Accurately measuring the abundance of benthic microalgae in spatially variable habitats

Although many studies measure the abundance of benthic microalgae (BMA), at the meters squared scale, comparing these studies is difficult due to the variety of sampling, extraction, and analysis techniques. This difficulty is exacerbated by the fact that BMA abundance has high spatial and temporal variability, at all spatial scales. A suitable standard sampling regimen would reduce variation in estimates due to different sample collection and processing greatly facilitating comparisons between studies. This study examined the effect of varying the volume of extraction solvent, sampling core diameter, and sample replication on BMA biomass estimates. Key findings, applicable to all spatial scales, to accurately determine biomass were the use of a minimum sediment to extraction solvent ratio of 1:2 and use of a sampling core diameter of 19 mm. Across a wide range of sediment types, at the meters squared scale and using spectrophotometric techniques, a minimum replication number of 8 was found to be appropriate. We report the significant effect coring depth and units of expression have on BMA biomass estimates across a range of sediment types, highlighting the potential pitfalls when comparing studies

Breast cancer risk reduction:is it feasible to initiate a randomised controlled trial of a lifestyle intervention programme (ActWell) within a national breast screening programme?

BackgroundBreast cancer is the most commonly diagnosed cancer and the second cause of cancer deaths amongst women in the UK. The incidence of the disease is increasing and is highest in women from least deprived areas. It is estimated that around 42% of the disease in post-menopausal women could be prevented by increased physical activity and reductions in alcohol intake and body fatness. Breast cancer control endeavours focus on national screening programmes but these do not include communications or interventions for risk reductionThis study aimed to assess the feasibility of delivery, indicative effects and acceptability of a lifestyle intervention programme initiated within the NHS Scottish Breast Screening Programme (NHSSBSP).MethodsA 1:1 randomised controlled trial (RCT) of the 3 month ActWell programme (focussing on body weight, physical activity and alcohol) versus usual care conducted in two NHSSBSP sites between June 2013 and January 2014. Feasibility assessments included recruitment, retention, and fidelity to protocol. Indicative outcomes were measured at baseline and 3 month follow-up (body weight, waist circumference, eating and alcohol habits and physical activity. At study end, a questionnaire assessed participant satisfaction and qualitative interviews elicited women¿s, coaches and radiographers¿ experiences. Statistical analysis used Chi squared tests for comparisons in proportions and paired t tests for comparisons of means. Linear regression analyses were performed, adjusted for baseline values, with group allocation as a fixed effectResultsA pre-set recruitment target of 80 women was achieved within 12 weeks and 65 (81%) participants (29 intervention, 36 control) completed 3 month assessments. Mean age was 58¿±¿5.6 years, mean BMI was 29.2¿±¿7.0 kg/m2 and many (44%) reported a family history of breast cancer.The primary analysis (baseline body weight adjusted) showed a significant between group difference favouring the intervention group of 2.04 kg (95%CI ¿3.24 kg to ¿0.85 kg). Significant, favourable between group differences were also detected for BMI, waist circumference, physical activity and sitting time. Women rated the programme highly and 70% said they would recommend it to others.ConclusionsRecruitment, retention, indicative results and participant acceptability support the development of a definitive RCT to measure long term effects.Trial registrationThe trial was registered with Current Controlled Trials (ISRCTN56223933)

Dephosphorylation of YB-1 is Required for Nuclear Localisation During G2 Phase of the Cell Cycle

Elevated levels of nuclear Y-box binding protein 1 (YB-1) are linked to poor prognosis in cancer. It has been proposed that entry into the nucleus requires specific proteasomal cleavage. However, evidence for cleavage is contradictory and high YB-1 levels are prognostic regardless of cellular location. Here, using confocal microscopy and mass spectrometry, we find no evidence of specific proteolytic cleavage. Doxorubicin treatment, and the resultant G2 arrest, leads to a significant increase in the number of cells where YB-1 is not found in the cytoplasm, suggesting that its cellular localisation is variable during the cell cycle. Live cell imaging reveals that the location of YB-1 is linked to progression through the cell cycle. Primarily perinuclear during G1 and S phases, YB-1 enters the nucleus as cells transition through late G2/M and exits at the completion of mitosis. Atomistic modelling and molecular dynamics simulations show that dephosphorylation of YB-1 at serine residues 102, 165 and 176 increases the accessibility of the nuclear localisation signal (NLS). We propose that this conformational change facilitates nuclear entry during late G2/M. Thus, the phosphorylation status of YB-1 determines its cellular location

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Upper crustal evolution across the Juan de Fuca ridge flanks

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 9 (2008): Q09006, doi:10.1029/2008GC002085.Recent P wave velocity compilations of the oceanic crust indicate that the velocity of the uppermost layer 2A doubles or reaches ∼4.3 km/s found in mature crust in <10 Ma after crustal formation. This velocity change is commonly attributed to precipitation of low-temperature alteration minerals within the extrusive rocks associated with ridge-flank hydrothermal circulation. Sediment blanketing, acting as a thermal insulator, has been proposed to further accelerate layer 2A evolution by enhancing mineral precipitation. We carried out 1-D traveltime modeling on common midpoint supergathers from our 2002 Juan de Fuca ridge multichannel seismic data to determine upper crustal structure at ∼3 km intervals along 300 km long transects crossing the Endeavor, Northern Symmetric, and Cleft ridge segments. Our results show a regional correlation between upper crustal velocity and crustal age. The measured velocity increase with crustal age is not uniform across the investigated ridge flanks. For the ridge flanks blanketed with a sealing sedimentary cover, the velocity increase is double that observed on the sparsely and discontinuously sedimented flanks (∼60% increase versus ∼28%) over the same crustal age range of 5–9 Ma. Extrapolation of velocity-age gradients indicates that layer 2A velocity reaches 4.3 km/s by ∼8 Ma on the sediment blanketed flanks compared to ∼16 Ma on the flanks with thin and discontinuous sediment cover. The computed thickness gradients show that layer 2A does not thin and disappear in the Juan de Fuca region with increasing crustal age or sediment blanketing but persists as a relatively low seismic velocity layer capping the deeper oceanic crust. However, layer 2A on the fully sedimented ridge-flank sections is on average thinner than on the sparsely and discontinuously sedimented flanks (330 ± 80 versus 430 ± 80 m). The change in thickness occurs over a 10–20 km distance coincident with the onset of sediment burial. Our results also suggest that propagator wakes can have atypical layer 2A thickness and velocity. Impact of propagator wakes is evident in the chemical signature of the fluids sampled by ODP drill holes along the east Endeavor transect, providing further indication that these crustal discontinuities may be sites of localized fluid flow and alteration.This research was supported by National Science Foundation grants OCE-00-02488, OCE-00-02551, and OCE-00- 02600

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Changes in gene expression of neo-squamous mucosa after endoscopic treatment for dysplastic Barrett’s esophagus and intramucosal adenocarcinoma

Author version made available in accordance with publisher copyright policy.Abstract Background: Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett’s esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). Objective: The purpose of this study was to investigate the molecular effects of endotherapy. Methods: mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pretreatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. Results: Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. Conclusion: Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more ‘‘normal’’ profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy