Schistosoma haematobium infection levels determine the effect of praziquantel treatment on anti-schistosome and anti-mite antibodies

Field studies show an association between schistosome infection and atopy, but the effects of anti-helminthic treatment on this association have not yet been investigated in human populations with different schistosome endemicity levels. This study aimed to compare the effects of anti-helminthic treatment on responses directed against the house dust mite Dermatophagoides pteronyssinus (Derp1) and Schistosoma haematobium in Zimbabwean populations living in high and low schistosome infection areas. Derp1- and schistosome-specific IgE and IgG4 antibodies were quantified by ELISA before and 6 weeks after anti-helminthic treatment. Following treatment, there were changes in the immune responses, which varied with place of residence. After allowing for the effects of sex, age and baseline infection intensity, there was no significant treatment effect on the change in anti-schistosome IgE and IgG4 in the high infection area. However, the anti-schistosome IgE/IgG4 ratio increased significantly, while anti-Derp1 IgE responses decreased as a result of treatment. In the low infection area, treatment resulted in a significant increase in anti-worm IgE levels, but there was no significant treatment effect on anti-schistosome or anti-Derp1 IgE/IgG4 ratios. Thus, the study shows that the level of schistosome endemicity affects the host responses to schistosome and mite antigens following anti-helminthic treatment

Optically trapped bacteria pairs reveal discrete motile response to control aggregation upon cell–cell approach

Aggregation of bacteria plays a key role in the formation of many biofilms. The critical first step is cell–cell approach, and yet the ability of bacteria to control the likelihood of aggregation during this primary phase is unknown. Here, we use optical tweezers to measure the force between isolated Bacillus subtilis cells during approach. As we move the bacteria towards each other, cell motility (bacterial swimming) initiates the generation of repulsive forces at bacterial separations of ~3 μm. Moreover, the motile response displays spatial sensitivity with greater cell–cell repulsion evident as inter-bacterial distances decrease. To examine the environmental influence on the inter-bacterial forces, we perform the experiment with bacteria suspended in Tryptic Soy Broth, NaCl solution and deionised water. Our experiments demonstrate that repulsive forces are strongest in systems that inhibit biofilm formation (Tryptic Soy Broth), while attractive forces are weak and rare, even in systems where biofilms develop (NaCl solution). These results reveal that bacteria are able to control the likelihood of aggregation during the approach phase through a discretely modulated motile response. Clearly, the force-generating motility we observe during approach promotes biofilm prevention, rather than biofilm formation

Population size and decadal trends of three penguin species nesting at Signy Island, South Orkney Islands

We report long-term changes in population size of three species of sympatrically breeding pygoscelid penguins: Adélie (Pygoscelis adeliae), chinstrap (Pygoscelis antarctica) and gentoo (Pygoscelis papua ellsworthii) over a 38 year period at Signy Island, South Orkney Islands, based on annual counts from selected colonies and decadal all-island systematic counts of occupied nests. Comparing total numbers of breeding pairs over the whole island from 1978/79 to 2015/16 revealed varying fortunes: gentoo penguin pairs increased by 255%, (3.5% per annum), chinstrap penguins declined by 68% (-3.6% per annum) and Adélie penguins declined by 42% (-1.5% per annum). The chinstrap population has declined steadily over the last four decades. In contrast, Adélie and gentoo penguins have experienced phases of population increase and decline. Annual surveys of selected chinstrap and Adélie colonies produced similar trends from those revealed by island-wide surveys, allowing total island population trends to be inferred relatively well. However, while the annual colony counts of chinstrap and Adélie penguins showed a trend consistent in direction with the results from all-island surveys, the magnitude of estimated population change was markedly different between colony wide and all island counts. Annual population patterns suggest that pair numbers in the study areas partly reflect immigration and emigration of nesting birds between different parts of the island. Breeding success for all three species remained broadly stable over time in the annually monitored colonies. Breeding success rates in gentoo and chinstrap penguins were strongly correlated, despite the differing trends in population size. This study shows the importance of effective, standardised monitoring to accurately determine long-term population trajectories. Our results indicate significant declines in the Adélie and chinstrap penguin populations at Signy Island over the last five decades, and a gradual increase in gentoo breeding pairs

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Increased risk of cancer among relatives of patients with lung cancer in China

BACKGROUND: Genetic factors were considered as one of the risk factors for lung cancer or other cancers. The aim of this work was to determine whether a genetic predisposition accounts for such familial aggregation of cancer among relatives of lung cancer probands. METHODS: A case-control study was conducted in 800 case families identified by lung cancer patients (probands), and in 800 control families identified by the probands'spouses. The data were analysed with logistic regression analysis model. RESULTS: The data revealed a significantly greater overall risk of cancer (OR = 1.82, P < 0.01) in the proband group. The relatives of lung cancer probands maintained an increased risk of non-lung cancer (P < 0.05) after adjusting for confounder factors. The crude odds ratio of a proband family having one family member with cancer was 1.67 compared with control families. Proband families were 2.56 times more likely to have two other family members with cancer. For three cancers and four or more cancers, the risk increased to 3.50 and 5.91, respectively. The most striking differences in cancer prevalence between proband and control families were noted for cancer risk among female relatives. The strongest effects were for not only lung cancer in any female relatives (OR 2.17, 95%CI 1.60–3.64) and mothers (OR 2.78, 95%CI 1.23–5.12) and sisters (OR 2.03, 95%CI 1.26–3.97), but also non-lung cancer in females and mothers (OR 2.00, 95%CI 1.26–3.01, and OR 2.34, 95%CI 1.28–4.40, respectively). CONCLUSION: These data support the hypothesis of a genetic susceptibility to cancer in families with lung cancer, and the female genetic susceptibility to cancer might be greater than male

Epidermal growth factor receptor structural alterations in gastric cancer

<p>Abstract</p> <p>Background</p> <p>EGFR overexpression has been described in many human tumours including gastric cancer. In NSCLC patients somatic EGFR mutations, within the kinase domain of the protein, as well as gene amplification were associated with a good clinical response to EGFR inhibitors. In gastric tumours data concerning structural alterations of EGFR remains controversial. Given its possible therapeutic relevance, we aimed to determine the frequency and type of structural alterations of the <it>EGFR </it>gene in a series of primary gastric carcinomas.</p> <p>Methods</p> <p>Direct sequencing of the kinase domain of the <it>EGFR </it>gene was performed in a series of 77 primary gastric carcinomas. FISH analysis was performed in 30 cases. Association studies between <it>EGFR </it>alterations and the clinical pathological features of the tumours were performed.</p> <p>Results</p> <p>Within the 77 primary gastric carcinomas we found two <it>EGFR </it>somatic mutations and several <it>EGFR </it>polymorphisms in exon 20. Six different intronic sequence variants of <it>EGFR </it>were also found. Four gastric carcinomas showed balanced polysomy or <it>EGFR </it>gene amplification. We verified that gastric carcinoma with alterations of <it>EGFR </it>(somatic mutations or copy number variation) showed a significant increase of tumour size (<it>p </it>= 0.0094) in comparison to wild-type <it>EGFR </it>carcinomas.</p> <p>Conclusion</p> <p>We demonstrate that <it>EGFR </it>structural alterations are rare in gastric carcinoma, but whenever present, it leads to tumour growth. We considered that searching for <it>EGFR </it>alterations in gastric cancer is likely to be clinically important in order to identify patients susceptible to respond to tyrosine kinase inhibitors.</p

The Genetic Interpretation of Area under the ROC Curve in Genomic Profiling

Genome-wide association studies in human populations have facilitated the creation of genomic profiles which combine the effects of many associated genetic variants to predict risk of disease. The area under the receiver operator characteristic (ROC) curve is a well established measure for determining the efficacy of tests in correctly classifying diseased and non-diseased individuals. We use quantitative genetics theory to provide insight into the genetic interpretation of the area under the ROC curve (AUC) when the test classifier is a predictor of genetic risk. Even when the proportion of genetic variance explained by the test is 100%, there is a maximum value for AUC that depends on the genetic epidemiology of the disease, i.e. either the sibling recurrence risk or heritability and disease prevalence. We derive an equation relating maximum AUC to heritability and disease prevalence. The expression can be reversed to calculate the proportion of genetic variance explained given AUC, disease prevalence, and heritability. We use published estimates of disease prevalence and sibling recurrence risk for 17 complex genetic diseases to calculate the proportion of genetic variance that a test must explain to achieve AUC = 0.75; this varied from 0.10 to 0.74. We provide a genetic interpretation of AUC for use with predictors of genetic risk based on genomic profiles. We provide a strategy to estimate proportion of genetic variance explained on the liability scale from estimates of AUC, disease prevalence, and heritability (or sibling recurrence risk) available as an online calculator

Microsatellite instability in thyroid tumours and tumour-like lesions

Fifty-one thyroid tumours and tumour-like lesions were analysed for instability at ten dinucleotide microsatellite loci and at two coding mononucleotide repeats within the transforming growth factor β (TGF-β) type II receptor (TβRII) and insulin-like growth factor II (IGF-II) receptor (IGFIIR) genes respectively. Microsatellite instability (MI) was detected in 11 out of 51 cases (21.5%), including six (11.7%) with MI at one or two loci and five (9.8%) with Ml at three or more loci (RER+ phenotype). No mutations in the TβRII and IGFIIR repeats were observed. The overall frequency of MI did not significantly vary in relation to age, gender, benign versus malignant status and tumour size. However, widespread MI was significantly more frequent in follicular adenomas and carcinomas than in papillary and Hürthle cell tumours: three out of nine tumours of follicular type (33.3%) resulted in replication error positive (RER+), versus 1 out of 29 papillary carcinomas (3.4%, P = 0.01), and zero out of eight Hürthle cell neoplasms. Regional lymph node metastases were present in five MI-negative primary cancers and resulted in MI-positive in two cases. © 1999 Cancer Research Campaig