Association of functional variants of PTPN22 and tp53 in psoriatic arthritis: a case-control study

Recent studies have implicated PTPN22 and tp53 in susceptibility to several autoimmune diseases, including rheumatoid arthritis, suggesting that these genes are important in maintaining immune homeostasis. Because autoimmune diseases may share similar susceptibility loci, investigation of these genes in psoriatic arthritis (PsA) is of potential relevance. As a result we investigated known coding polymorphisms in PTPN22 and tp53 in a homogenous Caucasian PsA cohort from Newfoundland, Canada and an admixed Caucasian PsA cohort from Toronto, Canada. We observed a moderate association of the R620W variant of PTPN22 with PsA in the Toronto population only. Because of the conflicting findings reported regarding the association of PTPN22 with PsA, further studies in other PsA populations are warranted.     

Multifactorial day hospital intervention to reduce falls in high risk older people in primary care: a multi-centre randomised controlled trial [ISRCTN46584556]

Background

There are many barriers to patient participation in randomised controlled trials of cancer treatments. To increase participation in trials, strategies need to be identified to overcome these barriers. Our aim was to assess the effectiveness of interventions to overcome barriers to patient participation in randomised controlled trials (RCTs) of cancer treatments.

Methods

A systematic review was conducted. Published and unpublished studies in any language were searched for in fifteen electronic databases, including MEDLINE, EMBASE, CINAHL and PsycINFO, from inception to the end of 2004. Studies of any interventions to improve cancer patient participation in RCTs, which reported the change in recruitment rates, were eligible for inclusion. RCTs and non-randomised controlled trials as well as before and after studies reporting baseline rates specific to the population being investigated were included. Data were extracted by one reviewer into structured summary tables and checked for accuracy by a second reviewer. Each included study was assessed against a checklist for methodological quality by one reviewer and checked by a second reviewer. A narrative synthesis was conducted.

Results

Eight studies were identified that met the inclusion criteria: three RCTs, two non-randomised controlled trials and three observational studies. Six of the studies had an intervention that had some relevance to the UK. There was no robust evidence that any of the interventions investigated led to an increase in cancer patient participation in RCTs, though one good quality RCT found that urologists and nurses were equally effective at recruiting participants to a treatment trial for prostate cancer. Although there was no evidence of an effect in any of the studies, the evidence was not of sufficient quality to be able to conclude that these interventions therefore do not work.

Conclusion

There is not a strong evidence-base for interventions that increase cancer patient participation in randomised trials. Further research is required to evaluate the effectiveness of strategies to increase participation in cancer treatment trials.     

Homestead tree holdings: Composition,uses and challenges in Checheche Growth Point,South East Lowveld,Zimbabwe

Understanding homestead tree holdings is important for developing local conservation and livelihood strategies. However, relative to urban homesteads, tree holdings in rural African homesteads remain little studied, especially in semi-arid settings. Using ecological and household surveys, this paper examines homestead tree composition, uses and challenges in Checheche, Zimbabwe. In total, 1,594 trees were encountered across 147 homesteads. Nearly, all homesteads (99%) had trees, and most of them were primarily planted for fruits and shade. Fuelwood, traditional medicines, windbreak and homestead decoration were considered as secondary benefits. Overall, tree density was approximately 112 trees/ha, with an average of 11 ± 7.1 trees per homestead. Homestead tree holdings were explained by age and gender of respondent, homestead ownership and importance attached to and knowledge of trees. Challenges to tree planting mentioned include termites, diseases, livestock damage, high temperatures, water shortages and poor quality soils. Overall, this study shows that homestead tree planting is widespread in semi-arid rural settings but constraints to tree planting ought to be addressed to optimise the benefits from trees. Further research is needed to fully understand the socioecological context that explains tree survival, as a basis for developing interventions for enabling homestead tree planting.     

Antigen-specific suppressor cell activity in man: I. Temporal, antigenic, and proliferative requirements

The temporal, antigenic, and proliferative requirements of antigen-specific suppression of the in vitro plaque-forming cell (PFC) response of human peripheral blood mononuclear cells (PBM) were studied. Suppressor cell activity (SCA) was generated by priming PBM with high doses of the T-cell-dependent antigen ovalbumin (OA) and measured by adding washed primed cells to target PFC cultures. Priming with high doses of OA was shown to induce a population of antigen-specific T lymphocytes which interfered with the anti-OA PFC response of optimally stimulated target cultures. The generation of SCA was demonstrated following as little as 24 hr of high-dose OA priming and could be abrogated by prolonged priming (72 hr) or by pretreatment with mitomycin prior to priming. The expression of optimal SCA required the addition of primed PBM at the initiation of the target culture and could be directly correlated to both the OA concentration used for priming and the number of primed cells added. Higher priming doses of OA (up to 100 μg) generated increasing numbers of cells capable of antigen-specific SCA as measured via a cell dilution protocol. Our data suggest that an antigen-driven and dose-dependent expansion of an antigen-specific T-suppressor cell pool is an early regulative event limiting the in vitro PFC response of human lymphocytes to OA.     

Lateral gene transfer between prokaryotes and multicellular eukaryotes: ongoing and significant?

The expansion of genome sequencing projects has produced accumulating evidence for lateral transfer of genes between prokaryotic and eukaryotic genomes. However, it remains controversial whether these genes are of functional importance in their recipient host. Nikoh and Nakabachi, in a recent paper in BMC Biology, take a first step and show that two genes of bacterial origin are highly expressed in the pea aphid Acyrthosiphon pisum. Active gene expression of transferred genes is supported by three other recent studies. Future studies should reveal whether functional proteins are produced and whether and how these are targeted to the appropriate compartment. We argue that the transfer of genes between host and symbiont may occasionally be of great evolutionary importance, particularly in the evolution of the symbiotic interaction itself.     

Noncontact dipole effects on channel permeation. III. Anomalous proton conductance effects in gramicidin

Proton transport on water wires, of interest for many problems in membrane biology, is analyzed in side-chain analogs of gramicidin A channels. In symmetrical 0.1 N HCl solutions, fluorination of channel Trp(11), Trp-(13), or Trp(15) side chains is found to inhibit proton transport, and replacement of one or more Trps with Phe enhances proton transport, the opposite of the effects on K(+) transport in lecithin bilayers. The current-voltage relations are superlinear, indicating that some membrane field-dependent process is rate limiting. The interfacial dipole effects are usually assumed to affect the rate of cation translocation across the channel. For proton conductance, however, water reorientation after proton translocation is anticipated to be rate limiting. We propose that the findings reported here are most readily interpreted as the result of dipole-dipole interactions between channel waters and polar side chains or lipid headgroups. In particular, if reorientation of the water column begins with the water nearest the channel exit, this hypothesis explains the negative impact of fluorination and the positive impact of headgroup dipole on proton conductance.     

The molecular organization of the beta-globin complex of the deer mouse, Peromyscus maniculatus

Recombinant DNA clones have been isolated that contain 80 kb of the beta-globin complex from the deer mouse, Peromyscus maniculatus. Comparisons of this complex with that from the laboratory mouse, Mus domesticus (with an order 5'-Hbby, Hbb-bhO, Hbb-bhl, Hbb-bh2, Hbb-bh3, Hbb-bl, Hbb-b2 3') highlight organizational trends in the beta-globin complex since the two species diverged. Unlike other mammals studied thus far, the deer mouse possesses three adult genes. Partial sequence analysis indicates that each of the three adult genes is intact and hence may be functional. Hybridization of one of the two Mus pseudogenes, Hbb-bh3, to genomic blots from Peromyscus reveals that it has a homologous counterpart in Peromyscus. Homologous genes to the two gamma-like Mus genes, Hbb-bhO and Hbb-bhl, are also found in Peromyscus. The strong hybridization between the Hbb-bhl genes and significant nucleotide similarity between the Hbb-bhO genes suggest that both pairs are important for the ontogeny of these mice although no known product has been identified for the Hbb-bhO genes. The presence of Hbb-bhO and Hbb-bhl in Peromyscus suggests that the duplication that created this related gene set occurred before the two lineages diverged. A single gene for Hbb-y has been isolated from Peromyscus. The adult region in Peromyscus has undergone significant divergence from the same region in Mus, having three rather than two adult genes, the acquisition of at least 15 kb of extra DNA relative to Mus, and possibly the loss of the Hbb-bh2 pseudogene. The nonadult region of the complex, in contrast, contains the same set of genes apparently distributed over the same amount of DNA as in the Mus beta- globin complex. This observation suggests that the embryonic region of the complex is more evolutionarily stable than the adult region.