Latrunculin A delays anaphase onset in fission yeast by disrupting an ase1-independent pathway controlling mitotic spindle stability

It has been proposed previously that latrunculin A, an inhibitor of actin polymerization, delays the onset of anaphase by causing spindle misorientation in fission yeast. However, we show that {Delta}mto1 cells, which are defective in nucleation of cytoplasmic microtubules, have profoundly misoriented spindles but are not delayed in the timing of sister chromatid separation, providing compelling evidence that fission yeast does not possess a spindle orientation checkpoint. Instead, we show that latrunculin A delays anaphase onset by disrupting interpolar microtubule stability. This effect is abolished in a latrunculin A-insensitive actin mutant and exacerbated in cells lacking Ase1, which cross-links antiparallel interpolar microtubules at the spindle midzone both before and after anaphase. These data indicate that both Ase1 and an intact actin cytoskeleton are required for preanaphase spindle stability. Finally, we show that loss of Ase1 activates a checkpoint that requires only the Mad3, Bub1, and Mph1, but not Mad1, Mad2, or Bub3 checkpoint proteins

Scaling out impacts: A study of three methods for introducing forage technologies to villages in Lao PDR

Research and Development/Tech Change/Emerging Technologies,

The gilded path: Capital, habitus and illusio in the fund management field

Purpose – The fund management sector plays an important role in society. The sector exists in close proximity to the accounting profession and the concerns of the paper reflect themes discussed by accounting scholars, particularly financialization, inequality, and life within elite professional service organizations. Design/methodology/approach – This is an interpretive study of the fund management field based in the UK. It is based on 32 semi-structured interviews with individuals with personal experience of the field, combined with reflections from the researcher’s own experience as a practitioner within the field. Findings – The paper describes the backgrounds and motivations of individuals entering the field, the recruitment processes through which they are admitted, and the different strategies used to gain admission to the field. It explores the habitus of successful professionals in the field and the effects of this habitus. Social implications – An important social implication of the paper is the problematization of the fund management industry’s dislocation from broader society. Originality/value – By identifying the different strategies employed by applicants from different backgrounds, it highlights the role of reflexive agency and the complicity between agent and field. Recognizing that professional fund management is organized as a game, it suggests that individuals are so committed to the game they know they are playing that they fail to realize that they are also drawn into a different game, namely the absorbing game of being a fund manager. Keywords Bourdieu, Cultural Capital, Social Capital, Habitus, Illusio, Fund Management, Recruitment, Socializatio

Treatment of common issues in General Electric's and IUE's local 201 employee publications

Thesis (M.S.)--Boston Universit

Global investor responses to the International Sustainability Standards Board draft sustainability and climate-change standards: Sites of dissonance or consensus

PurposeThis paper aims to examine sites of dissonance or consensus between global investor responses to the draft standards, International Financial Reporting Standards S1 (IFRS) (General Requirements for Disclosure of Sustainability-related Financial Information) and IFRS S2 (Climate-related Disclosures), issued by the International Sustainability Standards Board (ISSB).Design/methodology/approachA thematic content analysis was used to capture investor views expressed in their comment letters submitted in the consultation period (March to July 2022) in comparison to the ex ante position (issue of draft standards, March 2022) and ex post summary feedback (ISSB staff papers, September 2022) of the ISSB.FindingsThere was investor consensus in support of the ISSB and the development of the draft standards. However, there were sites of dissonance between investors and the ISSB, notably regarding the basis and focus of reporting (double or single/financial materiality and enterprise value); definitional clarity; emissions reporting; and assurance. Incrementally, the research further highlights that investors display heterogeneity of opinion.Practical and Social implicationsThe ISSB standards will provide a framework for future sustainability reporting. This research highlights the significance of such reporting to investors through their responses to the draft standards. The findings reveal sites of dissonance in the development and alignment of draft standards to user needs. The views of investors, as primary users, should help inform the development of sustainability-related standards by a global standard-setting body apposite to current policy and future reporting requirements, and their usefulness to users in practice.Originality/valueTo the best of the authors’ knowledge, this paper makes an original contribution to the comment letter literature, hitherto focused on financial reporting with a relative lack of investor engagement. Using thematic analysis, sites of dissonance are examined between the views of investors and the ISSB on their development of sustainability reporting standards

The role of the formyl-peptide receptor in multi-organ fibrosis mechanisms

PhD ThesisMitochondrial Damage-associated molecular patterns (mtDAMPs) are an emerging source of endogenous alarmins. N-formylated peptides bind members of the formyl-peptide receptor (FPR) family. From its original role in chemotaxis of immune cells towards sites of infection the part that this G-protein coupled receptor (GPCR) plays in the human body is expanding with expression evident in cells of non-phagocyte origin as well as neutrophils and macrophage. To investigate how FPR1 affects the development of pulmonary fibrosis the bleomycin acute injury in vivo model was employed as its pathogenesis shares features with Idiopathic pulmonary fibrosis (IPF). Transgenic mice lacking functional fpr1 displayed a reduced inflammatory profile and fibrotic phenotype at acute and end-stage endpoints respectively post-bleomycin instillation. In vivo models of fibrosis in different organs such as the liver and kidney there was not the same protective effect with deletion of fpr1 as with acute bleomycin lung injury mechanism. This in turn brought the pathogenesis of the in vivo models into question particularly due to the abundance of fpr1 expression on neutrophils, the first line of defense of the immune system. By depleting neutrophils prior to the bleomycin injury the nature of these myeloid cells in this lung fibrosis model and through evaluation of the inflammatory and fibrotic phases post-instillation it is evident that these cells play a major role in how the disease develops. Translation to the human disease (IPF) was a vital step to elucidate the true role of FPR1 in chronic fibrosis mechanisms. Expression was demonstrated by immunofluorescence in CD45+ leukocytes as well as in isolated fibroblasts. This was corroborated by mRNA levels in primary cultured cells when FPR1 expression was ‘primed’ by inflammatory stimuli such as lipopolysaccharide (LPS). With effects observed in a murine setting and also in primary tissue/cells the FPR1 effect may be microenvironment/neutrophil dependent

A clinical study of congenital hypertrophic pyloric stenosis: with investigation of 128 cases

In the eumydrin series, abnormalities were found in only 4 cases in these investigations. In only one of these cases was delay in gastric emptying still present. This child was 1 year and 7 months, which shows that the pyloric canal may take a long time to return to normal.Finally these radiological investigations confirm the conclusions arrived at by the clinical investigations, that after successful treatment of a case of congenital hypertrophic pyloric stenosis, the outlook is as good as that of a healthy infant.ADVANTAGES AND DISADVANTAGES OF SURGICAL AND MEDICAL TREATMENT: Certain factors, which will now be discussed, must influence one in deciding upon the method of treatment to be employed.LENGTH OF TIME IN HOSPITAL: The comparatively long period of hospitalisation found necessary in the treatment by eumydrin therapy, has been considered to be the chief disadvantage of this method. Swensgaard's cases had an average period of 77 days, while in my series, although it had been reduced to 41 days, this was 13 days longer than that of the surgical cases.The considerable difference in the period of hospitalisation has led to an increase in the liability to intercurrent infection in the medical series, especially acute gastro-enteritis.EXPENSE OF TREATMENT: The long period of hospitalisation of those treated by eumydrin increases the expense of treatment of each patient. Also the necessity for isolation of these cases in cubicles, raises the cost considerably.FEEDING DIFFICULTIES: I have attempted to show previously, that breast feeding plays an important part in reducing the mortality of these cases. If the baby is left in hospital for only a few days, the risk of causing cessation of breast feeding is small. It is very difficult indeed, however, to retain the supply of breast milk over several weeks, if most of the milk has to be drawn off by a breast pump.SURGICAL SKILL REQUIRED: The one formidable disadvantage of surgical treatment is the high degree of technical skill required to perform the Fredet-Rammstedt operation. This is easily obtained in the large cities where surgeons specialise in child surgery, but in the smaller provincial towns the expert skill is often lacking. Thus the geographical situation of a practise is apt to play a part in influencing a physician as to the method of treatment to be employed. However the greater nursing skill required in eumydrin therapy must be kept in mind when considering the type of hospital available.EUMYDRIN FAILURES: Surgery to-day offers a fairly low mortality rate. Parsons considers that the mortality rate, with good post operative treatment, should not exceed 5. Eumydrin, although in some cases produces an equally low mortality rate, does fail completely to effect a cure in a number of cases, 12% in the series investigated by me. The possibility of this failure of eumydrin therapy, must be always kept in mind by its adherants.CONCLUSIONS AS TO THE IDEAL FORM OF TREATMENT: The chief disadvantage of eumydrin therapy has been the prolonged stay in hospital. Dobbs and Vertue have treated cases as out-patients with considerable success. If this continues to be found satisfactory, the chief disadvantage of eumydrin therapy will be removed.In my opinion, eumydrin therapy should be tried in all cases for from one week to ten days, according to the degree of dehydration on admission. If improvement is not obtained by that time, a Fredet- Rammstedt operation should be performed v :ithout delay. The decision of changing the treatment should be based on three factors: - 1. The extent of the vomiting and constipation. 2. The extent of the gastric residue. 3. Whether the patient has gained weight or not.The most difficult decision to make is exactly how long to continue the eumydrin therapy, only a slight guide has been offered, as each case must be gauged separately on the physician's judgement. However, if surgery is employed, the post operative treatment of the patient should be carried out under the physician primarily, although of course, full co- :operation with the surgeon is essential for success

The complete amino acid sequence of 3-dehydroquinate synthase of Escherichia coli K 12

AbstractThe complete amino acid sequence of the Escherichia coli 3-dehydroquinate synthase has been determined by a combined nucleotide and direct amino acid sequencing strategy. E. coli 3-dehydroquinate synthase is 362 amino acids long and has a calculated Mr of 38 880. Analysis of the aroB nucleotide sequence and its 5'- and 3'-flanking regions has identified the aroB promoter elements and a possible 3'-terminator site