The CUPID (Cultural and Psychosocial Influences on Disability) study: methods of data collection and characteristics of study sample

Background

The CUPID (Cultural and Psychosocial Influences on Disability) study was established to explore the hypothesis that common musculoskeletal disorders (MSDs) and associated disability are importantly influenced by culturally determined health beliefs and expectations. This paper describes the methods of data collection and various characteristics of the study sample.

Methods/Principal Findings

A standardised questionnaire covering musculoskeletal symptoms, disability and potential risk factors, was used to collect information from 47 samples of nurses, office workers, and other (mostly manual) workers in 18 countries from six continents. In addition, local investigators provided data on economic aspects of employment for each occupational group. Participation exceeded 80% in 33 of the 47 occupational groups, and after pre-specified exclusions, analysis was based on 12,426 subjects (92 to 1018 per occupational group). As expected, there was high usage of computer keyboards by office workers, while nurses had the highest prevalence of heavy manual lifting in all but one country. There was substantial heterogeneity between occupational groups in economic and psychosocial aspects of work; three- to five-fold variation in awareness of someone outside work with musculoskeletal pain; and more than ten-fold variation in the prevalence of adverse health beliefs about back and arm pain, and in awareness of terms such as “repetitive strain injury” (RSI).

Conclusions/Significance

The large differences in psychosocial risk factors (including knowledge and beliefs about MSDs) between occupational groups should allow the study hypothesis to be addressed effectively.     

Mediterranean fruit fly subplot hot spots prediction by experts' experience

The Mediterranean fruit fly (medfly), Ceratitis capitata (Wiedemann), is a major pest, infesting hundreds of crop types. Since current field monitoring is mostly manual, understanding the spatiotemporal patterns of pest emergence at the fine scale can optimize precise trap placement and site‐specific treatment activities, also within area wide integrated pest management projects. We carried out a three‐year study in deciduous orchards in Israel, testing for the existence of subplot hot spots in which medfly populations display small‐scale aggregations over consecutive seasons, beyond the expected spatial variability resulting from host type and ripening sequence. medfly population increase in these locations often preceded or was parallel to infestations in surrounding orchards, suggesting that hot spots can provide an important tool for effective prediction and control of pest emergence. We also examined the use of expert knowledge to predict hot spot locations and suggest a methodology for verifying them.     

Mating disruption method against the vine mealybug,Planococcus ficus: effect of sequential treatment on infested vines

The vine mealybug, Planococcus ficus (Signoret) (Hemiptera: Pseudococcidae), is a major pest of vineyards. Here, we tested the efficacy of the mating disruption method against the pest when applied during one or two successive years in high and low infestation levels. Following 1 year of treatment, at low initial infestation levels a shutdown of pheromone traps was observed, along with a significant reduction in infested vines. With initially high infestation levels, a gradual reduction in infested vines was observed, with a trap shutdown seen only after the second year of pheromone application. We discuss the implications of the male mating disruption method for this pest in which the wingless females are aggregated with limited movement among vines, offering multiple mating opportunities for the flying male.     

Inbreeding variability and population structure in the invasive haplodiploid palm‐seed borer (Coccotrypes dactyliperda)

We investigated the mating system and population genetic structure of the invasive haplodiploid palm‐seed borer Coccotrypes dactyliperda in California. We focused on whether these primarily inbreeding beetles have a ‘mixed‐breeding’ system that includes occasional outbreeding, and whether local inbreeding coefficients (F_IS) varied with dominant environmental factors. We also analysed the genetic structure of C. dactyliperda populations across local and regional scales. Based on the analysis of genetic variation at seven microsatellite loci in 1034 individual beetles from 59 populations, we found both high rates of inbreeding and plentiful evidence of mixed‐breeding. F_IS ranged from ?0.56 to 0.90, the highest variability reported within any animal species. There was a negative correlation between F_IS and latitude, suggesting that some latitude‐associated factor affecting mating decisions influenced inbreeding rates. Multiple regressions suggested that precipitation, but not temperature, may be an important correlate. Finally, we found highly significant genetic differentiation among sites, even over short geographic distances (< 1000 m).     

Hsp90 recognizes a common surface on client kinases

Hsp90 is a highly abundant chaperone whose clientele includes hundreds of cellular proteins, many of which are central players in key signal transduction pathways and the majority of which are protein kinases. In light of the variety of Hsp90 clientele, the mechanism of selectivity of the chaperone toward its client proteins is a major open question. Focusing on human kinases, we have demonstrated that the chaperone recognizes a common surface in the amino-terminal lobe of kinases from diverse families, including two newly identified clients, NFkappaB-inducing kinase and death-associated protein kinase, and the oncoprotein HER2/ErbB-2. Surface electrostatics determine the interaction with the Hsp90 chaperone complex such that introduction of a negative charge within this region disrupts recognition. Compiling information on the Hsp90 dependence of 105 protein kinases, including 16 kinases whose relationship to Hsp90 is first examined in this study, reveals that surface features, rather than a contiguous amino acid sequence, define the capacity of the Hsp90 chaperone machine to recognize client kinases. Analyzing Hsp90 regulation of two major signaling cascades, the mitogen-activated protein kinase and phosphatidylinositol 3-kinase, leads us to propose that the selectivity of the chaperone to specific kinases is functional, namely that Hsp90 controls kinases that function as hubs integrating multiple inputs. These lessons bear significance to pharmacological attempts to target the chaperone in human pathologies, such as cancer.     

The role of Holliday junction resolvases in the repair of spontaneous and induced DNA damage

DNA double-strand breaks (DSBs) and other lesions occur frequently during cell growth and in meiosis. These are often repaired by homologous recombination (HR). HR may result in the formation of DNA structures called Holliday junctions (HJs), which need to be resolved to allow chromosome segregation. Whereas HJs are present in most HR events in meiosis, it has been proposed that in vegetative cells most HR events occur through intermediates lacking HJs. A recent screen in yeast has shown HJ resolution activity for a protein called Yen1, in addition to the previously known Mus81/Mms4 complex. Yeast strains deleted for both YEN1 and MMS4 show a reduction in growth rate, and are very sensitive to DNA-damaging agents. In addition, we investigate the genetic interaction of yen1 and mms4 with mutants defective in different repair pathways. We find that in the absence of Yen1 and Mms4 deletion of RAD1 or RAD52 have no further effect, whereas additional sensitivity is seen if RAD51 is deleted. Finally, we show that yeast cells are unable to carry out meiosis in the absence of both resolvases. Our results show that both Yen1 and Mms4/Mus81 play important (although not identical) roles during vegetative growth and in meiosis.     

Large TCR diversity of virus-specific CD8 T cells provides the mechanistic basis for massive TCR renewal after antigen exposure

Ex vivo analysis of virus-specific CD8 T cell populations by anchored PCR has shown that the CD8 TCR repertoire was less oligoclonal (seven to nine clonotypes per individual epitope) than previously thought. In the current study, TCR diversity was investigated by assessing both the overall TCR β-chain variable regions usage as well as the CDR3 regions in ex vivo-isolated CMV- and EBV-specific CD8 T cells from 27 healthy donors. The average number of clonotypes specific to most single viral epitopes comprised between 14 and 77. Changes in the CD8 TCR repertoire were also longitudinally assessed under conditions of HIV-1 chronic infection (i.e., in patients with suppressed virus replication and after treatment interruption and Ag re-exposure). The results showed that a large renewal (≤ 80%) of the TRB repertoire occurred after Ag re-exposure and was eventually associated with an increased T cell recognition functional avidity. These results demonstrate that the global CD8 TCR repertoire is much more diverse (≤ 9-fold) than previously estimated and provide the mechanistic basis for supporting massive repertoire renewal during chronic virus infection and Ag re-exposure.     

Endothelial cell E- and P-selectin up-regulation in murine contact sensitivity is prolonged by distinct mechanisms occurring in sequence

The selectins are adhesion molecules that mediate the tethering and rolling of leukocytes on vascular endothelium. Although E-selectin and P-selectin are known to be expressed by endothelial cells (EC) in response to proinflammatory stimuli, their pattern and mechanisms of expression in immune-mediated inflammation remain poorly understood. By quantifying luminal endothelial selectin expression via i.v. administration of radiolabeled mAb, we detected constitutive expression of P-selectin, but not E-selectin, in mouse skin. Both selectins were transiently up-regulated after intradermal TNF-alpha, IL-1alpha, or IL-1beta. In contrast, during a contact sensitivity response to oxazolone, expression of both selectins was prolonged, with distinct peaks at 6 and 48 h. Experiments with P-selectin gene-targeted mice showed that the P-selectin measured was exclusively expressed by EC rather than platelets. The early and late phases of selectin expression in contact sensitivity were differentiated in terms of their requirement for prior sensitization, and the action of IL-1. Whereas the early phase was a nonspecific 'irritant' response to oxazolone, the late phase was Ag specific and was partially IL-1 dependent. Therefore, persistence of both E- and P-selectin expression in vivo can occur as a result of sequential and distinct EC activation processes that appear to be at least partially different from those previously reported as stimulating ICAM-1 and VCAM-1 expression. The further elucidation of mechanisms of EC activation in this model may help determine the relative roles of selectins and ligands for leukocyte integrins in the sequential recruitment of T cells and other leukocyte subsets during ongoing immune-mediated inflammatory responses.     

Developmental patterns in the polyembryonic parasitoid wasp Copidosoma koehleri

Polyembryony is a unique mode of development in which multiple genetically identical embryos develop from a single egg. In some polyembryonic species a proportion of the embryos develop into soldier larvae, which attack competitors in the host. We studied the development of the polyembryonic wasp Copidosoma koehleri in its host Phthorimaea opercullela. We dissected hosts parasitized by either virgin or mated female wasps at 2day intervals from hatching to the final instars. We documented host mass and head width, the number and size of developing wasps and the presence of a soldier larva. Additionally, we kept a sample of parasitized hosts until emergence of wasps and measured the head width of emerging adults. We characterized wasp development in relation to host development. One half of the broods produced by mated wasps contained one soldier larva throughout development. This suggests that in C. koehleri each female brood produces a single soldier larva, and that the soldier probably survives and grows gradually during host development. Additionally, we found that female broods were larger than male broods during development and also upon emergence. Accordingly, body size was larger for males during development as well as upon emergence. These findings may extend the existing knowledge on polyembryonic development in general, and serve as a baseline for further experiments.