Serologic response to culture filtrate antigens of Mycobacterium ulcerans during Buruli ulcer disease.

Buruli ulcer (BU) is an emerging necrotic skin disease caused by Mycobacterium ulcerans. To assess the potential for a serodiagnostic test, we measured the humoral immune response of BU patients to M. ulcerans antigens and compared this response with delayed-type hypersensitivity responses to both Burulin and PPD. The delayed-type hypersensitivity response generally supported the diagnosis of BU, with overall reactivity to Burulin in 28 (71.8%) of 39 patients tested, compared with 3 (14%) of 21 healthy controls. However, this positive skin test response was observed primarily in patients with healed or active disease, and rarely in patients with early disease (p=0.009). When tested for a serologic response to M. ulcerans culture filtrate, 43 (70.5%) of 61 BU patients had antibodies to these antigens, compared with 10 (37.0%) of 27 controls and 4 (30. 8%) of 13 tuberculosis patients. There was no correlation between disease stage and the onset of this serum antibody response. Our findings suggest that serologic testing may be useful in the diagnosis and surveillance of BU

Low-Cost, Open-Source, and Low-Power: But What to Do With the Data?

There are now many ongoing efforts to develop low-cost, open-source, low-power sensors and datalogging solutions for environmental monitoring applications. Many of these have advanced to the point that high quality scientific measurements can be made using relatively inexpensive and increasingly off-the-shelf components. With the development of these innovative systems, however, comes the ability to generate large volumes of high-frequency monitoring data and the challenge of how to log, transmit, store, and share the resulting data. This paper describes a new web application that was designed to enable citizen scientists to stream sensor data from a network of Arduino-based dataloggers to a web-based Data Sharing Portal. This system enables registration of new sensor nodes through a Data Sharing Portal website. Once registered, any Internet connected data-logging device (e.g., connected via cellular or Wi-Fi) can then post data to the portal through a web service application programming interface (API). Data are stored in a back-end data store that implements Version 2 of the Observations Data Model (ODM2). Live data can then be viewed using multiple visualization tools, downloaded from the Data Sharing Portal in a simple text format, or accessed via WaterOneFlow web services for machine-to-machine data exchange. This system was built to support an emerging network of open-source, wireless water quality monitoring stations developed and deployed by the EnviroDIY community for do-it-yourself environmental science and monitoring, initially within the Delaware River Watershed. However, the architecture and components of the ODM2 Data Sharing Portal are generic, open-source, and could be deployed for use with any Internet connected device capable of making measurements and formulating an HTTP POST request

End of the road? The career intentions of under-represented STEM students in higher education

Background The analogy of the leaky pipeline has been used to describe STEM education, with lower student diversity from compulsory to post-compulsory education and beyond. Although extensive research has explored the views and experiences of school-aged children about STEM, fewer studies have examined the career intentions of STEM students at university, especially those from under-represented backgrounds (e.g., racial/ethnic minority, women and working class students). This paper draws on a large qualitative study that interviewed 110 under-represented STEM undergraduates in the UK. We focus on students’ STEM career intentions and the likely directions of their post-degree trajectories, drawing on the lenses of science identity and Social Cognitive Career Theory. Results Three pathways were identified. The first group plans to pursue a career in or from STEM. While social inequalities may persist, the potential impact of these challenges may be neutralised by the personal drive and passion of STEM career-oriented students, who seem committed to drive into an STEM future. The second group stated intentions for non-STEM-related careers, leaving the STEM pipeline. The reasons students gave for their imminent departure from STEM are the better financial reward on offer in some non-STEM sectors, especially in finance and business, as well as wider social inequalities and stereotypes. The third group was undecided, those who are uncertain or unclear about their futures. Students described a general lack of direction or clear career pathway, from a complete lack of career ideas to an overload of options. Conclusions We conclude with a reminder that the STEM pipeline is far from secured or equitable, despite apparent progress in participation and representation. We reiterate the importance of fostering a diverse, inclusive and supportive learning environment that maximises the participation, strengths and potential of all students, especially those from under-represented backgrounds. While it is not uncommon for STEM students to pursue careers outside of STEM, we need to be wary that those who exit the STEM pipeline are not forced off the road by social inequalities and exclusions

Bacterial Cell Enlargement Requires Control of Cell Wall Stiffness Mediated by Peptidoglycan Hydrolases.

Most bacterial cells are enclosed in a single macromolecule of the cell wall polymer, peptidoglycan, which is required for shape determination and maintenance of viability, while peptidoglycan biosynthesis is an important antibiotic target. It is hypothesized that cellular enlargement requires regional expansion of the cell wall through coordinated insertion and hydrolysis of peptidoglycan. Here, a group of (apparent glucosaminidase) peptidoglycan hydrolases are identified that are together required for cell enlargement and correct cellular morphology of Staphylococcus aureus, demonstrating the overall importance of this enzyme activity. These are Atl, SagA, ScaH, and SagB. The major advance here is the explanation of the observed morphological defects in terms of the mechanical and biochemical properties of peptidoglycan. It was shown that cells lacking groups of these hydrolases have increased surface stiffness and, in the absence of SagB, substantially increased glycan chain length. This indicates that, beyond their established roles (for example in cell separation), some hydrolases enable cellular enlargement by making peptidoglycan easier to stretch, providing the first direct evidence demonstrating that cellular enlargement occurs via modulation of the mechanical properties of peptidoglycan. IMPORTANCE: Understanding bacterial growth and division is a fundamental problem, and knowledge in this area underlies the treatment of many infectious diseases. Almost all bacteria are surrounded by a macromolecule of peptidoglycan that encloses the cell and maintains shape, and bacterial cells must increase the size of this molecule in order to enlarge themselves. This requires not only the insertion of new peptidoglycan monomers, a process targeted by antibiotics, including penicillin, but also breakage of existing bonds, a potentially hazardous activity for the cell. Using Staphylococcus aureus, we have identified a set of enzymes that are critical for cellular enlargement. We show that these enzymes are required for normal growth and define the mechanism through which cellular enlargement is accomplished, i.e., by breaking bonds in the peptidoglycan, which reduces the stiffness of the cell wall, enabling it to stretch and expand, a process that is likely to be fundamental to many bacteria

Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment

Copyright \ua9 2022 Li, Kitamura, Beverley, Koudelka, Duncombe, Lennen, Jansen, Marshall, Platt, Wiegand, Carare, Kalaria, Iliff and Horsburgh. Large vessel disease and carotid stenosis are key mechanisms contributing to vascular cognitive impairment (VCI) and dementia. Our previous work, and that of others, using rodent models, demonstrated that bilateral common carotid stenosis (BCAS) leads to cognitive impairment via gradual deterioration of the neuro-glial-vascular unit and accumulation of amyloid-β (Aβ) protein. Since brain-wide drainage pathways (glymphatic) for waste clearance, including Aβ removal, have been implicated in the pathophysiology of VCI via glial mechanisms, we hypothesized that glymphatic function would be impaired in a BCAS model and exacerbated in the presence of Aβ. Male wild-type and Tg-SwDI (model of microvascular amyloid) mice were subjected to BCAS or sham surgery which led to a reduction in cerebral perfusion and impaired spatial learning acquisition and cognitive flexibility. After 3 months survival, glymphatic function was evaluated by cerebrospinal fluid (CSF) fluorescent tracer influx. We demonstrated that BCAS caused a marked regional reduction of CSF tracer influx in the dorsolateral cortex and CA1-DG molecular layer. In parallel to these changes increased reactive astrogliosis was observed post-BCAS. To further investigate the mechanisms that may lead to these changes, we measured the pulsation of cortical vessels. BCAS impaired vascular pulsation in pial arteries in WT and Tg-SwDI mice. Our findings show that BCAS influences VCI and that this is paralleled by impaired glymphatic drainage and reduced vascular pulsation. We propose that these additional targets need to be considered when treating VCI

A review of climate change and the implementation of marine biodiversity legislation in the United Kingdom

1. Marine legislation, the key means by which the conservation of marine biodiversity is achieved, has been developing since the 1960s. In recent decades, an increasing focus on ‘holistic’ policy development is evident, compared with earlier ‘piecemeal’ sectoral approaches. Important marine legislative tools being used in the United Kingdom, and internationally, include the designation of marine protected areas and the Marine Strategy Framework Directive (MSFD) with its aim of meeting ‘Good Environmental Status’ (GES) for European seas by 2020. 2. There is growing evidence of climate change impacts on marine biodiversity, which may compromise the effectiveness of any legislation intended to promote sustainable marine resource management. 3. A review of key marine biodiversity legislation relevant to the UK shows climate change was not considered in the drafting of much early legislation. Despite the huge increase in knowledge of climate change impacts in recent decades, legislation is still limited in how it takes these impacts into account. There is scope, however, to account for climate change in implementing much of the legislation through (a) existing references to environmental variability; (b) review cycles; and (c) secondary legislation and complementary policy development. 4. For legislation relating to marine protected areas (e.g. the EC Habitats and Birds Directives), climate change has generally not been considered in the site-designation process, or for ongoing management, with the exception of the Marine (Scotland) Act. Given that changing environmental conditions (e.g. rising temperatures and ocean acidification) directly affect the habitats and species that sites are designated for, how this legislation is used to protect marine biodiversity in a changing climate requires further consideration. 5. Accounting for climate change impacts on marine biodiversity in the development and implementation of legislation is vital to enable timely, adaptive management responses. Marine modelling can play an important role in informing management decisions

Pillared two-dimensional metal-organic frameworks based on a lower-rim acid appended calix[4]arene

Solvothermal reactions of the lower-rim functionalized diacid calix[4]arene 25,27-bis(methoxycarboxylic acid)-26,28-dihydroxy-4-tert-butylcalix[4]arene (LH₂) with Zn(NO₃)₂•6H₂O and the dipyridyl ligands 4,4/-bipyridyl (4,4/-bipy), 1,2-di(4-pyridyl)ethylene (DPE) or 4,4/-azopyridyl (4,4/-azopy) afforded a series of 2-D structures of the formulae {[Zn(4,4/-bipy)(L)]•2¼DEF}n (1), {[Zn₂(L)(DPE)]•DEF}n (2) and {[Zn(OH₂)₂(L)(4,4/-azopy)]•DEF}n (3) (DEF = diethylformamide)

The impact of alcohol use on tuberculosis treatment outcomes : a systematic review and meta-analysis

CITATION: Ragan, E. J. et al. 2020. The impact of alcohol use on tuberculosis treatment outcomes: a systematic review and meta-analysis. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 24(1):73–82. doi:10.5588/ijtld.19.0080The original publication is available at https://www.ingentaconnect.com/content/iuatld/ijtldAlcohol use is associated with increased risk of developing tuberculosis (TB) disease, yet the impact of alcohol use on TB treatment outcomes has not been summarized. We aimed to quantitatively review evidence of the relationship between alcohol use and poor TB treatment outcomes. We conducted a systematic review of PubMed, EMBASE, and Web of Science (January 1980–May 2018). We categorized studies as having a high- or low-quality alcohol use definition and examined poor treatment outcomes individually and as two aggregated definitions (i.e., including or excluding loss to follow-up [LTFU]). We analyzed drug-susceptible (DS-) and multidrug-resistant (MDR-) TB studies separately. Our systematic review yielded 111 studies reporting alcohol use as a predictor of DS- and MDR-TB treatment outcomes. Alcohol use was associated with increased odds of poor treatment outcomes (i.e., death, treatment failure, and LTFU) in DS (OR 1.99, 95% CI 1.57–2.51) and MDR-TB studies (OR 2.00, 95% CI 1.73–2.32). This association persisted for aggregated poor treatment outcomes excluding LTFU, each individual poor outcome, and across sub-group and sensitivity analyses. Only 19% of studies used high-quality alcohol definitions. Alcohol use significantly increased the risk of poor treatment outcomes in both DS- and MDR-TB patients. This study highlights the need for improved assessment of alcohol use in TB outcomes research and potentially modified treatment guidelines for TB patients who consume alcohol.https://www.ingentaconnect.com/content/iuatld/ijtld/2020/00000024/00000001/art00012;jsessionid=1tueuoodqr1hi.x-ic-live-03Publishers versio

Programmatic Management of Drug-Resistant Tuberculosis: An Updated Research Agenda.

There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey