Spatial Models of Abundance and Habitat Preferences of Commerson’s and Peale’s Dolphin in Southern Patagonian Waters

Funding: This research was possible with the support of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Funding for travel to and accommodation for NAD in Aberdeen, Scotland was provided by CONICET and Cetacean Society International. The work of NAD was part of a postdoctoral fellowship funded by CONICET. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Quantifying the effect of population mixing on childhood leukaemia risk: the Seascale cluster

A statistical model was developed based on Poisson regression of incidence of childhood leukaemia and non-Hodgkin’s lymphoma (NHL) in relation to population mixing among all 119 539 children born 1969–1989 to mothers living in Cumbria, north-west England, (excluding Seascale). This model was used to predict the number of cases in Seascale (the village adjacent to the Sellafield nuclear installation) children, born 1950–1989 and diagnosed before 1993. After allowing for age, the incidence of acute lymphoblastic leukaemia (ALL) and NHL was significantly higher among children born in areas with the highest levels of population mixing, relative risk (RR) = 11.7 (95% confidence interval (CI) 3.2–43) and was highest among children of incomers. The model predicted up to 3.0 (95% CI 1.3–6.0) cases of ALL/NHL in children born in Seascale compared to six observed and 2.0 (95% CI 1.0–3.4) cases in children resident, but not born, in Seascale compared to two observed. Population mixing is a significant risk factor for ALL/NHL, especially in young children, accounting for over 50% of cases in Cumbria and most cases in Seascale. © 1999 Cancer Research Campaig

Towards condom skills: a cross-sectional study of the association between condom proficiency, condom problems and STI risk amongst MSM

<p>Abstract</p> <p>Background</p> <p>Condom use problems are common amongst Scotland’s men who have sex with men (MSM). To date condom errors have been associated with the likelihood of sexually transmitted infections in heterosexual sexually transmitted infection (STI) clinic attendees but not in MSM and direct evidence of a link between condom problems and STI acquisition in MSM have been lacking. This study investigated the possibility of an independent association between condom proficiency, condom problems and STI acquisition in MSM in Scotland.</p> <p>Methods</p> <p>An exploratory observational design employed cross-sectional surveys in both STI clinic and community settings. Respondents completed self-report measures of socio-demographic variables, scales of condom proficiency and condom problems and numbers of different partners with whom men have had unprotected anal intercourse (UAI partners) in the preceding year. Self-report data was corroborated with clinical STI diagnosis where possible. Analysis included chi-squared and Mann–Whitney tests and multiple logistic regression.</p> <p>Results</p> <p>792 respondents provided data with an overall response rate of 70% (n = 459 clinic sample, n = 333 community sample). Number of UAI partners was the strongest predictor of self-reported STI acquisition over the previous 12 months (p < 0.001 in both clinic and community samples). Demographic characteristics were not associated with self-reported STI diagnosis. However, condom proficiency score was associated with self-reported STI acquisition (p < 0.05 in both samples). Condom problem score was also associated with self-reported STI diagnosis in the clinic (p = 0.001) but not the community sample. Condom problem score remained associated with self-reported STI diagnosis in the clinic sample after adjusting for number of UAI partners with logistic regression.</p> <p>Conclusions</p> <p>This exploratory study highlights the potential importance of targeted condom use skills interventions amongst MSM. It demands further research examining the utility of condom problem measures in wider populations, across prospective and experimental research designs, and a programme of research exploring their feasibility as a tool determining candidacy for brief interventions.</p

Effects of Cu/Zn Superoxide Dismutase (sod1) Genotype and Genetic Background on Growth, Reproduction and Defense in Biomphalaria glabrata

Resistance of the snail Biomphalaria glabrata to the trematode Schistosoma mansoni is correlated with allelic variation at copper-zinc superoxide dismutase (sod1). We tested whether there is a fitness cost associated with carrying the most resistant allele in three outbred laboratory populations of snails. These three populations were derived from the same base population, but differed in average resistance. Under controlled laboratory conditions we found no cost of carrying the most resistant allele in terms of fecundity, and a possible advantage in terms of growth and mortality. These results suggest that it might be possible to drive resistant alleles of sod1 into natural populations of the snail vector for the purpose of controlling transmission of S. mansoni. However, we did observe a strong effect of genetic background on the association between sod1 genotype and resistance. sod1 genotype explained substantial variance in resistance among individuals in the most resistant genetic background, but had little effect in the least resistant genetic background. Thus, epistatic interactions with other loci may be as important a consideration as costs of resistance in the use of sod1 for vector manipulation

Ligand-induced sequestering of branchpoint sequence allows conditional control of splicing

<p>Abstract</p> <p>Background</p> <p>Despite tremendous progress in understanding the mechanisms of constitutive and alternative splicing, an important and widespread step along the gene expression pathway, our ability to deliberately regulate gene expression at this step remains rudimentary. The present study was performed to investigate whether a theophylline-dependent "splice switch" that sequesters the branchpoint sequence (BPS) within RNA-theophylline complex can regulate alternative splicing.</p> <p>Results</p> <p>We constructed a series of pre-mRNAs in which the BPS was inserted within theophylline aptamer. We show that theophylline-induced sequestering of BPS inhibits pre-mRNA splicing both in vitro and in vivo in a dose-dependent manner. Several lines of evidence suggest that theophylline-dependent inhibition of splicing is highly specific, and thermodynamic stability of RNA-theophylline complex as well as the location of BPS within this complex affects the efficiency of splicing inhibition. Finally, we have constructed an alternative splicing model pre-mRNA substrate in which theophylline caused exon skipping both in vitro and in vivo, suggesting that a small molecule-RNA interaction can modulate alternative splicing.</p> <p>Conclusion</p> <p>These findings provide the ability to control splicing pattern at will and should have important implications for basic, biotechnological, and biomedical research.</p

Protective paraspeckle hyper-assembly downstream of TDP-43 loss of function in amyotrophic lateral sclerosis

Background Paraspeckles are subnuclear bodies assembled on a long non-coding RNA (lncRNA) NEAT1. Their enhanced formation in spinal neurons of sporadic amyotrophic lateral sclerosis (ALS) patients has been reported but underlying mechanisms are unknown. The majority of ALS cases are characterized by TDP-43 proteinopathy. In current study we aimed to establish whether and how TDP-43 pathology may augment paraspeckle assembly. Methods Paraspeckle formation in human samples was analysed by RNA-FISH and laser capture microdissection followed by qRT-PCR. Mechanistic studies were performed in stable cell lines, mouse primary neurons and human embryonic stem cell-derived neurons. Loss and gain of function for TDP-43 and other microRNA pathway factors were modelled by siRNA-mediated knockdown and protein overexpression. Results We show that de novo paraspeckle assembly in spinal neurons and glial cells is a hallmark of both sporadic and familial ALS with TDP-43 pathology. Mechanistically, loss of TDP-43 but not its cytoplasmic accumulation or aggregation augments paraspeckle assembly in cultured cells. TDP-43 is a component of the microRNA machinery, and recently, paraspeckles have been shown to regulate pri-miRNA processing. Consistently, downregulation of core protein components of the miRNA pathway also promotes paraspeckle assembly. In addition, depletion of these proteins or TDP-43 results in accumulation of endogenous dsRNA and activation of type I interferon response which also stimulates paraspeckle formation. We demonstrate that human or mouse neurons in vitro lack paraspeckles, but a synthetic dsRNA is able to trigger their de novo formation. Finally, paraspeckles are protective in cells with compromised microRNA/dsRNA metabolism, and their assembly can be promoted by a small-molecule microRNA enhancer. Conclusions Our study establishes possible mechanisms behind paraspeckle hyper-assembly in ALS and suggests their utility as therapeutic targets in ALS and other diseases with abnormal metabolism of microRNA and dsRNA

Protective paraspeckle hyper-assembly downstream of TDP-43 loss of function in amyotrophic lateral sclerosis

BACKGROUND: Paraspeckles are subnuclear bodies assembled on a long non-coding RNA (lncRNA) NEAT1. Their enhanced formation in spinal neurons of sporadic amyotrophic lateral sclerosis (ALS) patients has been reported but underlying mechanisms are unknown. The majority of ALS cases are characterized by TDP-43 proteinopathy. In current study we aimed to establish whether and how TDP-43 pathology may augment paraspeckle assembly. METHODS: Paraspeckle formation in human samples was analysed by RNA-FISH and laser capture microdissection followed by qRT-PCR. Mechanistic studies were performed in stable cell lines, mouse primary neurons and human embryonic stem cell-derived neurons. Loss and gain of function for TDP-43 and other microRNA pathway factors were modelled by siRNA-mediated knockdown and protein overexpression. RESULTS: We show that de novo paraspeckle assembly in spinal neurons and glial cells is a hallmark of both sporadic and familial ALS with TDP-43 pathology. Mechanistically, loss of TDP-43 but not its cytoplasmic accumulation or aggregation augments paraspeckle assembly in cultured cells. TDP-43 is a component of the microRNA machinery, and recently, paraspeckles have been shown to regulate pri-miRNA processing. Consistently, downregulation of core protein components of the miRNA pathway also promotes paraspeckle assembly. In addition, depletion of these proteins or TDP-43 results in accumulation of endogenous dsRNA and activation of type I interferon response which also stimulates paraspeckle formation. We demonstrate that human or mouse neurons in vitro lack paraspeckles, but a synthetic dsRNA is able to trigger their de novo formation. Finally, paraspeckles are protective in cells with compromised microRNA/dsRNA metabolism, and their assembly can be promoted by a small-molecule microRNA enhancer. CONCLUSIONS: Our study establishes possible mechanisms behind paraspeckle hyper-assembly in ALS and suggests their utility as therapeutic targets in ALS and other diseases with abnormal metabolism of microRNA and dsRNA