18, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28422476/origin-dependent-variations-in-the-atmospheric-microbiome-community-in-eastern-mediterranean-dust-storms
#13
Daniella Gat, Yinon Mazar, Eddie Cytryn, Yinon Rudich
Dust storms transport through the atmosphere microorganisms that can potentially affect human health and the functionality of microbial communities in various environments. Characterizing the dust-borne microbiome in storms of different origin or that followed different paths provides valuable data to improve understanding of global health and environmental impacts. We present a comparative study on the diversity of dust-borne microbial communities in dust storms from three distinct origins-North Africa, Syria and Saudi-Arabia-and compare them with those on dust-free days...
April 19, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28422134/genetic-structure-and-signatures-of-selection-in-grey-reef-sharks-carcharhinus-amblyrhynchos
#14
P Momigliano, R Harcourt, W D Robbins, V Jaiteh, G N Mahardika, A Sembiring, A Stow
With overfishing reducing the abundance of marine predators in multiple marine ecosystems, knowledge of genetic structure and local adaptation may provide valuable information to assist sustainable management. Despite recent technological advances, most studies on sharks have used small sets of neutral markers to describe their genetic structure. We used 5517 nuclear single-nucleotide polymorphisms (SNPs) and a mitochondrial DNA (mtDNA) gene to characterize patterns of genetic structure and detect signatures of selection in grey reef sharks (Carcharhinus amblyrhynchos)...
April 19, 2017: Heredity
https://www.readbyqxmd.com/read/28421322/a-colorimetric-and-fluorescent-probe-based-on-michael-acceptor-type-diketopyrrolopyrrole-for-cyanide-detection
#15
Lingyun Wang, Shaochun Zhou, Derong Cao
A new probe 1 was synthesized by incorporating an α,β-unsaturated ketone to a diketopyrrolopyrrole fluorophore. The probe exhibited a selective and sensitive response to cyanide against other anions. Addition of CN(-) aqueous solution to 1 resulted in a rapid color change from pink to light yellow together with a blue shift from 518 to 421 nm, while other anions did not induce any significant color change. Furthermore, the Michael addition of cyanide to 1 elicited 98% fluorescence quenching at 608 nm, which constituted the fluorescence signature for cyanide detection...
April 18, 2017: Journal of Fluorescence
https://www.readbyqxmd.com/read/28419349/genomic-signature-of-kin-selection-in-an-ant-with-obligately-sterile-workers
#16
Michael R Warner, Alexander S Mikheyev, Timothy A Linksvayer
Kin selection is thought to drive the evolution of cooperation and conflict, but the specific genes and genome-wide patterns shaped by kin selection are unknown. We identified thousands of genes associated with the sterile ant worker caste, the archetype of an altruistic phenotype shaped by kin selection, and then used population and comparative genomic approaches to study patterns of molecular evolution at these genes. Consistent with population genetic theoretical predictions, worker-upregulated genes experienced reduced selection compared to genes upregulated in reproductive castes...
April 13, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28418902/igf1r-depletion-facilitates-met-amplification-as-mechanism-of-acquired-resistance-to-erlotinib-in-hcc827-nsclc-cells
#17
Dianna Hussmann, Anne Tranberg Madsen, Kristine Raaby Jakobsen, Yonglun Luo, Boe Sandahl Sorensen, Anders Lade Nielsen
EGFR-mutated non-small cell lung cancer patients experience relapse within 1-2 years of treatment with EGFR-inhibitors, such as erlotinib. Multiple resistance mechanisms have been identified including secondary EGFR-mutations, MET-amplification, and epithelial-mesenchymal transition (EMT). Previous studies have indicated a role of Insulin-like growth factor 1 receptor (IGF1R) in acquired resistance to EGFR-directed drugs as well as in EMT. In the present study, we have investigated the involvement of IGF1R in acquired high-dose erlotinib resistance in the EGFR-mutated lung adenocarcinoma cell line HCC827...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416970/dna-methylation-profiling-in-peripheral-lung-tissues-of-smokers-and-patients-with-copd
#18
Isaac K Sundar, Qiangzong Yin, Brian S Baier, Li Yan, Witold Mazur, Dongmei Li, Martha Susiarjo, Irfan Rahman
BACKGROUND: Epigenetics changes have been shown to be affected by cigarette smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD). We sought to determine whether genome-wide lung DNA methylation profiles of smokers and patients with COPD were significantly different from non-smokers. We isolated DNA from parenchymal lung tissues of patients including eight lifelong non-smokers, eight current smokers, and eight patients with COPD and analyzed the samples using Illumina's Infinium HumanMethylation450 BeadChip...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28416775/volatile-organic-compounds-in-gastrointestinal-stromal-tumour-tissue-originating-from-patient-derived-xenografts
#19
Renata Wawrzyniak, Agnieszka Woźniak, Yemarshet Gebreyohannes, Bartosz Dykcik, Patrick Schöffski, Michal Markuszewski
Gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract, localized mainly in the stomach or small intestine. The metabolomic signature of GIST signature associated with various mutations in KIT gene remains undiscovered and unexplored. The main aim of this pilot study was to determine and compare metabolomic profiles in GIST xenograft models with different genetic background. Metabolomic profiling using gas chromatography coupled with mass spectrometry followed by both univariate and multivariate statistical analyses was applied to select metabolites which differentiate the GIST models studied...
April 18, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/28415587/detection-of-a-combination-of-serum-igg-and-iga-antibodies-against-selected-mycobacterial-targets-provides-promising-diagnostic-signatures-for-active-tb
#20
Dolapo O Awoniyi, Ralf Baumann, Novel N Chegou, Belinda Kriel, Ruschca Jacobs, Martin Kidd, Andre G Loxton, Susanne Kaempfer, Mahavir Singh, Gerhard Walzl
Immunoglobulin G (IgG) based tests for the diagnosis of active tuberculosis (TB) disease often show a lack of specificity in TB endemic regions, which is mainly due to a high background prevalence of LTBI. Here, we investigated the combined performance of the responses of different Ig classes to selected mycobacterial antigens in primary healthcare clinic attendees with signs and symptoms suggestive of TB. The sensitivity and specificity of IgA, IgG and/or IgM to LAM and 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16kDa and 19kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 63 individuals who underwent diagnostic work-up for TB after presenting with symptoms and signs compatible with possible active TB were evaluated...
March 21, 2017: Oncotarget
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