A new family of phosphoinositide phosphatases in microorganisms: identification and biochemical analysis

<p>Abstract</p> <p>Background</p> <p>Phosphoinositide metabolism is essential to membrane dynamics and impinges on many cellular processes, including phagocytosis. Modulation of phosphoinositide metabolism is important for pathogenicity and virulence of many human pathogens, allowing them to survive and replicate in the host cells. Phosphoinositide phosphatases from bacterial pathogens are therefore key players in this modulation and constitute attractive targets for chemotherapy. MptpB, a virulence factor from <it>Mycobacterium tuberculosis</it>, has phosphoinositide phosphatase activity and a distinct active site P-loop signature HCXXGKDR that shares characteristics with eukaryotic lipid phosphatases and protein tyrosine phosphatases. We used this P-loop signature as a "diagnostic motif" to identify related putative phosphatases with phosphoinositide activity in other organisms.</p> <p>Results</p> <p>We found more than 200 uncharacterised putative phosphatase sequences with the conserved signature in bacteria, with some related examples in fungi and protozoa. Many of the sequences identified belong to recognised human pathogens. Interestingly, no homologues were found in any other organisms including Archaea, plants, or animals. Phylogenetic analysis revealed that these proteins are unrelated to classic eukaryotic lipid phosphatases. However, biochemical characterisation of those from <it>Listeria monocytogenes </it>and <it>Leishmania major</it>, demonstrated that, like MptpB, they have phosphatase activity towards phosphoinositides. Mutagenesis studies established that the conserved Asp and Lys in the P-loop signature (HCXXG<b>KD</b>R) are important in catalysis and substrate binding respectively. Furthermore, we provide experimental evidence that the number of basic residues in the P-loop is critical in determining activity towards poly-phosphoinositides.</p> <p>Conclusion</p> <p>This new family of enzymes in microorganisms shows distinct sequence and biochemical characteristics to classic eukaryotic lipid phosphatases and they have no homologues in humans. This study provides a foundation for examining the biological role of this new family of phosphatases and their potential as pharmaceutical targets against infectious diseases.</p

Students\u27 Perceptions of STEM Learning After Participating in a Summer Informal Learning Experience

Background: Informal learning environments increase students’ interest in STEM (e.g., Mohr‐Schroeder et al. School Sci Math 114: 291–301, 2014) and increase the chances a student will pursue a STEM career (Kitchen et al. Sci Educ 102: 529–547, 2018). The purpose of this study was to examine the impact of an informal STEM summer learning experience on student participants, to gain in-depth perspectives about how they felt this experience prepared them for their in-school mathematics and science classes as well as how it influenced their perception of STEM learning. Students’ attitudes and perceptions toward STEM are affected by their motivation, experience, and self-efficacy (Brown et al. J STEM Educ Innov Res 17: 27, 2016). The academic and social experiences students’ have are also important. Traditionally, formal learning is taught in a solitary form (Martin Science Education 88: S71–S82, 2004), while, informal learning is brimming with chances to connect and intermingle with peers (Denson et al. J STEM Educ: Innovations and Research 16: 11, 2015). Results: Informal learning environments increase students’ interest in STEM (e.g., Mohr‐Schroeder et al. School Sci Math 114: 291–301, 2014) and increase the chances a student will pursue a STEM career (Kitchen et al. Sci Educ 102: 529–547, 2018). The purpose of this study was to examine the impact of an informal STEM summer learning experience on student participants, to gain in-depth perspectives about how they felt this experience prepared them for their in-school mathematics and science classes as well as how it influenced their perception of STEM learning. Students’ attitudes and perceptions toward STEM are affected by their motivation, experience, and self-efficacy (Brown et al. J STEM Educ Innov Res 17: 27, 2016). The academic and social experiences students’ have are also important. Traditionally, formal learning is taught in a solitary form (Martin Science Education 88: S71–S82, 2004), while, informal learning is brimming with chances to connect and intermingle with peers (Denson et al. J STEM Educ: Innovations and Research 16: 11, 2015). Conclusions: By using authentic STEM workplaces, the STEM summer learning experience fostered a learning environment that extended and deepened STEM content learning while providing opportunity and access to content, settings, and materials that most middle level students otherwise would not have access to. Students also acknowledged the access they received to hands-on activities in authentic STEM settings and the opportunities they received to interact with STEM professionals were important components of the summer informal learning experience

Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA

In the early-diverging protozoan parasite Plasmodium, few telomere-binding proteins have been identified and several are unique. Plasmodium telomeres, like those of most eukaryotes, contain guanine-rich repeats that can form G-quadruplex structures. In model systems, quadruplex-binding drugs can disrupt telomere maintenance and some quadruplex-binding drugs are potent anti-plasmodial agents. Therefore, telomere-interacting and quadruplex-interacting proteins may offer new targets for anti-malarial therapy. Here, we report that P. falciparum GBP2 is such a protein. It was identified via ‘Proteomics of Isolated Chromatin fragments’, applied here for the first time in Plasmodium. In vitro, PfGBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. In vivo, PfGBP2 partially colocalises with the known telomeric protein HP1 but is also found in the cytoplasm, probably due to its affinity for RNA. Consistently, its interactome includes numerous RNA-associated proteins. PfGBP2 is evidently a multifunctional DNA/RNA-binding factor in Plasmodium.</jats:p

Testing the Effectiveness of the “Smelly” Elephant Repellent in Controlled Experiments in Semi-Captive Asian and African Savanna Elephants

Simple Summary: Mitigating and reducing the impacts of elephant crop-raiding has become a major focus of conservation intervention. By observing the behaviour amongst two groups of semi-captive African and Asian elephants in Zambia and Thailand, we found that a novel olfactory crop-raiding mitigation method called the “smelly elephant repellent” elicited clear reactions from the elephants. However, unlike trials with wild elephants, the repellent did not prevent the elephants from entering areas or eating food protected by the solution. We found that elephant personality played a role in responses towards the repellent, as the individuals that entered the experimental plots were bolder and more curious individuals. Although captive environments provide controlled settings for experimental testing, the ecological validity of testing human–elephant conflict mitigation methods with captive wildlife should be strongly considered. Understanding animal behaviour is essential for improving human–elephant coexistence and for designing deterrence mechanisms, and the smelly elephant repellent may be a useful mitigation method when used in combination with other methods. Abstract: Crop-raiding by elephants is one of the most prevalent forms of human–elephant conflict and is increasing with the spread of agriculture into wildlife range areas. As the magnitude of conflicts between people and elephants increases across Africa and Asia, mitigating and reducing the impacts of elephant crop-raiding has become a major focus of conservation intervention. In this study, we tested the responses of semi-captive elephants to the “smelly” elephant repellent, a novel olfactory crop-raiding mitigation method. At two trial sites, in Zambia and Thailand, African elephants (Loxodonta africana) and Asian elephants (Elephas maximus) were exposed to the repellent, in order to test whether or not they entered an area protected by the repellent and whether they ate the food provided. The repellent elicited clear reactions from both study groups of elephants compared to control conditions. Generalised linear models revealed that the elephants were more alert, sniffed more, and vocalised more when they encountered the repellent. Although the repellent triggered a response, it did not prevent elephants from entering plots protected by the repellent or from eating crops, unlike in trials conducted with wild elephants. Personality played a role in responses towards the repellent, as the elephants that entered the experimental plots were bolder and more curious individuals. We conclude that, although captive environments provide controlled settings for experimental testing, the ecological validity of testing human–elephant conflict mitigation methods with captive wildlife should be strongly considered. This study also shows that understanding animal behaviour is essential for improving human–elephant coexistence and for designing deterrence mechanisms. Appreciating personality traits in elephants, especially amongst “problem” elephants who have a greater propensity to crop raid, could lead to the design of new mitigation methods designed to target these individuals

Study protocol of a cluster randomised controlled trial investigating the effectiveness of a tailored energy balance programme for recent retirees

BACKGROUND: People in transitional life stages, such as occupational retirement, are likely to gain weight and accumulate abdominal fat mass caused by changes in physical activity and diet. Hence, retirees are an important target group for weight gain prevention programmes, as described in the present paper. METHODS/DESIGN: A systematic and stepwise approach (Intervention Mapping) is used to develop a low-intensity energy balance intervention programme for recent retirees. This one-year, low-intensity multifaceted programme aims to prevent accumulation of abdominal fat mass and general weight gain by increasing awareness of energy balance and influencing related behaviours of participants' preference. These behaviours are physical activity, fibre intake, portion size and fat consumption. The effectiveness of the intervention programme is tested in a cluster randomised controlled trial. Measurements of anthropometry, physical activity, energy intake, and related psychosocial determinants are performed at baseline and repeated at 6 months for intermediate effect, at 12 months to evaluate short-term intervention effects and at 24 months to test the sustainability of the effects. DISCUSSION: This intervention programme is unique in its focus on retirees and energy balance. It aims at increasing awareness and takes into account personal preferences of the users by offering several options for behaviour change. Moreover, the intervention programme is evaluated at short-term and long-term and includes consecutive outcome measures (determinants, behaviour and body composition)

Pre-Operative Cognitive Functioning and Inflammatory and Neuroendocrine Responses to Cardiac Surgery.

BACKGROUND: Cognitive functioning is linked to cardiac mortality and morbidity, but the mechanisms underlying this relationship are unclear. PURPOSE: To examine the relationship between pre-operative cognitive functioning and post-operative inflammatory and neuroendocrine responses in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: One-hundred ninety-three outpatients were screened to assess their cognitive function using the Montreal Cognitive Assessment (MoCA) on average 30 days prior to CABG surgery and provided blood samples for the measurement of interleukin (IL)-6 and C-reactive protein (CRP) and saliva samples for the measurement of diurnal cortisol. Participants were followed-up 4-8 days following surgery for the repeat measurement of IL-6 and CRP and 60 days after surgery for the measurement of diurnal salivary cortisol. RESULTS: Patients with low cognitive function (MoCA < 26) prior to surgery reached higher IL-6 concentrations in the days after surgery (β = -0.212, p = 0.021) and had greater cortisol output across the day 2 months after surgery (β = -0.179, p = 0.044). CONCLUSIONS: Low cognitive functioning is associated with a more negative pattern of biological response to surgery, indicative of poorer physical recovery. These pathways may contribute to the links between cognitive function and cardiovascular pathology

African-Caribbean cancer consortium for the study of viral, genetic and environmental cancer risk factors

This is a short summary of a meeting of the "African-Caribbean Cancer Consortium", jointly organized by the University of Pittsburgh, Department of Epidemiology and the University of Pittsburgh Cancer Institute, held in Montego Bay, Jamaica as a satellite meeting at the Caribbean Health Research Council, 52nd Annual Council and Scientific meeting on May 4, 2007

The global burden of falls: Global, regional and national estimates of morbidity and mortality from the Global Burden of Disease Study 2017

Background: Falls can lead to severe health loss including death. Past research has shown that falls are an important cause of death and disability worldwide. The Global Burden of Disease Study 2017 (GBD 2017) provides a comprehensive assessment of morbidity and mortality from falls. Methods: Estimates for mortality, years of life lost (YLLs), incidence, prevalence, years lived with disability (YLDs) and disability-adjusted life years (DALYs) were produced for 195 countries and territories from 1990 to 2017 for all ages using the GBD 2017 framework. Distributions of the bodily injury (eg, hip fracture) were estimated using hospital records. Results: Globally, the age-standardised incidence of falls was 2238 (1990-2532) per 100 000 in 2017, representing a decline of 3.7% (7.4 to 0.3) from 1990 to 2017. Age-standardised prevalence w