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https://www.readbyqxmd.com/read/28542189/mir-277-4989-regulate-transcriptional-landscape-during-juvenile-to-adult-transition-in-the-parasitic-helminth-schistosoma-mansoni
#1
Anna V Protasio, Stijn van Dongen, Julie Collins, Leonor Quintais, Diogo M Ribeiro, Florian Sessler, Martin Hunt, Gabriel Rinaldi, James J Collins, Anton J Enright, Matthew Berriman
Schistosomes are parasitic helminths that cause schistosomiasis, a disease affecting circa 200 million people, primarily in underprivileged regions of the world. Schistosoma mansoni is the most experimentally tractable schistosome species due to its ease of propagation in the laboratory and the high quality of its genome assembly and annotation. Although there is growing interest in microRNAs (miRNAs) in trematodes, little is known about the role these molecules play in the context of developmental processes...
May 23, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28538159/long-term-stochastic-editing-of-regenerative-anatomy-via-targeting-endogenous-bioelectric-gradients
#2
Fallon Durant, Junji Morokuma, Christopher Fields, Katherine Williams, Dany Spencer Adams, Michael Levin
We show that regenerating planarians' normal anterior-posterior pattern can be permanently rewritten by a brief perturbation of endogenous bioelectrical networks. Temporary modulation of regenerative bioelectric dynamics in amputated trunk fragments of planaria stochastically results in a constant ratio of regenerates with two heads to regenerates with normal morphology. Remarkably, this is shown to be due not to partial penetrance of treatment, but a profound yet hidden alteration to the animals' patterning circuitry...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28498102/chimeric-origins-of-ochrophytes-and-haptophytes-revealed-through-an-ancient-plastid-proteome
#3
Richard G Dorrell, Gillian Gile, Giselle McCallum, Raphaël Méheust, Eric P Bapteste, Christen M Klinger, Loraine Brillet-Guéguen, Katalina D Freeman, Daniel J Richter, Chris Bowler
Plastids are supported by a wide range of proteins encoded within the nucleus and imported from the cytoplasm. These plastid-targeted proteins may originate from the endosymbiont, the host, or other sources entirely. Here, we identify and characterise 770 plastid-targeted proteins that are conserved across the ochrophytes, a major group of algae including diatoms, pelagophytes and kelps, that possess plastids derived from red algae. We show that the ancestral ochrophyte plastid proteome was an evolutionary chimera, with 25% of its phylogenetically tractable proteins deriving from green algae...
May 12, 2017: ELife
https://www.readbyqxmd.com/read/28489574/targeting-neurokinin-3-receptor-a-novel-anti-angiogenesis-strategy-for-cancer-treatment
#4
Ting Wang, Siwei Chen, Shihui Wang, Liang Shi, Chenggong Wang, Jingxin Zhang, Yanfeng Gao, Guodong Li, Yuanming Qi, Xiuli An, Lixiang Chen
Angiogenesis is essential for tumor growth and metastasis, controlling angiogenesis is a promising strategy in cancer treatment. However, thus farther severe side effects of anti-angiogenic drugs have been rather demonstrated, stimulating interest in seeking novel targets of anti-angiogenesis. Neurokinin receptors, also known as tachykinin receptors, are usually considered as drug targets due to diverse physiological functions and their tractability. Although Neurokinin B, the selective natural agonist of neurokinin-3 receptor, have been shown to exhibit anti-angiogenesis activity, the effect and mechanism of neurokinin-3 receptor-mediated angiogenesis still remains unclear...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488276/cntnap2-is-a-direct-foxp2-target-in-vitro-and-in-vivo-in-zebra-finches-complex-regulation-by-age-and-activity
#5
Iris Adam, Ezequiel Mendoza, Ursula Kobalz, Sandra Wohlgemuth, Constance Scharff
Mutations of FOXP2 are associated with altered brain structure, including the striatal part of the basal ganglia, and cause a severe speech and language disorder. Songbirds serve as a tractable neurobiological model for speech and language research. Experimental downregulation of FoxP2 in zebra finch Area X, a nucleus of the striatal song control circuitry, affects synaptic transmission and spine densities. It also renders song learning and production inaccurate and imprecise, similar to the speech impairment of patients carrying FOXP2 mutations...
May 10, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28487472/bioinformatics-in-translational-drug-discovery
#6
Sarah K Wooller, Graeme Benstead-Hume, Xiangrong Chen, Yusuf Ali, Frances Pearl
Bioinformatics approaches are becoming ever more essential in translational drug discovery both in academia and within the pharmaceutical industry. Computational exploitation of the increasing volumes of data generated at all phases of drug discovery is enabling key challenges of the process to be addressed. Here we highlight some of the areas in which bioinformatics resources and methods are being developed to support drug discovery. These include the creation of large data warehouses, bioinformatics algorithms to analyse 'big data' that identify novel drug targets and/or biomarkers, programs to assess the tractability of targets, and the prediction of repositioning opportunities that use licensed drugs to treat additional indications...
May 9, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28486691/combined-kinase-inhibitors-of-mek1-2-and-either-pi3k-or-pdgfr-are-efficacious-in-intracranial-triple-negative-breast-cancer
#7
Amanda E D Van Swearingen, Maria J Sambade, Marni B Siegel, Shivani Sud, Robert S McNeill, Samantha M Bevill, Xin Chen, Ryan E Bash, Louisa Mounsey, Brian T Golitz, Charlene Santos, Allison Deal, Joel S Parker, Naim Rashid, C Ryan Miller, Gary L Johnson, Carey K Anders
Background: Triple-negative breast cancer (TNBC), lacking expression of hormone and human epidermal growth factor receptor 2 receptors, is an aggressive subtype that frequently metastasizes to the brain and has no FDA-approved systemic therapies. Previous literature demonstrates mitogen-activated protein kinase kinase (MEK) pathway activation in TNBC brain metastases. Thus, we aimed to discover rational combinatorial therapies with MEK inhibition, hypothesizing that co-inhibition using clinically available brain-penetrant inhibitors would improve survival in preclinical models of TNBC brain metastases...
May 9, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28485964/potent-pan-raf-and-rtks-inhibitors-based-on-cyclopropyl-formamide-fragment-overcome-resistance
#8
Yanmin Zhang, Lu Wang, Qing Zhang, Gaoyuan Zhu, Zhimin Zhang, Zhou Xiang, Yadong Chen, Tao Lu, Weifang Tang
While selective BRafV600E inhibitors have been proven effective clinically, acquired resistance rapidly develops through reactivation of MAPK pathway. Simultaneous targeting of multiple nodes in the pathway offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Replacement pyridine group of Y-1 by cyclopropyl formamide group afforded I-01 as a novel multi-targeted kinase inhibitor template. I-01 displayed enzyme potency against Pan-Raf and RTKs. Based on the binding mode of I-01, analogues I-02~I-18 were designed and synthesized...
May 9, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28476773/genome-stability-in-engineered-strains-of-the-extremely-thermophilic-lignocellulose-degrading-bacterium-caldicellulosiruptor-bescii
#9
Amanda M Williams-Rhaesa, Farris L Poole, Jessica T Dinsmore, Gina L Lipscomb, Gabriel M Rubinstein, Israel M Scott, Jonathan M Conway, Laura L Lee, Piyum A Khatibi, Robert M Kelly, Michael W W Adams
Caldicellulosiruptor bescii is the most thermophilic cellulose-degrader known and is of great interest because of its ability to degrade non-pretreated plant biomass. For biotechnological applications, an efficient genetic system is required to engineer it to convert plant biomass into desired products. To date, two different genetically-tractable lineages of C. bescii strains have been generated. The first (JWCB005) is based on a random deletion within the pyrimidine biosynthesis genes pyrFA, and the second (MACB1018) is based on the targeted deletion of pyrE making use of a kanamycin resistance marker...
May 5, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28471759/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#10
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts from June 2 to 3, 2016, in Bethesda, Maryland, to develop NHLBI recommendations aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MCS devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
April 29, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/28470611/expression-of-prokaryotic-integral-membrane-proteins-in-e-coli
#11
James D Love
Production of prokaryotic membrane proteins for structural and functional studies in E. coli can be parallelized and miniaturized. All stages from cloning, expression, purification to detergent selection can be investigated using high-throughput techniques to rapidly and economically find tractable targets.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28467046/a-targeted-mass-spectrometry-assay-for-detection-of-hiv-gag-protein-following-induction-of-latent-viral-reservoirs
#12
Daniela Schlatzer, Aiman A Haqqani, Xiaolin Li, Curtis Dobrowolski, Mark R Chance, John C Tilton
During early infection, HIV-1 establishes a reservoir of latently infected cells that persist during antiretroviral therapy. These reservoirs are considered the primary obstacle to eradicating HIV-1 from patients, and multiple strategies are being investigated to eliminate latently infected cells. Measuring the reservoir size using an affordable and scalable assay is critical as these approaches move into clinical trials: the current "gold-standard" viral outgrowth assay is costly, labor-intensive, and requires large numbers of cells...
May 3, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28458126/genetic-susceptibility-to-neuroblastoma
#13
REVIEW
Vanessa P Tolbert, Grace E Coggins, John M Maris
Until recently, the genetic basis of neuroblastoma, a heterogeneous neoplasm arising from the developing sympathetic nervous system, remained undefined. The discovery of gain-of-function mutations in the ALK receptor tyrosine kinase gene as the major cause of familial neuroblastoma led to the discovery of identical somatic mutations and rapid advancement of ALK as a tractable therapeutic target. Inactivating mutations in a master regulator of neural crest development, PHOX2B, have also been identified in a subset of familial neuroblastomas...
April 27, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28435104/drosophila-pink1-and-parkin-loss-of-function-mutants-display-a-range-of-non-motor-parkinson-s-disease-phenotypes
#14
Hannah Julienne, Edgar Buhl, David S Leslie, James J L Hodge
Parkinson's disease (PD) is more commonly associated with its motor symptoms and the related degeneration of dopamine (DA) neurons. However, it is becoming increasingly clear that PD patients also display a wide range of non-motor symptoms, including memory deficits and disruptions of their sleep-wake cycles. These have a large impact on their quality of life, and often precede the onset of motor symptoms, but their etiology is poorly understood. The fruit fly Drosophila has already been successfully used to model PD, and has been used extensively to study relevant non-motor behaviours in other contexts, but little attention has yet been paid to modelling non-motor symptoms of PD in this genetically tractable organism...
April 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28433665/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#15
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016, in Bethesda, Maryland, to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
May 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28428271/master-transcriptional-regulators-in-cancer-discovery-via-reverse-engineering-approaches-and-subsequent-validation
#16
REVIEW
Bruce Moran, Arman Rahman, Katja Palonen, Fiona T Lanigan, William M Gallagher
Reverse engineering of transcriptional networks using gene expression data enables identification of genes that underpin the development and progression of different cancers. Methods to this end have been available for over a decade and, with a critical mass of transcriptomic data in the oncology arena having been reached, they are ever more applicable. Extensive and complex networks can be distilled into a small set of key master transcriptional regulators (MTR), genes that are very highly connected and have been shown to be involved in processes of known importance in disease...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28418626/degradation-of-the-baf-complex-factor-brd9-by-heterobifunctional-ligands
#17
David Remillard, Dennis L Buckley, Joshiawa Paulk, Gerard L Brien, Matthew Sonnett, Hyuk-Soo Seo, Shiva Dastjerdi, Martin Wühr, Sirano Dhe-Paganon, Scott A Armstrong, James E Bradner
The bromodomain-containing protein BRD9, a subunit of the human BAF (SWI/SNF) nucleosome remodeling complex, has emerged as an attractive therapeutic target in cancer. Despite the development of chemical probes targeting the BRD9 bromodomain, there is a limited understanding of BRD9 function beyond acetyl-lysine recognition. We have therefore created the first BRD9-directed chemical degraders, through iterative design and testing of heterobifunctional ligands that bridge the BRD9 bromodomain and the cereblon E3 ubiquitin ligase complex...
May 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28406902/bicaudal-c-mutation-causes-myc-and-tor-pathway-up-regulation-and-polycystic-kidney-disease-like-phenotypes-in-drosophila
#18
Chiara Gamberi, David R Hipfner, Marie Trudel, William D Lubell
Progressive cystic kidney degeneration underlies diverse renal diseases, including the most common cause of kidney failure, autosomal dominant Polycystic Kidney Disease (PKD). Genetic analyses of patients and animal models have identified several key drivers of this disease. The precise molecular and cellular changes underlying cystogenesis remain, however, elusive. Drosophila mutants lacking the translational regulator Bicaudal C (BicC, the fly ortholog of vertebrate BICC1 implicated in renal cystogenesis) exhibited progressive cystic degeneration of the renal tubules (so called "Malpighian" tubules) and reduced renal function...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28404203/antifibrotics-in-chronic-liver-disease-tractable-targets-and-translational-challenges
#19
REVIEW
Prakash Ramachandran, Neil C Henderson
Chronic liver disease prevalence is increasing globally. Iterative liver damage, secondary to any cause of liver injury, results in progressive fibrosis, disrupted hepatic architecture, and aberrant regeneration, which are defining characteristics of liver cirrhosis. Liver transplantation is an effective treatment for end-stage liver disease; however, demand greatly outweighs donor organ supply, and in many parts of the world liver transplantation is unavailable. Hence, effective antifibrotic therapies are urgently required...
December 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28388102/a-new-efficient-method-for-the-calculation-of-interior-eigenpairs-and-its-application-to-vibrational-structure-problems
#20
Taras Petrenko, Guntram Rauhut
Vibrational configuration interaction theory is a common method for calculating vibrational levels and associated IR and Raman spectra of small and medium-sized molecules. When combined with appropriate configuration selection procedures, the method allows the treatment of configuration spaces with up to 10(10) configurations. In general, this approach pursues the construction of the eigenstates with significant contributions of physically relevant configurations. The corresponding eigenfunctions are evaluated in the subspace of selected configurations...
March 28, 2017: Journal of Chemical Physics
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