Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo.

Resistance to chemotherapy is a principal problem in the treatment of small cell lung cancer (SCLC). We show here that SCLC is surrounded by an extensive stroma of extracellular matrix (ECM) at both primary and metastatic sites. Adhesion of SCLC cells to ECM enhances tumorigenicity and confers resistance to chemotherapeutic agents as a result of beta1 integrin-stimulated tyrosine kinase activation suppressing chemotherapy-induced apoptosis. SCLC may create a specialized microenvironment, and the survival of cells bound to ECM could explain the partial responses and local recurrence of SCLC often seen clinically after chemotherapy. Strategies based on blocking beta1 integrin-mediated survival signals may represent a new therapeutic approach to improve the response to chemotherapy in SCLC.     

Demographic changes and the development of competition in a native Australian eucalypt forest invaded by exotic pines

Data from the second half of a 14-year study of a eucalypt dry sclerophyll forest invaded by Pinus radiata D. Don shows further progress in the development of a mixed eucalypt-pine stand. Earlier (Chilvers and Burdon 1983) it was clear that pines invading from an adjacent commercial plantation were starting to contribute their own progeny to the mixed stand. Initially the recruitment of established pines (> 1 m high) from these seedlings was very slow. However, since 1984, increasing numbers of seedlings have survived beyond their first year, suggesting the possibility of another wave of successful establishment in the near future. The established fraction of the pine population continued to grow rapidly and incurred no mortality. Many of these plants have now emerged through the top of the eucalypt canopy. In contrast, both juvenile and adult eucalypt numbers continued to decline. Despite these demographic and visual changes, comparative analysis of the growth of established pines over two consecutive 7-year periods (1974–1981; 1981–1988) showed that competition between neighbouring plants, especially pines, is beginning to affect individual growth rates. Growth rates of pines having other pines as nearest neighbours declined 40% between 1974–1981 and 1981–1988, while that of pines with eucalypts as nearest neighbours fell by 28%. In pine-pine nearest neighbour (NN) pairs, growth rates were significantly affected by the size (diameter) of the nearest neighbour. In pine-eucalypt NN pairs growth rates of the pines were not affected by the size of the eucalypt, but these were significantly negatively correlated with the inverse of the distance to the eucalypt. More broad-based assessment of 43 pines showed a significant relationship between their growth rates and the summed competitive effect of other pines within a 5-m radius. No such relationship was found between growth rate and the summed competitive effect of eucalypts in the 5-m zone.     

The effect of deprivation on variations in general practitioners' referral rates: a cross sectional study of computerised data on new medical and surgical outpatient referrals in Nottinghamshire.

OBJECTIVE: To determine the effect of deprivation on variations in general practitioners'' referral rates using the Jarman underprivileged area (UPA(8)) score as a proxy measure. DESIGN: Cross sectional survey of new medical and surgical referrals from general practices to hospitals (determined from hospital activity data). SETTING: All of the 183 general practices in Nottinghamshire and all of the 19 hospitals in Trent region. MAIN OUTCOME MEASURES: The relation between the referral rates per 1000 registered patients and the practice population''s UPA(8) score (calculated on the basis of electoral ward), with adjustment for the number of partners, percentage of patients aged over 65 years, and fundholding status of each practice. RESULTS: There was a significant independent association between deprivation, as measured by the UPA(8) score, and high total referral rates and high medical referral rates (P < 0.0001). The UPA(8) score alone explained 23% of the total variation in total referral rates and 32% of the variation in medical referral rates. On multivariate analysis, where partnership size, fundholding status, and percentage of men and women aged over 65 years were included, the UPA(8) score explained 29% and 35% of the variation in total and medical referral rates respectively. CONCLUSION: Of the variables studied, the UPA(8) score was the strongest predictor of variations in referral rates. This association is most likely to be through a link with morbidity, although it could reflect differences in patients'' perceptions, doctors'' behaviour, or the use and provision of services.     

Heterozygote advantage at MHC DRB may influence response to infectious disease epizootics

The effect of MHC polymorphism on individual fitness variation in the wild remains equivocal; however, much evidence suggests that heterozygote advantage is a major determinant. To understand the contribution of MHC polymorphism to individual disease resistance or susceptibility in natural populations, we investigated two MHC class II B loci, DQB and DRB, in the New Zealand sea lion (NZSL, Phocarctos hookeri). The NZSL is a threatened species which is unusually susceptible to death by bacterial infection at an early age; it has suffered three bacterial induced epizootics resulting in high mortality levels of young pups since 1997. The MHC DQB and DRB haplotypes of dead NZSL pups with known cause of death (bacteria, enteritis or trauma) were sequenced and reconstructed, compared to pups that survived beyond 2 months of age, and distinct MHC DRB allele frequency and genotype differences were identified. Two findings were striking: (i) one DRB allele was present only in dead pups, and (ii) one heterozygous DRB genotype, common in live pups, was absent from dead pups. These results are consistent with some functional relationship with these variants and suggest heterozygote advantage is operating at DRB. We found no association between heterozygosity and fitness at 17 microsatellite loci, indicating that general heterozygosity is not responsible for the effect on fitness detected here. This result may be a consequence of recurrent selection by multiple pathogen assault over recent years and highlights the importance of heterozygote advantage at MHC as a potential mechanism for fitness differences in wild populations.     

The food of Bagrus docmac (Forsk.) (Pisces: Siluriformes) and its relationship with Haplochromis Hilgendorf (Pisces: Cichlidae), in Lake Victoria, East Africa

The diet of the siluriform fish Bagrus docmac (Forsk.) is described in relation to various localities in Lake Victoria, East Africa. Invertebrates which are the principal food of young fish, but generally of little significance in adults, are particularly poorly represented in fishes from Tanzanian waters and most important in those from the Kavirondo Gulf where the ontogenetic changes in diet differ from those found elsewhere in the Lake. B. docmac starts feeding piscivorously at about 10 cm standard length with the transition from a principally invertebrate to a primarily piscivorous diet occurring at 15 cm S.L. In adult B. docmac fish are found in over 95 % of individuals with food. Haplochromis is the all important food type, and Tilapia , the most valuable commercial fish in the lake, is not preyed upon at all. Bathymetric changes with respect to the invertebrate food are noted, and it is shown that piscivorous feeding occurs mainly by day and invertebrate feeding by night. Quantitative estimates of consumption of Haplochromis by B, docmac are computed from the results of a series of 24 h fishing surveys and found to exceed published data from elsewhere. The formula for the computation of a daily ration is given as Log R =2.973 Log L —3.36089 and it is calculated that the mean annual consumption of Haplochromis by B. docmac is approximately 75% of the mean standing stock of the prey fish, as compared with a commercial catch of about 5% of the mean standing stock.     

Genome-wide association mapping of quantitative resistance to sudden death syndrome in soybean

Background

Sudden death syndrome (SDS) is a serious threat to soybean production that can be managed with host plant resistance. To dissect the genetic architecture of quantitative resistance to the disease in soybean, two independent association panels of elite soybean cultivars, consisting of 392 and 300 unique accessions, respectively, were evaluated for SDS resistance in multiple environments and years. The two association panels were genotyped with 52,041 and 5,361 single nucleotide polymorphisms (SNPs), respectively. Genome-wide association mapping was carried out using a mixed linear model that accounted for population structure and cryptic relatedness.

Result

A total of 20 loci underlying SDS resistance were identified in the two independent studies, including 7 loci localized in previously mapped QTL intervals and 13 novel loci. One strong peak of association on chromosome 18, associated with all disease assessment criteria across the two panels, spanned a physical region of 1.2 Mb around a previously cloned SDS resistance gene (GmRLK18-1) in locus Rfs2. An additional variant independently associated with SDS resistance was also found in this genomic region. Other peaks were within, or close to, sequences annotated as homologous to genes previously shown to be involved in plant disease resistance. The identified loci explained an average of 54.5% of the phenotypic variance measured by different disease assessment criteria.

Conclusions

This study identified multiple novel loci and refined the map locations of known loci related to SDS resistance. These insights into the genetic basis of SDS resistance can now be used to further enhance durable resistance to SDS in soybean. Additionally, the associations identified here provide a basis for further efforts to pinpoint causal variants and to clarify how the implicated genes affect SDS resistance in soybean.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-809) contains supplementary material, which is available to authorized users.     

Bronchoalveolar lavage in an immunosuppressed rabbit model of invasive pulmonary aspergillosis

A rabbit model of invasive aspergillosis has been used to investigate the pathogenesis of Aspergillus infection in the immunosuppressed host. The animals received hydrocortisone daily and a single dose of cyclophosphamide 2 days prior to intratracheal instillation of conidia from Aspergillus fumigatus. Bronchoalveolar lavage (BAL) was performed in 3 infected and 2 control saline treated animals sacrificed on days 1, 2, 4, 7 and 10 following inoculation. Infective load within the lung was quantified using an assay for chitin which is an important component of fungal cell walls (in particular the hyphal cell wall) and is not present in vertebrate tissue. The total BAL white cell count did not discriminate between infected and saline treated animals and Aspergillus was cultured from one lavage specimen only. Infected animals developed a marked neutrophil alveolitis by day 2 in contrast to a near total absence of neutrophils in the lavages of the control animals. Phagocytosis of conidia by alveolar macrophages was prominent but did not prevent progressive infection as confirmed by measurement of lung chitin. This pattern of cellular response within the alveolar airspace reflects the complex nature of the response to Aspergillus infection in the immunosuppressed host.     

Sexual behaviour of young and middle aged men in England and Wales.

Establishing patterns of sexual behaviour is essential in predicting the future spread of HIV. The sexual behaviour patterns of a randomly selected sample of 480 white men aged 15 to 49 were obtained by interview and analysed in relation to age, social class, and area of residence. Over half of the men had first had intercourse before the age of 18 and over three quarters had done so before the age of 20. Age at first intercourse tended to be lower in more recent birth cohorts and in social classes III, IV, and V. Men in earlier birth cohorts tended to have had fewer heterosexual partners, both regular and casual, than those born more recently, but there were no social class or regional differences in the number of partners. Eight of the 480 men (1.7%, 95% confidence interval 1.1 to 2.3%) stated that they had had homosexual intercourse, four of whom had had one casual homosexual partner. Only one man had had more than 25 homosexual partners. The number of men having had homosexual intercourse was lower than is widely thought. When possible, data were checked with national data or other surveys and thought to be accurate. The difficulties in collecting data of this nature are discussed.