Translational regulation in mycobacteria and its implications for pathogenicity

Protein synthesis is a fundamental requirement of all cells for survival and replication. To date, vast numbers of genetic and biochemical studies have been performed to address the mechanisms of translation and its regulation in Escherichia coli, but only a limited number of studies have investigated these processes in other bacteria, particularly in slow growing bacteria like Mycobacterium tuberculosis, the causative agent of human tuberculosis. In this Review, we highlight important differences in the translational machinery of M. tuberculosis compared with E. coli, specifically the presence of two additional proteins and subunit stabilizing elements such as the B9 bridge. We also consider the role of leaderless translation in the ability of M. tuberculosis to establish latent infection and look at the experimental evidence that translational regulatory mechanisms operate in mycobacteria during stress adaptation, particularly focussing on differences in toxin-antitoxin systems between E. coli and M. tuberculosis and on the role of tuneable translational fidelity in conferring phenotypic antibiotic resistance. Finally, we consider the implications of these differences in the context of the biological adaptation of M. tuberculosis and discuss how these regulatory mechanisms could aid in the development of novel therapeutics for tuberculosis

Wooded streets, but not streetlight dimming, favour bat activity in a temperate urban setting

Data availability: The data used as input in our statistical tests is available from Figshare - https://figshare.com/s/31c0c425512f6de67df0.Copyright © The Author(s) 2023. Urbanization damages biodiversity, reducing people's connection to nature and negatively impacting the survivability of local species. However, with small adjustments, the damage could be mitigated. In temperate regions, several bat species inhabit urban areas, and with urbanization set to increase, adapting urban areas to improve their suitability for bats is imperative. Therefore, we investigated if wooded streets and streetlight dimming in an urban setting influenced bat activity. Static bat detectors were used to compare wooded versus non-wooded, and bright versus dim streets in Leicester, UK, on predominantly residential streets. The collected calls were quantified into bat activity (passes per night). Six species were identified, but the common pipistrelle (Pipistrellus pipistrellus) was dominant, making up 94.1% of all calls, so it was the sole species included in the statistical model. Wooded streets had significantly higher bat activity than non-wooded streets, but bright and dim streets were not significantly different. The results suggest that wooded streets were being used as green corridors, with common pipistrelles possibly following them to conceal themselves from predators, such as the tawny owl, and the proliferation of wooded streets in urban areas could allow the formation of better-connected populations. Streetlight dimming did not affect bat activity, but no light-averse bats were detected, likely because even the most dimmed streets deterred them despite street lighting increasing food availability by attracting insects. Therefore, an alternate solution, such as part-night lighting, may be required to increase the suitability of urban areas to light-averse species

Translation of a leaderless reporter is robust during exponential growth and well sustained during stress conditions in Mycobacterium tuberculosis

Abstract Mycobacterium tuberculosis expresses a large number of leaderless mRNA transcripts; these lack the 5’ leader region, which usually contains the Shine-Dalgarno sequence required for translation initiation in bacteria. In M. tuberculosis, transcripts encoding proteins with secondary adaptive functions are predominantly leaderless and the overall ratio of leaderless to Shine-Dalgarno transcripts significantly increases during growth arrest, suggesting that leaderless translation might be important during persistence in the host. However, whether these two types of transcripts are translated with differing efficiencies during stress conditions that induce growth arrest and during optimal growth conditions, is unclear. Here, using bioluminescent reporter strains, we detect robust leaderless translation during exponential in vitro growth and we show that leaderless translation is more stable than Shine-Dalgarno translation during adaptation to stress conditions. Upon entrance into nutrient starvation and after nitric oxide exposure, leaderless translation is significantly less affected by the stress than Shine-Dalgarno translation. Similarly, during the early stages of infection of macrophages, the levels of leaderless translation are more stable than those of Shine-Dalgarno translation. These results suggest that leaderless translation may offer an advantage in the physiology of M. tuberculosis. Identification of the molecular mechanisms underlying this translational regulation may provide insights into persistent infection.</jats:p

Observation of epitaxially ordered twinned zinc aluminate “nanoblades” on c-capphire

We report the observation of a novel nanostructured growth mode of the ceramic spinel zinc aluminate grown on c-sapphire in the form of epitaxially ordered twinned crystallites with pronounced vertically aligned “nanoblades” on top of these crystallites. The nanostructures are formed on bare c-sapphire substrates using a vapour phase transport method. Electron microscopy images reveal the nanostructure morphology and dimensions and allow direct and indirect observation of the twin boundary location in a number of samples. The nanoblade structure with sharply rising sidewalls gives rise to a distinctive bright contrast in secondary electron images in scanning electron microscopy measurements

Bioluminescence imaging of human embryonic stem cells transplanted in vivo in murine and chick models

Research into the behavior, efficacy, and biosafety of stem cells with a view to clinical transplantation requires the development of noninvasive methods for in vivo imaging of cells transplanted into animal models. This is particularly relevant for human embryonic stem cells (hESCs), because transplantation of undifferentiated hESCs leads to tumor formation. The present study aimed to monitor hESCs in real time when injected in vivo. hESCs were stably transfected to express luciferase, and luciferase expression was clearly detected in the undifferentiated and differentiated state. When transfected hESCs were injected into chick embryos, bioluminescence could be detected both ex and in ovo. In the SCID mouse model, undifferentiated hESCs were detectable after injection either into the muscle layer of the peritoneum or the kidney capsule. Tumors became detectable between days 10-30, with approximately a 3 log increase in the luminescence signal by day 75. The growth phase occurred earlier in the kidney capsule and then reached a plateau, whilst tumors in the peritoneal wall grew steadily throughout the period analysed. These results show the widespread utility of bioluminescent for in vivo imaging of hESCs in a variety of model systems for preclinical research into regenerative medicine and cancer biology. © Copyright 2009, Mary Ann Liebert, Inc

Implementing a public web based GIS service for feedback of surveillance data on communicable diseases in Sweden

BACKGROUND: Surveillance data allow for analysis, providing public health officials and policy-makers with a basis for long-term priorities and timely information on possible outbreaks for rapid response (data for action). In this article we describe the considerations and technology behind a newly introduced public web tool in Sweden for easy retrieval of county and national surveillance data on communicable diseases. METHODS: The web service was designed to automatically present updated surveillance statistics of some 50 statutory notifiable diseases notified to the Swedish Institute for Infectious Disease Control (SMI). The surveillance data is based on clinical notifications from the physician having treated the patient and laboratory notifications, merged into cases using a unique personal identification number issued to all Swedish residents. The web service use notification data from 1997 onwards, stored in a relational database at the SMI. RESULTS: The web service presents surveillance data to the user in various ways; tabulated data containing yearly and monthly disease data per county, age and sex distribution, interactive maps illustrating the total number of cases and the incidence per county and time period, graphs showing the total number of cases per week and graphs illustrating trends in the disease data. The system design encompasses the database (storing the data), the web server (holding the web service) and an in-the-middle computer (to ensure good security standards). CONCLUSIONS: The web service has provided the health community, the media, and the public with easy access to both timely and detailed surveillance data presented in various forms. Since it was introduced in May 2003, the system has been accessed more than 1,000,000 times, by more than 10,000 different viewers (over 12.600 unique IP-numbers)

The graded Jacobi algebras and (co)homology

Jacobi algebroids (i.e. `Jacobi versions' of Lie algebroids) are studied in the context of graded Jacobi brackets on graded commutative algebras. This unifies varios concepts of graded Lie structures in geometry and physics. A method of describing such structures by classical Lie algebroids via certain gauging (in the spirit of E.Witten's gauging of exterior derivative) is developed. One constructs a corresponding Cartan differential calculus (graded commutative one) in a natural manner. This, in turn, gives canonical generating operators for triangular Jacobi algebroids. One gets, in particular, the Lichnerowicz-Jacobi homology operators associated with classical Jacobi structures. Courant-Jacobi brackets are obtained in a similar way and use to define an abstract notion of a Courant-Jacobi algebroid and Dirac-Jacobi structure. All this offers a new flavour in understanding the Batalin-Vilkovisky formalism.Comment: 20 pages, a few typos corrected; final version to be published in J. Phys. A: Math. Ge

Migration and diversity in a post-socialist context: Creating integrative encounters in Poland

This article explores ‘integrative encounters’ between immigrants and Polish people in Warsaw. Rather than focus on new arrivals we pay attention to the integration experiences of the host population in recognition that this is a group who have been relatively neglected in the literature. Post-socialist European countries where population mobility was circumscribed during the communist era and as a consequence became perceived as relatively homogenous white societies but which are now seeing a rise in immigration, have been largely neglected by non-domestic scholars. In Poland organised group activity is an important means to provide the established population with an opportunity to encounter migrants because such encounters are less likely to occur in everyday spaces. Drawing on research with a Warsaw based NGO which runs a football league to bring Polish people and immigrants together, we argue that attention needs to be paid to the issue of ‘motivation' to participate in integration projects and to the significance of sociality. In doing so, we suggest that creating the conditions for spontaneous connections to develop, even in contrived projects, is a way to overcome indifference to difference. Here, we highlight the qualities of football as a bridging activity to facilitate integrative encounters

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies