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Bergquist R.,Ingerod | Lustigman S.,Lindsley F Kimball Research Institute
Advances in Parasitology | Year: 2010

Among the tools available for the control of helminth infections, chemotherapy has come to totally dominate the field. In the veterinary field, development of drug resistance has appeared but this is not (yet) a problem in the control of human diseases. Although there is no vaccine commercially available for any human parasitic infection yet, recent progress in vaccine development is making this a future possibility for several diseases. The goal of chemotherapy is to alleviate infection and morbidity in the definitive host, or reduce transmission, while the effect of available vaccine candidates would mainly be to influence transmission through targeting the intermediate or reservoir host, when the infection is zoonotic. Apart from this general scheme, there are also vaccine candidates targeting the parasites in the definitive host, in particular the early developmental stages, which should reduce the risk of drug failure. Since the biological targets in most cases are different, vaccination would be synergistic with drug therapy. This review covers diseases caused by helminthes in both humans and animals and includes examples of diseases caused by cestodes, nematodes and trematodes. The focus is on infections for which vaccine development has been undertaken for a long time, resulting in products that could realistically become integrated into control strategies in the near future. © 2010 Elsevier Ltd. Source

Ney P.A.,Lindsley F Kimball Research Institute
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2015

Mitochondrial autophagy (mitophagy) is a core cellular activity. In this review, we consider mitophagy and related cellular processes and discuss their significance for human disease. Strong parallels exist between mitophagy and xenophagy employed in host defense. These mechanisms converge on receptors in the innate immune system in clinically relevant scenarios. Mitophagy is part of a cellular quality control mechanism, which is implicated in degenerative disease, especially neurodegenerative disease. Furthermore, mitophagy is an aspect of cellular remodeling, which is employed during development. BNIP3 and NIX are related multi-functional outer mitochondrial membrane proteins. BNIP3 regulates mitophagy during hypoxia, whereas NIX is required for mitophagy during development of the erythroid lineage. Recent advances in the field of BNIP3- and NIX-mediated mitophagy are discussed. This article is part of a Special Issue entitled: Mitophagy. © 2015 Elsevier B.V. Source

Shenoy N.,Yeshiva University | Vallumsetla N.,Yeshiva University | Rachmilewitz E.,Edith Wolfson Medical Center | Verma A.,Yeshiva University | Ginzburg Y.,Lindsley F Kimball Research Institute
Blood | Year: 2014

Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and potential for malignant transformation. Lower/intermediate-risk MDSs are associated with longer survival and high red blood cell (RBC) transfusion requirements resulting in secondary iron overload. Recent data suggest that markers of iron overload portend a relatively poor prognosis, and retrospective analysis demonstrates that iron chelation therapy is associated with prolonged survival in transfusion-dependent MDS patients. New data provide concrete evidence of iron's adverse effects on erythroid precursors in vitro and in vivo. Renewed interest in the iron field was heralded by the discovery of hepcidin, the main serum peptide hormone negative regulator of body iron. Evidence from β-thalassemia suggests that regulation of hepcidin by erythropoiesis dominates regulation by iron. Because iron overload develops in some MDS patients who do not require RBC transfusions, the suppressive effect of ineffective erythropoiesis on hepcidin may also play a role in iron overload. We anticipate that additional novel tools for measuring iron overload and a molecular-mechanism-driven description of MDS subtypes will provide a deeper understanding of how iron metabolism and erythropoiesis intersect in MDSs and improve clinical management of this patient population. © 2014 by The American Society of Hematology. Source

Debnath A.K.,Lindsley F Kimball Research Institute
Methods in Molecular Biology | Year: 2013

This chapter reviews studies that have used in silico techniques to design or identify potential HIV-1 entry inhibitors targeting cellular receptors CD4, CCR5, and CXCR4 and envelope glycoproteins, gp120 and gp41 of HIV-1. Both structure- and ligand-based design techniques have been used in those studies by applying diverse modeling techniques such as quantitative structure-activity relationship analysis, conformational analysis, molecular dynamics, pharmacophore generation, docking, virtual screening (using docking software and also shape-based ROCS techniques), and fragment-based design. © Springer Science+Business Media, LLC 2013. Source

Zhang N.,Lindsley F Kimball Research Institute | Jiang S.,Lindsley F Kimball Research Institute | Jiang S.,Fudan University | Du L.,Lindsley F Kimball Research Institute
Expert Review of Vaccines | Year: 2014

Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future. © 2014 Informa UK, Ltd. Source

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