A conditional Smg6 mutant mouse model reveals circadian clock regulation through the nonsense-mediated mRNA decay pathway.

Nonsense-mediated messenger RNA (mRNA) decay (NMD) has been intensively studied as a surveillance pathway that degrades erroneous transcripts arising from mutations or RNA processing errors. While additional roles in physiological control of mRNA stability have emerged, possible functions in mammalian physiology in vivo remain unclear. Here, we created a conditional mouse allele that allows converting the NMD effector nuclease SMG6 from wild-type to nuclease domain-mutant protein. We find that NMD down-regulation affects the function of the circadian clock, a system known to require rapid mRNA turnover. Specifically, we uncover strong lengthening of free-running circadian periods for liver and fibroblast clocks and direct NMD regulation of Cry2 mRNA, encoding a key transcriptional repressor within the rhythm-generating feedback loop. Transcriptome-wide changes in daily mRNA accumulation patterns in the entrained liver, as well as an altered response to food entrainment, expand the known scope of NMD regulation in mammalian gene expression and physiology

A novel Smg6 mouse model reveals regulation of circadian period and daily CRY2 accumulation through the nonsense-mediated mRNA decay pathway

Nonsense-mediated mRNA decay (NMD) has been intensively studied as a surveillance pathway that degrades erroneous transcripts arising from mutations or RNA processing errors. While additional roles in controlling regular mRNA stability have emerged, possible functions in mammalian physiology in vivo have remained unclear. Here, we report a novel conditional mouse allele that allows converting the NMD effector nuclease SMG6 from wild-type to nuclease domain-mutant protein. We analyzed how NMD downregulation affects the function of the circadian clock, a system known to require rapid mRNA turnover. We uncover strong lengthening of free-running circadian periods for liver and fibroblast clocks, and direct NMD regulation of Cry2 mRNA, encoding a key transcriptional repressor within the rhythm-generating feedback loop. In the entrained livers of Smg6 mutant animals we reveal transcriptome-wide alterations in daily mRNA accumulation patterns, altogether expanding the known scope of NMD regulation in mammalian gene expression and physiology

Local impact of temperature and precipitation on West Nile virus infection in Culex species mosquitoes in northeast Illinois, USA

<p>Abstract</p> <p>Background</p> <p>Models of the effects of environmental factors on West Nile virus disease risk have yielded conflicting outcomes. The role of precipitation has been especially difficult to discern from existing studies, due in part to habitat and behavior characteristics of specific vector species and because of differences in the temporal and spatial scales of the published studies. We used spatial and statistical modeling techniques to analyze and forecast fine scale spatial (2000 m grid) and temporal (weekly) patterns of West Nile virus mosquito infection relative to changing weather conditions in the urban landscape of the greater Chicago, Illinois, region for the years from 2004 to 2008.</p> <p>Results</p> <p>Increased air temperature was the strongest temporal predictor of increased infection in <it>Culex pipiens </it>and <it>Culex restuans </it>mosquitoes, with cumulative high temperature differences being a key factor distinguishing years with higher mosquito infection and higher human illness rates from those with lower rates. Drier conditions in the spring followed by wetter conditions just prior to an increase in infection were factors in some but not all years. Overall, 80% of the weekly variation in mosquito infection was explained by prior weather conditions. Spatially, lower precipitation was the most important variable predicting stronger mosquito infection; precipitation and temperature alone could explain the pattern of spatial variability better than could other environmental variables (79% explained in the best model). Variables related to impervious surfaces and elevation differences were of modest importance in the spatial model.</p> <p>Conclusion</p> <p>Finely grained temporal and spatial patterns of precipitation and air temperature have a consistent and significant impact on the timing and location of increased mosquito infection in the northeastern Illinois study area. The use of local weather data at multiple monitoring locations and the integration of mosquito infection data from numerous sources across several years are important to the strength of the models presented. The other spatial environmental factors that tended to be important, including impervious surfaces and elevation measures, would mediate the effect of rainfall on soils and in urban catch basins. Changes in weather patterns with global climate change make it especially important to improve our ability to predict how inter-related local weather and environmental factors affect vectors and vector-borne disease risk.</p> <p>Local impact of temperature and precipitation on West Nile virus infection in <it>Culex </it>species mosquitoes in northeast Illinois, USA.</p

Phylogeny and classification of novel diversity in Sainouroidea (Cercozoa, Rhizaria) sheds light on a highly diverse and divergent clade

Sainouroidea is a molecularly diverse clade of cercozoan flagellates and amoebae in the eukaryotic supergroup Rhizaria. Previous 18S rDNA environmental sequencing of globally collected fecal and soil samples revealed great diversity and high sequence divergence in the Sainouroidea. However, a very limited amount of this diversity has been observed or described. The two described genera of amoebae in this clade are Guttulinopsis, which displays aggregative multicellularity, and Rosculus, which does not. Although the identity of Guttulinopsis is straightforward due to the multicellular fruiting bodies they form, the same is not true for Rosculus, and the actual identity of the original isolate is unclear. Here we isolated amoebae with morphologies like that of Guttulinopsis and Rosculus from many environments and analyzed them using 18S rDNA sequencing, light microscopy, and transmission electron microscopy. We define a molecular species concept for Sainouroidea that resulted in the description of 4 novel genera and 12 novel species of naked amoebae. Aggregative fruiting is restricted to the genus Guttulinopsis, but other than this there is little morphological variation amongst these taxa. Taken together, simple identification of these amoebae is problematic and potentially unresolvable without the 18S rDNA sequence

Probing Teichoic Acid Genetics with Bioactive Molecules Reveals New Interactions among Diverse Processes in Bacterial Cell Wall Biogenesis

SummaryThe bacterial cell wall has been a celebrated target for antibiotics and holds real promise for the discovery of new antibacterial chemical matter. In addition to peptidoglycan, the walls of Gram-positive bacteria contain large amounts of the polymer teichoic acid, covalently attached to peptidoglycan. Recently, wall teichoic acid was shown to be essential to the proper morphology of Bacillus subtilis and an important virulence factor for Staphylococcus aureus. Additionally, recent studies have shown that the dispensability of genes encoding teichoic acid biosynthetic enzymes is paradoxical and complex. Here, we report on the discovery of a promoter (PywaC), which is sensitive to lesions in teichoic acid synthesis. Exploiting this promoter through a chemical-genetic approach, we revealed surprising interactions among undecaprenol, peptidoglycan, and teichoic acid biosynthesis that help explain the complexity of teichoic acid gene dispensability. Furthermore, the new reporter assay represents an exciting avenue for the discovery of antibacterial molecules

Dispersal of Adult Culex Mosquitoes in an Urban West Nile Virus Hotspot: A Mark-Capture Study Incorporating Stable Isotope Enrichment of Natural Larval Habitats

Dispersal is a critical life history behavior for mosquitoes and is important for the spread of mosquito-borne disease. We implemented the first stable isotope mark-capture study to measure mosquito dispersal, focusing on Culex pipiens in southwest suburban Chicago, Illinois, a hotspot of West Nile virus (WNV) transmission. We enriched nine catch basins in 2010 and 2011 with 15N-potassium nitrate and detected dispersal of enriched adult females emerging from these catch basins using CDC light and gravid traps to distances as far as 3 km. We detected 12 isotopically enriched pools of mosquitoes out of 2,442 tested during the two years and calculated a mean dispersal distance of 1.15 km and maximum flight range of 2.48 km. According to a logistic distribution function, 90% of the female Culex mosquitoes stayed within 3 km of their larval habitat, which corresponds with the distance-limited genetic variation of WNV observed in this study region. This study provides new insights on the dispersal of the most important vector of WNV in the eastern United States and demonstrates the utility of stable isotope enrichment for studying the biology of mosquitoes in other disease systems.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

Dangerous work: The gendered nature of bullying in the context of higher education

This paper discusses results from a research project which set out to investigate gender differences in the nature and experience of bullying within the higher education sector. Gender differences emerged in the form and perception of bullying as well as in target response. Results also indicate that, irrespective of gender, bullies can capture and subvert organizational structures and procedures (official hierarchies, mentoring systems, probationary reviews) to further their abuse of the target and to conceal aggressive intent. These outcomes are discussed in relation to gendered assumptions behind management practices and in relation to the masculinist ethic that underpins many higher education management initiatives. Overall, results indicate that bullying cannot be divorced from gender and that such behaviour needs to be seen in a gendered context

High resolution X-ray spectroscopy and imaging of Mrk573

We present a detailed analysis of the XMM-Newton RGS high resolution X-ray spectra of the Seyfert 2 galaxy, Mrk573. This analysis is complemented by the study of the Chandra image, and its comparison to optical (HST) and radio (VLA) data. The soft X-ray emission is mainly due to gas photoionised by the central AGN, as indicated by the detection of radiative recombination continua from OVII and OVIII, as well as by the prominence of the OVII forbidden line. This result is confirmed by the best fit obtained with a self-consistent CLOUDY photoionisation model. However, a collisionally excited component is also required, in order to reproduce the FeXVII lines, accounting for about 1/3 of the total luminosity in the 15-26 A band. Once adopted the same model in the Chandra ACIS data, another photoionised component, with higher ionisation parameter, is needed to take into account emission from higher Z metals. The broadband ACIS spectrum also confirms the Compton-thick nature of the source. The imaging analysis shows the close morphological correspondence between the soft X-ray and the [OIII] emission. The radio emission appears much more compact, although clearly aligned with the narrow line region. The collisional phase of the soft X-ray emission may be due to starburst, requiring a star formation rate of $\simeq5-9$ M$_\odot$ yr$^{-1}$, but there is no clear evidence of this kind of activity from other wavelengths. On the other hand, it may be related to the radio ejecta, responsible for the heating of the plasma interacting with the outflow, but the estimated pressure of the hot gas is much larger than the pressure of the radio jets, assuming equipartition and under reasonable physical parameters.Comment: 12 pages, 6 figures, accepted for publication in Monthly Notices of the Royal Astronomical Society Main Journa

Efficacy of language intervention in the early years

Background: Oral language skills in the preschool and early school years are critical to educational success and provide the foundations for the later development of reading comprehension. Methods: In a randomized controlled trial, 180 children from 15 UK nursery schools (n = 12 from each setting; Mage = 4;0) were randomly allocated to receive a 30-week oral language intervention or to a waiting control group. Children in the intervention group received 30 weeks of oral language intervention, beginning in nursery (preschool), in three group sessions per week, continuing with daily sessions on transition to Reception class (pre-Year 1). The intervention was delivered by nursery staff and teaching assistants trained and supported by the research team. Following screening, children were assessed preintervention, following completion of the intervention and after a 6-month delay. Results: Children in the intervention group showed significantly better performance on measures of oral language and spoken narrative skills than children in the waiting control group immediately after the 30 week intervention and after a 6 month delay. Gains in word-level literacy skills were weaker, though clear improvements were observed on measures of phonological awareness. Importantly, improvements in oral language skills generalized to a standardized measure of reading comprehension at maintenance test. Conclusions: Early intervention for children with oral language difficulties is effective and can successfully support the skills, which underpin reading comprehensio