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Contains fulltext : 226530.pdf (Publisher’s version ) (Open Access) 29 maart 2021

Limited information exists regarding the dormancy of secondary and tertiary buds within the compound bud of grapevines. We were interested to evaluate how extended chilling duration would affect the budbreak percentage of all three bud orders within the compound bud. Dormant potted 'Shiraz' grapevines, with thirty retained buds per vine, were placed in a cool room at 4 °C over a 20-month period to extend dormancy. Vines were then systematically removed over five dates and placed in a controlled growth environment to assess budbreak percentages and cane tissue concentrations of abscisic acid and cytokinins. Budbreak was hastened by at least 13 d with vines receiving any extra chilling compared to no initial chilling. Furthermore, the firstly observed correlative inhibition of basal buds was apparently removed with chilling. Removal of correlative inhibition within the compound bud with increased chilling duration was also observed with the increases of secondary (doubles) and tertiary (triples) buds breaking simultaneously with the primary bud at each node. This resulted in 91 % of the nodes having two developing shoots and 56 % of the nodes presenting three developing shoots by the end of the experiment. Furthermore, a sigmoidal relationship between percent secondary buds and chilling duration was observed. Possible phytohormone connections were observed with the decline of ABA as secondary and tertiary buds broke at 414 d of chilling and depletion of the CKs, which coincided with the greatest rate of primary bud break after 242 d of chilling. Other possible involvement of ABA and Cis-type cytokinin interactions with secondary and tertiary bud dormancy is discussed. The results suggest future investigations into secondary and tertiary bud release within the grapevine using similar techniques may help to better understand the biochemical mechanisms associated with dormancy., VITIS - Journal of Grapevine Research, Vol. 60 No. 1 (2021): Vitis

BACKGROUND: In the United Kingdom, tuberculosis (TB) predominantly affects the most deprived populations, yet the extent to which deprivation affects TB care outcomes is unknown. METHODS: Since 2011, the North West TB Cohort Audit collaboration has undertaken quarterly reviews of outcomes against consensus-defined care standard indicators for all individuals notified with TB. We investigated associations between adverse TB care outcomes and Index of Multiple Deprivation (IMD) 2010 scores measured at lower super output area of residence using logistic regression models. RESULTS: Of 1831 individuals notified with TB between 2011 and 2014, 62% (1131/1831) came from the most deprived national quintile areas. In single variable analysis, greater deprivation was significantly associated with increased likelihood of the completion of a standardised risk assessment (OR 2.99, 95%CI 5.27–19.65) and offer of a human immunodeficiency virus test (OR 1.72, 95%CI 1.10–2.62). In multivariable analysis, there were no significant associations. CONCLUSIONS: TB patients in the most deprived areas had similar care indicators across a range of standards to those of individuals living in the more affluent areas, suggesting that the delivery of TB care in the North West of England is equitable. The extent to which the cohort review process contributes to, and sustains, this standard of care deserves further study. Publisher PDF

Neutrophils are essential for host defence and are recruited to sites of inflammation in response to tissue injury or infection. For inflammation to resolve, these cells must be cleared efficiently and in a controlled manner, either by apoptosis or reverse migration. If the inflammatory response is not well-regulated, persistent neutrophils can cause damage to host tissues and contribute to the pathogenesis of chronic inflammatory diseases, which respond poorly to current treatments. It is therefore important to develop drug discovery strategies that can identify new therapeutics specifically targeting neutrophils, either by promoting their clearance or by preventing their recruitment. Our recent in vivo chemical genetic screen for accelerators of inflammation resolution identified a subset of compounds sharing a common chemical signature, the bicyclic benzopyrone rings. Here, we further investigate the mechanisms of action of the most active of this chemical series, isopimpinellin, in our zebrafish model of neutrophilic inflammation. We found that this compound targets both the recruitment and resolution phases of the inflammatory response. Neutrophil migration towards a site of injury is reduced by isopimpinellin and this occurs as a result of PI3K inhibition. We also show that isopimpinellin induces neutrophil apoptosis to drive inflammation resolution in vivo using a new zebrafish reporter line detecting in vivo neutrophil caspase-3 activity and allowing quantification of flux through the apoptotic pathway in real time. Finally, our studies reveal that clinically available ‘cromones’ are structurally related to isopimpinellin and have previously undescribed pro-resolution activity in vivo. These findings could have implications for the therapeutic use of benzopyrones in inflammatory disease., Summary: Zebrafish inflammation screen identifies a new series of structurally related compounds with combined anti-inflammatory and pro-resolution activity, and reveals a previously unknown mechanism of action of clinical cromones.

The Death Receptor 3 (DR3)/Tumour Necrosis Factor-like cytokine 1A (TL1A) axis stimulates effector T cells and type 2 innate lymphocytes (ILC2) that trigger cytokine release and drive disease pathology in several inflammatory and autoimmune diseases, including murine models of acute allergic lung inflammation (ALI). The aim of this study was to elucidate the role of DR3 in chronic ALI compared to acute ALI, using mice genetically deficient in the DR3 gene (DR3ko). Results showed DR3 expression in the lungs of wild-type mice was up-regulated following induction of acute ALI and this increased expression was maintained in chronic disease. DR3ko mice were resistant to cellular accumulation within the alveolar passages in acute, but not chronic ALI. However, DR3ko mice displayed reduced immuno-histopathology and goblet cell hyperplasia; hallmarks of the asthmatic phenotype; in chronic, but not acute ALI. These data suggest DR3 is a potential therapeutic target, involved in temporally distinct aspects of ALI progression and pathogenesis.

Various alternative allocation methods for internship and residency appointments are discussed and examples given. The results of the first five allocations are presented. The percentage of applicants obtaining one of their first three choices varied from 61 to 70 percent; for consultants the range was 72 to 94 percent. (Author/LBH)