Abstract The restricted use of immunoglobulin heavy chain variable (IGHV) family 4 gene segments by clonally expanded B cells in brain lesions and cerebrospinal fluid (CSF) of multiple sclerosis (MS) ...patients is well documented. Specifically, the overrepresentation of gene IGHV4-39 has been highlighted in multiple studies. To investigate the role of IGHV4-39 in MS, we screened 193 MS cases, representing the extremes of clinical outcome (benign and malignant), and 187 controls for a previously reported germline deletion polymorphism containing IGHV4-39. We did not reveal a genetic association linking this polymorphism to MS risk or progression.
The distribution of genetic variance within and among socially interacting groups, often quantified as the average relatedness or r̄ is an important determinant of the evolution of social behaviors. ...Models of social evolution often treat this average as a constant characteristic of a species. In this paper, we present data documenting the degree of temporal and spatial variation in the average relatedness of larval groups of imported willow leaf beetles, a species whose immatures display several primitive social behaviors. Collections of groups were made over three generations at three localities in Virginia and three localities in Illinois. Average relatedness was estimated from the distribution of electrophoretically determined genotypic frequencies within and among groups for each collection. Average relatedness ranged from 0.20 at one locality in Illinois to 0.65 at one locality in Virginia. Individual cases of pairwise differences between samples indicated that there were both temporal and locality effects. Further, statistical analysis showed the set of relatedness values to be heterogeneous with significant locality effects. Geographic genetic variance was also partitioned among trees sampled within localities in Illinois, among localities within each state, and between states. Notably, significant gene-frequency variation among groups of beetles occupying closely spaced trees was detected at several localities.
The curveback lineage of guppy is characterized by heritable idiopathic-type spinal curvature that develops during growth. Prior work has revealed several important developmental similarities to the ...human idiopathic scoliosis (IS) syndrome. In this study we investigate structural and histological aspects of the vertebrae that are associated with spinal curvature in the curveback guppy and test for sexual dimorphism that might explain a female bias for severe curve magnitudes in the population.
Vertebrae were studied from whole-mount skeletal specimens of curved and non-curved adult males and females. A series of ratios were used to characterize structural aspects of each vertebra. A three-way analysis of variance tested for effects of sex, curvature, vertebral position along the spine, and all 2-way interactions (i.e., sex and curvature, sex and vertebra position, and vertebra position and curvature). Histological analyses were used to characterize micro-architectural changes in affected vertebrae and the intervertebral region.
In curveback, vertebrae that are associated with curvature demonstrate asymmetric shape distortion, migration of the intervertebral ligament, and vertebral thickening on the concave side of curvature. There is sexual dimorphism among curved individuals such that for several vertebrae, females have more slender vertebrae than do males. Also, in the region of the spine where lordosis typically occurs, curved and non-curved females have a reduced width at the middle of their vertebrae, relative to males.
Based on similarities to human spinal curvatures and to animals with induced curves, the concave-convex biases described in the guppy suggest that there is a mechanical component to curve pathogenesis in curveback. Because idiopathic-type curvature in curveback is primarily a sagittal deformity, it is structurally more similar to Scheuermann kyphosis than IS. Anatomical differences between teleosts and humans make direct biomechanical comparisons difficult. However, study of basic biological systems involved in idiopathic-type spinal curvature in curveback may provide insight into the relationship between a predisposing aetiology, growth, and biomechanics. Further work is needed to clarify whether observed sex differences in vertebral characteristics are related to the female bias for severe curves that is observed in the population.
Antibody Engineering and Therapeutics Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix ...
mAbs,
05/2014, Letnik:
6, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The 24
th
Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC ...Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates.
In this paper, we characterize microsatellite "death." We hypothesize that "death," as it relates to microsatellites, also refers to a combination of two mutations. The first mutation interrupts the ...repeat, preventing slipped-strand mispairing and stabilizing the repeat. The second involves the deletion of large sections of the repeat. We use the term "death," because the ultimate result of these interruptions and deletions is an almost unrecognizable homologous DNA sequence that includes only a small portion of the original repeat region. The first component of microsatellite death, interruption-induced microsatellite stability, has been reported elsewhere (Weber 1990; Garza, Slatkin, and Freimer 1995; Bichara, Schumacher, and Fuchs 1995; Petes, Greenwell, and Dominska 1997). Interruptions may inhibit the formation of mutational intermediates (e.g., hairpin structures) or alter intermediates such that they are more easily recognized and repaired (Bichara, Schumacher, and Fuchs 1995). The second component of microsatellite death, a reduction in allele size, was observed by mapping sequences of a (TTA) sub(n) microsatellite locus from five Poecilia (Cyprinodontiformes: Poeciliidae) species onto a phylogeny. Poecilia reticulata, Poecilia picta, and Poecilia caucana are variable at the (TTA) sub(n) locus, with allele length ranging from 30 to 117 bp, whereas Poecilia parae and Poecilia bifurca are monomorphic and short, possessing 30- and 27-bp alleles, respectively.
In which b(z) is parasite transmissibility, z is parasite virulence, dp is the rate at which parasite offspring 'disperse' to new, randomly chosen patches, i is the number of uninfected hosts, j is ...the number of infected hosts, class (k, l) is a patch with k uninfected hosts and l infected hosts,r(k,l) is the relatedness between two different parasites on the same class-(k, l) patch, v(k, l) is the reproductive value of a class- (k, l) parasite, and prime denotes differentiation. ... the reduction in optimal virulence does not seem to be the simple "individual-level adaptation" that the authors claim1. ... they suggest that models of meiotic drive could also be used to define individual-level adaptation out of existence2.
Members of the genus Poecilia exhibit extensive morphological, behavioral, and life history variation within and between species. This natural variation, coupled with short generation times and the ...ease with which members of this genus can be cultured in the lab, have made several species model systems for studying the effects of sexual and natural selection on the evolution of natural populations. Given that there is no clear understanding of the phylogenetic relationships within the genus, these studies have not been put into a historical context, and between-species comparisons have been limited. We sequenced the complete NADH Dehydrogenase Subunit 2 (ND2) mitochondrial gene (1047 bp) in representatives of the major divisions of the genus in order to examine these relationships. The subgeneric groups of Rosen and Bailey (1963) are, for the most part, supported, with some adjustment within the subgenera Poecilia and Pamphorichthys. The morphological distinctness of the groups within Poecilia suggest that the original generic designations be reinstated, but this awaits a more thorough analysis. Two implications from the phylogeny are particularly relevant to sexual selection studies: within the North and Central American mollies, the three species of sailfin mollies form a monophyletic group, and within the subgenus Lebistes, the sister taxon to the guppy, P. reticulata, is most likely the group of species previously designated as Micropoecilia.
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