Citations

The presence of microbialite structures in a freshwater, dimictic mid-latitudelake and their establishment after the last ice age about 10,000 years ago is puzzling.Freshwater calcite microbialites at Pavilion Lake, British Columbia, Canada, consist of acomplex community of microorganisms that collectively form large, ordered structuredaggregates. This distinctive assemblage of freshwater calcite microbialites was studied through standard microbial methods, morphological observations, phospholipid fatty acid(PLFA) analysis, DNA sequencing and the identification of quorum sensing molecules.Our results suggest that the microbialites may represent a transitional form from theexclusively prokaryotic colonial precursors of stromatolites to the multicellular organismicaggregates that give rise to coral reefs.

R231H Causes a High Penetrance for Familial AFBackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia, and its incidence is expected to grow. A genetic predisposition for AF has long been recognized, but its manifestation in these patients likely involves a combination of rare and common genetic variants. Identifying genetic variants that associate with a high penetrance for AF would represent a significant breakthrough for understanding the mechanisms that associate with disease.Method and ResultsCandidate gene sequencing in 5 unrelated families with familial AF identified the KCNQ1 missense mutation p.Arg231His (R231H). In addition to AF, several of the family members have abnormal QTc intervals, syncope or experienced sudden cardiac arrest or death. KCNQ1 encodes the voltage‐gated K+ channel that conducts the slowly activating delayed rectifier K+ current in the heart. Functional and computational analyses suggested that R231H increases KCNQ1 current (IKCNQ1) to shorten the atrial action potential (AP) duration. R231H is predicted to minimally affect ventricular excitability, but it prevented the increase in IKCNQ1 following PKA activation. The unique properties of R231H appeared to be caused by a loss in voltage‐dependent gating.ConclusionsThe R231H variant causes a high penetrance for interfamilial early‐onset AF. Our study indicates R231H likely shortens atrial refractoriness to promote a substrate for reentry. Additionally, R231H might cause abnormal ventricular repolarization by disrupting PKA activation of IKCNQ1. We conclude genetic variants, which increase IKs during the atrial AP, decrease the atrial AP duration, and/or shorten atrial refractoriness, present a high risk for interfamilial AF.

Background and purposeThe European Federation of the Neurological Societies (EFNS) guidelines on the use of neuroimaging in the diagnosis and management of dementia are designed to revise and expand previous EFNS recommendations for the diagnosis and management of patients with Alzheimer's disease (AD) and to provide an overview of the evidence for the use of neuroimaging techniques in non‐AD dementias, as well as general recommendations that apply to all types of dementia in clinical practice.MethodsThe task force working group reviewed evidence from original research articles, meta‐analyses and systematic reviews, published before April 2012. The evidence was classified, and consensus recommendations were given and graded according to the EFNS guidance regulations.ResultsStructural imaging, which should be performed at least once in the diagnostic work‐up of patients with cognitive impairment, serves to exclude other potentially treatable diseases, to recognize vascular lesions and to identify specific findings to help distinguish different forms of neurodegenerative types of dementia. Although typical cases of dementia may not benefit from routine functional imaging, these tools are recommended in those cases where diagnosis remains in doubt after clinical and structural imaging work‐up and in particular clinical settings. Amyloid imaging is likely to find clinical utility in several fields, including the stratification of patients with mild cognitive impairment into those with and without underlying AD and the evaluation of atypical AD presentations.ConclusionsA number of recommendations and good practice points are made to improve the diagnosis of AD and other dementias.

Abstract Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1610–6)

Objectives. This review details the tobacco industry's scientific campaign aimed against policies addressing environmental tobacco smoke (ETS) and efforts to undermine US regulatory agencies from approximately 1988 to 1993. Methods. The public availability of more than 40 million internal, once-secret tobacco company documents allowed an unedited and historical look at tobacco industry strategies. Results. The analysis showed that the tobacco industry went to great lengths to battle the ETS issue worldwide by camouflaging its involvement and creating an impression of legitimate, unbiased scientific research. Conclusions. There is a need for further international monitoring of industry-produced science and for significant improvements in tobacco document accessibility.