Mitochondria and nuclei move by different mechanisms in Aspergillus nidulans

This is the publisher's version, also available electronically from "http://jcb.rupress.org".We have examined the effects of the antimicrotubule agent benomyl and several mutations on nuclear and mitochondrial movement in germlings of the filamentous fungus Aspergillus nidulans. While, as previously reported, benomyl inhibited nuclear division and movement, it did not inhibit mitochondrial movement. To test the effects of benomyl more rigorously, we germinated two benomyl super-sensitive, beta-tubulin mutants at a benomyl concentration 50-100 times greater than that required to inhibit colony formation completely. Again nuclear division and movement were inhibited, but mitochondrial movement was not. We also examined conditionally lethal beta-tubulin mutations that disrupt microtubule function under restrictive conditions. Nuclear division and movement were inhibited but, again, mitochondrial movement was not. Finally we examined the effects of five heat-sensitive mutations that inhibit nuclear movement but not nuclear division at restrictive temperatures. These mutations strongly inhibited nuclear movement at a restrictive temperature but did not inhibit mitochondrial movement. These data demonstrate that the mechanisms of nuclear and mitochondrial movement in Aspergillus nidulans are not identical and suggest that mitochondrial movement does not require functional microtubules

Kinetic and Spectroscopic Characterisation of Highly Reactive Methanesulfonates. Leaving Group Effects for Solvolyses and Comments on Geminal Electronic Effects Influencing SN_N1 Reactivity

Highly reactive methanesulfonates (mesylates, ROMs) have been prepared from 1-phenylethanol. cyclohex-2-en-1-ol, diphenylmethanol and p-methoxybenzyl alcohol by treatment with methanesulfonyl chloride and triethylamine in dichloro- or trichloro-methane at - 20 to 0 °C. The mesylates. characterised in solution by $^1$H and $^{13}$C NMR at -20 °C, were obtained in satisfactory purity (ca. 95%) in cold solutions but they decomposed by reaction with chloride, triethylamine or the parent alcohol. Rate constants for solvolyses in aqueous acetone and aqueous ethanol have been determined by a fast response conductimetric method. Product selectivities for solvolyses of pmethoxybenzyl mesylate in aqueous ethanol and methanol at 0 °C have been determined by HPLC. From additional new or Iiterature kinetic data for solvolyses of corresponding bromides. chlorides and p-nitrobenzoates (OPNB). Br/CI. OMs/Br and OMs/OPNB rate ratios were calculated; the results are consistent with electronic effects stabilising the carbocationic transition states and increasing OMs/Br rate ratios for these SN 1 solvolyses; none of the evidence supports a geminal electronic effect on Br/CI rate ratios (e.g. caused by stabilisation of the initial state in pmethoxybenzyl chloride). Steric effects on ester /halide rate ratios for solvolyses of tertiary substrates are confirmed. Relative rates over a 10$^{16}$ range for ester and halide leaving groups are evaluated for solvolyses of 1-phenylethyl substrates in 80% ethanol-water. updating previous work by Noyce et al. (1972)

Hyperinnervation Produces Inhibitory Interactions between Two Taste Nerves a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74872/1/j.1749-6632.1987.tb43629.x.pd

Azaphilones inhibit tau aggregation and dissolve tau aggregates in vitro

The aggregation of the microtubule-associated protein tau is a seminal event in many neurodegenerative diseases, including Alzheimer’s disease. The inhibition or reversal of tau aggregation is therefore a potential therapeutic strategy for these diseases. Fungal natural products have proven to be a rich source of useful compounds having wide varieties of biological activities. We have previously screened Aspergillus nidulans secondary metabolites for their ability to inhibit tau aggregation in vitro using an arachidonic acid polymerization protocol. One aggregation inhibitor identified was asperbenzaldehyde, an intermediate in azaphilone biosynthesis. We therefore tested 11 azaphilone derivatives to determine their tau assembly inhibition properties in vitro. All compounds tested inhibited tau filament assembly to some extent, while four of the 11 compounds had the advantageous property of disassembling preformed tau aggregates in a dose-dependent fashion. The addition of these compounds to the tau aggregates reduced both the total length and numbers of tau polymers. The most potent compounds were tested in in vitro reactions to determine whether they interfere with tau’s normal function of stabilizing microtubules (MTs). We found that they did not completely inhibit MT assembly in the presence of tau. These derivatives are very promising lead compounds for tau aggregation inhibitors and, more excitingly, for compounds that can disassemble pre-existing tau filaments. They also represent a new class of anti-tau aggregation compounds with a novel structural scaffold

Stem Cells in the Nervous System

Given their capacity to regenerate cells lost through injury or disease, stem cells offer new vistas into possible treatments for degenerative diseases and their underlying causes. As such, stem cell biology is emerging as a driving force behind many studies in regenerative medicine. This review focuses on the current understanding of the applications of stem cells in treating ailments of the human brain, with an emphasis on neurodegenerative diseases. Two types of neural stem cells are discussed: endogenous neural stem cells residing within the adult brain and pluripotent stem cells capable of forming neural cells in culture. Endogenous neural stem cells give rise to neurons throughout life, but they are restricted to specialized regions in the brain. Elucidating the molecular mechanisms regulating these cells is key in determining their therapeutic potential as well as finding mechanisms to activate dormant stem cells outside these specialized microdomains. In parallel, patient-derived stem cells can be used to generate neural cells in culture, providing new tools for disease modeling, drug testing, and cell-based therapies. Turning these technologies into viable treatments will require the integration of basic science with clinical skills in rehabilitation

Academic motherhood and fieldwork: Juggling time, emotions and competing demands

The idea and practice of going ‘into the field’ to conduct research and gather data is a deeply rooted aspect of Geography as a discipline. For global North Development Geographers, amongst others, this usually entails travelling to, and spending periods of time in, often far-flung parts of the global South. Forging a successful academic career as a Development Geographer in the UK, is therefore to some extent predicated on mobility. This paper aims to critically engage with the gendered aspects of this expected mobility, focusing on the challenges and time constraints that are apparent when conducting overseas fieldwork as a mother, unaccompanied by her children. The paper emphasises the emotion work that is entailed in balancing the competing demands of overseas fieldwork and mothering, and begins to think through the implications of these challenges in terms of the types of knowledge we produce, as well as in relation to gender equality within the academy

Enhancing the experience of carers in the chemotherapy outpatient setting: an exploratory randomised controlled trial to test impact, acceptability and feasibility of a complex intervention co-designed by carers and staff

PurposeSupporting someone through chemotherapy can be emotionally and physically demanding. However, research has yet to establish the type of support carers require or the best way to provide this. This study tested the feasibility and acceptability of a complex intervention for carers that was co-designed by staff and carers of patients starting chemotherapy.MethodsForty-seven carers were recruited, randomised between the intervention (n?=?24) and control (n?=?23) groups. A questionnaire was completed pre- and post-intervention measuring knowledge of chemotherapy and its side effects, experience of care, satisfaction with outpatient services, coping and emotional wellbeing. The intervention process was evaluated by carers and healthcare professionals (HCPs) in focus groups.ResultsRecruitment to the study was unproblematic and attrition from it was low, suggesting the intervention and study processes were acceptable to patients and carers. Carers in receipt of the ‘Take Care’ intervention reported statistically significantly better understanding of symptoms and side effects and their information needs being more frequently met than carers in the control. Confidence in coping improved between baseline and follow-up for the intervention group and declined for the control although differences were insufficient to achieve statistical significance. There was no significant difference between the two groups’ emotional wellbeing. HCP and carer focus groups confirmed the feasibility and acceptability of the intervention.ConclusionsThe ‘Take Care’ intervention proved acceptable to carers and HCPs and demonstrates considerable promise and utility in practice. Study findings support the conduct of a fully powered RCT to determine the intervention’s effectiveness and cost-effectiveness

Gender and educational leadership in England: a comparison of secondary headteachers' views over time

In the context of gender being a barrier to accessing leadership, this paper presents a comparison of the views of men and women head teacher (principals) of secondary schools in England in the 1990s and in 2004. The same survey instrument was used on both occasions. The perceptions of the head teachers show change in some areas and no change in others. Overall, women are more likely to become head teachers and are now less likely to be categorised into pastoral roles, but in some cases women still meet prejudice from governors and others in the wider community. Women head teachers are more likely to have partners and children than in the 1990s, sharing equally or carrying most of the domestic responsibilities, whereas male colleagues are most likely to have partners who take the majority of responsibility in the home. Essentialist stereotypes about women and men as leaders still prevail, although both the women and men head teachers see themselves as adopting a traditionally ‘feminine’ style of leadership. Women head teachers are likely to see some benefits in being a woman in a role stereotypically associated with men. However, there has been an increase in the proportion of women who feel that they have to prove their worth as a leader, and this may be linked with increased levels of accountability in schools