Selection for Increased Natural Antibody Levels to Improve Disease Resilience in Pigs

Breeding animals are typically raised under high health conditions in nucleus herds, but their offspring are often exposed to multiple disease challenges in commercial production facilities. Because breeding animals are not exposed to many common swine pathogens, it is difficult to select for resilience to disease. A possible solution is selecting for levels of natural antibodies (NAb), which can be measured in a high health environment and in this study are shown to correlate with disease resilience and to be heritable (h2 = 0.11 to 0.39). Therefore, breeding for increased NAb levels in clean conditions could be a valuable method to improve resilience and decrease mortality in market pigs. Work is ongoing to verify the potential of this prediction

The human iliotibial band is specialized for elastic energy storage compared with the chimp fascia lata

This study examines whether the human iliotibial band (ITB) is specialized for elastic energy storage relative to the chimpanzee fascialata (FL). To quantify the energy storage potential of these structures, we created computer models of human and chimpanzee lower limbs based on detailed anatomical dissections. We characterized the geometry andforce–length properties of the FL,tensorfascia lata (TFL) and gluteus maximus (GMax) in four chimpanzee cadavers based on measurements of muscle architecture and moment arms about the hip and knee. We used the chimp model to estimate the forces and corresponding strains in the chimp FL during bipedal walking, and compared these data with analogous estimates from a model of the human ITB, accounting for differences in body mass and lower extremity posture. We estimate that the human ITB stores 15- to 20- times more elastic energy per unit body mass and stride than the chimp FL during bipedal walking. Because chimps walk with persistent hip flexion, the TFL and portions of GMax that insert on the FL undergo smaller excursions (origin to insertion) than muscles that insert on the human ITB. Also, because a smaller fraction of GMax inserts on the chimp FL than on the human ITB, and thus its mass-normalized physiological cross-sectional area is about three times less in chimps, the chimp FL probably transmits smaller muscle forces. These data provide new evidence that the human ITB is anatomically derived compared with the chimp FL and potentially contributes to locomotor economy during bipedal locomotion.Human Evolutionary Biolog

The Fc region of an antibody impacts the neutralization of West Nile viruses in different maturation states

Flavivirus-infected cells secrete a structurally heterogeneous population of viruses because of an inefficient virion maturation process. Flaviviruses assemble as noninfectious, immature virions composed of trimers of envelope (E) and precursor membrane (prM) protein heterodimers. Cleavage of prM is a required process during virion maturation, although this often remains incomplete for infectious virus particles. Previous work demonstrated that the efficiency of virion maturation could impact antibody neutralization through changes in the accessibility of otherwise cryptic epitopes on the virion. In this study, we show that the neutralization potency of monoclonal antibody (MAb) E33 is sensitive to the maturation state of West Nile virus (WNV), despite its recognition of an accessible epitope, the domain III lateral ridge (DIII-LR). Comprehensive epitope mapping studies with 166 E protein DIII-LR variants revealed that the functional footprint of MAb E33 on the E protein differs subtly from that of the well-characterized DIII-LR MAb E16. Remarkably, aromatic substitutions at E protein residue 306 ablated the maturation state sensitivity of E33 IgG, and the neutralization efficacy of E33 Fab fragments was not affected by changes in the virion maturation state. We propose that E33 IgG binding on mature virions orients the Fc region in a manner that impacts subsequent antibody binding to nearby sites. This Fc-mediated steric constraint is a novel mechanism by which the maturation state of a virion modulates the efficacy of the humoral immune response to flavivirus infection

A Very Low-Carbohydrate Diet Improves Symptoms and Quality of Life in Diarrhea-Predominant Irritable Bowel Syndrome

Patients with diarrhea-predominant IBS (IBS-D) anecdotally report symptom improvement after initiating a very low-carbohydrate diet (VLCD). This is the first study to prospectively evaluate a VLCD in IBS-D

Rituximab therapy for juvenile-onset systemic lupus erythematosus

Rituximab (RTX), an anti-CD20 monoclonal antibody, has been proposed for use in the therapy of systemic lupus erythematosus (SLE). We present the initial long-term experience of the safety and efficacy of rituximab for treatment of SLE in children. Eighteen patients (mean age 14 ± 3 years) with severe SLE were treated with rituximab after demonstrating resistance or toxicity to conventional regimens. There was a predominance of female (16/18) and ethnic African (13/18) patients. All had lupus nephritis [World Health Organization (WHO) classes 3–5] and systemic manifestations of vasculitis. Clinical disease activity of the SLE was scored with the SLE-disease activity index 2K (SLEDAI-2K). Patients were followed-up for an average of 3.0 ± 1.3 years (range 0.5 to 4.8 years). B-cell depletion occurred within 2 weeks in all patients and persisted for up to 1 year in some. Clinical activity scores, double-stranded DNA (dsDNA) antibodies, renal function and proteinuria [urine protein to creatinine ratio (Upr/cr)] improved in 93% of the patients. Five patients required multiple courses of RTX for relapse, with B-cell repopulation. One died of infectious endocarditis related to severe immunosuppression. In conclusion, our data support the efficacy of rituximab as adjunctive treatment for SLE in children. Although rituximab was well tolerated by the majority of patients, randomized controlled trials are required to establish its long-term safety and efficacy

Finding Our Way through Phenotypes

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility

Dissonance-Based Interventions for the Prevention of Eating Disorders: Using Persuasion Principles to Promote Health

The limited efficacy of prior eating disorder (ED) prevention programs led to the development of dissonance-based interventions (DBI) that utilize dissonance-based persuasion principles from social psychology. Although DBIs have been used to change other attitudes and behaviors, only recently have they been applied to ED prevention. This article reviews the theoretical rationale and empirical support for this type of prevention program. Relative to assessment-only controls, DBIs have produced greater reductions in ED risk factors, ED symptoms, future risk for onset of threshold or subthreshold EDs, future risk for obesity onset, and mental health utilization, with some effects persisting through 3-year follow-up. DBIs have also produced significantly stronger effects than alternative interventions for many of these outcomes, though these effects typically fade more quickly. A meta-analysis indicated that the average effects for DBIs were significantly stronger than those for non-DBI ED prevention programs that have been evaluated. DBIs have produced effects when delivered to high-risk samples and unselected samples, as well as in efficacy and effectiveness trials conducted by six independent labs, suggesting that the effects are robust and that DBIs should be considered for the prevention of other problems, such as smoking, substance abuse, HIV, and diabetes care