Paternally transmitted FMR1 alleles are less stable than maternally transmitted alleles in the common and intermediate size range

Fragile X syndrome, a form of X-linked mental retardation, results from the hyperexpansion of a CGG trinucleotide repeat located in the 5' untranslated region of the fragile X mental retardation (FMR1) gene. Relatively little is known about the initial mutation that causes a stable allele to become unstable and, eventually, to expand to the full mutation. In the present study, we have examined 1,452 parent-child transmissions of alleles of common (< or =39 repeats) or intermediate (40-59 repeats) sizes to study the initial mutation events. Of these, 201 have been sequenced and haplotyped. Using logistic regression analysis, we found that parental origin of transmission, repeat size (for unsequenced alleles), and number of the 3' CGGs (for sequenced alleles) were significant risk factors for repeat instability. Interestingly, transmission of the repeat through males was less stable than that through females, at the common- and intermediate-size level. This pattern differs from that seen for premutation-size alleles: paternally transmitted alleles are far more stable than maternally transmitted alleles. This difference that depends on repeat size suggests either a different mutational mechanism of instability or an increase in selection against sperm as their repeat size increases.     

The plug domain of the SecY protein stabilizes the closed state of the translocation channel and maintains a membrane seal

Proteins are translocated across membranes through a channel that is formed by the prokaryotic SecY or eukaryotic Sec61 complex. The crystal structure of the SecY channel from M. jannaschii revealed a plug domain that appears to seal the channel in its closed state. However, the role of the plug remains unclear, particularly because plug deletion mutants in S. cerevisiae are functional. Here, we demonstrate that plug deletion mutants in E. coli SecY are also functional and even efficiently translocate proteins with defective or missing signal sequences. The crystal structures of equivalent plug deletions in SecY of M. jannaschii show that, although the overall structures are maintained, new plugs are formed. These lack many interactions that normally stabilize the closed channel, explaining why the channels can open for proteins with signal-sequence mutations. Our data show that the plug domain is required to maintain a closed state of the channel and suggest a mechanism for channel gating.     

Experimental logging alters the abundance and community composition of ovipositing mosquitoes in the southern Appalachians

1. The loss of intact forest via logging can influence vector‐borne disease dynamics in part by altering the abundance or diversity of mosquito species. Using an experimental field approach, we characterised how two types of logging (clearcut and repeat‐entry shelterwood) affected temperate forest mosquito abundance and diversity in southwestern Virginia. 2.From May to September in 2008–2010, infusion‐baited gravid traps were used to collect ovipositing female mosquitoes across experimental forest plots that varied in logging treatment. Of the 29 680 collected adult female mosquitoes, the three dominant taxa captured were Aedes triseriatus (55%), Aedes japonicus (21%), and Culex pipiens/restuans (20%). 3. Logging treatment had a significant effect on the overall number of female mosquitoes caught per trap night, with lower average abundance of females on both logged treatments relative to two types of unlogged, control plots. When the three most abundant mosquito species were examined separately, logging treatment significantly influenced the abundance of both Aedes species, but did not significantly affect C. pipiens/restuans abundance. 4. Logging treatment did not influence the richness or diversity of mosquito species captured in gravid traps. However, logging treatment significantly altered the multivariate community composition of captured mosquitoes, an effect probably mediated by differential species‐specific impacts of logging on abundance. 5. Overall, the results of the present study suggest that the risk of arboviruses transmitted by container‐breeding Aedes species may be lower following a logging event in Appalachian forests because of reduced A. japonicus and A. triseriatus abundance with logging.     

Genome-Wide Linkage Analysis of Cardiovascular Disease Biomarkers in a Large,Multigenerational Family

Given the importance of cardiovascular disease (CVD) to public health and the demonstrated heritability of both disease status and its related risk factors, identifying the genetic variation underlying these susceptibilities is a critical step in understanding the pathogenesis of CVD and informing prevention and treatment strategies. Although one can look for genetic variation underlying susceptibility to CVD per se, it can be difficult to define the disease phenotype for such a qualitative analysis and CVD itself represents a convergence of diverse etiologic pathways. Alternatively, one can study the genetics of intermediate traits that are known risk factors for CVD, which can be measured quantitatively. Using the latter strategy, we have measured 21 cardiovascular-related biomarkers in an extended multigenerational pedigree, the CARRIAGE family (Carolinas Region Interaction of Aging, Genes, and Environment). These biomarkers belong to inflammatory and immune, connective tissue, lipid, and hemostasis pathways. Of these, 18 met our quality control standards. Using the pedigree and biomarker data, we have estimated the broad sense heritability (H2) of each biomarker (ranging from 0.09–0.56). A genome-wide panel of 6,015 SNPs was used subsequently to map these biomarkers as quantitative traits. Four showed noteworthy evidence for linkage in multipoint analysis (LOD score ≥ 2.6): paraoxonase (chromosome 8p11, 21), the chemokine RANTES (22q13.33), matrix metalloproteinase 3 (MMP3, 17p13.3), and granulocyte colony stimulating factor (GCSF, 8q22.1). Identifying the causal variation underlying each linkage score will help to unravel the genetic architecture of these quantitative traits and, by extension, the genetic architecture of cardiovascular risk.     

Growth of a species,an association,a science: 80 years of growth and development research

Physical anthropological research was codified in the United States with the creation of the American Association of Physical Anthropology (AAPA) in 1929. That same year, a study began in yellow springs, Ohio, with a goal of identifying “what makes people different.” The approach used to answer that question was to study the growth and development of Homo sapiens. The resulting study, the Fels Longitudinal Study, is currently the longest continuous study of human growth and development in the world. Although the AAPA and the Fels Longitudinal Study have existed as separate entities for more than 80 years now, it is not surprising, given the relationship between anatomical and developmental research, there has been considerable overlap between the two. As the field of physical anthropology has blossomed to include subdisciplines such as forensics, genetics, primatology, as well as sophisticated statistical methodologies, the importance of growth and development research has escalated. Although current Fels Longitudinal Study research is largely directed at biomedical questions, virtually all findings are relevant to physical anthropology, providing insights into basic biological processes and life history parameters. Some key milestones from the early years of the AAPA and the Fels Longitudinal Study are highlighted here that address growth and development research in physical anthropology. These are still held as fundamental concepts that underscore the importance of this line of inquiry, not only across the subdisciplines of physical anthropology, but also among anthropological, biological, and biomedical inquiries. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.     

Female Barbary macaque (Macaca sylvanus) copulation calls do not reveal the fertile phase but influence mating outcome

In a number of primate species, females utter loud and distinctive calls during mating. Here we aim to clarify the information content and function of Barbary macaque (Macaca sylvanus) copulation calls by testing (i) whether or not copulation calls advertise the female fertile phase and (ii) whether and how copulation calls influence male ejaculatory behaviour. In order to do this, we combined hormone measurements with acoustic analysis and behavioural observations. In contrast to a previous study implying that the structure of copulation calls indicates the timing of the fertile phase, our results, using objective endocrine criteria for assessing ovulation, provide evidence that the structure of copulation calls of female Barbary macaques does not reveal the timing of the fertile phase. More importantly, females seem to influence the likelihood of ejaculation by calling versus remaining silent and by adjusting the timing of call onset. Females make use of this ability to influence mating outcome to ensure ejaculatory matings with almost all males in the group. In addition, calls given during ejaculatory copulations differ from those during non-ejaculatory copulations, providing information about mating outcome for listeners. We conclude that in this species, copulation calls apparently serve to enhance sperm competition and maximize paternity confusion.     

Rapid cross-linking of elastin-like polypeptides with (hydroxymethyl)phosphines in aqueous solution

In situ gelation of injectable polypeptide-based materials is attractive for minimally invasive in vivo implantation of biomaterials and tissue engineering scaffolds. We demonstrate that chemically cross-linked elastin-like polypeptide (ELP) hydrogels can be rapidly formed in aqueous solution by reacting lysine-containing ELPs with an organophosphorous cross-linker, beta-[tris(hydroxymethyl)phosphino]propionic acid (THPP) under physiological conditions. The mechanical properties of the cross-linked ELP hydrogels were largely modulated by the molar concentration of lysine residues in the ELP and the pH at which the cross-linking reaction was carried out. Fibroblasts embedded in ELP hydrogels survived the cross-linking process and were viable after in vitro culture for 3 days. DNA quantification of ELP hydrogels with encapsulated fibroblasts indicated that there was no significant difference in DNA content between day 0 and day 3 when ELP hydrogels were formed with an equimolar ratio of THPP and lysine residues of the ELPs. These results suggest that THPP cross-linking may be a biocompatible strategy for the in situ formation of cross-linked hydrogels.