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De Novo

David Jukam, Charles Limouse, Owen K Smith, Viviana I Risca, Jason C Bell, Aaron F Straight
RNA is a fundamental component of chromatin. Noncoding RNAs (ncRNAs) can associate with chromatin to influence gene expression and chromatin state; many also act at long distances from their transcriptional origin. Yet we know almost nothing about the functions or sites of action for most ncRNAs. Current methods to identify sites of RNA interaction with the genome are limited to the study of a single RNA at a time. Here we describe a protocol for ChAR-seq, a strategy to identify all chromatin-associated RNAs and map their DNA contacts genome-wide...
February 20, 2019: Current Protocols in Molecular Biology
Boris Sattarov, Igor I Baskin, Dragos Horvath, Gilles Gérard Marcou, Esben Jannik Bjerrum, Alexandre Varnek
Here we show that Generative Topographic Mapping (GTM) can be used to explore the latent space of the SMILES-based autoencoders and generate focused molecular libraries of interest. We have built a sequence-to-sequence neural network with Bidirectional Long Short-Term Memory layers and trained it on the SMILES strings from ChEMBL23. Very high reconstruction rates of the test set molecules were achieved (>98%), which are comparable to the ones reported in related publications [2,3]. Using GTM, we have visualized the autoencoder latent space on the two-dimensional topographic map...
February 20, 2019: Journal of Chemical Information and Modeling
Marcos Vinicius de Araújo Cavalcanti, Luciane Paula Batista Araújo de Oliveira, Anna Cecília Queiroz de Medeiros, Rafaela Carolini de Oliveira Távora
OBJECTIVES: To identify the habits of life in elderly hypertensive men of the city of Currais Novos/RN; correlate life habits and presence of comorbidities. METHODS: An exploratory and descriptive, quantitative study with a sample of 136 elderly hypertensive patients. Data collection took place from August to October 2016, through the structured interview technique. Descriptive and inferential analysis was performed using the Statistical Package for the Social Sciences 20...
February 18, 2019: Revista Gaúcha de Enfermagem
Lina Marcela Piedrahíta-Rojas, Claudia Juliana Díaz, Kevin Escandón-Vargas
Histoid leprosy is an uncommon form of lepromatous leprosy with distinct clinical, histopathological, immunological, and bacteriological features. This variant usually occurs in multibacillary patients who have irregular or inadequate treatment. Herein, we report a case of de novo histoid leprosy diagnosed in a patient from Cali, Colombia. In endemic areas, histoid leprosy should be in the differential diagnosis of any patient presenting with skin nodules. Early diagnosis and appropriate treatment are recommended for mitigating the impact of histoid leprosy cases, which are important reservoirs of Mycobacterium leprae...
February 14, 2019: Revista da Sociedade Brasileira de Medicina Tropical
Sebastian Vogt, Marc Irqsusi, Hamid Naraghi, Alexander Sattler, Volker Ruppert, Petra Weber, Annika Rhiel, Rabia Ramzan
Induction of Heat Shock Proteins results in cytoprotection. Beneficial effect results from transcription and translational cellular components' involvement that defends metabolism and thus induce ischemic protection of the tissue. Mitochondrial respiration is also involved in stress- induced conditions. It is not a uniform process. Cytochrome c Oxidase (CytOx) representing complex IV of the Electron Transfer Chain (ETC) has a regulatory role for mitochondrial respiratory activity, which is tested in our study after hsp induction...
February 2019: Journal of Thermal Biology
Catherine E Mercado, William F Hartsell, Charles B Simone, Henry K Tsai, Carlos E Vargas, He J Zhu, Randal H Henderson, Jing Zeng, Gary L Larson, Bradford S Hoppe
OBJECTIVE: Thymic malignancies (TM) are rare tumors with long-term survivorship, causing concerns for radiotherapy-related late side effects. Proton therapy (PT) reduces the radiation dose to organs at risk, potentially decreasing long-term toxicities while preserving disease control. We report patterns-of-care and early clinical outcomes after PT for thymoma and thymic carcinoma. METHODS: Between January 2008 and March 2017, 30 patients with TMs enrolled on one of two IRB-approved prospective protocols and received postoperative or definitive PT...
February 20, 2019: Acta Oncologica
Amaury De Barros, Justine Attal, Margaux Roques, Julien Nicolau, Jean-Christophe Sol, Elizabeth Cohen-Jonathan-Moyal, Franck-Emmanuel Roux
PURPOSE: Systematic pre-radiotherapy MRI in patients with newly resected glioblastoma (OMS 2016) sometimes reveals tumor growth in the period between surgery and radiotherapy. We evaluated the relation between early tumor growth and overall survival (OS) with the aim of finding predictors of regrowth. METHODS: Seventy-five patients from 25 to 84 years old (Median age 62 years) with preoperative, immediate postoperative, and preradiotherapy MRI were included. Volumetric measurements were made on each of the three MRI scans and clinical and molecular parameters were collected for each case...
February 19, 2019: Journal of Neuro-oncology
A Picciariello, V Papagni, G Martines, M De Fazio, R Digennaro, D F Altomare
AIM: To evaluate the reason for failure of STARR (stapled transanal rectal resection) operation for obstructed defecation. METHODS: A retrospective study (June 2012-December 2017) was performed using a prospectively maintained database of patients who underwent STARR operation for ODS (obstructed defecation syndrome), complaining of persisting or de novo occurrence of pelvic floor dysfunctions. Postoperative St Mark's and ODS scores were evaluated. A VAS was used to score pelvic pain...
February 19, 2019: International Journal of Colorectal Disease
Yang Liao, Gordon K Smyth, Wei Shi
We present Rsubread, a Bioconductor software package that provides high-performance alignment and read counting functions for RNA-seq reads. Rsubread is based on the successful Subread suite with the added ease-of-use of the R programming environment, creating a matrix of read counts directly as an R object ready for downstream analysis. It integrates read mapping and quantification in a single package and has no software dependencies other than R itself. We demonstrate Rsubread's ability to detect exon-exon junctions de novo and to quantify expression at the level of either genes, exons or exon junctions...
February 20, 2019: Nucleic Acids Research
Christoph Nitsche, Toby Passioura, Paul Varava, Mithun C Mahawaththa, Mila M Leuthold, Christian D Klein, Hiroaki Suga, Gottfried Otting
The Zika virus presents a major public health concern due to severe fetal neurological disorders associated with infections in pregnant women. In addition to vaccine development, the discovery of selective antiviral drugs is essential to combat future epidemic Zika virus outbreaks. The Zika virus NS2B-NS3 protease, which performs replication-critical cleavages of the viral polyprotein, is a promising drug target. We report the first macrocyclic peptide-based inhibitors of the NS2B-NS3 protease, discovered de novo through in vitro display screening of a genetically reprogrammed library including noncanonical residues...
February 14, 2019: ACS Medicinal Chemistry Letters
Katie A O'Brien, R Andrew Atkinson, Larissa Richardson, Albert Koulman, Andrew J Murray, Stephen D R Harridge, Daniel S Martin, Denny Z H Levett, Kay Mitchell, Monty G Mythen, Hugh E Montgomery, Michael P W Grocott, Julian L Griffin, Lindsay M Edwards
At high altitude oxygen delivery to the tissues is impaired leading to oxygen insufficiency (hypoxia). Acclimatisation requires adjustment to tissue metabolism, the details of which remain incompletely understood. Here, metabolic responses to progressive environmental hypoxia were assessed through metabolomic and lipidomic profiling of human plasma taken from 198 human participants before and during an ascent to Everest Base Camp (5,300 m). Aqueous and lipid fractions of plasma were separated and analysed using proton (1 H)-nuclear magnetic resonance spectroscopy and direct infusion mass spectrometry, respectively...
February 19, 2019: Scientific Reports
Chuang Zhou, Jiazheng Jin, Changjun Peng, Qinchao Wen, Guannan Wang, Weideng Wei, Xue Jiang, Megan Price, Kai Cui, Yang Meng, Zhaobin Song, Jing Li, Xiuyue Zhang, Zhenxin Fan, Bisong Yue
Raptors are carnivorous birds including accipitrids (Accipitridae, Accipitriformes) and owls (Strigiformes), which are diurnal and nocturnal, respectively. To examine the evolutionary basis of adaptations to different light cycles and hunting behavior between accipitrids and owls, we de novo assembled besra (Accipiter virgatus, Accipitridae, Accipitriformes) and oriental scops owl (Otus sunia, Strigidae, Strigiformes) draft genomes. Comparative genomics demonstrated four PSGs (positively selected genes) (XRCC5, PRIMPOL, MDM2, and SIRT1) related to the response to ultraviolet (UV) radiation in accipitrids, and one PSG (ALCAM) associated with retina development in owls, which was consistent with their respective diurnal/nocturnal predatory lifestyles...
February 19, 2019: Scientific Reports
Kirk D Wyatt, Lea M Coon, Dawn N Rusk, Vilmarie Rodriguez, Deepti M Warad
The development of factor VIII inhibitors remains a significant clinical challenge in the management of hemophilia A. We present a patient of mixed ethnicity with severe hemophilia A who was found to have a F8 gene hemizygous c.5815G>T mutation resulting in an Ala1939Ser substitution (Ala1920Ser in legacy nomenclature) and possible splice site change that has been reported in only 1 patient previously. He developed an inhibitor shortly after starting replacement recombinant factor VIII (Advate®; Baxalta, Bannockburn, IL, USA) and was successfully treated with immune tolerance therapy...
February 15, 2019: Acta Haematologica
Karthik Rajasekar, Shuangxi Ji, Rachael J Coulthard, Jon P Ride, Gillian L Reynolds, Peter J Winn, Michael P Wheeler, Eva I Hyde, Lorna J Smith
SPH proteins are a large family of small, disulphide-bonded, secreted proteins, initially found in the self-incompatibility response in the field poppy (Papaver rhoeas) , but now known to be widely distributed in plants, many containing multiple members of this protein family. Using the Origami strain of E. coli , we expressed one member of this family, SPH15 from Arabidopsis thaliana , as a folded thioredoxin-fusion protein and purified it from the cytosol. The fusion protein was cleaved and characterised by analytical ultracentrifugation, circular dichroism, and NMR spectroscopy...
February 19, 2019: Biochemical Journal
Chompunut Lumsangkul, Hsin-I Chiang, Neng-Wen Lo, Yang-Kwang Fan, Jyh-Cherng Ju
A teratogenic agent or teratogen can disturb the development of an embryo or a fetus. Fumonisin B₁ (FB₁), produced by Fusarium verticillioides and F. proliferatum , is among the most commonly seen mycotoxins and contaminants from stale maize and other farm products. It may cause physical or functional defects in embryos or fetuses, if the pregnant animal is exposed to mycotoxin FB₁. Due to its high similarity in chemical structure with lipid sphinganine (Sa) and sphingosine (So), the primary component of sphingolipids, FB₁ plays a role in competitively inhibiting Sa and So, which are key enzymes in de novo ceramide synthase in the sphingolipid biosynthetic pathway...
February 13, 2019: Toxins
Gwo-Chin Ma, Wen-Hsiang Lin, Chung-Er Huang, Ting-Yu Chang, Jia-Yun Liu, Ya-Jun Yang, Mei-Hui Lee, Wan-Ju Wu, Yun-Shiang Chang, Ming Chen
Circulating fetal cells (CFCs) in maternal blood are rare but have a strong potential to be the target for noninvasive prenatal diagnosis (NIPD). "Cell RevealTM system" is a silicon-based microfluidic platform capable to capture rare cell populations in human circulation. The platform is recently optimized to enhance the capture efficiency and system automation. In this study, spiking tests of SK-BR-3 breast cancer cells were used for the evaluation of capture efficiency. Then, peripheral bloods from 14 pregnant women whose fetuses have evidenced non-maternal genomic markers (e...
February 17, 2019: Micromachines
Katleen Peymen, Jan Watteyne, Charline Borghgraef, Elien Van Sinay, Isabel Beets, Liliane Schoofs
Aversive learning and memories are crucial for animals to avoid previously encountered stressful stimuli and thereby increase their chance of survival. Neuropeptides are essential signaling molecules in the brain and are emerging as important modulators of learned behaviors, but their precise role is not well understood. Here, we show that neuropeptides of the evolutionarily conserved MyoInhibitory Peptide (MIP)-family modify salt chemotaxis behavior in Caenorhabditis elegans according to previous experience...
February 2019: PLoS Genetics
Ivar Grytten, Knut D Rand, Alexander J Nederbragt, Geir O Storvik, Ingrid K Glad, Geir K Sandve
Graph-based representations are considered to be the future for reference genomes, as they allow integrated representation of the steadily increasing data on individual variation. Currently available tools allow de novo assembly of graph-based reference genomes, alignment of new read sets to the graph representation as well as certain analyses like variant calling and haplotyping. We here present a first method for calling ChIP-Seq peaks on read data aligned to a graph-based reference genome. The method is a graph generalization of the peak caller MACS2, and is implemented in an open source tool, Graph Peak Caller...
February 19, 2019: PLoS Computational Biology
Daniel Rüdiger, Sascha Young Kupke, Tanja Laske, Pawel Zmora, Udo Reichl
Influenza A viruses (IAV) are commonly used to infect animal cell cultures for research purposes and vaccine production. Their replication is influenced strongly by the multiplicity of infection (MOI), which ranges over several orders of magnitude depending on the respective application. So far, mathematical models of IAV replication have paid little attention to the impact of the MOI on infection dynamics and virus yields. To address this issue, we extended an existing model of IAV replication in adherent MDCK cells with kinetics that explicitly consider the time point of cell infection...
February 19, 2019: PLoS Computational Biology
Minna Pekkinen, Paulien A Terhal, Lorenzo D Botto, Petra Henning, Riikka E Mäkitie, Paul Roschger, Amrita Jain, Matthijs Kol, Matti A Kjellberg, Eleftherios P Paschalis, Koen van Gassen, Mary Murray, Pinar Bayrak-Toydemir, Maria K Magnusson, Judith Jans, Mehran Kausar, John C Carey, Pentti Somerharju, Ulf H Lerner, Olkkonen M Vesa, Klaus Klaushofer, Joost Cm Holthuis, Outi Mäkitie
Mechanisms leading to osteoporosis are incompletely understood. Genetic disorders with skeletal fragility provide insight into metabolic pathways contributing to bone strength. We evaluated six families with rare skeletal phenotypes and osteoporosis by next-generation sequencing. In all families we identified a heterozygous variant in SGMS2, a gene prominently expressed in cortical bone and encoding the plasma membrane-resident sphingomyelin synthase SMS2. Four unrelated families shared the same nonsense variant c...
February 19, 2019: JCI Insight
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