A broad‐spectrum synthesis of Tetravinylethylenes

The first general synthesis of compounds of the tetravinylethylene (TVE) family is reported. Ramirez‐type dibromo‐olefination of readily accessible penta‐1,4‐dien‐3‐ones generates 3,3‐dibromo[3]dendralenes, which undergo twofold Negishi, Suzuki–Miyaura or Mizoroki–Heck reactions with a wide variety of olefinic coupling partners. This route delivers a broad range of unsymmetrically substituted tetravinylethylenes with up to three different alkenyl substituents attached to the central C=C bond. The extensive scope of the approach is demonstrated by the preparation of the first higher order oligo‐alkenic through‐conjugated/cross‐conjugated hybrid compounds. An unsymmetrically substituted TVE is shown to undergo a domino electrocyclization–cycloaddition with high site‐selectivity and diastereoselectivity, thereby demonstrating the substantial synthetic potential of substituted TVEs for controlled, rapid structural complexity generation.This work was supported by the Australian Research Counci

Status of nearshore finfish stocks in south-western Western Australia Part 3: Whiting (Sillaginidae): NRM Project 09003

The whiting family (Sillaginidae) is common in nearshore waters of south-western Western Australia (WA) where it is highly valued by recreational and commercial fishers. The importance of these species to recreational fishers is reflected in this category of fishes being ranked as the most or 2nd most retained finfish species group by boat- and shore-based fishers in several recreational fishing surveys in WA. Whiting are commercially important in a number of fisheries, with total state catches averaging over 200 tonnes per annum since 1980. The composition of the whiting catch, however, is largely unknown, with a number of whiting species potentially contributing substantially to the overall catch of this family. The recreational and commercial fisheries that capture whiting can therefore be considered very data-limited, due to the lack of species-specific data that prohibit a robust assessment of the status of the stocks of the different whiting species. The main purpose of this report is to determine the species composition of whiting landings caught recreationally and commercially in south-western WA. This report then investigates the stock status of the key (most abundant) whiting species identified in the recreational catch

Cyanobacteria and chloroflexi-dominated hypolithic colonization of quartz at the hyper-arid core of the Atacama Desert, Chile

Quartz stones are ubiquitous in deserts and are a substrate for hypoliths, microbial colonists of the underside of such stones. These hypoliths thrive where extreme temperature and moisture stress limit the occurrence of higher plant and animal life. Several studies have reported the occurrence of green hypolithic colonization dominated by cyanobacteria. Here, we describe a novel red hypolithic colonization from Yungay, at the hyper-arid core of the Atacama Desert in Chile. Comparative analysis of green and red hypoliths from this site revealed markedly different microbial community structure as revealed by 16S rRNA gene clone libraries. Green hypoliths were dominated by cyanobacteria (Chroococcidiopsis and Nostocales phylotypes), whilst the red hypolith was dominated by a taxonomically diverse group of chloroflexi. Heterotrophic phylotypes common to all hypoliths were affiliated largely to desiccation-tolerant taxa within the Actinobacteria and Deinococci. Alphaproteobacterial phylotypes that affiliated with nitrogen-fixing taxa were unique to green hypoliths, whilst Gemmatimonadetes phylotypes occurred only on red hypolithon. Other heterotrophic phyla recovered with very low frequency were assumed to represent functionally relatively unimportant taxa

The Anticonvulsant Ethosuximide Disrupts Sensory Function to Extend C. elegans Lifespan

Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases. To identify genes that mediate the activity of ethosuximide, we conducted a genetic screen and identified mutations in two genes, che-3 and osm-3, that cause resistance to ethosuximide-mediated toxicity. Mutations in che-3 and osm-3 cause defects in overlapping sets of chemosensory neurons, resulting in defective chemosensation and an extended lifespan. These findings suggest that ethosuximide extends lifespan by inhibiting the function of specific chemosensory neurons. This model is supported by the observation that ethosuximide-treated animals displayed numerous phenotypic similarities with mutants that have chemosensory defects, indicating that ethosuximide inhibits chemosensory function. Furthermore, ethosuximide extends lifespan by inhibiting chemosensation, since the long-lived osm-3 mutants were resistant to the lifespan extension caused by ethosuximide. These studies demonstrate a novel mechanism of action for a lifespan-extending drug and indicate that sensory perception has a critical role in controlling lifespan. Sensory perception also influences the lifespan of Drosophila, suggesting that sensory perception has an evolutionarily conserved role in lifespan control. These studies highlight the potential of ethosuximide and related drugs that modulate sensory perception to extend lifespan in diverse animals

Cumulative and temporal associations between antimicrobial prescribing and community-associated <i>Clostridium difficile</i> infection:population-based case-control study using administrative data

Background. Community-associated (CA) Clostridium difficile infection (CDI) is a major public health problem. This study estimates the magnitude of the association between temporal and cumulative prescription of antimicrobials in primary care and CA-CDI. CA-CDI is defined as cases without prior hospitalisation in the previous 12 weeks who were either tested outside of hospital or tested within 2 days of admission to hospital. Methods. Three National patient level datasets –covering CDI cases, community prescriptions and hospitalisations were linked by the NHS Scotland unique patient identifier, the community health index, CHI. All validated cases of CDI from August 2010 to July 2013 were extracted and up to six population-based controls were matched to each case from the CHI register for Scotland. Statistical analysis used conditional logistic regression. Results. 1446 unique cases of CA-CDI were linked with 7964 age, sex and location matched controls. Cumulative exposure to any antimicrobial in the previous 6 months has a monotonic dose-response association with CA-CDI. Individuals with excess of 28 defined daily doses (DDD) to any antimicrobial (19.9% of cases) had an odds ratio (OR)=4.4 (95% CI:3.4-5.6) compared to those unexposed. Individuals exposed to 29+ DDD of high risk antimicrobials (cephalosporins, clindamycin co-amoxiclav, or fluoroquinolones) had an OR=17.9 (95% CI:7.6-42.2). Elevated CA-CDI risk following high risk antimicrobial exposure was greatest in the first month (OR=12.5 (8.9-17.4)) but was still present 4-6 months later (OR=2.6 (1.7-3.9)). Cases exposed to 29+DDD had prescription patterns more consistent with repeated therapeutic courses, using different antimicrobials, than long term prophylactic use. Conclusions. This analysis demonstrated temporal and dose-response associations between CA-CDI risk and antimicrobials with an impact of exposure to high risk antimicrobials remaining 4-6 months later

A Software Tool for Automated Upload of Large Clinical Datasets Using REDCap and the CAPO Database

Introduction: Obtaining clinical data from healthcare sources is necessary for conducting clinical research. New technologies now allow for connecting a research database to Electronic Medical Records remotely, allowing the automatic import of clinical research data. In this paper we design and evaluate a REDCap extension to import clinical records from an external health database. Methods: Many hospital EHRs are designed to use secure file transfer protocol (SFTP) repositories for data communication. We develop a REDCap plugin to connect to an external SFTP file repository for the import of clinical record data. We use the CAPO instance of REDCap and a sample set of clinical pneumonia variables for the connection. Results: The plugin allows the input of record data in a much shorter time than traditional data entry in addition to being less error prone. However, the formatting of the data in the SFTP file repository must be exact in order for the import to be successful. This can require setup time on the part of EHR IT staff. Conclusion: Developing a direct connection from EHR to research database can be an effective way to lower the overhead for conducting clinical research. We demonstrate a means to do this using REDCap and SFTP

Status of nearshore finfish stocks in south-western Western Australia: Part 1: Australian herring

The status of the popular nearshore finfish resource in the West Coast Bioregion (WCB) of Western Australia (WA) was largely unknown prior to this study. Previously, declining catches of several nearshore species had highlighted the risk to their sustainability and the need for greater certainty about their status. Recently, the risk further increased due to management changes in the WCB aimed at reducing the catch of demersal scalefish, which are likely to result in a shift in targeting towards nearshore species. This increase in fishing pressure on nearshore species will be on top of any increase due to the continuing human population growth in the WCB

The Adhesion-GPCR BAI1 Regulates Synaptogenesis by Controlling the Recruitment of the Par3/Tiam1 Polarity Complex to Synaptic Sites

Excitatory synapses are polarized structures that primarily reside on dendritic spines in the brain. The small GTPase Rac1 regulates the development and plasticity of synapses and spines by modulating actin dynamics. By restricting the Rac1-guanine nucleotide exchange factor Tiam1 to spines, the polarity protein Par3 promotes synapse development by spatially controlling Rac1 activation. However, the mechanism for recruiting Par3 to spines is unknown. Here, we identify brain-specific angiogenesis inhibitor 1 (BAI1) as a synaptic adhesion GPCR that is required for spinogenesis and synaptogenesis in mice and rats. We show that BAI1 interacts with Par3/Tiam1 and recruits these proteins to synaptic sites. BAI1 knockdown results in Par3/Tiam1 mislocalization and loss of activated Rac1 and filamentous actin from spines. Interestingly, BAI1 also mediates Rac-dependent engulfment in professional phagocytes through its interaction with a different Rac1-guanine nucleotide exchange factor module, ELMO/DOCK180. However, this interaction is dispensable for BAI1’s role in synapse development because a BAI1 mutant that cannot interact with ELMO/DOCK180 rescues spine defects in BAI1-knockdown neurons, whereas a mutant that cannot interact with Par3/Tiam1 rescues neither spine defects nor Par3 localization. Further, overexpression of Tiam1 rescues BAI1 knockdown spine phenotypes. These results indicate that BAI1 plays an important role in synaptogenesis that is mechanistically distinct from its role in phagocytosis. Furthermore, our results provide the first example of a cell surface receptor that targets members of the PAR polarity complex to synapses

Public decisions about COVID-19 vaccines: a UK-based qualitative study

Objective To explore UK public decisions around whether or not to get COVID-19 vaccines, and the facilitators and barriers behind participants’ decisions. Design This qualitative study consisted of six online focus groups conducted between 15th March and 22nd April 2021. Data were analysed using a framework approach. Setting Focus groups took place via online videoconferencing (Zoom). Participants Participants (n=29) were a diverse group (by ethnicity, age and gender) UK residents aged 18 years and older. Results We used the World Health Organization’s vaccine hesitancy continuum model to look for, and explore, three main types of decisions related to COVID-19 vaccines: vaccine acceptance, vaccine refusal and vaccine hesitancy (or vaccine delay). Two reasons for vaccine delay were identified: delay due to a perceived need for more information and delay until vaccine was “required” in the future. Nine themes were identified: three main facilitators (Vaccination as a social norm; Vaccination as a necessity; Trust in science) and six main barriers (Preference for “natural immunity”; Concerns over possible side effects; Perceived lack of information; Distrust in government;; Conspiracy theories; “Covid echo chambers”) to vaccine uptake. Conclusion In order to address vaccine uptake and vaccine hesitancy, it is useful to understand the reasons behind people’s decisions to accept or refuse an offer of a vaccine, and to listen to them and engage with, rather than dismiss, these reasons. Those working in public health or health communication around vaccines, including COVID-19 vaccines, in and beyond the UK, might benefit from incorporating the facilitators and barriers found in this study