Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation

Total and Methyl Mercury Contents and Distribution Characteristics in Cicada, Cryptotympana atrata (Fabricius)

Total and methyl mercury concentrations of cicada bodies, wings, and exuviae were investigated to study the mercury distribution characteristics. Results indicated that total and methyl mercury concentrations of cicada bodies were 2.64 mg/kg and 123.93 ng/g on average, respectively. In cicada tissues, total mercury concentrations were found to increase in the order of exuviae (0.50 mg/kg on average) < wings (0.98 mg/kg on average) < cicada bodies (2.64 mg/kg on average) and methyl mercury concentrations of cicada bodies were 123.93 ng/g on average and were the highest. Methyl mercury concentrations accounted for about 4.69% of total mercury in cicada bodies and most mercury was in inorganic forms in cicada. Sex differences of total mercury concentrations were significantly great (F = 8.433, p < 0.01) and total mercury concentrations of the males, which were 3.38 mg/kg on average, were much higher. Correlation analysis showed that neither total nor methyl mercury concentrations of cicada bodies was significantly related to the corresponding contents of soil (r = 0.0598, p > 0.05)

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

This work was financially support by a Marie Curie Initial Training Network grant, “Understanding the evolutionary origin of biological diversity” (ITN-2008–213780 SPECIATION), grants from the Academy of Finland to A.H. (project 132619) and M.K. (projects 268214 and 272927), a grant from NERC, UK to M.G.R. (grant NE/J020818/1), and NERC, UK PhD studentship to D.J.P. (NE/I528634/1).For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.PostprintPeer reviewe

Letter processing and font information during reading: beyond distinctiveness, where vision meets design

Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Clues from nearby galaxies to a better theory of cosmic evolution

The great advances in the network of cosmological tests show that the relativistic Big Bang theory is a good description of our expanding universe. But the properties of nearby galaxies that can be observed in greatest detail suggest a still better theory would more rapidly gather matter into galaxies and groups of galaxies. This happens in theoretical ideas now under discussion.Comment: published in Natur

Hepatic P450 Enzyme Activity, Tissue Morphology and Histology of Mink (Mustela vison) Exposed to Polychlorinated Dibenzofurans

Dose- and time-dependent effects of environmentally relevant concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ) of 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of these two congeners on hepatic P450 enzyme activity and tissue morphology, including jaw histology, of adult ranch mink were determined under controlled conditions. Adult female ranch mink were fed either TCDF (0.98, 3.8, or 20 ng TEQTCDF/kg bw/day) or PeCDF (0.62, 2.2, or 9.5 ng TEQPeCDF/kg bw/day), or a mixture of TCDF and PeCDF (4.1 ng TEQTCDF/kg bw/day and 2.8 ng TEQPeCDF/kg bw/day, respectively) for 180 days. Doses used in this study were approximately eight times greater than those reported in a parallel field study. Activities of the cytochrome P450 1A enzymes, ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-deethylase (MROD) were significantly greater in livers of mink exposed to TCDF, PeCDF, and a mixture of the two congeners; however, there were no significant histological or morphological effects observed. It was determined that EROD and MROD activity can be used as sensitive biomarkers of exposure to PeCDF and TCDF in adult female mink; however, under the conditions of this study, the response of EROD/MROD induction occurred at doses that were less than those required to cause histological or morphological changes

Avian Use of Perennial Biomass Feedstocks as Post-Breeding and Migratory Stopover Habitat

Increased production of biomass crops in North America will require new agricultural land, intensify the cultivation of land already under production and introduce new types of biomass crops. Assessing the potential biodiversity impacts of novel agricultural systems is fundamental to the maintenance of biodiversity in agricultural landscapes, yet the consequences of expanded biomass production remain unclear. We evaluate the ability of two candidate second generation biomass feedstocks (switchgrass, Panicum virgatum, and mixed-grass prairie) not currently managed as crops to act as post-breeding and fall migratory stopover habitat for birds. In total, we detected 41 bird species, including grassland specialists and species of state and national conservation concern (e.g. Henslow's Sparrow, Ammodramus henslowii). Avian species richness was generally comparable in switchgrass and prairie and increased with patch size in both patch types. Grassland specialists were less abundant and less likely to occur in patches within highly forested landscapes and were more common and likely to occur in larger patches, indicating that this group is also area-sensitive outside of the breeding season. Variation in the biomass and richness of arthropod food within patches was generally unrelated to richness and abundance metrics. Total bird abundance and that of grassland specialists was higher in patches with greater vegetation structural heterogeneity. Collectively, we find that perennial biomass feedstocks have potential to provide post-breeding and migratory stopover habitat for birds, but that the placement and management of crops will be critical factors in determining their suitability for species of conservation concern. Industrialization of cellulosic bioenergy production that results in reduced crop structural heterogeneity is likely to dramatically reduce the suitability of perennial biomass crops for birds

Inhibition of apoptosis prevents West Nile virus induced cell death

We found that WNV infection induces cell death in the brain-derived tumour cell line T98G by apoptosis under involvement of constituents of the extrinsic as well as the intrinsic apoptotic pathways. Our results illuminate the molecular mechanism of WNV-induced neural cell death

Workplace Health Promotion and Mental Health: Three-Year Findings from Partnering Healthy@Work

This study aimed to investigate the association between mental health and comprehensive workplace health promotion (WHP) delivered to an entire state public service workforce (~28,000 employees) over a three-year period. Government departments in a state public service were supported to design and deliver a comprehensive, multi-component health promotion program, Healthy@Work, which targeted modifiable health risks including unhealthy lifestyles and stress. Repeated cross-sectional surveys compared self-reported psychological distress (Kessler-10; K10) at commencement (N = 3406) and after 3 years (N = 3228). WHP availability and participation over time was assessed, and associations between the K10 and exposure to programs estimated. Analyses were repeated for a cohort subgroup (N = 580). Data were weighted for non-response. Participation in any mental health and lifestyle programs approximately doubled after 3 years. Both male and female employees with poorer mental health participated more often over time. Women's psychological distress decreased over time but this change was only partially attributable to participation in WHP, and only to lifestyle interventions. Average psychological distress did not change over time for men. Unexpectedly, program components directly targeting mental health were not associated with distress for either men or women. Cohort results corroborated findings. Healthy@Work was successful in increasing participation across a range of program types, including for men and women with poorer mental health. A small positive association of participation in lifestyle programs with mental health was observed for women but not men. The lack of association of mental health programs may have reflected program quality, its universality of application or other contextual factors