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Perspective Article (perspective + article)
Selected AbstractsPERSPECTIVE ARTICLE: Why do adaptive immune responses cross-react?EVOLUTIONARY APPLICATIONS (ELECTRONIC), Issue 1 2009Karen J. Fairlie-Clarke Abstract Antigen specificity of adaptive immune responses is often in the host's best interests, but with important and as yet unpredictable exceptions. For example, antibodies that bind to multiple flaviviral or malarial species can provide hosts with simultaneous protection against many parasite genotypes. Vaccinology often aims to harness such imprecision, because cross-reactive antibodies might provide broad-spectrum protection in the face of antigenic variation by parasites. However, the causes of cross-reactivity among immune responses are not always known, and here, we explore potential proximate and evolutionary explanations for cross-reactivity. We particularly consider whether cross-reactivity is the result of constraints on the ability of the immune system to process information about the world of antigens, or whether an intermediate level of cross-reactivity may instead represent an evolutionary optimum. We conclude with a series of open questions for future interdisciplinary research, including the suggestion that the evolutionary ecology of information processing might benefit from close examination of immunological data. [source] Perspective articles in the Journal of Orthopaedic ResearchJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2007Timothy M. Wright Co-Editor No abstract is available for this article. [source] Antisense applications for biological controlJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Wei-Hua Pan Abstract Although Nature's antisense approaches are clearly impressive, this Perspectives article focuses on the experimental uses of antisense reagents (ASRs) for control of biological processes. ASRs comprise antisense oligonucleotides (ASOs), and their catalytically active counterparts ribozymes and DNAzymes, as well as small interfering RNAs (siRNAs). ASOs and ribozymes/DNAzymes target RNA molecules on the basis of Watson-Crick base pairing in sequence-specific manner. ASOs generally result in destruction of the target RNA by RNase-H mediated mechanisms, although they may also sterically block translation, also resulting in loss of protein production. Ribozymes and DNAzymes cleave target RNAs after base pairing via their antisense flanking arms. siRNAs, which contain both sense and antisense regions from a target RNA, can mediate target RNA destruction via RNAi and the RISC, although they can also function at the transcriptional level. A considerable number of ASRs (mostly ASOs) have progressed into clinical trials, although most have relatively long histories in Phase I/II settings. Clinical trial results are surprisingly difficult to find, although few ASRs appear to have yet established efficacy in Phase III levels. Evolution of ASRs has included: (a) Modifications to ASOs to render them nuclease resistant, with analogous modifications to siRNAs being developed; and (b) Development of strategies to select optimal sites for targeting. Perhaps the biggest barrier to effective therapies with ASRs is the "Delivery Problem." Various liposomal vehicles have been used for systemic delivery with some success, and recent modifications appear to enhance systemic delivery, at least to liver. Various nanoparticle formulations are now being developed which may also enhance delivery. Going forward, topical applications of ASRs would seem to have the best chances for success. In summary, modifications to ASRs to enhance stability, improve targeting, and incremental improvements in delivery vehicles continue to make ASRs attractive as molecular therapeutics, but their advance toward the bedside has been agonizingly slow. J. Cell. Biochem. 98: 14,35, 2006. © 2006 Wiley-Liss, Inc. [source] Spatiotemporal Delivery Strategies for Promoting Musculoskeletal Tissue Regeneration,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2009Robert E Guldberg PhD Abstract A primary regenerative medicine strategy is to stimulate or augment endogenous repair mechanisms that promote functional restoration of damaged or degenerated tissues. There is increasing evidence that maximizing the potency of tissue regenerative therapies will require design and development of delivery approaches that provide controlled spatiotemporal release of key signaling molecules. Guidance on which factors to deliver and the timing of delivery is emerging from advances in understanding of critical pathways involved in the development of integrated musculoskeletal tissues. A broad range of biomaterials-based deployment technologies are becoming available that allow controlled spatial presentation and release kinetics of biological cues. The purpose of this perspective article is to review promising spatiotemporal delivery strategies designed to promote functional tissue regeneration with an emphasis on vascularized bone repair. [source] A Mitochondrial view of aging, reactive oxygen species and metastatic cancerAGING CELL, Issue 4 2010Warren Ladiges Summary This perspective article highlights the growing evidence placing mitochondria and mitochondrial function at the center of cancer as an age-related disease. The discussion starts from the mitochondrial free radical hypothesis that predicts the involvement of endogenous mitochondrial reactive oxygen species (ROS) in cancer development and summarizes studies demonstrating the impact of the modulation of ROS levels on cancer development and metastasis. Cancer is fundamentally a complex interplay of cell growth, division, metastasis and death- processes connected to mitochondria through energy metabolism. Based on this evidence, therapeutics focused on mitochondrial function and mitochondrial ROS production are an attractive approach to modulating the progression of metastatic cancer and the general improvement of human health span. [source] Promises of Biomarkers in Drug Development , A Reality CheckCHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2007Estelle Marrer Biomarkers have been a buzz word in drug development for the last 5 years. But where do we stand now? This perspective article will demonstrate to which extent biomarkers have impacted drug development and the use of drugs. In particular, the different types of biomarkers, their identification, validation and use in different phases of drug development from drug discovery, to approval, to clinical application will be discussed as well as the state-of-the-art biomarker technologies and promising future methods. The high interest in biomarkers has generated the need for development of new technologies and refinement of existing ones. Besides discussing their perspectives of applications, the present article also illustrates the future of biomarker development in terms of qualification for regulatory use and co-development. [source] | ||||||||||