Comparison of the impact of two key fungal signalling pathways on Zymoseptoria tritici infection reveals divergent contribution to invasive growth through distinct regulation of infection-associated genes

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: RNA sequencing reads have been deposited on the European Nucleotide Archive (ENA) at www.ebi.ac.uk/ena under the accession number PRJEB58154.The lifecycle of Zymoseptoria tritici requires a carefully regulated asymptomatic phase within the wheat leaf following penetration of the mesophyll via stomata. Here we compare the roles in this process of two key fungal signalling pathways, mutants of which were identified through forward genetics due to their avirulence on wheat. Whole-genome resequencing of avirulent Z. tritici T-DNA transformants identified disruptive mutations in ZtBCK1 from the kinase cascade of the cell wall integrity (CWI) pathway, and the adenylate cyclase gene ZtCYR1. Targeted deletion of these genes abolished the pathogenicity of the fungus and led to similar in vitro phenotypes to those associated with disruption of putative downstream kinases, both supporting previous studies and confirming the importance of these pathways in virulence. RNA sequencing was used to investigate the effect of ZtBCK1 and ZtCYR1 deletion on gene expression in both the pathogen and host during infection. ZtBCK1 was found to be required for the adaptation to the host environment, controlling expression of infection-associated secreted proteins, including known virulence factors. Meanwhile, ZtCYR1 is implicated in controlling the switch to necrotrophy, regulating expression of effectors associated with this transition. This represents the first study to compare the influence of CWI and cAMP signalling on in planta transcription of a fungal plant pathogen, providing insights into their differential regulation of candidate effectors during invasive growth.Biotechnology and Biological Sciences Research Council (BBSRC)Wellcome Trus

The structure, coherence and limits of inchoate liability: the new ulterior element

This article explores the role of ulterior intention (and ulterior mens rea more generally) within the criminal law. Divided into three Parts, we first question the role and location of ulterior mens rea within the offence elements of acts, circumstances and results. Concluding that such accommodation is conceptually unsound, we highlight the problems this has caused in the context of inchoate liability where the separation of elements is now essential to the application of the law. Central to this discussion is the problematic attempts case of AG Ref (No.3 of 1992) [1994] 1 WLR. 409. We contend that best way forward is to recognise a new ulterior mens rea element. Such an element has the potential to maintain conceptual coherence between offence elements, resolve substantive problems arising in the context of inchoate liability, as well as creating a new method for limiting inchoate liability (and infinite inchoate liability) from the potential for over-criminalisation

Distinct roles for different autophagy-associated genes in the virulence of the fungal wheat pathogen Zymoseptoria tritici

This is the final version. Available on open access from Elsevier via the DOI in this record. The fungal wheat pathogen Zymoseptoria tritici causes major crop losses as the causal agent of the disease Septoria tritici blotch. The infection cycle of Z. tritici displays two distinct phases, beginning with an extended symptomless phase of 1–2 weeks, before the fungus induces host cell death and tissue collapse in the leaf. Recent evidence suggests that the fungus uses little host-derived nutrition during asymptomatic colonisation, raising questions as to the sources of energy required for this initial growth phase. Autophagy is crucial for the pathogenicity of other fungal plant pathogens through its roles in supporting cellular differentiation and growth under starvation. Here we characterised the contributions of the autophagy genes ZtATG1 and ZtATG8 to the development and virulence of Z. tritici. Deletion of ZtATG1 led to inhibition of autophagy but had no impact on starvation-induced hyphal differentiation or virulence, suggesting that autophagy is not required for Z. tritici pathogenicity. Contrastingly, ZtATG8 deletion delayed the transition to necrotrophic growth, despite having no influence on filamentous growth under starvation, pointing to an autophagy-independent role of ZtATG8 during Z. tritici infection. To our knowledge, this study represents the first to find autophagy not to contribute to the virulence of a fungal plant pathogen, and reveals novel roles for different autophagy-associated proteins in Z. tritici.Biotechnology and Biological Sciences Research Council (BBSRC

Plutonium transfer to wildlife at legacy sites

When internalized within an organism’s body, plutonium (Pu) can be important in dose calculation due to its relatively high-energy alpha emissions (~5-6 MeV). In this paper we quantify transfer of Pu to a range of wildlife types at legacy nuclear weapons sites and evaluate the importance of body tissue Pu distribution in the transfer of Pu through the food chain. The paper presents new data from Maralinga, Australia, as well as past data from terrestrial and marine settings of the US nuclear research program

ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair

Background: The H69CIS200 and H69OX400 cell lines are novel models of low-level platinum-drug resistance. Resistance was not associated with increased cellular glutathione or decreased accumulation of platinum, rather the resistant cell lines have a cell cycle alteration allowing them to rapidly proliferate post drug treatment. Results: A decrease in ERCC1 protein expression and an increase in RAD51B foci activity was observed in association with the platinum induced cell cycle arrest but these changes did not correlate with resistance or altered DNA repair capacity. The H69 cells and resistant cell lines have a p53 mutation and consequently decrease expression of p21 in response to platinum drug treatment, promoting progression of the cell cycle instead of increasing p21 to maintain the arrest. Conclusion: Decreased ERCC1 protein and increased RAD51B foci may in part be mediating the maintenance of the cell cycle arrest in the sensitive cells. Resistance in the H69CIS200 and H69OX400 cells may therefore involve the regulation of ERCC1 and RAD51B independent of their roles in DNA repair. The novel mechanism of platinum resistance in the H69CIS200 and H69OX400 cells demonstrates the multifactorial nature of platinum resistance which can occur independently of alterations in DNA repair capacity and changes in ERCC1

Using the Ages and Stages Questionnaire to teach medical students developmental assessment: a descriptive analysis

BACKGROUND: After a survey of medical graduates' skills found a lack of confidence in developmental assessment, a program was introduced with the broad aims of increasing medical student confidence and respect for the parents' role in childhood developmental assessment. Research has shown that parents' concerns are as accurate as quality screening tests in assessing development, so the program utilised the Ages and Stages Questionnaire, a parent completed, child development assessment tool. METHOD: To evaluate the program, an interpretative analysis was completed on the students' reports written during the program and a questionnaire was administered to the parents to gain their perception of the experience. As well, student confidence levels in assessing growth and development were measured at the end of the paediatric term. RESULTS: Although there was an increase in student confidence in developmental assessment at the end of the term, it was not statistically significant. However the findings indicated that students gained increased understanding of the process and enhanced recognition of the parental role, and the study suggested there was increased confidence in some students. Parents indicated that they thought they should be involved in the teaching of students. CONCLUSION: The ASQ was shown to have been useful in an education program at the level of advanced beginners in developmental assessment

The Reform of Employee Compensation in China’s Industrial Enterprises

Although employee compensation reform in Chinese industrial sector has been discussed in the literature, the real changes in compensation system and pay practices have received insufficient attention and warrant further examination. This paper briefly reviews the pre- and post-reform compensation system, and reports the results of a survey of pay practices in the four major types of industrial enterprises in China. The research findings indicate that the type of enterprise ownership has little influence on general compensation practices, adoption of profit-sharing plans, and subsidy and allowance packages. In general, pay is linked more to individual performance and has become an important incentive to Chinese employees. However, differences are found across the enterprise types with regard to performance-related pay. Current pay practices are positively correlated to overall effectiveness of the enterprise

High prevalence of vitamin D deficiency among children aged 1 month to 16 years in Hangzhou, China

<p>Abstract</p> <p>Background</p> <p>Recent studies have suggested that vitamin D deficiency in children is widespread. But the vitamin D status of Chinese children is seldom investigated. The objective of the present study was to survey the serum levels of 25-hydroxyvitamin D [25(OH)D] in more than 6,000 children aged 1 month to 16 years in Hangzhou (latitude: 30°N), the capital of Zhejiang Province, southeast China.</p> <p>Methods</p> <p>The children aged 1 month to 16 years who came to the child health care department of our hospital, the children's hospital affiliated to Zhejiang university school of medicine, for health examination were taken blood for 25(OH) D measurement. Serum 25(OH) D levels were determined by direct enzyme-linked immunosorbent assay and categorized as < 25, < 50, and < 75 nmol/L.</p> <p>Results</p> <p>A total of 6,008 children aged 1 month to 16 years participated in this cross-sectional study. All the subjects were divided into subgroups according to their age: 0-1y, 2-5y, 6-11y and 12-16y representing infancy, preschool, school age and adolescence stages respectively. The highest mean level of serum 25(OH)D was found in the 0-1y stage (99 nmol/L) and the lowest one was found in 12-16y stage (52 nmol/L). Accordingly, the prevalence of serum 25(OH)D levels of < 75 nmol/L and < 50 nmol/L were at the lowest among infants (33.6% and 5.4% respectively) and rose to the highest among adolescents (89.6% and 46.4% respectively). The mean levels of serum 25(OH)D and the prevalence of vitamin D deficiency changed according to seasons. In winter and spring, more than 50% of school age children and adolescents had a 25(OH)D level at < 50 nmol/L. If the threshold is changed to < 75 nmol/L, all of the adolescents (100%) had low 25(OH)D levels in winter and 93.7% school age children as well.</p> <p>Conclusions</p> <p>The prevalence of vitamin D deficiency and insufficiency among children in Hangzhou Zhejiang province is high, especially among children aged 6-16 years. We suggest that the recommendation for vitamin D supplementation in Chinese children should be extended to adolescence.</p

Effect of a peer-educational intervention on provider knowledge and reported performance in family planning services: a cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>Peer education is an interactive method of teaching or learning which is widely used for educating school and college students, in a variety of different forms. However, there are few studies on its effectiveness for in-service education. The aim of this study was to evaluate the effect of an educational programme including peer discussions, based on a needs assessment, on the providers' knowledge and reported performance in family planning services.</p> <p>Methods</p> <p>An educational programme was designed and applied in a random selection of half of in-charges of the 74 family health units (intervention group) in Tabriz at a regular monthly meeting. The other half constituted the control group. The programme included eight pages of written material and a two-hour, face-to-face discussion session with emphasis on the weak areas identified through a needs assessment questionnaire. The educated in-charges were requested to carry out a similar kind of programme with all peers at their health facilities within one month. All in-charges received one self-administered questionnaire containing knowledge questions one month after the in-charge education (follow-up I: 61 responses), and another one containing knowledge and self-reported performance questions 26 months later (follow-up II: 61 responses). Also, such tests were done for the peers facilitated by the in-charges one (105 responses) and 27 months (114 responses) after the peer discussions. Multiple linear regression was used for comparing mean total scores, and Chi square for comparing proportions between control and intervention groups, after defining facility as the unit of randomization.</p> <p>Results</p> <p>The mean total percentage scores of knowledge (percent of maximal possible score) in the intervention group were significantly higher than in the control group, both at follow-up I (63%) and at follow-up II (57%); with a difference of 16 (95% CI: 11, 22) and 5 (95% CI: 0.4, 11) percentage units, respectively. Only two of the nine reported performance items were significantly different among the non in-charges in the intervention group at follow-up II.</p> <p>Conclusions</p> <p>The educational programme including peer discussions using existing opportunities with no need for additional absence from the workplace might be a useful complement to formal large group education for the providers.</p

Transfer of thawed frozen embryo versus fresh embryo to improve the healthy baby rate in women undergoing IVF : the E-Freeze RCT

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