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Combined Influence of Genetic Polymorphism and DNA Methylation on ABCB1 Expression and Function in Healthy Chinese Males.

Eur J Drug Metab Pharmacokinet. 2017 Aug;42(4):627-634

Authors: Wu LX, Zhao HB, Wen CJ, Li Y, Shao YY, Yang Z, Zhou HH

Abstract
BACKGROUND AND OBJECTIVES: It is well known that the expression and function of ATP-binding cassette transporter B1 (ABCB1) show high interindividual variability, but the reasons have not yet been fully elucidated. In this study, combined influence of genetic polymorphism and DNA methylation on ABCB1 mRNA expression and digoxin pharmacokinetics in healthy Chinese males was analyzed.
METHODS: A total of 93 subjects who were homozygous for the ABCB1 1236-2677-3435 TTT or CGC haplotype were enrolled in this study. DNA methylation status of the ABCB1 promoter and ABCB1 mRNA expression level in exfoliated intestinal epithelial cells were analyzed using bisulfite sequencing PCR and real-time PCR. The pharmacokinetics of digoxin in subjects were investigated after administration of a single oral dose of digoxin 0.5 mg.
RESULTS: The DNA methylation levels of ABCB1 promoter showed no significant difference between TTT/TTT and CGC/CGC carriers (P = 0.54). Subjects with TTT/TTT haplotype pair and high methylation status (TTT/TTT-HM) showed a significantly lower ABCB1 mRNA level compared to other subjects. Compared with TTT/TTT-HM subgroup, the area under the plasma concentration-time curve from time zero to 72 h (AUC0-72) of digoxin was decreased by 26.9 %, the maximum plasma concentration (C max) was decreased by 25 % and the apparent oral clearance (CL/F) was increased by 21.2 % in CGC/CGC-LM subgroup. The values of time to maximum concentration (t max) and terminal elimination half-life (t 1/2) showed no significant difference.
CONCLUSIONS: Both genetic polymorphism and DNA methylation variation should be taken into consideration to explain the interindividual variability in ABCB1 expression and function more clearly.

PMID: 27683186 [PubMed - indexed for MEDLINE]

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CFTR prevents neuronal apoptosis following cerebral ischemia reperfusion via regulating mitochondrial oxidative stress.

J Mol Med (Berl). 2018 May 14;:

Authors: Zhang YP, Zhang Y, Xiao ZB, Zhang YB, Zhang J, Li ZQ, Zhu YB

Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is linked to cell apoptosis and abundantly expressed in brain tissue. Mitochondrial oxidative stress plays a key role in activating apoptotic pathway following cerebral ischemia reperfusion (IR) injury. Reduced glutathione (GSH) is exclusively synthesized in cytosol but distributed in mitochondria. In the present study, we investigated whether CFTR affected mitochondrial oxidative stress via regulating GSH and thereby protected neurons against apoptosis following cerebral IR. Brains were subjected to global IR by four-vessel occlusion and CFTR activator forskolin (FSK) was used in vivo. CFTR silence was performed in vitro for neurons by RNA interference. We found that FSK suppressed neuronal apoptosis whereas CFTR silence enhanced neuronal apoptosis. FSK prevented the elevations in reactive oxygen species (ROS) and caspase activities while FSK inhibited the reductions in complex I activity and mitochondrial GSH level following IR. FSK decreased mitochondrial oxidative stress partially and preserved mitochondrial function. On the contrary, CFTR silence exaggerated mitochondrial dysfunction. CFTR loss increased hydrogen peroxide (H2O2) level and decreased GSH level in mitochondria. Importantly, we showed that CFTR was located on mitochondrial membrane. GSH transport assay suggested that GSH decrease may be a consequence not a reason for mitochondrial oxidative stress mediated by CFTR disruption. Our results highlight the central role of CFTR in the pathogenesis of cerebral IR injury. CFTR regulates neuronal apoptosis following cerebral IR via mitochondrial oxidative stress-dependent pathway. The mechanism of CFTR-mediated mitochondrial oxidative stress needs further studies.
KEY MESSAGES: CFTR activation protects brain tissue against IR-induced apoptosis and oxidative stress. CFTR disruption enhances H2O2-induced neuronal apoptosis and CFTR loss leads to mitochondrial oxidative stress. CFTR regulates IR-induced neuronal apoptosis via mitochondrial oxidative stress. CFTR may be a potential therapeutic target to cerebral IR damage.

PMID: 29761302 [PubMed - as supplied by publisher]

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Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus.

Nat Chem. 2018 May 14;:

Authors: Mousnier A, Bell AS, Swieboda DP, Morales-Sanfrutos J, Pérez-Dorado I, Brannigan JA, Newman J, Ritzefeld M, Hutton JA, Guedán A, Asfor AS, Robinson SW, Hopkins-Navratilova I, Wilkinson AJ, Johnston SL, Leatherbarrow RJ, Tuthill TJ, Solari R, Tate EW

Abstract
Rhinoviruses (RVs) are the pathogens most often responsible for the common cold, and are a frequent cause of exacerbations in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Here we report the discovery of IMP-1088, a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 and NMT2, and use it to demonstrate that pharmacological inhibition of host-cell N-myristoylation rapidly and completely prevents rhinoviral replication without inducing cytotoxicity. The identification of cooperative binding between weak-binding fragments led to rapid inhibitor optimization through fragment reconstruction, structure-guided fragment linking and conformational control over linker geometry. We show that inhibition of the co-translational myristoylation of a specific virus-encoded protein (VP0) by IMP-1088 potently blocks a key step in viral capsid assembly, to deliver a low nanomolar antiviral activity against multiple RV strains, poliovirus and foot and-mouth disease virus, and protection of cells against virus-induced killing, highlighting the potential of host myristoylation as a drug target in picornaviral infections.

PMID: 29760414 [PubMed - as supplied by publisher]

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RpoN-dependent direct regulation of quorum sensing and the Type VI secretion system in Pseudomonas aeruginosa PAO1.

J Bacteriol. 2018 May 14;:

Authors: Shao X, Zhang X, Zhang Y, Zhu M, Yang P, Yuan J, Xie Y, Zhou T, Wang W, Chen S, Liang H, Deng X

Abstract
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen of humans, particularly those with cystic fibrosis. As a global regulator, RpoN controls a group of virulence-related factors and quorum sensing (QS) genes in P. aeruginosa To further gain insights into the direct targets of RpoN in vivo, the present study focused on identifying the direct targets of RpoN regulation in QS and the type VI secretion system (T6SS). We performed a chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-seq) assay that identified 1,068 binding sites of RpoN, mostly including metabolic genes, a group of genes in QS (lasI, rhlI and pqsR) and the T6SS (hcpA and hcpB). The direct targets of RpoN have been verified by EMSA, lux-reporter assay, RT-qPCR and phenotypic detection. The ΔrpoN::Tc mutant resulted in the reduced production of pyocyanin, motility and proteolytic activity. However, the production of rhamnolipids and biofilm formation were higher in the ΔrpoN::Tc mutant than in the wild type. In summary, the results indicated that RpoN had direct and profound effects on QS and the T6SS.IMPORTANCE As a global regulator, RpoN controls a wide range of biological pathways including virulence in P. aeruginosaPAO1. This work shows that RpoN plays critical and global roles in the regulation of bacterial pathogenicity and fitness. ChIP-seq provided a useful database to characterize additional functions and targets of RpoN in the future. The functional characterization of RpoN-mediated regulation will improve the current understanding of the regulatory network of quorum sensing and virulence in P. aeruginosa and other bacteria.

PMID: 29760208 [PubMed - as supplied by publisher]

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Pseudomonas aeruginosa transcriptome during human infection.

Proc Natl Acad Sci U S A. 2018 May 14;:

Authors: Cornforth DM, Dees JL, Ibberson CB, Huse HK, Mathiesen IH, Kirketerp-Møller K, Wolcott RD, Rumbaugh KP, Bjarnsholt T, Whiteley M

Abstract
Laboratory experiments have uncovered many basic aspects of bacterial physiology and behavior. After the past century of mostly in vitro experiments, we now have detailed knowledge of bacterial behavior in standard laboratory conditions, but only a superficial understanding of bacterial functions and behaviors during human infection. It is well-known that the growth and behavior of bacteria are largely dictated by their environment, but how bacterial physiology differs in laboratory models compared with human infections is not known. To address this question, we compared the transcriptome of Pseudomonas aeruginosa during human infection to that of P. aeruginosa in a variety of laboratory conditions. Several pathways, including the bacterium's primary quorum sensing system, had significantly lower expression in human infections than in many laboratory conditions. On the other hand, multiple genes known to confer antibiotic resistance had substantially higher expression in human infection than in laboratory conditions, potentially explaining why antibiotic resistance assays in the clinical laboratory frequently underestimate resistance in patients. Using a standard machine learning technique known as support vector machines, we identified a set of genes whose expression reliably distinguished in vitro conditions from human infections. Finally, we used these support vector machines with binary classification to force P. aeruginosa mouse infection transcriptomes to be classified as human or in vitro. Determining what differentiates our current models from clinical infections is important to better understand bacterial infections and will be necessary to create model systems that more accurately capture the biology of infection.

PMID: 29760087 [PubMed - as supplied by publisher]

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Whole Exome Sequencing identifies PLEC, EXO5 and DNAH7 as novel susceptibility genes in testicular cancer.

Int J Cancer. 2018 May 15;:

Authors: Paumard-Hernández B, Calvete O, Inglada Pérez L, Tejero H, Al-Shahrour F, Pita G, Barroso A, Triviño JC, Urioste M, Valverde C, González Billalabeitia E, Quiroga V, Rodríguez Moreno JF, Fernández Aramburo A, López C, Maroto P, Sastre J, Juan Fita MJ, Duran I, Lorenzo-Lorenzo I, Iranzo P, García Del Muro X, Ros S, Zambrana F, Autran AM, Benítez J

Abstract
Testicular germ cell tumors (TGCTs) are a clinically and pathologically heterogeneous disease, and little is known of its genetic basis. Only low susceptibility risk loci have been identified for both sporadic and familial cases. Therefore, we tried to identify new susceptibility genes responsible for familial testicular cancer that may contribute to increasing our knowledge about the genetic basis of the disease. Nineteen Spanish families with at least two affected individuals with TGCT were selected. WES was performed on those individuals using an Illumina Hiseq2000 sequencing platform. Data were analyzed under a monogenic and polygenic model of inheritance, and candidate variants were evaluated in a case-control association study performed on 391 Spanish sporadic cases and 1170 healthy Spanish controls. Results were replicated in a second series consisting of 101 TGCTs from the Cancer Genome Atlas (TGCA) and 27000 controls from the Exome Aggregation Consortium (ExAC) database. Logistic regression was carried out to analyze the association strength (risk) of candidate variants obtained among cases and controls in different populations. Despite the sample size, we detected a significant earlier age of onset in familial TGCT (28 y) than sporadic cases (33 y), using a Mann-Whitney U test. We identified significant variants in the comparative study of TGCT cases (391) vs controls (almost 1170), and three of them [PLEC (OR=6.28, p-value=6.42 x 10-23) (p.Arg2016Trp), EXO5 (OR=3.37, p-value=4.82 x 10-09) (p.Arg344AlafsTer10) and DNAH7 (OR=1.64, p-value=0.048)] were replicated as potential candidates that may contribute to explaining the genetic basis of TGCT. This article is protected by copyright. All rights reserved.

PMID: 29761480 [PubMed - as supplied by publisher]

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Microcephaly, short stature, and limb abnormality disorder due to novel autosomal biallelic DONSON mutations in two German siblings.

Eur J Hum Genet. 2018 May 14;:

Authors: Schulz S, Mensah MA, de Vries H, Fröber R, Romeike B, Schneider U, Borte S, Schindler D, Kentouche K

Abstract
Recently, variants in DONSON have been reported to cause different disorders of the microcephalic primordial dwarfism spectrum. Using whole-exome sequencing, we identified two novel, compound heterozygous DONSON variants in a pair of siblings, one of whom was previously diagnosed with Fanconi anemia. This occurred because the present cases exhibited clinical findings in addition to those of the microcephalic primordial dwarfism disorder, including severe limb malformations. These findings suggest that the DONSON and Fanconi anemia proteins could have supplementary roles in developmental processes as they have in the maintenance of genomic integrity, resulting in related disease phenotypes.

PMID: 29760432 [PubMed - as supplied by publisher]

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Genomics and pharmacogenomics of pediatric acute lymphoblastic leukemia.

Crit Rev Oncol Hematol. 2018 Jun;126:100-111

Authors: Wu C, Li W

Abstract
Acute lymphoblastic leukaemia (ALL) is a prevalent form of pediatric cancer that accounts for 70-80% of all leukemias. Genome-based analysis, exome sequencing, transcriptomics and proteomics have provided insight into genetic classification of ALL and helped identify novel subtypes of the disease. B and T cell-based ALL are two well-characterized genomic subtypes, significantly marked by bone marrow disorders, along with mutations in trisomy 21 and T53. The other ALLs include Early T-cell precursor ALL, Philadelphia chromosome-like ALL, Down syndrome-associated ALL and Relapsed ALL. Chromosomal number forms a basis of classification, such as, hypodiploid ALL, near-haploid, low-hypodiploid, high-hypodiploid and hypodiploid-ALL. Advances in therapies targeting ALL have been noteworthy, with significant pre-clinical and clinical studies on drug pharmacokinetics and pharmacodynamics. Methotrexate and 6-mercaptopurine are leading drugs with best demonstrated efficacies against childhood ALL. The drugs in combination, following dose titration, have also been used for maintenance therapy. Methotrexate-polyglutamate is a key metabolite that specifically targets the disease pathogenesis, and 6-thioguanine nucleotides, derived from 6-mercaptopurine, impede replication and transcription processes, inducing cytotoxicity. Additionally, glucocorticoids, asparaginase, anthracycline, vincristine and cytarabine that trans-repress gene expression, deprives cells of asparagine, triggers cell cycle arrest, influences cytochrome-P450 polymorphism and inhibits DNA polymerase, respectively, have been used in chemotherapy in ALL patients. Overall, this review covers the progress in genome technology related to different sub-types of ALL and pharmacokinetics and pharmacodynamics of its medications. It also enlightens adverse effects of current drugs, and emphasizes the necessity of genome-wide association studies for restricting childhood ALL.

PMID: 29759551 [PubMed - in process]

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Characterization of Thermally Activated Metalloenediyne Cytotoxicity in Human Melanoma Cells.

Radiat Res. 2018 May 15;:

Authors: Keller EJ, Porter M, Garrett JE, Varie M, Wang H, Pollok KE, Turchi JJ, Zaleski JM, Dynlacht JR

Abstract
Enediynes are a highly cytotoxic class of compounds. However, metallation of these compounds may modulate their activation, and thus their cytotoxicity. We previously demonstrated that cytotoxicity of two different metalloenediynes, including (Z)-N,N'-bis[1-pyridyl-2-yl-meth-(E)-ylidene]octa-4-ene-2,6-diyne-1,8-diamine] (PyED), is potentiated when the compounds are administered to HeLa cells during hyperthermia treatment at concentrations that are minimally or not cytotoxic at 37°C. In this study, we further characterized the concentration, time and temperature dependence of cytotoxicity of PyED on human U-1 melanoma cells. We also investigated the potential mechanisms by which PyED cytotoxicity is enhanced during hyperthermia treatment. Cell killing with PyED was dependent on concentration, temperature during treatment and time of exposure. Potentiation of cytotoxicity was observed when cells were treated with PyED at temperatures ≥39.5°C, and enhancement of cell killing increased with temperature and with increasing time at a given temperature. All cells treated with PyED were shown to have DNA damage, but substantially more damage was observed in cells treated with PyED during heating. DNA repair was also inhibited in cells treated with the drug during hyperthermia. Thus, potentiation of PyED cytotoxicity by hyperthermia may be due to enhancement of drug-induced DNA lesions, and/or the inhibition of repair of sublethal DNA damage. While the selective thermal activation of PyED supports the potential clinical utility of metalloenediynes as cancer thermochemotherapeutic agents, therapeutic gain could be optimized by identifying compounds that produce minimal toxicity at 37°C but which become activated and show enhancement of cytotoxicity within a tumor subjected to localized hyperthermic or thermal ablative treatment, or which might act as bifunctional agents. We thus also describe the development and initial characterization of a novel cofactor complex of PyED, platinated PyED (Pt-PyED). Pt-PyED binds to DNA-like cisplatin, and much like PyED, cytotoxicity is greatly enhanced after treatment with the drug at elevated temperatures. However, in contrast to PyED, Pt-PyED is only minimally cytotoxic at 37°C, at concentrations at which cytotoxicity is enhanced by hyperthermia. Further development of cisplatin-based enediynes may result in compounds which, when activated, will possess multiple DNA binding modalities similar to cisplatin, but produce less side effects in tissues at normothermic temperatures.

PMID: 29763378 [PubMed - as supplied by publisher]

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Efficacy, safety and quality of life in patients receiving subcutaneous IgG treatment: experience in Bogotá, Colombia.

Immunotherapy. 2018 May 15;:

Authors: Ortega-López MC, Garay J, Pinilla ML

Abstract
AIM: Investigate efficacy, safety and quality of life of gammanorm® 16.5% (subcutaneous immunoglobulin [SCIG]) in patients with primary immunodeficiencies (PIDs) and safety and to lesser extent efficacy in autoimmune diseases.
PATIENTS & METHODS: Medical records were extracted from 31 pediatric and 12 adult patients who received SCIG as part of the Personalized Program at University Children's Hospital, Bogotá, Colombia.
RESULTS: Mean SCIG dose was 28.7 g/month. Serious bacterial infections were observed in 7/33 patients in the PID group, most often bacterial pneumonia (3/33). There were no serious adverse events related to SCIG treatment. Drug-related adverse reactions were reported in 2/43 patients.
CONCLUSION: Self-administration of SCIG provided effective protection, favorable tolerability and improved quality of life in patients with PIDs and autoimmune diseases from Colombia.

PMID: 29761739 [PubMed - as supplied by publisher]

Related Articles

[Pharmacological action and clinical outcome of newly developed NSAIDs patch, "LOQOA® tape"].

Nihon Yakurigaku Zasshi. 2018;151(5):221-227

Authors: Otsuka N, Yataba I

Abstract
Topical non-steroidal anti-inflammatory drugs (NSAIDs) patches are indispensable for the treatment of musculoskeletal diseases, while they are considered less effective than oral NSAIDs. LOQOA® tape is a tape-type patch containing esflurbiprofen (SFP) as a major active ingredient with potent cyclooxygenase inhibition and sufficient skin permeability. SFP patch (SFPP) showed higher percutaneous absorption rate, rapid pain relief, and potent anti-inflammatory efficacy comparing with existing NSAIDs patches in rat. SFPP showed dramatically higher synovial fluid and tissue concentration on SFP than that of flurbiprofen (FP) patch after single application to knee osteoarthritis (OA) patients. On the other hand, clinical dosage of SFPP was determined as not more than two patches a day from the estimation of systemic exposure to SFP of SFPP and oral FP. SFPP showed statistically significant differences in pain relief and all the other efficacy end points compared to inactive placebo or FP patch in knee OA patients. Efficacy on OA other than knee joint was also observed. In long-term study of SFPP, using up to two patches a day, a total of 201 patients was included and 161 patients achieved 52-week application. Among drug-related side effects, skin reaction at the application sites was observed in 46.8% and discontinued in 4.3%. Although gastro-intestinal reaction and abnormal changes in laboratory tests related to kidney function were observed as systemic drug-related side effects, most of them were mild in severity. SFPP, the new generation NSAIDs patch, would be one of effective options for the treatment of symptomatic OA patients.

PMID: 29760367 [PubMed - in process]

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A content analysis of the representation of statins in the British newsprint media.

BMJ Open. 2017 Aug 21;7(8):e012613

Authors: Chisnell J, Marshall T, Hyde C, Zhelev Z, Fleming LE

Abstract
OBJECTIVE: This study reviewed the news media coverage of statins, seeking to identify specific trends or differences in viewpoint between media outlets and examine common themes.
DESIGN: The study is a content analysis of the frequency and content of the reporting of statins in a selection of the British newsprint media. It involved an assessment of the number, timing and thematic content of articles followed by a discourse analysis examining the underlying narratives. The sample was the output of four UK newspapers, covering a broad-spectrum readership, over a six month timeframe 1 October 2013 to 31 March 2014.
RESULTS: A total of 67 articles included reference to statins. The majority (39, 58%) were reporting or responding to publication of a clinical study. The ratio of negative to positive coverage was greater than 2:1 overall. In the more politically right-leaning newspapers, 67% of coverage was predominantly negative (30/45 articles); 32% in the more left-leaning papers (7/22 articles). Common themes were the perceived 'medicalisation' of the population; the balance between lifestyle modification and medical treatments in the primary prevention of heart disease; side effects and effectiveness of statins; pharmaceutical sponsorship and implications for the reliability of evidence; trust between the public and government, institutions, research organisations and the medical profession.
CONCLUSIONS: Newsprint media coverage of statins was substantially influenced by the publication of national guidance and by coverage in the medical journals of clinical studies and comment. Statins received a predominantly negative portrayal, notably in the more right-leaning press. There were shared themes: concern about the balance between medication and lifestyle change in the primary prevention of heart disease; the adverse effects of treatment; and a questioning of the reliability of evidence from research institutions, scientists and clinicians in the light of their potential allegiances and funding.

PMID: 28827228 [PubMed - indexed for MEDLINE]

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Short-term treatment with taurolidine is associated with liver injury.

BMC Pharmacol Toxicol. 2017 Aug 11;18(1):61

Authors: Fahrner R, Möller A, Press AT, Kortgen A, Kiehntopf M, Rauchfuss F, Settmacher U, Mosig AS

Abstract
BACKGROUND: Taurolidine has been used for peritonitis, oncological and catheter-lock treatment because of its anti-inflammatory properties. It has been suggested that taurolidine has no severe side-effects, but after long-term use morphological and functional changes of the liver were reported. The aim of this study was to investigate the effect of short-term use of taurolidine on the liver.
METHODS: In HepaRG cell cultures and on a novel liver biochip dose-dependent effects of taurolidine treatment on hepatocyte adherence and cell viability was investigated. Furthermore, liver enzymes and interleukin- (IL-) 6 were measured in supernatants. Male rats were treated with low- or high-dose taurolidine, respectively, and compared to controls with physiological saline solution administration regarding blood serum parameters and histology.
RESULTS: In HepaRG cell cultures, hepatocyte adherence was significantly decreased, cell death and cleaved caspase-3 were significantly increased after administration of taurolidine in a dose-dependent manner. High-dose application of taurolidine led to elevated liver enzymes and IL-6 secretion in hepatic organoid. After 24 h a significant increase of serum GLDH and ASAT was observed in rats treated with high-dose taurolidine treatment.
CONCLUSIONS: Our results suggest that taurolidine caused liver injury after short-term use in in vitro and in vivo models probably due to direct toxic effects on hepatocytes. Therefore, the taurolidine dose should be titrated in further investigations regarding liver injury and inflammation.

PMID: 28800748 [PubMed - indexed for MEDLINE]

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

"systems biology"

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Funding Opportunity PA-18-785 from the NIH Guide for Grants and Contracts. The purpose of this funding opportunity announcement is to encourage Small Business Innovation Research (SBIR) applications from eligible small business concerns proposing to design and produce a non-invasive, discreet, wearable device to monitor blood alcohol levels in real time. Methods that quantify alcohol in blood or interstitial fluid as opposed to detection of alcohol that has exuded through the skin are of highest priority.

Funding Opportunity PA-18-786 from the NIH Guide for Grants and Contracts. The purpose of this funding opportunity announcement is to encourage Small Business Innovation Research (SBIR) applications from eligible small business concerns proposing to design and produce a non-invasive, discreet, wearable device to monitor blood alcohol levels in real time. Methods that quantify alcohol in blood or interstitial fluid as opposed to detection of alcohol that has exuded through the skin are of highest priority.

Funding Opportunity PA-18-784 from the NIH Guide for Grants and Contracts. The purpose of this funding opportunity announcement (FOA) is to support functional microbiome research focused on understanding the molecular, immunological and physiological mechanisms by which the microbiota (gut, lung, oral, including bacteria, viral and fungal microflora) and its derived factors modulate heart, lung, blood and sleep (HLBS) biology and physiology to promote health or contribute to disease. This FOA encourages mechanistic studies using in vitro, in vivo and/or ex vivo models that focus on the mechanistic and functional involvement of the microbiome and their components in the modulation or activation of host pathways. The goal is to provide the critical knowledge to guide early translational approaches for better understanding and treatment of HLBS conditions in adults and children. This FOA encourages multidisciplinary collaborations among scientists in a wide range of disciplines including (but not limited to) cardiology, pulmonology, hematology, sleep science, circadian biology, immunology, '-omic' sciences, microbiology, microbial ecology, biotechnology, and bioinformatics.

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

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