24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/08

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Funding Opportunity RFA-TR-18-021 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) is to invite applications for new applications for the Data Management and Coordinating Center (DMCC) for the Rare Diseases Clinical Research Network (RDCRN). Each consortium within the RDCRN is intended to advance the diagnosis, management, and treatment of rare diseases. The DMCC will facilitate and support the activities of each Rare Diseases Clinical Research Consortium (RDCRC) along with trans-network activities that broadly facilitate the advancement of rare disease research via four Cores; 1) Administrative; 2) Data Management; 3) Clinical Research and; 4) Engagement and Dissemination.

Funding Opportunity RFA-TR-18-020 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to invite new and re-competing applications to apply to the Rare Diseases Clinical Research Consortia (RDCRC) that comprise the Rare Diseases Clinical Research Network (RDCRN). The RDCRCs are intended to advance the diagnosis, management, and treatment of rare diseases with a focus on clinical trial readiness. Each RDCRC will promote highly collaborative, multi-site, patient-centric, translational and clinical research with the intent of addressing unmet clinical trial readiness needs.

Funding Opportunity RFA-AG-19-017 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) invites early-stage physician and other health professional investigators with a commitment to aging and/or aging-related diseases to apply for this award to advance their research and leadership skills in their specialty and in the broader field of aging and geriatrics research. The National Institute on Aging is pursuing this initiative to recruit new investigators who have begun to establish research programs and who, through this award, will be ready to assume leadership roles in their field of expertise and will be poised to change theory, practice and health outcomes related to the health of older individuals. Unlike other mentored K awards, candidates for this award must have received competitively awarded research support as a PD/PI at the faculty level or have otherwise leveraged faculty-level research support to develop an independent line of research. They must show evidence of leadership in the clinical or research domain. This Funding Opportunity Announcement (FOA) is designed specifically for applicants proposing research that does not involve leading an independent clinical trial, a clinical trial feasibility study, or an ancillary study to a clinical trial. Applicants to this FOA are permitted to propose research experience in a clinical trial led by a mentor or co-mentor. Applicants proposing a clinical trial or an ancillary study to an ongoing clinical trial as lead investigator, should apply to the companion FOA (RFA-AG-19-018).

Funding Opportunity RFA-AG-19-018 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) invites early-stage physician and other health professional investigators with a commitment to aging and/or aging-related diseases to apply for this award to advance their research and leadership skills in their specialty and in the broader field of aging and geriatrics research. The National Institute on Aging is pursuing this initiative to recruit new investigators who have begun to establish research programs and who, through this award, will be ready to assume leadership roles in their field of expertise and will be poised to change theory, practice and health outcomes related to the health of older individuals. Unlike other mentored K awards, candidates for this award must have received competitively awarded research support as a PD/PI at the faculty level or have otherwise leveraged faculty-level research support to develop an independent line of research. They must show evidence of leadership in the clinical or research domain. This Funding Opportunity Announcement (FOA) is designed specifically for applicants proposing to serve as the lead investigator of an independent clinical trial, a clinical trial feasibility study, or a separate ancillary study to an existing trial, as part of their research and career development. Applicants not planning an independent clinical trial, or proposing to gain research experience in a clinical trial led by another investigator, must apply to companion FOA (FOA #).

Funding Opportunity RFA-FD-18-024 from the NIH Guide for Grants and Contracts. The Cooperative Agreement will build upon the extensive experience of an institution with well-established and globally recognized collaboration with inspectorates of National Regulatory Authorities (NRAs) around the globe in support of data-driven and science-based regulatory and public health strategies and approaches that align with FDA domestic and global priorities to assure a pharmaceutical quality integration of assessment, inspection, policy, and research activities within a pharmaceutical context, including Good Manufacturing Practices (GMP). The funding will catalyze and support the institution's activities that are focused on consensus around what optimal good manufacturing practices are and the competencies for Inspectors within the context of emerging and increasingly complex science, research and innovation in manufacturing of pharmaceutical products. Based on such consensus, the institution and its network of NRA Inspectorates will work toward a systems-approach and sustainable alignment across and among NRA Inspectorates in GMP quality manufacturing.

Funding Opportunity RFA-MH-19-201 from the NIH Guide for Grants and Contracts. This initiative will foster collaborative and coordinated efforts to characterize the underlying genetic architecture of diverse neuropsychiatric phenotypes within and across rare genetic disorders and identify the shared genetic risk across rare and idiopathic neuropsychiatric disorders. Projects from multi-disciplinary teams will utilize genome-wide data to comprehensively assess the contribution of genetic variation to the variable expressivity and incomplete penetrance of neuropsychiatric phenotypes across rare genetic disorders. Projects are encouraged to leverage existing resources, cohorts, and collaborative networks with established infrastructure for consistent and high-quality phenotypic data collection and genomic data generation. Projects should seek to enhance the quality of the phenotypic data available for rare genetic disorders by developing or applying phenotyping methodologies that create a pipeline for standardizing assessments and that cut across rare genetic disorders and across developmental time points. Under this initiative, investigators will form a network to facilitate data sharing and harmonization of clinical and genetic data across different studies within the network, as well as accelerate characterization of genotype to phenotype relationships across rare genetic disorders. This network will also generate a resource of bio-samples, as well as phenotypic and genetic data for broader dissemination to the scientific community. This FOA should be used for applications that are not collaborative between sites. Applications requiring two or more collaborating sites to complete the proposed research should apply as a linked set of collaborative U01 applications to the companion collaborative U01 FOA (RFA-MH-19-201). All awards supported under this FOA and the companion collaborative U01 FOA (RFA -MH-19-201) will be governed by the Mental Health Rare Genetic Disease Network (MHRGDN).

Funding Opportunity RFA-MH-19-200 from the NIH Guide for Grants and Contracts. This initiative will foster collaborative and coordinated efforts to characterize the underlying genetic architecture of diverse neuropsychiatric phenotypes within and across rare genetic disorders and identify the shared genetic risk across rare and idiopathic neuropsychiatric disorders. Projects from multi-disciplinary teams will utilize genome-wide data to comprehensively assess the contribution of genetic variation to the variable expressivity and incomplete penetrance of neuropsychiatric phenotypes across rare genetic disorders. Projects are encouraged to leverage existing resources, cohorts, and collaborative networks with established infrastructure for consistent and high-quality phenotypic data collection and genomic data generation. Projects should seek to enhance the quality of the phenotypic data available for rare genetic disorders by developing or applying phenotyping methodologies that create a pipeline for standardizing assessments and that cut across rare genetic disorders and across developmental time points. Under this initiative, investigators will form a network to facilitate data sharing and harmonization of clinical and genetic data across different studies within the network, as well as accelerate characterization of genotype to phenotype relationships across rare genetic disorders. This network will also generate a resource of bio-samples, as well as phenotypic and genetic data for broader dissemination to the scientific community. This FOA should be used for applications that are not collaborative between sites. Applications requiring two or more collaborating sites to complete the proposed research should apply as a linked set of collaborative U01 applications to the companion collaborative U01 FOA (RFA-MH-19-201). All awards supported under this FOA and the companion collaborative U01 FOA (RFA -MH-19-201) will be governed by the Mental Health Rare Genetic Disease Network (MHRGDN).

Funding Opportunity PA-18-821 from the NIH Guide for Grants and Contracts. The purpose of the Administrative Supplements for Collaborative Activities to Promote Cachexia Research is to support collaborative, multidisciplinary basic and translational research that addresses an important question in cancer cachexia and to expand the cadre of investigators experienced in cancer cachexia study design, model systems and data interpretation. These supplement applications must propose a collaboration between cancer researchers and researchers with documented expertise in cachexia research. The parent grant for the supplement must have an NCI primary assignment. Overall, the long-term goal of this supplement program is to encourage a focused examination of the biology of cancer cachexia and its effect on organs and systems beyond the tumor site(s). Applicants are strongly encouraged to discuss potential requests with the NCI scientific contacts listed below.

39 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/07

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles

Analysis of the substrate recognition state of TDP-43 to single-stranded DNA using fluorescence correlation spectroscopy.

Biochem Biophys Rep. 2018 Jul;14:58-63

Authors: Kitamura A, Shibasaki A, Takeda K, Suno R, Kinjo M

Abstract
Normal function and abnormal aggregation of transactivation response (TAR) DNA/RNA-binding protein 43 kDa (TDP-43) are directly associated with the lethal genetic diseases: cystic fibrosis, amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration (FTLD). The binding of TDP-43 to single-stranded DNA (ssDNA) or RNA is involved in transcriptional repression, regulation of RNA splicing, and RNA stabilization. Equilibrium dissociation constants (Kd) of TDP-43 and ssDNA or RNA have been determined using various methods; however, methods that can measure Kd with high sensitivity in a short time using a small amount of TDP-43 in solution would be advantageous. Here, in order to determine the Kd of TDP-43 and fluorescence-labeled ssDNA as well as the binding stoichiometry, we use fluorescence correlation spectroscopy (FCS), which detects the slowed diffusion of molecular interactions in solution with single-molecule sensitivity, in addition to electrophoretic mobility shift assay (EMSA). Using tandem affinity chromatography of TDP-43 dually tagged with glutathione-S-transferase and poly-histidine tags, highly purified protein was obtained. FCS successfully detected specific interaction between purified TDP-43 and TG ssDNA repeats, with a Kd in the nanomolar range. The Kd of the TDP-43 mutant was not different from the wild type, although mutant oligomers, which did not bind ssDNA, were observed. Analysis of the fluorescence brightness per dimerized TDP-43/ssDNA complex was used to evaluate their binding stoichiometry. The results suggest that an assay combining FCS and EMSA can precisely analyze ssDNA recognition mechanisms, and that FCS may be applied for the rapid and quantitative determination of the interaction strength between TDP-43 and ssDNA or RNA. These methods will aid in the elucidation of the substrate recognition mechanism of ALS- and FTLD-associated variants of TDP-43.

PMID: 29872735 [PubMed]

Related Articles

Evaluation of the Risk for Acute Kidney Injury in Adult Cystic Fibrosis Patients Receiving Concomitant Vancomycin and Tobramycin.

Cureus. 2017 Dec 06;9(12):e1912

Authors: Muirhead C, Lim JY, Lapidus J, MacDonald K

Abstract
Background The risk for acute kidney injury (AKI) has been associated with both tobramycin and vancomycin. Objective To determine whether the rate of drug therapy-related nephrotoxicity is greater in Cystic Fibrosis (CF) patients receiving concomitant vancomycin and tobramycin than patients receiving either agent alone. Methods Adult CF patients admitted for acute pulmonary exacerbation (APE) over a seven-year period (2008-2014), who received at least 72 hours of intravenous vancomycin, tobramycin or a combination of the two agents were evaluated for AKI. AKI was defined as a 1.5-fold increase in serum creatinine per RIFLE criteria. One hundred seventy-four hospital encounters from 72 unique patients were assessed in this single-center, cross-sectional study. Results AKI outcomes were not statistically different. AKI rates were 19% for vancomycin, 8.7% for tobramycin, and 19.7% for combination cohorts (p = 0.16). Conclusion Our data suggest there is no significant difference in AKI risk when vancomycin and tobramycin combination therapy is used.

PMID: 29872606 [PubMed]

Related Articles

Testing Calibration of Cox Survival Models at Extremes of Event Risk.

Front Genet. 2018;9:177

Authors: Soave DM, Strug LJ

Abstract
Risk prediction models can translate genetic association findings for clinical decision-making. Most models are evaluated on their ability to discriminate, and the calibration of risk-prediction models is largely overlooked in applications. Models that demonstrate good discrimination in training datasets, if not properly calibrated to produce unbiased estimates of risk, can perform poorly in new patient populations. Poorly calibrated models arise due to missing covariates, such as genetic interactions that may be unknown or not measured. We demonstrate that models omitting interactions can lead to increased bias in predicted risk for patients at the tails of the risk distribution; i.e., those patients who are most likely to be affected by clinical decision making. We propose a new calibration test for Cox risk-prediction models that aggregates martingale residuals for subjects from extreme high and low risk groups with a test statistic maximum chosen by varying which risk groups are included in the extremes. To estimate the empirical significance of our test statistic, we simulate from a Gaussian distribution using the covariance matrix for the grouped sums of martingale residuals. Simulation shows the new test maintains control of type 1 error with improved power over a conventional goodness-of-fit test when risk prediction deviates at the tails of the risk distribution. We apply our method in the development of a prediction model for risk of cystic fibrosis-related diabetes. Our study highlights the importance of assessing calibration and discrimination in predictive modeling, and provides a complementary tool in the assessment of risk model calibration.

PMID: 29872446 [PubMed]

Related Articles

Identification of the CFTR c.1666A>G Mutation in Hereditary Inclusion Body Myopathy Using Next-Generation Sequencing Analysis.

Front Neurosci. 2018;12:329

Authors: Lu Y, Da YW, Zhang YB, Li XG, Wang M, Di L, Pang M, Lei L

Abstract
Hereditary inclusion body myopathy (HIBM) is a rare autosomal recessive adult onset muscle disease which affects one to three individuals per million worldwide. This disease is autosomal dominant and occurs in adulthood. Our previous study reported a new subtype of HIBM linked to the susceptibility locus at 7q22.1-31.1. The present study is aimed to identify the candidate gene responsible for the phenotype in HIBM pedigree. After multipoint linkage analysis, we performed targeted capture sequencing on 16 members and whole-exome sequencing (WES) on 5 members. Bioinformatics filtering was performed to prioritize the candidate pathogenic gene variants, which were further genotyped by Sanger sequencing. Our results showed that the highest peak of LOD score (4.70) was on chromosome 7q22.1-31.1.We identified 2 and 22 candidates using targeted capture sequencing and WES respectively, only one of which as CFTRc.1666A>G mutation was well cosegregated with the HIBM phenotype. Using transcriptome analysis, we did not detect the differences of CFTR's mRNA expression in the proband compared with healthy members. Due to low incidence of HIBM and there is no other pedigree to assess, mutation was detected in three patients with duchenne muscular dystrophyn (DMD) and five patients with limb-girdle muscular dystrophy (LGMD). And we found that the frequency of mutation detected in DMD and LGMD patients was higher than that of being expected in normal population. We suggested that the CFTRc.1666A>G may be a candidate marker which has strong genetic linkage with the causative gene in the HIBM family.

PMID: 29872374 [PubMed]

Funding Opportunity RFA-AG-19-008 from the NIH Guide for Grants and Contracts. This FOA invites applications from qualified institutions to create a Roybal Center Coordinating Center (CC), serving the needs of the Roybal Centers for Translational Research on Aging program as well as the Roybal Centers for Translational Research on Dementia Care Provider Support program. The Roybal Coordinating Center will serve as a hub for the Roybal Center grant program. Roybal Center programs conduct translational in the behavioral and social sciences of aging, structured in accordance with the NIH Stage Model. Roybal Center program resources are intended for pilot and preliminary translational, multi-directional research at Stages 0 through IV of the behavioral intervention development pipeline with the goal of creating principle-driven interventions that improve the lives of mid-life and older people and the capacity of institutions to adapt to societal aging. The Roybal Coordinating Center will facilitate and coordinate trans-Roybal activities. The Center will work closely with the NIA Program Officer and, in coordination with all Roybal sites, will be responsive to requests generated by key Roybal site personnel, NIA, NIH, the scientific community, and the general public.

Funding Opportunity RFA-AG-19-007 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) solicits Edward R. Roybal Centers for translational intervention development research for Alzheimers Disease and Alzheimers Disease related dementias care provider support. The purpose of the Roybal Centers is to develop behavioral interventions that improve the health, well-being and/or capacity of individuals and/or systems that provide care to persons with AD-ADRD. Roybal Centers will conduct Stage 0 through IV pilot studies in accordance with the multidirectional, translational NIH Stage Model, to produce potent and implementable principle-driven behavioral interventions.

Funding Opportunity RFA-AG-19-006 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) solicits Edward R. Roybal Centers for Translation Research in the Behavioral and Social Sciences of Aging. The purpose of the Roybal Centers is to develop behavioral interventions that improve the health and well-being of people as they are aging and the capacity of institutions to adapt to societal aging. Roybal Centers will conduct Stage 0 through IV pilot studies in accordance with the multidirectional, translational NIH Stage Model, to produce potent and implementable principle-driven behavioral interventions.

Funding Opportunity PAR-18-820 from the NIH Guide for Grants and Contracts. The goal of this Funding Opportunity Announcement (FOA) is to provide funding support for the pre-clinical and early stage clinical (Phase I) development of novel small-molecule and biologic therapeutic agents that prevent Alzheimer's disease (AD), slow its progression or treat its cognitive and behavioral symptoms. Participants in this program will receive funding for therapy development activities such as medicinal chemistry, pharmacokinetics (PK), Absorption, Distribution, Metabolism, Excretion, Toxicology (ADMET), efficacy in animal models, formulation development, chemical synthesis under Good Manufacturing Practices (GMP), Investigational New Drug (IND) enabling studies and initial Phase I clinical testing. This program does not support research on basic mechanisms of disease, mechanisms of drug action, development of biomarkers, devices, non-pharmacological interventions (e.g., exercise, diet, cognitive training), repurposed drugs and combinations therapies, or discovery activities such as high throughput screening and hit optimization.

Topical delivery of ebselen encapsulated in biopolymeric nanocapsules: drug repurposing enhanced antifungal activity.

Nanomedicine (Lond). 2018 Jun 06;:

Authors: Jaromin A, Zarnowski R, Piętka-Ottlik M, Andes DR, Gubernator J

Abstract
AIM: Ebselen (Eb) is an example of a repurposed drug with poor aqueous solubility which requires sophisticated delivery system such as nanoencapsulation in nanocapsules for topical application.
MATERIALS & METHODS: Eb-nanocapsules were examined for morphology, activity against Candida spp., cytotoxicity and skin permeation.
RESULTS: Eb-nanocapsules were active against skin-infecting Candida tropicalis, Candida albicans and Candida parapsilosis yeasts (minimal inhibitory concentration values were about 4-, 2- and 1.25-times lower vs free Eb, respectively) and able to suppress induced lipid oxidation in the oil/water emulsion. Moreover, demonstrated minimal toxicity in normal human dermal fibroblast cell line, whereas ex vivo skin permeation studies showed no transdermal passage and strong interactions with stratum corneum.
CONCLUSION: Eb-nanocapsules represent a promising, safe and complementary alternative to the treatment of cutaneous candidiasis.

PMID: 29873597 [PubMed - as supplied by publisher]

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Repurposing Valproate, Enteral Clonidine, and Phenobarbital for Comfort in Adult ICU Patients: A Literature Review with Practical Considerations.

Pharmacotherapy. 2017 Oct;37(10):1309-1321

Authors: Gagnon DJ, Fontaine GV, Riker RR, Fraser GL

Abstract
Provision of adequate sedation is a fundamental part of caring for critically ill patients. Propofol, dexmedetomidine, and benzodiazepines are the most commonly administered sedative medications for adult patients in the intensive care unit (ICU). These agents are limited by adverse effects, need for a monitored environment for safe administration, and lack of universal effectiveness. Increased interest has recently been expressed about repurposing older pharmacologic agents for patient comfort in the ICU. Valproate, enteral clonidine, and phenobarbital are three agents with increasing evidence supporting their use. Potential benefits associated with their utilization are cost minimization and safe administration after transition out of the ICU. This literature review describes the historical context, pharmacologic characteristics, supportive data, and practical considerations associated with the administration of these agents for comfort in critically ill adult patients.

PMID: 28833346 [PubMed - indexed for MEDLINE]