Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation

Somatic hypermutation of immunoglobulin variable region genes occurs within germinal centres (GCs) and is the process responsible for affinity maturation of antibodies during an immune response. Previous studies have focused almost exclusively on the immune response to haptens, which may be unrepresentative of epitopes on protein antigens. In this study, we have exploited a model system that uses transgenic B and CD4<sup>+</sup> T cells specific for hen egg lysozyme (HEL) and a chicken ovalbumin peptide, respectively, to investigate a tightly synchronized immune response to protein antigens of widely differing affinities, thus allowing us to track many facets of the development of an antibody response at the antigen-specific B cell level in an integrated system <i>in</i> <i>vivo</i>. Somatic hypermutation of immunoglobulin variable genes was analysed in clones of transgenic B cells proliferating in individual GCs in response to HEL or the cross-reactive low-affinity antigen, duck egg lysozyme (DEL). Molecular modelling of the antibody–antigen interface demonstrates that recurring mutations in the antigen-binding site, selected in GCs, enhance interactions of the antibody with DEL. The effects of these mutations on affinity maturation are demonstrated by a shift of transgenic serum antibodies towards higher affinity for DEL in DEL-cOVA immunized mice. The results show that B cells with high affinity antigen receptors can revise their specificity by somatic hypermutation and antigen selection in response to a low-affinity, cross-reactive antigen. These observations shed further light on the nature of the immune response to pathogens and autoimmunity and demonstrate the utility of this novel model for studies of the mechanisms of somatic hypermutation

The effects of rider size and saddle fit for horse and rider on forces and pressure distribution under saddles: a pilot study

Background: There is limited scientific evidence concerning the effect of rider weight on pressures under the saddle and equine performance. Objectives: To assess pressure distribution and magnitude in horses ridden by four riders of similar ability, but differing in bodyweight and height. Study Design: Prospective, cross-over, randomised trial. Methods: Six horses in regular work were ridden by four riders (rider bodyweight: horse body weight percentage >10-≤12 [L=Light], >12≤15 [M=Moderate], >1520 [VH=VeryHeavy]), performing a purpose-designed dressage test (30 minutes). The test was abandoned for ≥grade 3/8 lameness or ≥10 behavioural markers (assessed in real-time). A calibrated force mat (Pliance) was used to record pressures under the saddle in walk, trot and canter on left and right reins. Rider position was assessed. Results: All 13 H and VH rider tests were abandoned (lameness, n=12; behaviour, n=1), as was one of 12 M rider tests (lameness). At walk, the seat of rider VH extended beyond the cantle of the saddle; rider H sat on the cantle of the saddle. At trot and canter the heels of rider VH were consistently cranial to the tubera coxae and shoulders. Pressures were significantly higher under the caudal aspect of the saddle compared with cranially for rider VH in walk (P<0.05, Anova, Bonferroni). At rising trot pressures were higher cranially for riders L, M and H (P<0.05, Anova, Bonferroni), but were similar cranially and caudally for rider VH. The highest maximum peak pressure was recorded for rider VH in canter. Limitations: Speed can alter pressure measurements, but was not controlled or recorded. Conclusions: There were differences in magnitude and distribution of pressures among the four riders according to their size, which may have contributed to the development of musculoskeletal pain. This may also have been influenced by saddle fit for riders and their positions

The Iowa Homemaker vol.23, no.13

Winter in Iowa, page 2 Keeping Up With Today, D. Jean Merrill, page 3 “We’re in The Army Now”, Jeannette Pickford, page 4 Decorate For Christmas Festivities, June Hudek, page 5 Make Your Christmas Gifts, Marian Hoppe, page 6 Public Relations To The Fore, Dorothy Ann Roost, page 7 Vicky Fashions Her Christmas, Josephine Ahern, page 8 Occupational Therapists, Gertrud Ortgies, page 10 Dress Up Your Christmas Packages, Rosalie Riglin, page 11 Express Yourself To Impress Others, Doris Ann Gregg, page 12 Their Diets Are Supervised, Eugenia Crawford, page 13 What’s New In Home Economics, Marilyn Mitchell, page 14 Across Alumnae Desks, Harriet Keen, page 18 He Cooked In The Clouds¸ Dick Crowther, page 20 Plans For Her Country’s Future, Thelma Estevez, page 22 Foods of the Future, Shirley Rolfs, page 24 Yuletide Celebrations In Other Lands, Mary Rothacker, page 26 Alums In The News, Patricia Maddex, page 2

The contribution of international health volunteers to the health workforce in sub-Saharan Africa

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

No Humanitarian Intervention in Asian Genocides: How Possible and Legitimate?

This paper addresses an important empirical puzzle: why has the United States, without exception, chosen not to intervene in the six humanitarian catastrophes in post-war Asia, namely in Indonesia, East Pakistan/Bangladesh, Cambodia, East Timor, Sri Lanka and Myanmar? We use an eclectic approach that blends arguments about the international normative structure and geostrategic interests to examine what has made the absence of humanitarian intervention in Asia by the US possible and legitimate. Specifically, we focus on the paradox between calls for humanitarian intervention and the historically and geographically contingent social construction of the norms of humanity, national sovereignty and UN-backed multilateralism in conjunction with US and Chinese concerns over their regional geostrategic interests. The normative narratives about race, ‘communists’, ‘terrorists’, international order and inclusive multilateral process, and geostrategic interests of the US and China combine to make non-intervention possible and legitimate

BMP-SMAD Signaling Regulates Lineage Priming, but Is Dispensable for Self-Renewal in Mouse Embryonic Stem Cells

Biological and Soft Matter Physic

Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI): A Prospective Longitudinal Observational Study

BACKGROUND: Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies. OBJECTIVE: To improve characterization and classification of TBI and to identify best clinical care, using comparative effectiveness research approaches. METHODS: This multicenter, longitudinal, prospective, observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting patients, presenting within 24 hours of injury, with a clinical diagnosis of TBI and an indication for computed tomography. Broader registry-level data collection in approximately 20 000 patients will assess generalizability. Cross sectional comprehensive outcome assessments, including quality of life and neuropsychological testing, will be performed at 6 months. Longitudinal assessments will continue up to 24 months post TBI in patient subsets. Advanced neuroimaging and genomic and biomarker data will be used to improve characterization, and analyses will include neuroinformatics approaches to address variations in process and clinical care. Results will be integrated with living systematic reviews in a process of knowledge transfer. The study initiation was from October to December 2014, and the recruitment period was for 18 to 24 months. EXPECTED OUTCOMES: Collaborative European NeuroTrauma Effectiveness Research in TBI should provide novel multidimensional approaches to TBI characterization and classification, evidence to support treatment recommendations, and benchmarks for quality of care. Data and sample repositories will ensure opportunities for legacy research. DISCUSSION: Comparative effectiveness research provides an alternative to reductionistic clinical trials in restricted patient populations by exploiting differences in biology, care, and outcome to support optimal personalized patient management