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https://www.readbyqxmd.com/read/28108836/smad-dependent-signaling-plays-a-detrimental-role-in-a-fly-model-of-smarcb1-deficiency-and-the-biology-of-atypical-teratoid-rhabdoid-tumors
#1
Astrid Jeibmann, Jacqueline Schulz, Kristin Eikmeier, Pascal D Johann, Katharina Thiel, Isabel Tegeder, Oliver Ambrée, Michael C Frühwald, Stefan M Pfister, Marcel Kool, Werner Paulus, Martin Hasselblatt
Atypical teratoid/rhabdoid tumors (ATRT) are highly malignant brain tumors arising in young children. The majority of ATRT is characterized by inactivation of the chromatin remodeling complex member SMARCB1 (INI1/hSNF5). Little is known, however, on downstream pathways involved in the detrimental effects of SMARCB1 deficiency which might also represent targets for treatment. Using Drosophila melanogaster and the Gal4-UAS system, modifier screens were performed in order to identify the role of SMAD dependent signaling in the lethal phenotype associated with knockdown of snr1, the fly homolog of SMARCB1...
January 20, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28107392/upon-accounting-for-the-impact-of-isoenzyme-loss-gene-deletion-costs-anticorrelate-with-their-evolutionary-rates
#2
Christopher Jacobs, Luke Lambourne, Yu Xia, Daniel Segrè
System-level metabolic network models enable the computation of growth and metabolic phenotypes from an organism's genome. In particular, flux balance approaches have been used to estimate the contribution of individual metabolic genes to organismal fitness, offering the opportunity to test whether such contributions carry information about the evolutionary pressure on the corresponding genes. Previous failure to identify the expected negative correlation between such computed gene-loss cost and sequence-derived evolutionary rates in Saccharomyces cerevisiae has been ascribed to a real biological gap between a gene's fitness contribution to an organism "here and now" and the same gene's historical importance as evidenced by its accumulated mutations over millions of years of evolution...
2017: PloS One
https://www.readbyqxmd.com/read/28106223/next-generation-of-network-medicine-interdisciplinary-signaling-approaches
#3
REVIEW
Tamas Korcsmaros, Maria Victoria Schneider, Giulio Superti-Furga
In the last decade, network approaches have transformed our understanding of biological systems. Network analyses and visualizations have allowed us to identify essential molecules and modules in biological systems, and improved our understanding of how changes in cellular processes can lead to complex diseases, such as cancer, infectious and neurodegenerative diseases. "Network medicine" involves unbiased large-scale network-based analyses of diverse data describing interactions between genes, diseases, phenotypes, drug targets, drug transport, drug side-effects, disease trajectories and more...
January 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28105946/a-physarum-inspired-prize-collecting-steiner-tree-approach-to-identify-subnetworks-for-drug-repositioning
#4
Yahui Sun, Pathima Nusrath Hameed, Karin Verspoor, Saman Halgamuge
BACKGROUND: Drug repositioning can reduce the time, costs and risks of drug development by identifying new therapeutic effects for known drugs. It is challenging to reposition drugs as pharmacological data is large and complex. Subnetwork identification has already been used to simplify the visualization and interpretation of biological data, but it has not been applied to drug repositioning so far. In this paper, we fill this gap by proposing a new Physarum-inspired Prize-Collecting Steiner Tree algorithm to identify subnetworks for drug repositioning...
December 5, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/28105719/allostatic-load-and-biological-anthropology
#5
Ashley N Edes, Douglas E Crews
Multiple stressors affect developing and adult organisms, thereby partly structuring their phenotypes. Determining how stressors influence health, well-being, and longevity in human and nonhuman primate populations are major foci within biological anthropology. Although much effort has been devoted to examining responses to multiple environmental and sociocultural stressors, no holistic metric to measure stress-related physiological dysfunction has been widely applied within biological anthropology. Researchers from disciplines outside anthropology are using allostatic load indices (ALIs) to estimate such dysregulation and examine life-long outcomes of stressor exposures, including morbidity and mortality...
January 2017: American Journal of Physical Anthropology
https://www.readbyqxmd.com/read/28099883/beta2-adrenergic-signaling-affects-the-phenotype-of-human-cardiac-progenitor-cells-through-emt-modulation
#6
Francesca Pagano, Francesco Angelini, Camilla Siciliano, Julia Tasciotti, Giorgio Mangino, Elena De Falco, Roberto Carnevale, Sebastiano Sciarretta, Giacomo Frati, Isotta Chimenti
Human cardiac progenitor cells (CPCs) offer great promises to cardiac cell therapy for heart failure. Many in vivo studies have shown their therapeutic benefits, paving the way for clinical translation. The 3D model of cardiospheres (CSs) represents a unique niche-like in vitro microenvironment, which includes CPCs and supporting cells. CSs have been shown to form through a process mediated by epithelial-to-mesenchymal transition (EMT). β2-adrenergic signaling significantly affects stem/progenitor cells activation and mobilization in multiple tissues, and crosstalk between β2-adrenergic signaling and EMT processes has been reported...
January 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28097447/mannose-binding-lectin-mbl-codon-54-rs1800450-polymorphism-predisposes-towards-medium-vessel-vasculitis-in-patients-with-systemic-lupus-erythematosus
#7
Vir Singh Negi, Panneer Devaraju, Durga Prasanna Misra, Vikramraj K Jain, Jignesh Babulal Usdadiya, Paul T Antony, Reena Gulati
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple etiological factors. Mannose-binding lectin (MBL) plays a key role in innate immunity by activating antibody-independent lectin complement pathway, opsonisation, phagocytosis, and immune complex (IC) clearance. Genetic polymorphisms in the promoter and coding regions of MBL gene affect the circulatory levels and biological activity of MBL. Defects in MBL can lead to defective opsonisation and, hence, hamper clearance of apoptotic debris, the persistence of which can drive autoantibody formation in lupus...
January 17, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28097057/a-gene-expression-study-of-dorso-ventrally-restricted-pigment-pattern-in-adult-fins-of-neolamprologus-meeli-an-african-cichlid-species
#8
Ehsan Pashay Ahi, Kristina M Sefc
Fish color patterns are among the most diverse phenotypic traits found in the animal kingdom. Understanding the molecular and cellular mechanisms that control in chromatophore distribution and pigmentation underlying this diversity is a major goal in developmental and evolutionary biology, which has predominantly been pursued in the zebrafish model system. Here, we apply results from zebrafish work to study a naturally occurring color pattern phenotype in the fins of an African cichlid species from Lake Tanganyika...
2017: PeerJ
https://www.readbyqxmd.com/read/28094815/drd2-co-expression-network-and-a-related-polygenic-index-predict-imaging-behavioral-and-clinical-phenotypes-linked-to-schizophrenia
#9
G Pergola, P Di Carlo, E D'Ambrosio, B Gelao, L Fazio, M Papalino, A Monda, G Scozia, B Pietrangelo, M Attrotto, J A Apud, Q Chen, V S Mattay, A Rampino, G Caforio, D R Weinberger, G Blasi, A Bertolino
Genetic risk for schizophrenia (SCZ) is determined by many genetic loci whose compound biological effects are difficult to determine. We hypothesized that co-expression pathways of SCZ risk genes are associated with system-level brain function and clinical phenotypes of SCZ. We examined genetic variants related to the dopamine D2 receptor gene DRD2 co-expression pathway and associated them with working memory (WM) behavior, the related brain activity and treatment response. Using two independent post-mortem prefrontal messenger RNA (mRNA) data sets (total N=249), we identified a DRD2 co-expression pathway enriched for SCZ risk genes...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28094442/identifying-niche-mediated-regulatory-factors-of-stem-cell-phenotypic-state-a-systems-biology-approach
#10
Srikanth Ravichandran, Antonio Del Sol
Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and non-linear stem cell-niche interactions. Here, we propose a systems biology view that considers stem cell-niche interactions as a many-body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants)...
January 17, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28093352/cyp24a1-loss-of-function-clinical-phenotype-of-monoallelic-and-biallelic-mutations
#11
REVIEW
Thomas O Carpenter
CYP24A1, encoding the vitamin D-24-hydroxylase, is of major clinical and physiologic importance, serving to regulate the catabolism of 1,25-(OH)2D, the physiologically active vitamin D metabolite. In addition to facilitating catabolism of 1,25-(OH)2D, CYP24A1 also enhances the turnover and elimination of 25-OHD, the abundant precursor metabolite and storage form of the vitamin. CYP24A1 can be stimulated hormonally by 1,25-(OH)2D and by FGF23, whereas CYP27B1, encoding the vitamin D-1α-hydroxylase, is stimulated hormonally by parathyroid hormone (PTH) and downregulated by FGF23...
January 13, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28093337/nk-cell-phenotypic-and-functional-shifts-coincide-with-specific-clinical-phases-in-the-natural-history-of-chronic-hbv-infection
#12
Rik A de Groen, Jun Hou, Gertine W van Oord, Zwier M A Groothuismink, Marieke van der Heide, Robert J de Knegt, André Boonstra
BACKGROUND: Chronic HBV infection can be divided into 4 distinct clinical phases: immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis. Using a systems biology approach, we recently identified innate immune response components, specifically NK cells as a distinctive factor of specific HBV clinical phases. To expand on this study and identify the underlying immunological mechanisms, we performed a comprehensive profiling of NK cells in chronic HBV infection. METHODS: Peripheral blood from untreated chronic HBV patients was used to analyze phenotypic markers, as well as cytokine production and cytoxicity of NK cells...
January 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28092796/global-open-data-management-in-metabolomics
#13
REVIEW
Kenneth Haug, Reza M Salek, Christoph Steinbeck
Chemical Biology employs chemical synthesis, analytical chemistry and other tools to study biological systems. Recent advances in both molecular biology such as next generation sequencing (NGS) have led to unprecedented insights towards the evolution of organisms' biochemical repertoires. Because of the specific data sharing culture in Genomics, genomes from all kingdoms of life become readily available for further analysis by other researchers. While the genome expresses the potential of an organism to adapt to external influences, the Metabolome presents a molecular phenotype that allows us to asses the external influences under which an organism exists and develops in a dynamic way...
January 13, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28092408/network-structure-and-local-adaptation-in-coevolving-bacteria-phage-interactions
#14
James Gurney, Lafi Aldakak, Alex Betts, Claire Gougat-Barbera, Timothée Poisot, Oliver Kaltz, Michael E Hochberg
Numerous theoretical and experimental studies have investigated antagonistic coevolution between parasites and their hosts. Although experimental tests of theory from a range of biological systems are largely concordant regarding the influence of several driving processes, we know little as to how mechanisms acting at the smallest scales (individual molecular and phenotypic changes) may result in the emergence of structures at larger scales, such as coevolutionary dynamics and local adaptation. We capitalized on methods commonly employed in community ecology to quantify how the structure of community interaction matrices, so called 'bipartite networks', reflected observed coevolutionary dynamics, and how phages from these communities may or may not have adapted locally to their bacterial hosts...
January 16, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28089747/metabolic-engineering-of-a-diazotrophic-bacterium-improves-ammonium-release-and-biofertilization-of-plants-and-microalgae
#15
Rafael Ambrosio, Juan Cesar Federico Ortiz-Marquez, Leonardo Curatti
The biological nitrogen fixation carried out by some Bacteria and Archaea is one of the most attractive alternatives to synthetic nitrogen fertilizers. However, with the exception of the symbiotic rhizobia-legumes system, progress towards a more extensive realization of this goal has been slow. In this study we manipulated the endogenous regulation of both nitrogen fixation and assimilation in the aerobic bacterium Azotobacter vinelandii. Substituting an exogenously inducible promoter for the native promoter of glutamine synthetase produced conditional lethal mutant strains unable to grow diazotrophically in the absence of the inducer...
January 9, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28089652/hippocampal-prefrontal-connectivity-as-a-translational-phenotype-for-schizophrenia
#16
REVIEW
Florian Bähner, Andreas Meyer-Lindenberg
Finding novel biological targets in psychiatry has been difficult, partly because current diagnostic categories are not defined by pathophysiology and difficult to model in animals. The study of species-conserved systems-level mechanisms implicated in psychiatric disease could be a promising strategy to address some of these difficulties. Altered hippocampal-prefrontal (HC-PFC) connectivity during working memory (WM) processing is a candidate for such a translational phenotype as it has been repeatedly associated with impaired cognition in schizophrenia patients and animal models for psychiatric risk factors...
January 12, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28087837/off-target-effects-of-neuroleptics-and-antidepressants-on-saccharomyces-cerevisiae
#17
M Caldara, S Graziano, M Gullì, S Cadonici, Nelson Marmiroli
Over the past years, the use of antidepressants and neuroleptics has steadily increased. Although incredibly useful to treat disorders like depression, schizophrenia, epilepsy, or mental retardation, these drugs display many side effects. Toxicogenomic studies aim to limit this problem by trying to identify cellular targets and off-targets of medical compounds. The baker yeast Saccharomyces cerevisiae has been shown to be a key player in this approach, as it represents an incredible toolbox for the dissection of complex biological processes...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087486/enhanced-articular-cartilage-by-human-mesenchymal-stem-cells-in-enzymatically-mediated-transiently-rgds-functionalized-collagen-mimetic-hydrogels
#18
Paresh A Parmar, Jean-Philippe St-Pierre, Lesley W Chow, Christopher D Spicer, Violet Stoichevska, Yong Y Peng, Jerome A Werkmeister, John A M Ramshaw, Molly M Stevens
: Recapitulation of the articular cartilage microenvironment for regenerative medicine applications faces significant challenges due to the complex and dynamic biochemical and biomechanical nature of native tissue. Towards the goal of biomaterial designs that enable the temporal presentation of bioactive sequences, recombinant bacterial collagens such as Streptococcal collagen-like 2 (Scl2) proteins can be employed to incorporate multiple specific bioactive and biodegradable peptide motifs into a single construct...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28080989/overview-of-chytrid-emergence-and-impacts-on-amphibians
#19
REVIEW
Karen R Lips
Chytridiomycosis is an emerging infectious disease of amphibians that affects over 700 species on all continents where amphibians occur. The amphibian-chytridiomycosis system is complex, and the response of any amphibian species to chytrid depends on many aspects of the ecology and evolutionary history of the amphibian, the genotype and phenotype of the fungus, and how the biological and physical environment can mediate that interaction. Impacts of chytridiomycosis on amphibians are varied; some species have been driven extinct, populations of others have declined severely, whereas still others have not obviously declined...
December 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28079878/a-complete-workflow-for-high-resolution-spectral-stitching-nanoelectrospray-direct-infusion-mass-spectrometry-based-metabolomics-and-lipidomics
#20
Andrew D Southam, Ralf J M Weber, Jasper Engel, Martin R Jones, Mark R Viant
Metabolomic and lipidomic studies measure and discover metabolic and lipid profiles in biological samples, enabling a better understanding of the metabolism of specific biological phenotypes. Accurate biological interpretations require high analytical reproducibility and sensitivity, and standardized and transparent data processing. Here we describe a complete workflow for nanoelectrospray ionization (nESI) direct-infusion mass spectrometry (DIMS) metabolomics and lipidomics. After metabolite and lipid extraction from tissues and biofluids, samples are directly infused into a high-resolution mass spectrometer (e...
February 2016: Nature Protocols
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