Synthesis and Localization of a Development-Specific Protein in Sclerotia of \u3ci\u3eSclerotinia sclerotiorum\u3c/i\u3e

A development-specific protein (SSP) makes up about 35 to 40% of the total protein in sclerotia of the fungus Sclerotinia sclerotiorum. The protein consists of three charge isomers, with one isomer making up 80 to 90% of the total. In vitro translation of poly(A)+ RNA isolated from cells in early stages of sclerotia formation revealed that 44% of the amino acids incorporated was into SSP. In vivo- and in vitro-synthesized forms of SSP migrated at identical rates on both isoelectric focusing and denaturing polyacrylamide gels, indicating that SSP was not synthesized as a larger precursor. This was significant because SSP accumulated in membrane-bound, organellelike structures which resemble protein bodies found in seeds of many higher plants

Synthesis and Localization of a Development-Specific Protein in Sclerotia of \u3ci\u3eSclerotinia sclerotiorum\u3c/i\u3e

A development-specific protein (SSP) makes up about 35 to 40% of the total protein in sclerotia of the fungus Sclerotinia sclerotiorum. The protein consists of three charge isomers, with one isomer making up 80 to 90% of the total. In vitro translation of poly(A)+ RNA isolated from cells in early stages of sclerotia formation revealed that 44% of the amino acids incorporated was into SSP. In vivo- and in vitro-synthesized forms of SSP migrated at identical rates on both isoelectric focusing and denaturing polyacrylamide gels, indicating that SSP was not synthesized as a larger precursor. This was significant because SSP accumulated in membrane-bound, organellelike structures which resemble protein bodies found in seeds of many higher plants

Measuring children’s involvement as an indicator of curriculum effectiveness : a curriculum evaluation of a selected child study centre in Singapore

This paper presents one aspect of a research project evaluating a curriculum model of a selected child study centre in Singapore. An issue of worldwide interest and concern is the ‘quality of learning’ debate as it relates to early childhood centres. In Singapore, the government is focusing on expansion in child care settings and increases in the amount of funded training. One of the issues surrounding prior-to-school education raises the question of how one measures the quality of teaching and learning, to describe the value of using, funding and promoting early education. The research reported in this study used a quasi experimental research paradigm to assess one aspect of the quality of a curriculum programme in a child study centre in Singapore. Children aged between 18 months and 6 years (N = 81) participated in the research. Using the observation scale of Laevers’ Child Involvement Scale, the active involvement of children in learning experiences was measured. The findings are presented and discussed

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

STUDIES ON DEVELOPMENT-SPECIFIC MAJOR PROTEINS IN SCLEROTIA OF SCLEROTINIA SCLEROTIORUM, SCLEROTINIA TRIFOLIORUM, AND SCLEROTINIA MINOR (PROTEIN BODIES)

A major protein of approximately 36,000 daltons was identified in sclerotia of Sclerotinia sclerotiorum. The protein was not detected in vegetative cells, indicating that it is development-specific. It accumulated rapidly during sclerotia formation, ultimately comprising 38% of the mature sclerotial protein. The protein did not decrease in concentration in sclerotial residue or appear in vegetative cells when sclerotia germinated myceliogenically. In contrast, the concentration of the protein decreased in sclerotia undergoing carpogenic germination and a small amount of the protein was present in the resultant apothecia. The protein was purified and characterized. It exists as three charge isomers, and contains all 20 common amino acids. The major isomer has an isoelectric point of 6.0; the two minor isomers have isoelectric points of 5.8 and 6.2 respectively. Development-specific major proteins were also identified in sclerotia of Sclerotinia trifoliorum and Sclerotinia minor, which comprised 27 and 31% of the total cellular protein, respectively. Comparative analyses performed on the major sclerotial proteins from the three Sclerotinia species indicated that the proteins are similar, but not identical. Poly(A+)RNA was isolated from presclerotial polysomes of S. sclerotiorum and translated in vitro in a rabbit reticulocyte translation system. Approximately 44% of the incorporation of (\u2735)S-methionine into protein translated from this RNA was incorporated into the major sclerotial protein. Electrophoretic analysis of the in vivo and in vitro synthesized major sclerotial protein of S. sclerotiorum on one dimensional denaturing polyacrylamide gels indicated that the protein is not synthesized as a large precursor. The major protein of S. sclerotiorum was localized in membrane-bound protein bodies , i.e., subcellular organelles of the sclerotium, by transmission electron microscopy using a gold-labelled double antibody technique. The protein is transported across the membrane of the protein body via a mechanism other than a cleavable amino-terminal signal sequence

Making a spectacle out of herself - Bobby Baker's take a peek!

Drawing on Mary Russo's theorization of 'female grotesques', this article analyses Take a Peek! - a circus, fairground-styled 'freak' show by British performance artist, Bobby Baker. While making a display of or a spectacle out of herself can be argued for all of Baker's work, Take a Peek!, the third show in her 'Daily Life' series, is especially concerned with 'woman' on display. The article argues that in Take a Peek! Baker turns herself into a 'spectacular' demonstration of 'failed' femininity in a way that constitutes a site/sight of feminist critical 'work'. The analysis proceeds by detailing the various ways in which Baker realizes her performance through strategies that serve to grotesque the feminine and figure an archaic maternal, the sorceress and the hysteric. In conclusion, Baker's invitation to laugh at the grotesquing of her own body is proposed as a means of empowering those who look, to look differently at the ideas and 'ideals' that shape the feminine in contemporary cultural and social systems, and to expose the symbolic feminine for what it truly is - a freak show