Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Biophysically Realistic Filament Bending Dynamics in Agent-Based Biological Simulation

An appealing tool for study of the complex biological behaviors that can emerge from networks of simple molecular interactions is an agent-based, computational simulation that explicitly tracks small-scale local interactions – following thousands to millions of states through time. For many critical cell processes (e.g. cytokinetic furrow specification, nuclear centration, cytokinesis), the flexible nature of cytoskeletal filaments is likely to be critical. Any computer model that hopes to explain the complex emergent behaviors in these processes therefore needs to encode filament flexibility in a realistic manner. Here I present a numerically convenient and biophysically realistic method for modeling cytoskeletal filament flexibility in silico. Each cytoskeletal filament is represented by a series of rigid segments linked end-to-end in series with a variable attachment point for the translational elastic element. This connection scheme allows an empirically tuning, for a wide range of segment sizes, viscosities, and time-steps, that endows any filament species with the experimentally observed (or theoretically expected) static force deflection, relaxation time-constant, and thermal writhing motions. I additionally employ a unique pair of elastic elements – one representing the axial and the other the bending rigidity– that formulate the restoring force in terms of single time-step constraint resolution. This method is highly local –adjacent rigid segments of a filament only interact with one another through constraint forces—and is thus well-suited to simulations in which arbitrary additional forces (e.g. those representing interactions of a filament with other bodies or cross-links / entanglements between filaments) may be present. Implementation in code is straightforward; Java source code is available at www.celldynamics.org

Social media use, attitudes, behaviours and perceptions of online professionalism amongst dental students

Use of social media has increased amongst health professionals. This has benefits for patient care but also introduces risks for confidentiality and professional fitness to practise. This study aimed to examine dental student attitudes towards professional behaviour on social media. The secondary aim was to establish the extent and nature of social media use and exposure to potentially unprofessional behaviours. A cross-sectional study was carried out in one dental school. Data were collected using questionnaires to examine social media use, perceptions and attitudes towards social media and professional behaviours online. Students who responded (n=155) all used social media at least once per week; most used more than one platform. Students were aware of the relationship between social media use and professional practice. Posting drunken photographs and interacting with staff and patients online were widely considered as unprofessional. Security settings affected behaviour and most had seen inappropriate behaviours online. Students use social media extensively. Students are aware of the risks but there is a greater sense of safety in closed groups and many students are exposed to potentially inappropriate content online. This suggests that there are opportunities to reduce these risks through training to help students manage these risks

The development and piloting of the graduate assessment of preparedness for practice (GAPP) questionnaire

Introduction Most new dental graduates in the UK begin their professional career following a year in dental foundation training (DFT). There has been little investigation of how prepared they feel for independent general dental practice across all four domains of the General Dental Council’s curriculum ‘Preparing for practice’. This paper describes the development of the Graduate Assessment of Preparedness for Practice (GAPP) questionnaire to address this. Methodology The GAPP questionnaire was developed and piloted using a cohort of educational supervisors (ESs) and foundation dentists (FDs). The questionnaire comprised three parts, the first of which collected respondent demographic data. The second was based on Preparing for practice and was used to develop 34 ‘competence areas’ and required a tick-box response on a 7‑category Likert Scale. The third comprised free text questions in order to further explore the subject’s responses. Results Pilot feedback was positive, the statements were felt to be clear and unambiguous, allowing them sufficient scope to state their position. The pilot study informed small cosmetic changes to the GAPP questionnaire and inclusion of a ‘comments’ column for respondents to qualify their responses. The pilot results indicated that both FDs and their ESs felt that at ten months of DFT, the FDs were very well prepared for independent general dental practice. Discussion The paper describes the important considerations relating to the reliability and validity of the GAPP questionnaire. Conclusions GAPP appears to be a suitable questionnaire to measure preparedness of new graduates with a degree of reliability and validity. The instrument is designed to be simple to complete and provides a useful analytical instrument for both self-assessment of competence and for wider use within dental education

Climate forcing of an emerging pathogenic fungus across a montane multi-host community

Changes in the timings of seasonality as a result of anthropogenic climate change are predicted to occur over the coming decades. While this is expected to have widespread impacts on the dynamics of infectious disease through environmental forcing, empirical data are lacking. Here, we investigated whether seasonality, specifically the timing of spring ice-thaw, affected susceptibility to infection by the emerging pathogenic fungus Batrachochytrium dendrobatidis (Bd) across a montane community of amphibians that are suffering declines and extirpations as a consequence of this infection. We found a robust temporal association between the timing of the spring thaw and Bd infection in two host species, where we show that an early onset of spring forced high prevalences of infection. A third highly susceptible species (the midwife toad, Alytes obstetricans) maintained a high prevalence of infection independent of time of spring thaw. Our data show that perennially overwintering midwife toad larvae may act as a year-round reservoir of infection with variation in time of spring thaw determining the extent to which infection spills over into sympatric species. We used future temperature projections based on global climate models to demonstrate that the timing of spring thaw in this region will advance markedly by the 2050s, indicating that climate change will further force the severity of infection. Our findings on the effect of annual variability on multi-host infection dynamics show that the community-level impact of fungal infectious disease on biodiversity will need to be re-evaluated in the face of climate change

Mothers Matter Too: Benefits of Temperature Oviposition Preferences in Newts

The maternal manipulation hypothesis states that ectothermic females modify thermal conditions during embryonic development to benefit their offspring (anticipatory maternal effect). However, the recent theory suggests that the ultimate currency of an adaptive maternal effect is female fitness that can be maximized also by decreasing mean fitness of individual offspring. We evaluated benefits of temperature oviposition preferences in Alpine newts (Ichthyosaura [formerly Triturus] alpestris) by comparing the thermal sensitivity of maternal and offspring traits across a range of preferred oviposition temperatures (12, 17, and 22°C) and by manipulating the egg-predation risk during oviposition in a laboratory thermal gradient (12–22°C). All traits showed varying responses to oviposition temperatures. Embryonic developmental rates increased with oviposition temperature, whereas hatchling size and swimming capacity showed the opposite pattern. Maternal oviposition and egg-predation rates were highest at the intermediate temperature. In the thermal gradient, females oviposited at the same temperature despite the presence of caged egg-predators, water beetles (Agabus bipustulatus). We conclude that female newts prefer a particular temperature for egg-deposition to maximize their oviposition performance rather than offspring fitness. The evolution of advanced reproductive modes, such as prolonged egg-retention and viviparity, may require, among others, the transition from selfish temperature preferences for ovipositon to the anticipatory maternal effect

Conservation Genetics of a Critically Endangered Limpet Genus and Rediscovery of an Extinct Species

A third of all known freshwater mollusk extinctions worldwide have occurred within a single medium-sized American drainage. The Mobile River Basin (MRB) of Alabama, a global hotspot of temperate freshwater biodiversity, was intensively industrialized during the 20(th) century, driving 47 of its 139 endemic mollusk species to extinction. These include the ancylinid limpet Rhodacmea filosa, currently classified as extinct (IUCN Red List), a member of a critically endangered southeastern North American genus reduced to a single known extant population (of R. elatior) in the MRB.We document here the tripling of known extant populations of this North American limpet genus with the rediscovery of enduring Rhodacmea filosa in a MRB tributary and of R. elatior in its type locality: the Green River, Kentucky, an Ohio River Basin (ORB) tributary. Rhodacmea species are diagnosed using untested conchological traits and we reassessed their systematic and conservation status across both basins using morphometric and genetic characters. Our data corroborated the taxonomic validity of Rhodacmea filosa and we inferred a within-MRB cladogenic origin from a common ancestor bearing the R. elatior shell phenotype. The geographically-isolated MRB and ORB R. elatior populations formed a cryptic species complex: although overlapping morphometrically, they exhibited a pronounced phylogenetic disjunction that greatly exceeded that of within-MRB R. elatior and R. filosa sister species.Rhodacmea filosa, the type species of the genus, is not extinct. It persists in a Coosa River tributary and morphometric and phylogenetic analyses confirm its taxonomic validity. All three surviving populations of the genus Rhodacmea merit specific status. They collectively contain all known survivors of a phylogenetically highly distinctive North American endemic genus and therefore represent a concentrated fraction of continental freshwater gastropod biodiversity. We recommend the establishment of a proactive targeted conservation program that may include their captive propagation and reintroduction