Structure and expression of the maize (Zea mays L.) SUN-domain protein gene family: evidence for the existence of two divergent classes of SUN proteins in plants

<p>Abstract</p> <p>Background</p> <p>The nuclear envelope that separates the contents of the nucleus from the cytoplasm provides a surface for chromatin attachment and organization of the cortical nucleoplasm. Proteins associated with it have been well characterized in many eukaryotes but not in plants. SUN (Sad1p/Unc-84) domain proteins reside in the inner nuclear membrane and function with other proteins to form a physical link between the nucleoskeleton and the cytoskeleton. These bridges transfer forces across the nuclear envelope and are increasingly recognized to play roles in nuclear positioning, nuclear migration, cell cycle-dependent breakdown and reformation of the nuclear envelope, telomere-led nuclear reorganization during meiosis, and karyogamy.</p> <p>Results</p> <p>We found and characterized a family of maize SUN-domain proteins, starting with a screen of maize genomic sequence data. We characterized five different maize <it>ZmSUN </it>genes <it>(ZmSUN1-5)</it>, which fell into two classes (probably of ancient origin, as they are also found in other monocots, eudicots, and even mosses). The first (<it>ZmSUN1</it>, <it>2</it>), here designated canonical C-terminal SUN-domain (CCSD), includes structural homologs of the animal and fungal SUN-domain protein genes. The second (<it>ZmSUN3, 4, 5</it>), here designated plant-prevalent mid-SUN 3 transmembrane (PM3), includes a novel but conserved structural variant SUN-domain protein gene class. Mircroarray-based expression analyses revealed an intriguing pollen-preferred expression for <it>ZmSUN5 </it>mRNA but low-level expression (50-200 parts per ten million) in multiple tissues for all the others. Cloning and characterization of a full-length cDNA for a PM3-type maize gene, <it>ZmSUN4</it>, is described. Peptide antibodies to ZmSUN3, 4 were used in western-blot and cell-staining assays to show that they are expressed and show concentrated staining at the nuclear periphery.</p> <p>Conclusions</p> <p>The maize genome encodes and expresses at least five different SUN-domain proteins, of which the PM3 subfamily may represent a novel class of proteins with possible new and intriguing roles within the plant nuclear envelope. Expression levels for <it>ZmSUN</it>1-4 are consistent with basic cellular functions, whereas <it>ZmSUN</it>5 expression levels indicate a role in pollen. Models for possible topological arrangements of the CCSD-type and PM3-type SUN-domain proteins are presented.</p

The 'dirty dozen' of freshwater science: detecting then reconciling hydrological data biases and errors

Sound water policy and management rests on sound hydrometeorological and ecological data. Conversely, unrepresentative, poorly collected, or erroneously archived data introduce uncertainty regarding the magnitude, rate, and direction of environmental change, in addition to undermining confidence in decision-making processes. Unfortunately, data biases and errors can enter the information flow at various stages, starting with site selection, instrumentation, sampling/measurement procedures, postprocessing and ending with archiving systems. Techniques such as visual inspection of raw data, graphical representation, and comparison between sites, outlier, and trend detection, and referral to metadata can all help uncover spurious data. Tell-tale signs of ambiguous and/or anomalous data are highlighted using 12 carefully chosen cases drawn mainly from hydrology (‘the dirty dozen’). These include evidence of changes in site or local conditions (due to land management, river regulation, or urbanization); modifications to instrumentation or inconsistent observer behavior; mismatched or misrepresentative sampling in space and time; treatment of missing values, postprocessing and data storage errors. Also for raising awareness of pitfalls, recommendations are provided for uncovering lapses in data quality after the information has been gathered. It is noted that error detection and attribution are more problematic for very large data sets, where observation networks are automated, or when various information sources have been combined. In these cases, more holistic indicators of data integrity are needed that reflect the overall information life-cycle and application(s) of the hydrological data

Financing Direct Democracy: Revisiting the Research on Campaign Spending and Citizen Initiatives

The conventional view in the direct democracy literature is that spending against a measure is more effective than spending in favor of a measure, but the empirical results underlying this conclusion have been questioned by recent research. We argue that the conventional finding is driven by the endogenous nature of campaign spending: initiative proponents spend more when their ballot measure is likely to fail. We address this endogeneity by using an instrumental variables approach to analyze a comprehensive dataset of ballot propositions in California from 1976 to 2004. We find that both support and opposition spending on citizen initiatives have strong, statistically significant, and countervailing effects. We confirm this finding by looking at time series data from early polling on a subset of these measures. Both analyses show that spending in favor of citizen initiatives substantially increases their chances of passage, just as opposition spending decreases this likelihood

Rationale and design of the Early valve replacement in severe ASYmptomatic Aortic Stenosis Trial

Background: Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims to determine whether early aortic valve replacement improves clinical outcomes, quality of life and cost-effectiveness compared to a guideline recommended strategy of ‘watchful waiting’. Methods: In a pragmatic international, open parallel group randomized controlled trial (NCT04204915), 2844 patients with severe aortic stenosis will be randomized 1:1 to either a strategy of early (surgical or transcatheter) aortic valve replacement or aortic valve replacement only if symptoms or impaired left ventricular function develop, or other cardiac surgery becomes nessessary. Exclusion criteria include other severe valvular disease, planned cardiac surgery, ejection fraction &lt;50%, previous aortic valve replacement or life expectancy &lt;2 years. The primary outcome is a composite of cardiovascular mortality or heart failure hospitalization. The primary analysis will be undertaken when 663 primary events have accrued, providing 90% power to detect a reduction in the primary endpoint from 27.7% to 21.6% (hazard ratio 0.75). Secondary endpoints include disability-free survival, days alive and out of hospital, major adverse cardiovascular events and quality of life. Results: Recruitment commenced in March 2020 and is open in the UK, Australia, New Zealand, and Serbia. Feasibility requirements were met in July 2022, and the main phase opened in October 2022, with additional international centers in set-up. Conclusions: The EASY-AS trial will establish whether a strategy of early aortic valve replacement in asymptomatic patients with severe aortic stenosis reduces cardiovascular mortality or heart failure hospitalization and improves other important outcomes.</p

Re-interpreting conventional interval estimates taking into account bias and extra-variation

BACKGROUND: The study design with the smallest bias for causal inference is a perfect randomized clinical trial. Since this design is often not feasible in epidemiologic studies, an important challenge is to model bias properly and take random and systematic variation properly into account. A value for a target parameter might be said to be "incompatible" with the data (under the model used) if the parameter's confidence interval excludes it. However, this "incompatibility" may be due to bias and/or extra-variation. DISCUSSION: We propose the following way of re-interpreting conventional results. Given a specified focal value for a target parameter (typically the null value, but possibly a non-null value like that representing a twofold risk), the difference between the focal value and the nearest boundary of the confidence interval for the parameter is calculated. This represents the maximum correction of the interval boundary, for bias and extra-variation, that would still leave the focal value outside the interval, so that the focal value remained "incompatible" with the data. We describe a short example application concerning a meta analysis of air versus pure oxygen resuscitation treatment in newborn infants. Some general guidelines are provided for how to assess the probability that the appropriate correction for a particular study would be greater than this maximum (e.g. using knowledge of the general effects of bias and extra-variation from published bias-adjusted results). SUMMARY: Although this approach does not yet provide a method, because the latter probability can not be objectively assessed, this paper aims to stimulate the re-interpretation of conventional confidence intervals, and more and better studies of the effects of different biases

An inherited duplication at the gene p21 protein-activated Kinase 7 (PAK7) is a risk factor for psychosis

FUNDING Funding for this study was provided by the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z), the Wellcome Trust (072894/Z/03/Z, 090532/Z/09/Z and 075491/Z/04/B), NIMH grants (MH 41953 and MH083094) and Science Foundation Ireland (08/IN.1/B1916). We acknowledge use of the Trinity Biobank sample from the Irish Blood Transfusion Service; the Trinity Centre for High Performance Computing; British 1958 Birth Cohort DNA collection funded by the Medical Research Council (G0000934) and the Wellcome Trust (068545/Z/02) and of the UK National Blood Service controls funded by the Wellcome Trust. Chris Spencer is supported by a Wellcome Trust Career Development Fellowship (097364/Z/11/Z). Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust. ACKNOWLEDGEMENTS The authors sincerely thank all patients who contributed to this study and all staff who facilitated their involvement. We thank W. Bodmer and B. Winney for use of the People of the British Isles DNA collection, which was funded by the Wellcome Trust. We thank Akira Sawa and Koko Ishzuki for advice on the PAK7–DISC1 interaction experiment and Jan Korbel for discussions on mechanism of structural variation.Peer reviewedPublisher PD

Changing climate both increases and decreases European river floods

Climate change has led to concerns about increasing river floods resulting from the greater water-holding capacity of a warmer atmosphere. These concerns are reinforced by evidence of increasing economic losses associated with flooding in many parts of the world, including Europe. Any changes in river floods would have lasting implications for the design of flood protection measures and flood risk zoning. However, existing studies have been unable to identify a consistent continental-scale climatic-change signal in flood discharge observations in Europe, because of the limited spatial coverage and number of hydrometric stations. Here we demonstrate clear regional patterns of both increases and decreases in observed river flood discharges in the past five decades in Europe, which are manifestations of a changing climate. Our results—arising from the most complete database of European flooding so far—suggest that: increasing autumn and winter rainfall has resulted in increasing floods in northwestern Europe; decreasing precipitation and increasing evaporation have led to decreasing floods in medium and large catchments in southern Europe; and decreasing snow cover and snowmelt, resulting from warmer temperatures, have led to decreasing floods in eastern Europe. Regional flood discharge trends in Europe range from an increase of about 11 per cent per decade to a decrease of 23 per cent. Notwithstanding the spatial and temporal heterogeneity of the observational record, the flood changes identified here are broadly consistent with climate model projections for the next century, suggesting that climate-driven changes are already happening and supporting calls for the consideration of climate change in flood risk management

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes