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271.
272.
Sarah Cobey Patrick Wilson Frederick A. Matsen IV 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2015,370(1676)
The B-cell immune response is a remarkable evolutionary system found in jawed vertebrates. B-cell receptors, the membrane-bound form of antibodies, are capable of evolving high affinity to almost any foreign protein. High germline diversity and rapid evolution upon encounter with antigen explain the general adaptability of B-cell populations, but the dynamics of repertoires are less well understood. These dynamics are scientifically and clinically important. After highlighting the remarkable characteristics of naive and experienced B-cell repertoires, especially biased usage of genes encoding the B-cell receptors, we contrast methods of sequence analysis and their attempts to explain patterns of B-cell evolution. These phylogenetic approaches are currently unlinked to explicit models of B-cell competition, which analyse repertoire evolution at the level of phenotype, the affinities and specificities to particular antigenic sites. The models, in turn, suggest how chance, infection history and other factors contribute to different patterns of immunodominance and protection between people. Challenges in rational vaccine design, specifically vaccines to induce broadly neutralizing antibodies to HIV, underscore critical gaps in our understanding of B cells'' evolutionary and ecological dynamics. 相似文献
273.
Secondhand smoke and traffic exhaust confer opposing risks for asthma in normal and overweight children 下载免费PDF全文
274.
Malcolm Stein IV Chien-Fan Chen Daniel J. Robles Christopher Rhodes Partha P. Mukherjee 《Journal of visualized experiments : JoVE》2016,(108)
Research into new and improved materials to be utilized in lithium-ion batteries (LIB) necessitates an experimental counterpart to any computational analysis. Testing of lithium-ion batteries in an academic setting has taken on several forms, but at the most basic level lies the coin cell construction. In traditional LIB electrode preparation, a multi-phase slurry composed of active material, binder, and conductive additive is cast out onto a substrate. An electrode disc can then be punched from the dried sheet and used in the construction of a coin cell for electrochemical evaluation. Utilization of the potential of the active material in a battery is critically dependent on the microstructure of the electrode, as an appropriate distribution of the primary components are crucial to ensuring optimal electrical conductivity, porosity, and tortuosity, such that electrochemical and transport interaction is optimized. Processing steps ranging from the combination of dry powder, wet mixing, and drying can all critically affect multi-phase interactions that influence the microstructure formation. Electrochemical probing necessitates the construction of electrodes and coin cells with the utmost care and precision. This paper aims at providing a step-by-step guide of non-aqueous electrode processing and coin cell construction for lithium-ion batteries within an academic setting and with emphasis on deciphering the influence of drying and calendaring. 相似文献
275.
Abhay K. Varma Arabinda Das Gerald Wallace IV John Barry Alexey A. Vertegel Swapan K. Ray Naren L. Banik 《Neurochemical research》2013,38(5):895-905
The incidence of acute and chronic spinal cord injury (SCI) in the United States is more than 10,000 per year, resulting in 720 cases per million persons enduring permanent disability each year. The economic impact of SCI is estimated to be more than 4 billion dollars annually. Preclinical studies, case reports, and small clinical trials suggest that early treatment may improve neurological recovery. To date, no proven therapeutic modality exists that has demonstrated a positive effect on neurological outcome. Emerging data from recent preclinical and clinical studies offer hope for this devastating condition. This review gives an overview of current basic research and clinical studies for the treatment of SCI. 相似文献
276.
S. Schaack D. E. Allen L. C. Latta IV K. K. Morgan M. Lynch 《Journal of evolutionary biology》2013,26(2):451-456
Understanding the impact of spontaneous mutations on fitness has many theoretical and practical applications in biology. Although mutational effects on individual morphological or life‐history characters have been measured in several classic genetic model systems, there are few estimates of the rate of decline due to mutation for complex fitness traits. Here, we estimate the effects of mutation on competitive ability, an important complex fitness trait, in a model system for ecological and evolutionary genomics, Daphnia. Competition assays were performed to compare fitness between mutation‐accumulation (MA) lines and control lines from eight different genotypes from two populations of Daphnia pulicaria after 30 and 65 generations of mutation accumulation. Our results show a fitness decline among MA lines relative to controls as expected, but highlight the influence of genomic background on this effect. In addition, in some assays, MA lines outperform controls providing insight into the frequency of beneficial mutations. 相似文献
277.
Peter Vanderslice Ronald J. Biediger Darren G. Woodside Wells S. Brown Sayadeth Khounlo Navin D. Warier C. William Gundlach IV Amy R. Caivano William G. Bornmann David S. Maxwell Bradley W. McIntyre James T. Willerson Richard A. F. Dixon 《The Journal of biological chemistry》2013,288(27):19414-19428
Activation of the integrin family of cell adhesion receptors on progenitor cells may be a viable approach to enhance the effects of stem cell-based therapies by improving cell retention and engraftment. Here, we describe the synthesis and characterization of the first small molecule agonist identified for the integrin α4β1 (also known as very late antigen-4 or VLA-4). The agonist, THI0019, was generated via two structural modifications to a previously identified α4β1 antagonist. THI0019 greatly enhanced the adhesion of cultured cell lines and primary progenitor cells to α4β1 ligands VCAM-1 and CS1 under both static and flow conditions. Furthermore, THI0019 facilitated the rolling and spreading of cells on VCAM-1 and the migration of cells toward SDF-1α. Molecular modeling predicted that the compound binds at the α/β subunit interface overlapping the ligand-binding site thus indicating that the compound must be displaced upon ligand binding. In support of this model, an analog of THI0019 modified to contain a photoreactive group was used to demonstrate that when cross-linked to the integrin, the compound behaves as an antagonist instead of an agonist. In addition, THI0019 showed cross-reactivity with the related integrin α4β7 as well as α5β1 and αLβ2. When cross-linked to αLβ2, the photoreactive analog of THI0019 remained an agonist, consistent with it binding at the α/β subunit interface and not at the ligand-binding site in the inserted (“I”) domain of the αL subunit. Co-administering progenitor cells with a compound such as THI0019 may provide a mechanism for enhancing stem cell therapy. 相似文献
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