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排序方式: 共有536条查询结果,搜索用时 15 毫秒
531.
Julie A Douthwaite Sudharsan Sridharan Catherine Huntington Jayne Hammersley Rose Marwood Jonna K Hakulinen Margareta Ek Tove Sj?gren David Rider Cyril Privezentzev Jonathan C Seaman Peter Cariuk Vikki Knights Joyce Young Trevor Wilkinson Matthew Sleeman Donna K Finch David C Lowe Tristan J Vaughan 《MABS-AUSTIN》2015,7(1):152-166
Therapeutic monoclonal antibodies targeting G-protein-coupled receptors (GPCRs) are desirable for intervention in a wide range of disease processes. The discovery of such antibodies is challenging due to a lack of stability of many GPCRs as purified proteins. We describe here the generation of Fpro0165, a human anti-formyl peptide receptor 1 (FPR1) antibody generated by variable domain engineering of an antibody derived by immunization of transgenic mice expressing human variable region genes. Antibody isolation and subsequent engineering of affinity, potency and species cross-reactivity using phage display were achieved using FPR1 expressed on HEK cells for immunization and selection, along with calcium release cellular assays for antibody screening. Fpro0165 shows full neutralization of formyl peptide-mediated activation of primary human neutrophils. A crystal structure of the Fpro0165 Fab shows a long, protruding VH CDR3 of 24 amino acids and in silico docking with a homology model of FPR1 suggests that this long VH CDR3 is critical to the predicted binding mode of the antibody. Antibody mutation studies identify the apex of the long VH CDR3 as key to mediating the species cross-reactivity profile of the antibody. This study illustrates an approach for antibody discovery and affinity engineering to typically intractable membrane proteins such as GPCRs. 相似文献
532.
Peter W Thomas Sarah Thomas Paula Kersten Rosemary Jones Alison Nock Vicky Slingsby Colin Green Roger Baker Kate Galvin Charles Hillier 《BMC neurology》2010,10(1):43
Background
Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. 相似文献533.
Kristien Peeters Ivan Litvinenko Bob Asselbergh Leonardo Almeida-Souza Teodora Chamova Thomas Geuens Elke Ydens Magdalena Zimoń Joy Irobi Els De?Vriendt Vicky De?Winter Tinne Ooms Vincent Timmerman Ivailo Tournev Albena Jordanova 《American journal of human genetics》2013,92(6):955-964
The most common form of spinal muscular atrophy (SMA) is a recessive disorder caused by deleterious SMN1 mutations in 5q13, whereas the genetic etiologies of non-5q SMA are very heterogeneous and largely remain to be elucidated. In a Bulgarian family affected by autosomal-dominant proximal SMA, we performed genome-wide linkage analysis and whole-exome sequencing and found a heterozygous de novo c.320C>T (p.Ser107Leu) mutation in bicaudal D homolog 2 (Drosophila) (BICD2). Further analysis of BICD2 in a cohort of 119 individuals with non-5q SMA identified a second de novo BICD2 mutation, c.2321A>G (p.Glu774Gly), in a simplex case. Detailed clinical and electrophysiological investigations revealed that both families are affected by a very similar disease course, characterized by early childhood onset, predominant involvement of lower extremities, and very slow disease progression. The amino acid substitutions are located in two interaction domains of BICD2, an adaptor protein linking the dynein molecular motor with its cargo. Our immunoprecipitation and localization experiments in HeLa and SH-SY5Y cells and affected individuals’ lymphoblasts demonstrated that p.Ser107Leu causes increased dynein binding and thus leads to accumulation of BICD2 at the microtubule-organizing complex and Golgi fragmentation. In addition, the altered protein had a reduced colocalization with RAB6A, a regulator of vesicle trafficking between the Golgi and the endoplasmic reticulum. The interaction between p.Glu744Gly altered BICD2 and RAB6A was impaired, which also led to their reduced colocalization. Our study identifies BICD2 mutations as a cause of non-5q linked SMA and highlights the importance of dynein-mediated motility in motor neuron function in humans. 相似文献
534.
Emanuela W. A. Weidlich Cara R. Nelson John L. Maron Ragan M. Callaway Benjamin M. Delory Vicky M. Temperton 《Restoration Ecology》2021,29(1)
Priority effects refer to the order or timing of species arrival, including how species that arrive early at a site either positively or negatively affect establishment, growth, or reproduction of species that arrive later. Despite the clear implications of priority effects for ecological restoration, there have been no reviews of how and where priority effects have been studied and the extent to which findings can be applied to restoration. Here, we systematically review the literature on priority effects by (1) synthesizing information from papers that compared simultaneous and nonsimultaneous planting or sowing; (2) discussing the mechanisms through which priority effects operate, (3) considering how these mechanisms might be manipulated to achieve restoration goals; and (4) highlighting future research needed to improve the use of priority effects in restoration. In a term‐targeted search, we found 43 studies that experimentally manipulated the order of arrival of different species. Overall, these concluded that even small delays in arrival time, as opposed to simultaneous arrival of species, can promote differences in subsequent community composition as well as ecosystem functions. There were very few studies on the long‐term stability of these priority effects, and the majority were conducted in temperate grasslands. Our findings suggest that creating alternative vegetation states via priority treatments is a promising avenue for restoration. However, for the concept to be best operationalized for restoration, we need research in more ecosystems that are priorities for restoration, and treatments that are followed over extended time periods. 相似文献
535.