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https://www.readbyqxmd.com/read/28723478/low-t-cell-receptor-diversity-high-somatic-mutation-burden-and-high-neoantigen-load-as-predictors-of-clinical-outcome-in-muscle-invasive-bladder-cancer
#1
Noura J Choudhury, Kazuma Kiyotani, Kai Lee Yap, Alexa Campanile, Tatjana Antic, Poh Yin Yew, Gary Steinberg, Jae Hyun Park, Yusuke Nakamura, Peter H O'Donnell
BACKGROUND: The success of cancer immunotherapies has highlighted the potent ability of local adaptive immune responses to eradicate cancer cells by targeting neoantigens generated by somatic alterations. However, how these factors interact to drive the natural history of muscle-invasive bladder cancer (MIBC) is not well understood. OBJECTIVE: To investigate the role of immune regulation in MIBC disease progression, we performed massively parallel T-cell receptor (TCR) sequencing of tumor-infiltrating T cells (TILs), in silico neoantigen prediction from exome sequences, and expression analysis of immune-related genes...
October 2016: European Urology Focus
https://www.readbyqxmd.com/read/28722539/an-autophagy-driven-pathway-of-atp-secretion-supports-the-aggressive-phenotype-of-braf-v600e-inhibitor-resistant-metastatic-melanoma-cells
#2
Shaun Martin, Aleksandra M Dudek-Peric, Abhishek D Garg, Heleen Roose, Seyma Demirsoy, Sofie Van Eygen, Freya Mertens, Peter Vangheluwe, Hugo Vankelecom, Patrizia Agostinis
The ingrained capacity of melanoma cells to rapidly evolve towards an aggressive phenotype is manifested by their increased ability to develop drug-resistance, evident in the case of vemurafenib, a therapeutic-agent targeting BRAF(V600E). Previous studies indicated a tight correlation between heightened melanoma-associated macroautophagy/autophagy and acquired Vemurafenib resistance. However, how this vesicular trafficking pathway supports Vemurafenib resistance remains unclear. Here, using isogenic human and murine melanoma cell lines of Vemurafenib-resistant and patient-derived melanoma cells with primary resistance to the BRAF(V600E) inhibitor, we found that the enhanced migration and invasion of the resistant melanoma cells correlated with an enhanced autophagic capacity and autophagosome-mediated secretion of ATP...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28722181/historical-biome-distribution-and-recent-human-disturbance-shape-the-diversity-of-arbuscular-mycorrhizal-fungi
#3
Meelis Pärtel, Maarja Öpik, Mari Moora, Leho Tedersoo, Robert Szava-Kovats, Søren Rosendahl, Matthias C Rillig, Ylva Lekberg, Holger Kreft, Thorunn Helgason, Ove Eriksson, John Davison, Francesco de Bello, Tancredi Caruso, Martin Zobel
The availability of global microbial diversity data, collected using standardized metabarcoding techniques, makes microorganisms promising models for investigating the role of regional and local factors in driving biodiversity. Here we modelled the global diversity of symbiotic arbuscular mycorrhizal (AM) fungi using currently available data on AM fungal molecular diversity (small subunit (SSU) ribosomal RNA (rRNA) gene sequences) in field samples. To differentiate between regional and local effects, we estimated species pools (sets of potentially suitable taxa) for each site, which are expected to reflect regional processes...
July 19, 2017: New Phytologist
https://www.readbyqxmd.com/read/28722124/pancreatic-undifferentiated-carcinoma-with-osteoclast-like-giant-cells-is-genetically-similar-to-but-clinically-distinct-from-conventional-ductal-adenocarcinoma
#4
Claudio Luchini, Antonio Pea, Gemma Lionheart, Andrea Mafficini, Alessia Nottegar, Nicola Veronese, Peter Chianchiano, Lodewijk A A Brosens, Michaël Noë, G Johan A Offerhaus, Raluca Yonescu, Yi Ning, Giuseppe Malleo, Giulio Riva, Paola Piccoli, Ivana Cataldo, Paola Capelli, Giuseppe Zamboni, Aldo Scarpa, Laura D Wood
Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGC, including the whole exome sequencing of 8 UCOGC. We observed that 60% of the UCOGC contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28720716/pi3k%C3%AE-activity-in-leukocytes-promotes-adipose-tissue-inflammation-and-early-onset-insulin-resistance-during-obesity
#5
Ludovic Breasson, Barbara Becattini, Claudia Sardi, Angela Molinaro, Fabio Zani, Romina Marone, Fabrizio Botindari, Mélanie Bousquenaud, Curzio Ruegg, Matthias P Wymann, Giovanni Solinas
The phosphoinositide 3-kinase γ (PI3Kγ) plays a major role in leukocyte recruitment during acute inflammation and has been proposed to inhibit classical macrophage activation by driving immunosuppressive gene expression. PI3Kγ plays an important role in diet-induced obesity and insulin resistance. In seeking to determine the underlying molecular mechanisms, we showed that PI3Kγ action in high-fat diet-induced inflammation and insulin resistance depended largely on its role in the control of adiposity, which was due to PI3Kγ activity in a nonhematopoietic cell type...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28720700/hitchhiking-and-epistasis-give-rise-to-cohort-dynamics-in-adapting-populations
#6
Sean W Buskirk, Ryan Emily Peace, Gregory I Lang
Beneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection; yet these targets are inherently enriched for genes of large target size and mutations of large effect. A comprehensive study of individual mutations is necessary to create a realistic picture of the evolutionarily significant spectrum of beneficial mutations...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28718829/aspirin-prevention-of-colorectal-cancer-focus-on-nf-%C3%AE%C2%BAb-signalling-and-the-nucleolus
#7
REVIEW
Jingyu Chen, Lesley A Stark
Overwhelming evidence indicates that aspirin and related non-steroidal anti-inflammatory drugs (NSAIDs) have anti-tumour activity and the potential to prevent cancer, particularly colorectal cancer. However, the mechanisms underlying this effect remain hypothetical. Dysregulation of the nuclear factor-kappaB (NF-κB) transcription factor is a common event in many cancer types which contributes to tumour initiation and progression by driving expression of pro-proliferative/anti-apoptotic genes. In this review, we will focus on the current knowledge regarding NSAID effects on the NF-κB signalling pathway in pre-cancerous and cancerous lesions, and the evidence that these effects contribute to the anti-tumour activity of the agents...
July 18, 2017: Biomedicines
https://www.readbyqxmd.com/read/28717200/genome-wide-rna-sequencing-analysis-identifies-a-distinct-fibrosis-gene-signature-in-the-conjunctiva-after-glaucoma-surgery
#8
Cynthia Yu-Wai-Man, Nicholas Owen, Jonathan Lees, Aristides D Tagalakis, Stephen L Hart, Andrew R Webster, Christine A Orengo, Peng T Khaw
Fibrosis-related events play a part in most blinding diseases worldwide. However, little is known about the mechanisms driving this complex multifactorial disease. Here we have carried out the first genome-wide RNA-Sequencing study in human conjunctival fibrosis. We isolated 10 primary fibrotic and 7 non-fibrotic conjunctival fibroblast cell lines from patients with and without previous glaucoma surgery, respectively. The patients were matched for ethnicity and age. We identified 246 genes that were differentially expressed by over two-fold and p < 0...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717043/tandem-amplification-of-sccmec-can-drive-high-level-methicillin-resistance-in-mrsa
#9
Laura A Gallagher, Simone Coughlan, Nikki S Black, Pierce Lalor, Elaine M Waters, Bryan Wee, Mick Watson, Tim Downing, J Ross Fitzgerald, Gerard T A Fleming, James P O'Gara
Hospital-associated methicillin-resistant Staphylococcus aureus strains typically express high level, homogenous (HoR) β-lactam resistance, whereas community-associated MRSA (CA-MRSA) more commonly express low level heterogeneous (HeR) resistance. Expression of the HoR phenotype typically requires both increased expression of the mecA gene, carried on the Staphylococcus cassette chromosome SCCmec element, and additional mutational event(s) elsewhere on the chromosome. Here the oxacillin concentration in a chemostat culture of the CA-MRSA strain USA300 was increased from 8 μg/ml to 130 μg/ml over 13 days to isolate highly oxacillin resistant derivatives...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28716960/bacterial-tubulin-a-b-exhibit-polarized-growth-mixed-polarity-bundling-and-destabilization-by-gtp-hydrolysis
#10
César Díaz-Celis, Viviana I Risca, Felipe Hurtado, Jessica K Polka, Scott D Hansen, Daniel Maturana, Rosalba Lagos, R Dyche Mullins, Octavio Monasterio
Bacteria of the genus Prosthecobacter express homologs of eukaryotic α- and β-tubulin, called BtubA and BtubB, that have been observed to assemble into filaments in presence of GTP. BtubA/B polymers are proposed to be composed in vitro by two to six protofilaments, in contrast to in vivo where they have been reported to form 5-protofilaments tubes named bacterial microtubules (bMTs). The btubAB genes likely entered the Prosthecobacter lineage via horizontal gene transfer and may derive from an early ancestor of the modern eukaryotic microtubule (MT)...
July 17, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28716951/a-calcium-diacylglycerol-stimulated-protein-kinase-c-c-elegans-pkc-2-links-thermal-signals-to-learned-behavior-by-acting-in-a-sensory-neuron-and-intestinal-cells
#11
Marianne Land, Charles S Rubin
Ca(2+) and diacylglycerol (DAG) activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a C. elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc) and migrates along Tc within a 17-25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2(-/-) animals...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28716941/cryptic-oxygen-cycling-in-anoxic-marine-zones
#12
Emilio Garcia-Robledo, Cory C Padilla, Montserrat Aldunate, Frank J Stewart, Osvaldo Ulloa, Aurélien Paulmier, Gerald Gregori, Niels Peter Revsbech
Oxygen availability drives changes in microbial diversity and biogeochemical cycling between the aerobic surface layer and the anaerobic core in nitrite-rich anoxic marine zones (AMZs), which constitute huge oxygen-depleted regions in the tropical oceans. The current paradigm is that primary production and nitrification within the oxic surface layer fuel anaerobic processes in the anoxic core of AMZs, where 30-50% of global marine nitrogen loss takes place. Here we demonstrate that oxygenic photosynthesis in the secondary chlorophyll maximum (SCM) releases significant amounts of O2 to the otherwise anoxic environment...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716713/n-myc-regulates-growth-and-fiber-cell-differentiation-in-lens-development
#13
Gabriel R Cavalheiro, Gabriel E Matos-Rodrigues, Yilin Zhao, Anielle L Gomes, Deepti Anand, Danilo Predes, Silmara de Lima, Jose G Abreu, Deyou Zheng, Salil A Lachke, Ales Cvekl, Rodrigo A P Martins
Myc proto-oncogenes regulate diverse cellular processes during development, but their roles during morphogenesis of specific tissues are not fully understood. We found that c-myc regulates cell proliferation in mouse lens development and previous genome-wide studies suggested functional roles for N-myc in developing lens. Here, we examined the role of N-myc in mouse lens development. Genetic inactivation of N-myc in the surface ectoderm or lens vesicle impaired eye and lens growth, while "late" inactivation in lens fibers had no effect...
July 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28716118/evolutionary-and-genetic-analysis-of-the-vp2-gene-of-canine-parvovirus
#14
Gairu Li, Senlin Ji, Xiaofeng Zhai, Yuxiang Zhang, Jie Liu, Mengyan Zhu, Jiyong Zhou, Shuo Su
BACKGROUND: Canine parvovirus (CPV) type 2 emerged in 1978 in the USA and quickly spread among dog populations all over the world with high morbidity. Although CPV is a DNA virus, its genomic substitution rate is similar to some RNA viruses. Therefore, it is important to trace the evolution of CPV to monitor the appearance of mutations that might affect vaccine effectiveness. RESULTS: Our analysis shows that the VP2 genes of CPV isolated from 1979 to 2016 are divided into six groups: GI, GII, GIII, GIV, GV, and GVI...
July 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28716036/short-dna-sequence-patterns-accurately-identify-broadly-active-human-enhancers
#15
Laura L Colbran, Ling Chen, John A Capra
BACKGROUND: Enhancers are DNA regulatory elements that influence gene expression. There is substantial diversity in enhancers' activity patterns: some enhancers drive expression in a single cellular context, while others are active across many. Sequence characteristics, such as transcription factor (TF) binding motifs, influence the activity patterns of regulatory sequences; however, the regulatory logic through which specific sequences drive enhancer activity patterns is poorly understood...
July 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28715769/high-throughput-profiling-and-analysis-of-antibiotic-resistance-genes-in-east-tiaoxi-river-china
#16
Ji Zheng, Ruixia Gao, Yuanyuan Wei, Tao Chen, Jiqing Fan, Zhenchao Zhou, Tiimub Benjamin Makimilua, Yanan Jiao, Hong Chen
The rapid human activities and urbanization exacerbate the human health risks induced by antibiotic resistance genes (ARGs). In this study, the profiling of ARGs was investigated using high-throughput qPCR from water samples of 13 catchment areas in East Tiaoxi River, China. High prevalence of ARGs indicated significant antibiotic resistance pollution in the research area (absolute abundance: 6.1 × 10(8)-2.1 × 10(10) copies/L; relative abundance: 0.033-0.158 copies/cell). Conventional water qualities (COD, TN, TP, NH3-N), bacterial communities and mobile gene elements (MGEs) were detected and analyzed as factors of ARGs shift...
July 14, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28715438/a-sequence-level-model-of-an-intact-locus-predicts-the-location-and-function-of-nonadditive-enhancers
#17
Kenneth A Barr, John Reinitz
Metazoan gene expression is controlled through the action of long stretches of noncoding DNA that contain enhancers-shorter sequences responsible for controlling a single aspect of a gene's expression pattern. Models built on thermodynamics have shown how enhancers interpret protein concentration in order to determine specific levels of gene expression, but the emergent regulatory logic of a complete regulatory locus shows qualitative and quantitative differences from isolated enhancers. Such differences may arise from steric competition limiting the quantity of DNA that can simultaneously influence the transcription machinery...
2017: PloS One
https://www.readbyqxmd.com/read/28714987/comparison-of-algorithms-for-the-detection-of-cancer-drivers-at-subgene-resolution
#18
Eduard Porta-Pardo, Atanas Kamburov, David Tamborero, Tirso Pons, Daniela Grases, Alfonso Valencia, Nuria Lopez-Bigas, Gad Getz, Adam Godzik
Understanding genetic events that lead to cancer initiation and progression remains one of the biggest challenges in cancer biology. Traditionally, most algorithms for cancer-driver identification look for genes that have more mutations than expected from the average background mutation rate. However, there is now a wide variety of methods that look for nonrandom distribution of mutations within proteins as a signal for the driving role of mutations in cancer. Here we classify and review such subgene-resolution algorithms, compare their findings on four distinct cancer data sets from The Cancer Genome Atlas and discuss how predictions from these algorithms can be interpreted in the emerging paradigms that challenge the simple dichotomy between driver and passenger genes...
July 17, 2017: Nature Methods
https://www.readbyqxmd.com/read/28714247/-molecular-cytogenetics-to-characterize-mechanisms-of-gene-duplication-in-pesticide-resistance
#19
REVIEW
Mithila Jugulam, Bikram S Gill
Recent advances in molecular cytogenetics empower construction of physical maps to illustrate the precise position of genetic loci on the chromosomes. Such maps provide visible information about the position of DNA sequences, including the distribution of repetitive sequences on the chromosomes. This will be an important step forward toward unraveling the genetic mechanisms implicated in chromosomal aberrations (e.g., gene duplication). In response to stress, such as pesticide selection, the duplicated genes provide an immediate adaptive advantage to organisms that overcome unfavorable conditions...
July 17, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28713922/selection-of-an-optimal-promoter-for-gene-transfer-in-normal-b-cells
#20
Magdalena Winiarska, Dominika Nowis, Malgorzata Firczuk, Agnieszka Zagozdzon, Magdalena Gabrysiak, Radoslaw Sadowski, Joanna Barankiewicz, Michal Dwojak, Jakub Golab
Gene transfer into normal quiescent human B cells is a challenging procedure. The present study aimed to investigate whether it is possible to increase the levels of transgene expression by using various types of promoters to drive the expression of selected genes‑of‑interest. To produce lentiviral particles, the present study used the 2nd generation psPAX2 packaging vector and the vesicular stomatitis virus ‑expressing envelope vector pMD2.G. Subsequently, lentiviral vectors were generated containing various promoters, including cytomegalovirus (CMV), elongation factor‑1 alpha (EF1α) and spleen focus‑forming virus (SFFV)...
July 14, 2017: Molecular Medicine Reports
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