Notice NOT-AT-17-006 from the NIH Guide for Grants and Contracts

Funding Opportunity PAR-17-235 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to promote exploratory and developmental research to understand the underlying mechanisms of sleep deficiencies among health disparity populations and how sleep deficiencies may lead to disparities in health outcomes.

Funding Opportunity PAR-17-234 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to promote research to understand the underlying mechanisms of sleep deficiencies among health disparity populations and how sleep deficiencies may lead to disparities in health outcomes.

Notice NOT-HS-17-011 from the NIH Guide for Grants and Contracts

Notice NOT-MH-17-019 from the NIH Guide for Grants and Contracts

Funding Opportunity PAR-17-236 from the NIH Guide for Grants and Contracts. The purpose of this funding opportunity announcement (FOA) is to support innovative applications that will inform our understanding of structural birth defects through the use of animal models in conjunction with translational/clinical approaches. Applicants are encouraged to take advantage of advances in genetics, biochemistry, molecular, and developmental biology to identify specific genetic, epigenetic, environmental, or gene/environment interactions associated with the susceptibility to and variability of structural birth defects in human populations. Applicants funded through this FOA will join the NICHD Birth Defects Working Group and participate in annual meetings designed to provide a forum to discuss research progress, exchange ideas, share resources, and foster collaborations relevant to the goals of the NICHD's Birth Defects Initiative.

Notice NOT-MH-17-018 from the NIH Guide for Grants and Contracts

Funding Opportunity PAR-17-199 from the NIH Guide for Grants and Contracts. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and participating Institutes within the National Institutes of Health (NIH) encourage small business SBIR grant applications to address different and complementary research needs for the development of appropriate pediatric drug formulations in different age groups. This FOA also encourages the development and testing of novel drug delivery systems in the pediatric population. The goal of this FOA is to complement and accelerate the development of appropriate pediatric drugs formulations and drug delivery systems.

Funding Opportunity PAR-17-200 from the NIH Guide for Grants and Contracts. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and participating Institutes within the National Institutes of Health (NIH) encourage small business grant applications to address different and complementary research needs for the development appropriate pediatric drug formulations in different age groups. This FOA also encourages the development and testing of novel drug delivery systems in the pediatric population. The goal of this FOA is to complement and accelerate the development of appropriate pediatric drugs formulations and drug delivery systems.

Funding Opportunity PAR-17-192 from the NIH Guide for Grants and Contracts. The purpose of this funding opportunity announcement (FOA) is to address different and complementary research needs for the development and acceptability of pediatric drug formulations in different age groups. This FOA also encourages the development of novel drug delivery systems in the pediatric population. Investigators are encouraged to explore approaches and concepts new to the area of pediatric formulation development and testing and use newly developed techniques superior to the ones currently used in the field. Applications submitted under this mechanism should be exploratory and novel.

Funding Opportunity PAR-17-191 from the NIH Guide for Grants and Contracts. The purpose of this funding opportunity announcement (FOA) is to address different and complementary research needs for the development and acceptability of pediatric drug formulations in different age groups. This FOA also encourages the development of novel drug delivery systems in the pediatric population. Investigators are encouraged to explore approaches and concepts new to the area of pediatric formulation development and testing and use newly developed techniques superior to the ones currently used in the field. This FOA supports discrete, well-defined projects that realistically can be completed in two years and that require limited levels of funding.

Funding Opportunity PAR-17-193 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) encourages grant applications to address different and complementary research needs for the development and acceptability of pediatric drug formulations in different age groups. Development and testing of novel pediatric drug delivery systems is also part of this initiative.

Funding Opportunity PAR-17-233 from the NIH Guide for Grants and Contracts. Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) encourages grant applications for support of the core functions of Cancer Epidemiology Cohorts (CECs), as well as methodological research. This FOA is intended to support maintenance of existing CECs infrastructure and resource sharing with broader scientific communities.

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Related Articles

Combinatorial requirement of W- and WT-boxes in microbe-associated molecular pattern-responsive synthetic promoters.

Plant Cell Rep. 2017 Mar 24;:

Authors: Kanofsky K, Bahlmann AK, Hehl R, Dong DX

Abstract
KEY MESSAGE: The WT-box GGACTTTC belongs to a novel class of MAMP-responsive cis-regulatory sequences that are part of combinatorial elements. Microbe-associated molecular pattern (MAMP)-responsive synthetic promoters were generated with two cis-regulatory modules (CRM1 and CRM2) from the Arabidopsis thaliana WRKY30 promoter. Both modules harbour two W-boxes and one WT-box. Mutation analysis of the synthetic promoters and transient gene expression analysis in parsley protoplasts underline the importance of the W- and WT-boxes for MAMP-responsive gene expression and reveal the combinatorial requirement of at least two boxes for full MAMP responsivity. In the context of the native promoter, CRM1 is required for MAMP responsivity, while CRM2 alone is not sufficient. Yeast one-hybrid screenings using CRM1 with a transcription factor (TF) only prey library select only WRKY factors. Selection of WRKY26, 40, 41, and 70 requires the W-boxes. The WT-box is also required for selection of WRKY26 and 41 in yeast. In plant cells, WRKY26, 40, and 41 act as repressors of MAMP-responsive gene expression, whereas WRKY70 is an activator. To investigate whether the WT-box is also required for WRKY26 and 41 mediated gene expression in plant cells, both were converted into transcriptional activators by adding the GAL4 activating domain (AD). In contrast to yeast, transient gene expression in parsley protoplasts shows that only the W-boxes from CRM1 are required for WRKY41AD-activated reporter gene activity but not the WT-box. In addition, WRKY70-activated reporter gene activity in parsley cells does not require the WT-box of CRM1. The results demonstrate the importance of the WT-box as a new cis-regulatory sequence for MAMP-responsive gene expression. Based on these and earlier results, two types of WT-boxes are proposed.

PMID: 28341984 [PubMed - as supplied by publisher]

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Drug Repurposing of the Anthelmintic Niclosamide to Treat Multidrug-Resistant Leukemia.

Front Pharmacol. 2017;8:110

Authors: Hamdoun S, Jung P, Efferth T

Abstract
Multidrug resistance, a major problem that leads to failure of anticancer chemotherapy, requires the development of new drugs. Repurposing of established drugs is a promising approach for overcoming this problem. An example of such drugs is niclosamide, a known anthelmintic that is now known to be cytotoxic and cytostatic against cancer cells. In this study, niclosamide showed varying activity against different cancer cell lines. It revealed better activity against hematological cancer cell lines CCRF-CEM, CEM/ADR5000, and RPMI-8226 compared to the solid tumor cell lines MDA-MB-231, A549, and HT-29. The multidrug resistant CEM/ADR5000 cells were similar sensitive as their sensitive counterpart CCRF-CEM (resistance ration: 1.24). Furthermore, niclosamide caused elevations in reactive oxygen species and glutathione (GSH) levels in leukemia cells. GSH synthetase (GS) was predicted as a target of niclosamide. Molecular docking showed that niclosamide probably binds to the ATP-binding site of GS with a binding energy of -9.40 kcal/mol. Using microscale thermophoresis, the binding affinity between niclosamide and recombinant human GS was measured (binding constant: 5.64 μM). COMPARE analyses of the NCI microarray database for 60 cell lines showed that several genes, including those involved in lipid metabolism, correlated with cellular responsiveness to niclosamide. Hierarchical cluster analysis showed five major branches with significant differences between sensitive and resistant cell lines (p = 8.66 × 10(5)). Niclosamide significantly decreased nuclear factor of activated T-cells (NFAT) activity as predicted by promoter binding motif analysis. In conclusion, niclosamide was more active against hematological malignancies compared to solid tumors. The drug was particularly active against the multidrug-resistant CEM/ADR5000 leukemia cells. Inhibition of GSH synthesis and NFAT signaling were identified as relevant mechanisms for the anticancer activity of niclosamide. Gene expression profiling predicted the sensitivity or resistance of cancer cells to niclosamide.

PMID: 28344555 [PubMed - in process]

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Approved drugs are to be studied for use in Alzheimer's disease.

BMJ. 2016 Sep 19;354:i5063

Authors: Hopkins Tanne J

PMID: 27644990 [PubMed - indexed for MEDLINE]

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The anti-Aspergillus drug pipeline: Is the glass half full or empty?

Med Mycol. 2017 Jan 01;55(1):118-124

Authors: Osherov N, Kontoyiannis DP

Abstract
Aspergillosis has emerged as important human mycoses, in view of the ever expanding population at risk. The emergence of resistance to the most commonly used drugs for aspergillosis, the azoles, the mediocre activity, and frequent toxicity of the current antifungal armamentarium, support the need for development of novel antifungals for treatment of this disease. In this minireview, we describe recent efforts by small drug companies and University research labs to develop novel therapies for invasive aspergillus infections. We specifically discuss four small-molecule antifungals (T-2307, E1210/APX001, ASP2397, and F901318) with novel modes-of-action, which are currently entering phase I clinical trials. In addition, we provide a nonexhaustive discussion of some interesting, yet early developments in the quest for improved therapeutic strategies such as (i) novel formulations of amphotericin B including AMB nanoparticle suspensions and AMB-arabinogalactan or AMB-PEG conjugates that show low toxicity and high efficacy in preclinical animal models, (ii) repurposed drugs that synergize with existing antifungals (clozafimine, trichostatin A, MGCD290, geldanamycin, tacrolimus, cyclosporin), (iii) natural products (psoriasin, humidimycin), and (iv) immunotherapy using adoptive transfer of activated immune cells with antifungal activity. We argue that despite the plethora of candidates, the extremely low success rates of drug development leading to clinically useful drugs reinforces the need for continued clinical reliance on mainstream antifungals and their improved derivatives.

PMID: 27562862 [PubMed - indexed for MEDLINE]