The maize preligule band is subdivided into distinct domains with contrasting cellular properties prior to ligule outgrowth.

The maize ligule is an epidermis-derived structure that arises from the preligule band (PLB) at a boundary between the blade and sheath. A hinge-like auricle also develops immediately distal to the ligule and contributes to blade angle. Here, we characterize the stages of PLB and early ligule development in terms of topography, cell area, division orientation, cell wall rigidity and auxin response dynamics. Differential thickening of epidermal cells and localized periclinal divisions contributed to the formation of a ridge within the PLB, which ultimately produces the ligule fringe. Patterns in cell wall rigidity were consistent with the subdivision of the PLB into two regions along a distinct line positioned at the nascent ridge. The proximal region produces the ligule, while the distal region contributes to one epidermal face of the auricles. Although the auxin transporter PIN1 accumulated in the PLB, observed differential auxin transcriptional response did not underlie the partitioning of the PLB. Our data demonstrate that two zones with contrasting cellular properties, the preligule and preauricle, are specified within the ligular region before ligule outgrowth.

Nonmedical prescriber experiences of training and competence to report adverse drug reactions in the UK.

WHAT IS KNOWN AND OBJECTIVE: Adverse drug reaction reporting in the UK is lower than expected based on epidemiological data. This study aims to explore (a) nonmedical prescribers' (NMP) confidence in identifying and reporting ADRs, (b) NMP prescribing habits and engagement with the Yellow Card Scheme (YCS) and (c) NMP desire for future training in the identification and reporting of ADRs. METHODS: A survey was distributed across NMP networks in the north-west of England using Survey Monkey. Univariate analyses were performed to compare the features of reporters and nonreporters, Kruskal-Wallis H tests for comparisons within multiple subgroups and Spearman's rank correlation coefficient for response associations between answers to ordered-category questions. RESULTS AND DISCUSSION: A total of 570 responses were available for analysis, an estimated response rate of 20%. Less than half (n = 219; 38.4%) reported submitting a Yellow Card to the YCS, and the majority of those individuals have submitted five or less Yellow Cards; 28 responders reported more than five submissions. Being professionally qualified for more years (linear regression: B = 0.30, P < 0.0005; 95% CI 1.01 to 1.05) and receiving additional training support about the YCS (chi-squared: χ2  = 14.7, P < 0.0005) were associated with an increased likelihood of submitting to the YCS. There was a positive linear relationship between confidence in identifying ADRs and likelihood of reporting to YCS. The most common reason given (n = 261) for never having reported to the YCS was "I have never seen an adverse drug reaction." Training appears to give NMPs confidence in reporting ADRs, but there seems to be a gap in actually identifying ADRs given the comment that most had never seen an ADR. WHAT IS NEW AND CONCLUSION: Strategies for improving the translation of theoretical knowledge about ADRs into practical skills in identifying ADRs, and subsequently reporting them, will be important for improving pharmacovigilance practice.

Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM.

In recent work with large high-symmetry viruses, single-particle electron cryomicroscopy (cryo-EM) has achieved the determination of near-atomic-resolution structures by allowing direct fitting of atomic models into experimental density maps. However, achieving this goal with smaller particles of lower symmetry remains challenging. Using a newly developed single electron-counting detector, we confirmed that electron beam-induced motion substantially degrades resolution, and we showed that the combination of rapid readout and nearly noiseless electron counting allow image blurring to be corrected to subpixel accuracy, restoring intrinsic image information to high resolution (Thon rings visible to ∼3 Å). Using this approach, we determined a 3.3-Å-resolution structure of an ∼700-kDa protein with D7 symmetry, the Thermoplasma acidophilum 20S proteasome, showing clear side-chain density. Our method greatly enhances image quality and data acquisition efficiency-key bottlenecks in applying near-atomic-resolution cryo-EM to a broad range of protein samples.

CORD-19: The Covid-19 Open Research Dataset.

The Covid-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on Covid-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 200K times and has served as the basis of many Covid-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and describe several shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for Covid-19.

A charge coupled device camera with electron decelerator for intermediate voltage electron microscopy.

Electron microscopists are increasingly turning to intermediate voltage electron microscopes (IVEMs) operating at 300-400 kV for a wide range of studies. They are also increasingly taking advantage of slow-scan charge coupled device (CCD) cameras, which have become widely used on electron microscopes. Under some conditions, CCDs provide an improvement in data quality over photographic film, as well as the many advantages of direct digital readout. However, CCD performance is seriously degraded on IVEMs compared to the more conventional 100 kV microscopes. In order to increase the efficiency and quality of data recording on IVEMs, we have developed a CCD camera system in which the electrons are decelerated to below 100 kV before impacting the camera, resulting in greatly improved performance in both signal quality and resolution compared to other CCDs used in electron microscopy. These improvements will allow high-quality image and diffraction data to be collected directly with the CCD, enabling improvements in data collection for applications including high-resolution electron crystallography, single particle reconstruction of protein structures, tomographic studies of cell ultrastructure, and remote microscope operation. This approach will enable us to use even larger format CCD chips that are being developed with smaller pixels.

Risk assessment in offenders with intellectual disability: a comparison across three levels of security.

In mainstream offender samples, several risk assessments have been evaluated for predictive validity. This study extends this work to male offenders with intellectual disabilities. Participants from high-, medium-, and low-security settings, as well as community settings, were compared on a range of risk assessments. The Violence Risk Appraisal Guide, HCR-20-Historical Scale, the Risk Matrix 2000-C (combined risk), and the Emotional Problems Scales-Internalising discriminated between groups, with participants from high security having higher scores than those in medium security, who had higher scores than those in the community. The Violence Risk Appraisal Guide, all HCR-20 scales, the Short Dynamic Risk Scale, and the Emotional Problems Scales (Internalising and Externalising) showed significant areas under the curve for the prediction of violence. The Static-99 showed a significant area under the curve for the prediction of sexual incidents. The discussion reviews the value of these various scales to intellectual disability services.

Tau-based fluorescent protein fusions to visualize microtubules.

The ability to visualize cytoskeletal proteins and their dynamics in living cells has been critically important in advancing our understanding of numerous cellular processes, including actin- and microtubule (MT)-dependent phenomena such as cell motility, cell division, and mitosis. Here, we describe a novel set of fluorescent protein (FP) fusions designed specifically to visualize MTs in living systems using fluorescence microscopy. Each fusion contains a FP module linked in frame to a modified phospho-deficient version of the MT-binding domain of Tau (mTMBD). We found that expressed and purified constructs containing a single mTMBD decorated Xenopus egg extract spindles more homogenously than similar constructs containing the MT-binding domain of Ensconsin, suggesting that the binding affinity of mTMBD is minimally affected by localized signaling gradients generated during mitosis. Furthermore, MT dynamics were not grossly perturbed by the presence of Tau-based FP fusions. Interestingly, the addition of a second mTMBD to the opposite terminus of our construct caused dramatic changes to the spatial localization of probes within spindles. These results support the use of Tau-based FP fusions as minimally perturbing tools to accurately visualize MTs in living systems.

GeneDB: a resource for prokaryotic and eukaryotic organisms.

GeneDB (http://www.genedb.org/) is a genome database for prokaryotic and eukaryotic organisms. The resource provides a portal through which data generated by the Pathogen Sequencing Unit at the Wellcome Trust Sanger Institute and other collaborating sequencing centres can be made publicly available. It combines data from finished and ongoing genome and expressed sequence tag (EST) projects with curated annotation, that can be searched, sorted and downloaded, using a single web based resource. The current release stores 11 datasets of which six are curated and maintained by biologists, who review and incorporate information from the scientific literature, public databases and the respective research communities.

Integration of tools and resources for display and analysis of genomic data for protozoan parasites.

Centralisation of tools for analysis of genomic data is paramount in ensuring that research is always carried out on the latest currently available data. As such, World Wide Web sites providing a range of online analyses and displays of data can play a crucial role in guaranteeing consistency of in silico work. In this respect, the protozoan parasite research community is served by several resources, either focussing on data and tools for one species or taking a broader view and providing tools for analysis of data from many species, thereby facilitating comparative studies. In this paper, we give a broad overview of the online resources available. We then focus on the GeneDB project, detailing the features and tools currently available through it. Finally, we discuss data curation and its importance in keeping genomic data 'relevant' to the research community.

Changes in cytoplasmic volume are sufficient to drive spindle scaling.

The mitotic spindle must function in cell types that vary greatly in size, and its dimensions scale with the rapid, reductive cell divisions that accompany early stages of development. The mechanism responsible for this scaling is unclear, because uncoupling cell size from a developmental or cellular context has proven experimentally challenging. We combined microfluidic technology with Xenopus egg extracts to characterize spindle assembly within discrete, geometrically defined volumes of cytoplasm. Reductions in cytoplasmic volume, rather than developmental cues or changes in cell shape, were sufficient to recapitulate spindle scaling observed in Xenopus embryos. Thus, mechanisms extrinsic to the spindle, specifically a limiting pool of cytoplasmic component(s), play a major role in determining spindle size.

Predictive validity of the PCL-R for offenders with intellectual disability in a high security hospital: treatment progress.

BACKGROUND: Among mainstream offenders, the severe personality disorder of psychopathy has considerable importance as a construct. The disorder has long been associated with failure to make treatment progress. Previous work has identified that psychopathy as a disorder occurs in samples of offenders with intellectual disability (ID), and suggests that the Psychopathy Checklist - Revised (PCL-R: Hare, 1991, 2003) as a measure of the disorder has adequate reliability and validity (Morrissey et al., 2005). The present study aimed to compare the predictive power of the PCL-R in relation to treatment progress with a more general assessment of violence risk, the HCR-20 (Webster, Douglas, Eaves, & Hart, 1997). METHOD: A sample of 73 residents in a high security intellectual disability service, who had previously been assessed using the PCL-R and the HCR-20, were followed up at 2 years post-assessment, and their outcome determined in terms of two distinct dichotomous variables reflecting definite positive treatment progress and definite negative treatment progress respectively. RESULTS: In line with predictions, the PCL-R Total score and Factor 1 score (Interpersonal and Affective aspects of psychopathy) and the HCR-20 Total score were significantly inversely associated with a positive move from high to medium security hospital conditions within 2 years of assessment. However against prediction, the PCL-R Total score had incremental validity over the HCR-20. The PCL-R Total and Factor 1, but not the HCR-20 Total score, were also significantly associated with negative treatment progress in terms of a move to more restricted treatment conditions. CONCLUSION: Psychopathy, and in particular its interpersonal and affective manifestations, is a construct which appears to be associated with indirect measures of treatment progress in this high security ID group. However, caution should be applied in the use of a construct with potentially negative connotations in an already devalued population.

Internal consistency and factor structure of personality disorders in a forensic intellectual disability sample.

BACKGROUND: The publication of the DSM-III (American Psychiatric Association (APA), 1980) prompted a significant increase in interest and research on personality disorder (PD), and the concept has subsequently been incorporated into mental health legislation in the developed world. Despite this, such research on people with intellectual disability (ID) has been sporadic, with widely varying results. The present study addresses a number of criticisms directed at previous research. METHOD: DSM-IV (APA, 2000) diagnoses of PD were made on 164 participants with ID on the basis of four independent sources of classification. RESULTS: Reliability data for each PD was acceptable and alpha was .74 or above, with the exception of schizotypal PD (.63). Exploratory and confirmatory factor analyses were conducted, with the former revealing a 4-factor solution accounting for 58.9% of the variance, and a 2-factor solution accounting for 37.2% of the variance emerging for the latter. The factors were orthogonal, and we called the first factor "avoidant/rumination/inhibited" and the second factor "acting out". DISCUSSION: We review these findings in relation to previous research on PD and alternative frameworks for the understanding of personality. We hypothesise consistencies between these findings and previous work on personality and ID. A number of drawbacks to the research are discussed, including a caution on the pejorative nature of a diagnosis of PD in an already devalued population.

The putative use of alpha-1-acid glycoprotein as a non-invasive marker of fibrosis.

The acute phase response to injury or infection results in alterations in the expression of the plasma proteins produced by the liver. Many of these biomolecules are glycosylated with oligosaccharide chains covalently attached to the polypeptide backbone and the extent and composition of this glycosylation can be altered in a disease-dependent manner. Of particular interest is the observation that the acute phase glycoprotein, alpha-1-acid glycoprotein (AGP) has altered glycosylation in several physiological and pathological conditions. It is posited that changes induced in liver diseases may reflect disease severity and may therefore act as a non-invasive marker of fibrosis. This study has investigated the glycosylation of AGP in the plasma of people with varying degrees of cirrhosis and fibrosis. Hyperfucosylation was observed in all disease samples in comparison to normal plasma and was significantly increased in cirrhosis. Both sialic acid and N-acetylgalactosamine (GalNAc) were negatively associated with fibrosis. Two samples were found to express GalNAc, which as a constituent of the glycosylation of serum proteins is rare. In conclusion, fucose, sialic acid and other aspects of the glycosylation of AGP are influenced by the degree of fibrosis and as such may prove a valuable prognostic indicator of the development of cirrhosis.

A comparison of offenders with intellectual disability across three levels of security.

BACKGROUND: A number of authors have described, with disparate results, the prevalence of people with intellectual disability and their characteristics, in a range of offender cohorts defined by service use. These have included high security, a range of criminal justice services and community services. There is a need for research comparing cohorts of offenders with intellectual disabilities across different settings. AIM AND HYPOTHESIS: To conduct such a comparison and test the hypothesis that severity of characteristics measured will be highest in highest levels of residential security. METHOD: A clinical-record-based comparison a offenders with intellectual disability in high security (n = 73), medium/low security (n = 70), and a community service (n = 69). RESULTS: Groups were similar in age and tested IQ levels. Early psychiatric service contact had been more likely in the lower security groups. In line with the hypothesis, more complex presentations, in particular comorbid personality disorder, was more likely in the highest security group. Both fatal and non-fatal interpersonal violence convictions were significantly related to group, with more in the high security group sustaining a conviction both at the index offence and prior to that. Over 50% of all groups had at least one conviction for a sexual offence. A regression model accounting for 78% of the variance was made up largely of disposal variables (Mental Health Act status and probation) and indications of antisocial traits (criminal damage, lifetime conviction for murder and ICD-10 personality disorder classification). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The authors show that context of sampling affects most relationships between intellectual disability (ID) and offending when the methods for measuring ID are held constant. The results also present several questions on the relationship between risk, services available in an area and referral to higher security.

Genome of the host-cell transforming parasite Theileria annulata compared with T. parva.

Theileria annulata and T. parva are closely related protozoan parasites that cause lymphoproliferative diseases of cattle. We sequenced the genome of T. annulata and compared it with that of T. parva to understand the mechanisms underlying transformation and tropism. Despite high conservation of gene sequences and synteny, the analysis reveals unequally expanded gene families and species-specific genes. We also identify divergent families of putative secreted polypeptides that may reduce immune recognition, candidate regulators of host-cell transformation, and a Theileria-specific protein domain [frequently associated in Theileria (FAINT)] present in a large number of secreted proteins.

Sertraline as a treatment for PTSD: a systematic review and meta-analysis.

OBJECTIVE: Post-traumatic stress disorder (PTSD) is one of the most prevalent psychological disorders. Methods to alleviate its symptoms range from 'talking therapies' to pharmaceutical interventions. Our objective was to carry out a systematic review of the effectiveness of sertraline, an SSRI, as a treatment for PTSD. METHOD: Databases were searched to identify relevant research on sertraline as a treatment for PTSD. RESULTS: Five randomised control trials were identified, along with seven open trials and case series studies. CONCLUSIONS: The review and meta-analysis supported the use of sertraline for PTSD though further research on sub-group differences (eg. gender) is required.

Automated image acquisition and processing using a new generation of 4K x 4K CCD cameras for cryo electron microscopic studies of macromolecular assemblies.

We have previously reported the development of AutoEM, a software package for semi-automated acquisition of data from a transmission electron microscope. In continuing efforts to improve the speed of structure determination of macromolecular assemblies by electron microscopy, we report here on the performance of a new generation of 4 K CCD cameras for use in cryo electron microscopic applications. We demonstrate that at 120 kV, and at a nominal magnification of 67000 x, power spectra and signal-to-noise ratios for the new 4 K CCD camera are comparable to values obtained for film images scanned using a Zeiss scanner to resolutions as high as approximately 1/6.5A(-1). The specimen area imaged for each exposure on the 4 K CCD is about one-third of the area that can be recorded with a similar exposure on film. The CCD camera also serves the purpose of recording images at low magnification from the center of the hole to measure the thickness of vitrified ice in the hole. The performance of the camera is satisfactory under the low-dose conditions used in cryo electron microscopy, as demonstrated here by the determination of a three-dimensional map at 15 A for the catalytic core of the 1.8 MDa Bacillus stearothermophilus icosahedral pyruvate dehydrogenase complex, and its comparison with the previously reported atomic model for this complex obtained by X-ray crystallography.