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integrative approach

Benjamin M Vincent, Daniel F Tardiff, Jeff S Piotrowski, Rebecca Aron, Matthew C Lucas, Chee Yeun Chung, Helene Bacherman, YiQun Chen, Michelle Pires, Radha Subramaniam, Dimple B Doshi, Heather Sadlish, Waseem K Raja, Eric J Solís, Vikram Khurana, Bertrand Le Bourdonnec, Robert H Scannevin, Kenneth J Rhodes
The lack of disease-modifying treatments for neurodegenerative disease stems in part from our rudimentary understanding of disease mechanisms and the paucity of targets for therapeutic intervention. Here we used an integrated discovery paradigm to identify a new therapeutic target for diseases caused by α-synuclein (α-syn), a small lipid-binding protein that misfolds and aggregates in Parkinson's disease and other disorders. Using unbiased phenotypic screening, we identified a series of compounds that were cytoprotective against α-syn-mediated toxicity by inhibiting the highly conserved enzyme stearoyl-CoA desaturase (SCD)...
December 4, 2018: Cell Reports
Cheng-Cheng Liu, Li-Da Zhang, Wei-Qiang Chen, Fan Yang
We model the newly synthesized magic-angle-twisted bilayer graphene superconductor with two p_{x,y}-like Wannier orbitals on the superstructure honeycomb lattice, where the hopping integrals are constructed via the Slater-Koster formulism by symmetry analysis. The characteristics exhibited in this simple model are well consistent with both the rigorous calculations and experiment observations. A van Hove singularity and Fermi-surface (FS) nesting are found in the doping levels relevant to the correlated insulator and unconventional superconductivity revealed experimentally, based on which we identify the two phases as weak-coupling FS instabilities...
November 23, 2018: Physical Review Letters
Akram Hernández-Vásquez, Carlos Rojas-Roque, Marilina Santero, Francisco Javier Prado-Galbarro, Diego Rosselli
OBJECTIVES: . To estimate out-of-pocket spending on health (GBS) and identify its associated factors in Peruvian older adults. MATERIALS AND METHODS.: Analytical cross-sectional study of the National Household Survey on Living Conditions and Poverty (ENAHO) 2017. Older adults were considered to be all individuals aged 60 and over and the GBS was considered the main study variable. Prevalence ratios (PR) and adjusted prevalence ratios (PRa) were estimated for each of the factors associated with GBS...
July 2018: Revista Peruana de Medicina Experimental y Salud Pública
Luciana Netto, Kênia Lara Silva
OBJECTIVE: To analyze the insertion in reflective professional practice as a strategy for the development of competencies for health promotion in nurses' training. METHOD: Case study, qualitative approach anchored in the theoretical-methodological framework of the Marxist dialectic. Data were obtained from documents, interviews with graduated students and focus groups with teachers from a nursing higher education institution located in the state of Minas Gerais, Brazil...
December 3, 2018: Revista da Escola de Enfermagem da U S P
Indu Warrier, Nikhil Ram-Mohan, Zeyu Zhu, Ariana Hazery, Haley Echlin, Jason Rosch, Michelle M Meyer, Tim van Opijnen
Efficient and highly organized regulation of transcription is fundamental to an organism's ability to survive, proliferate, and quickly respond to its environment. Therefore, precise mapping of transcriptional units and understanding their regulation is crucial to determining how pathogenic bacteria cause disease and how they may be inhibited. In this study, we map the transcriptional landscape of the bacterial pathogen Streptococcus pneumoniae TIGR4 by applying a combination of high-throughput RNA-sequencing techniques...
December 5, 2018: PLoS Pathogens
Joel Pel, Amy Leung, Wendy W Y Choi, Milenko Despotovic, W Lloyd Ung, Gosuke Shibahara, Laura Gelinas, Andre Marziali
Targeted Next Generation Sequencing (NGS) is being adopted increasingly broadly in many research, commercial and clinical settings. Currently used target capture methods, however, typically require complex and lengthy (sometimes multi-day) workflows that complicates their use in certain applications. In addition, small panels for high sequencing depth applications such as liquid biopsy typically have low on-target rates, resulting in unnecessarily high sequencing cost. We have developed a novel targeted sequencing library preparation method, named Linked Target Capture (LTC), which replaces typical multi-day target capture workflows with a single-day, combined 'target-capture-PCR' workflow...
2018: PloS One
Ajay Ravindranathan, Beth Cimini, Morgan E Diolaiti, Bradley A Stohr
The telomerase enzyme enables unlimited proliferation of most human cancer cells by elongating telomeres and preventing replicative senescence. Despite the critical importance of telomerase in cancer biology, challenges detecting telomerase activity and expression in individual cells have hindered the ability to study patterns of telomerase expression and function across heterogeneous cell populations. While sensitive assays to ascertain telomerase expression and function exist, these approaches have proven difficult to implement at the single cell level...
2018: PloS One
Panagiotis C Petris, Stefanos D Anogiannakis, Panagiotis-Nikolaos Tzounis, Doros N Theodorou
A complete thermodynamic analysis of mixtures consisting of molecules with complex chemical constitution can be rather demanding. Kirkwood-Buff theory of solutions allows the estimation of thermodynamic properties which cannot be directly extracted from atomistic simulations, such as the Gibbs energy of mixing (Δmix G). In this work we perform molecular dynamics simulations of n-hexane/ethanol binary mixtures in the liquid state under two temperature-pressure conditions and at various mole fractions. Based on the recently published methodology of Galata et al...
December 5, 2018: Journal of Physical Chemistry. B
Lucia Rivera Lara, Hans Adrian Püttgen
PURPOSE OF REVIEW: This article focuses on the multiple neuromonitoring devices that can be used to collect bedside data in the neurocritical care unit and the methodology to integrate them into a multimodality monitoring system. The article describes how to apply the collected data to appreciate the physiologic changes and develop therapeutic approaches to prevent secondary injury. RECENT FINDINGS: The neurologic examination has served as the primary monitor for secondary brain injury in patients admitted to the neurocritical care unit...
December 2018: Continuum: Lifelong Learning in Neurology
Hao Li, Haochen Xu, Hongyan Wen, Tianlong Liu, Yingying Sun, Ning Xiao, Congxia Bai, Jing Ge, Xuliang Wang, Li Song, Yan Song, Yinhui Zhang, Jingzhou Chen
Hypertensive intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease with no effective treatment. Lysyl hydroxylase 3 (LH3) is essential for collagen IV intermolecular crosslinking and stabilization. Deficiency in LH3 affects the assembly and secretion of collagen IV and basement membrane (BM) integrity of vessels. Here, we investigated whether LH3 has significant implications for disease progression and therapeutic intervention. Spontaneous hypertensive ICH of mice was induced by angiotensin II and L-NAME treatment...
December 5, 2018: Journal of Cerebral Blood Flow and Metabolism
Kamila Dvořáková, Mark T Greenberg, Robert W Roeser
In this paper, we aim to integrate the current conceptual approaches to stress and coping processes during the college transition with the potential role of mindfulness and compassion skills on students' well-being and development. First, we provide an overview of the issues and challenges emerging adults are facing during the transition to college, drawing on the revised version of the transactional stress model by Lazarus and Folkman (1984). Second, we introduce a conceptual model of adaptive stress and coping processes enhanced by mindfulness and compassion (MC) skills to positively impact the appraisal and coping resources and emerging adults' mental health...
December 5, 2018: Stress and Health: Journal of the International Society for the Investigation of Stress
Michael J O'Connell, Eric F Lock
Several recent methods address the dimension reduction and decomposition of linked high-content data matrices. Typically, these methods consider one dimension, rows or columns, that is shared among the matrices. This shared dimension may represent common features measured for different sample sets (horizontal integration) or a common sample set with features from different platforms (vertical integration). We introduce an approach for simultaneous horizontal and vertical integration, Linked Matrix Factorization (LMF), for the general case where some matrices share rows (e...
December 5, 2018: Biometrics
Lin Zhang, Yong Hu, Shuquan Chang, Ying-Shi Guan, Shenqiang Ren
Multicomponent crystalline heterostructures are a powerful approach to integrate different functional materials into the ordered structures. Here we describe three-dimensional spherical assembly of binary organic solids that consist of electron donor and acceptor molecules. A mechanistic study of heterostructure formation reveals that the dewetting and drying-mediated assembly processes are responsible for the spherical crystallite formation. The assembled spherical heterostructures are highly tunable, crystalline and chemically stable, exhibiting phase separation controlled optoelectronic behavior...
December 5, 2018: Nanoscale
Anita Chung, Aileen Collier, Merryn Gott
BACKGROUND: Public health approaches to palliative care prioritise community-focused initiatives to support people with palliative care needs and their families. The nature and extent of these initiatives have not previously been reported. AIM: To identify community-led and/or focused initiatives that have been developed to support family carers of people with palliative care needs and for which evaluation information is reported in the empirical literature. DESIGN: An integrative study design was undertaken using systematic methods...
December 5, 2018: Palliative Medicine
Matthew Jian-Qiao Peng, Hai-Yan Chen, XiangYang Ju, Yong Hu, Ashraf Ayoub, Balvinder Khambay, ZiQing Liu, Bo Bai
BACKGROUND: Little is known about how biomechanics govern the five fixtures such as DHS, MLS, DHS + LS, LP, and HA are accepted as common therapeutic techniques. AIMS AND OBJECTIVES: A series of numerical models for a femoral neck fracture of Pauwels-I will be constructed by innovative approach of finite element in order to determine the most optimized option in comparison with biomechanical performance. METHOD: Twenty sets of computer tomography scanned femora were imported onto Mimics to extract 3 D models; these specimens were transferred to Geomagic-Studio for a simulative osteotomy and kyrtograph; then, they underwent UG to fit simulative solid models; 5 sorts of fixture were then expressed by Pro-Engineer virtually...
December 5, 2018: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
Vidya Ramakrishnan, Donald E Mager
The heterogeneous polyclonal nature of multiple myeloma complicates the identification of protein biomarkers predictive of drug response. In this study, a pharmacodynamic systems modeling approach was used to link in vitro bortezomib exposure and myeloma cell death. The exposure-response was integrated through a network of important protein biomarker dynamics activated by bortezomib in four myeloma cell lines. The pharmacodynamic models reasonably characterized the protein and myeloma cell dynamics simultaneously following bortezomib (20 nM) treatment...
December 4, 2018: CPT: Pharmacometrics & Systems Pharmacology
Christian Bortolini, Tadas Kartanas, Davor Copic, Itzel Condado Morales, Yuewen Zhang, Pavan K Challa, Quentin Peter, Tamás Jávorfi, Rohanah Hussain, Mingdong Dong, Giuliano Siligardi, Tuomas P J Knowles, Jérôme Charmet
Circular dichroism spectroscopy has become a powerful tool to characterise proteins and other biomolecules. For heterogeneous samples such as those present for interacting proteins, typically only average spectroscopic features can be resolved. Here we overcome this limitation by using free-flow microfluidic size separation in-line with synchrotron radiation circular dichroism to resolve the secondary structure of each component of a model protein mixture containing monomers and fibrils. To enable this objective, we have integrated far-UV compatible measurement chambers into PDMS-based microfluidic devices...
December 5, 2018: Lab on a Chip
Hao-Yang Mi, Xin Jing, Zhiyong Cai, Yuejun Liu, Lih-Sheng Turng, Shaoqin Gong
Boosting power generation performance while employing economical and biocompatible materials is an ongoing direction in the field of triboelectric nanogenerators (TENGs). Here, highly porous, biocompatible, cellulose nanofibril (CNF) composite-based TENGs are developed through an environmentally friendly freeze-drying approach. High tribopositivity materials, including silica fiber, human hair, and rabbit fur, are used as fillers in composite TENG fabrication for the first time to enhance the triboelectric output performance...
December 5, 2018: Nanoscale
Artem Lysenko, Alok Sharma, Keith A Boroevich, Tatsuhiko Tsunoda
Recent trends in drug development have been marked by diminishing returns caused by the escalating costs and falling rates of new drug approval. Unacceptable drug toxicity is a substantial cause of drug failure during clinical trials and the leading cause of drug withdraws after release to the market. Computational methods capable of predicting these failures can reduce the waste of resources and time devoted to the investigation of compounds that ultimately fail. We propose an original machine learning method that leverages identity of drug targets and off-targets, functional impact score computed from Gene Ontology annotations, and biological network data to predict drug toxicity...
December 2018: Life science alliance
Giorgia Renga, Monica Borghi, Vasileios Oikonomou, Paolo Mosci, Andrea Bartoli, Jean-Christophe Renauld, Luigina Romani, Claudio Costantini
Vulvovaginal candidiasis (VVC) is a common fungal infection caused by Candida albicans . The antifungal therapy represents the standard of care but due to the high costs of treatment and to the inability to prevent recurrences, the development of alternative therapeutic approaches is much-awaited. Recently, we have shown that the pathogenesis of C. albicans in the gut is modulated by IL-9, a pleiotropic cytokine able to promote both inflammation and tolerance during C. albicans infection. Herein, by using a mouse model of VVC, we similarly demonstrated that IL-9 might exert a dual role in VVC by contributing to inflammation during the initial immune activation and promoting resolution thereafter...
2018: Frontiers in Immunology
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