II. Proton and Magnesium Binding to 5-phosphoribosyl A-1- Pyrophosphate

Biochemistr

Characterization of structures in biofilms formed by a Pseudomonas fluorescens isolated from soil

<p>Abstract</p> <p>Background</p> <p>Microbial biofilms represent an incompletely understood, but fundamental mode of bacterial growth. These sessile communities typically consist of stratified, morphologically-distinct layers of extracellular material, where numerous metabolic processes occur simultaneously in close proximity. Limited reports on environmental isolates have revealed highly ordered, three-dimensional organization of the extracellular matrix, which may hold important implications for biofilm physiology <it>in vivo</it>.</p> <p>Results</p> <p>A <it>Pseudomonas </it>spp. isolated from a natural soil environment produced flocculent, nonmucoidal biofilms <it>in vitro </it>with unique structural features. These mature biofilms were made up of numerous viable bacteria, even after extended culture, and contained up to 50% of proteins and accumulated 3% (by dry weight) calcium, suggesting an important role for the divalent metal in biofilm formation. Ultrastructurally, the mature biofilms contained structural motifs consisting of dense, fibrillary clusters, nanofibers, and ordered, honeycomb-like chambers enveloped in thin sheets.</p> <p>Conclusion</p> <p>Mature biofilms contained living bacteria and were structurally, chemically, and physiologically heterogeneous. The principal architectural elements observed by electron microscopy may represent useful morphological clues for identifying bacterial biofilms <it>in vivo</it>. The complexity and reproducibility of the structural motifs observed in bacterial biofilms appear to be the result of organized assembly, suggesting that this environmental isolate may possess ecological advantages in its natural habitat.</p

Magnetic phase separation in ordered alloys

We present a lattice model to study the equilibrium phase diagram of ordered alloys with one magnetic component that exhibits a low temperature phase separation between paramagnetic and ferromagnetic phases. The model is constructed from the experimental facts observed in Cu$_{3-x}$AlMn$_{x}$ and it includes coupling between configurational and magnetic degrees of freedom which are appropriated for reproducing the low temperature miscibility gap. The essential ingredient for the occurrence of such a coexistence region is the development of ferromagnetic order induced by the long-range atomic order of the magnetic component. A comparative study of both mean-field and Monte Carlo solutions is presented. Moreover, the model may enable the study of the structure of the ferromagnetic domains embedded in the non-magnetic matrix. This is relevant in relation to phenomena such as magnetoresistance and paramagnetism.Comment: 12 pages, 11 figures, accepted in Phys. Rev.

Developing pedagogies that work for Pre-Service and Early Career Teachers to reduce the Attainment Gap in Literacy, Numeracy and Health and Wellbeing. Research Question 3: What other practice or research might assist us in our purpose?

This report contributes to the Scottish Council of Deans of Education project related to the Scottish Attainment Challenge. It presents a literature review that responds to the third research question of the SCDE collaborative project: What other practice or research might assist us in our purpose? The purpose of this phase was to resource professional conversations and thinking in the teacher education sector, and to inform the final trial phase of the project. A literature search was undertaken using a range of strategies, to identify published accounts of innovative work from beyond Scotland in the following fields: initial teacher education for high poverty settings; pedagogies in literacy, numeracy and health and wellbeing; mentoring and induction. Each group of studies is summarised under themes with their potential for the SAC, ITE programmes and professional learning noted

Short-range hunters: exploring the function and constraints of water shooting in dwarf gouramis

Ballistic predation is a rare foraging adaptation: in fishes, most attention has focused on a single genus, the archerfish, known to manipulate water to shoot down prey above the water surface. However, several gourami species also exhibit apparently similar ‘shooting’ behaviour, spitting water up to 5 cm above the surface. In a series of experiments, we explored the shooting behaviour and aspects of its significance as a foraging ability in the dwarf gourami (Trichogaster lalius). We investigated sex differences in shooting abilities to determine whether gourami shooting is related to the sex-specific bubble nest manufacture where males mix air and water at the surface to form bubbles. We found that, actually, both sexes were equally able to shoot and could learn to shoot a novel target. In a second experiment, we presented untrained gouramis with opportunities to shoot at live prey and found they successfully shot down both fruit flies and crickets. Finally, we explored the effect of target height on shooting performance to establish potential constraints of shooting as a foraging ability. The frequency of attempted shots and success of hitting targets decreased with height, whereas latency to shoot increased. We also observed that repeatable individual differences account for variation in these measures of shooting performance. Together, our results provide evidence that gourami shooting has a foraging function analogous to that of archerfish. Gourami shooting may serve as an example of convergent evolution and provide opportunities for comparative studies into the, as yet unexplored, ecology and evolution of shooting in fishes.Peer reviewe

Key Data Gaps for Understanding Trends in Prescription Opioid Analgesic Abuse and Diversion Among Chronic Pain Patients and Nonmedical Users

Population dynamics of medical and nonmedical prescription opioid usage and adverse outcomes were modeled. Critical parameter values were determined by their amount of influence on model behavior. Results suggest that closing these data gaps would help researchers to better identify ways to reduce the risk of adverse outcomes

The Evolution of the Kinematics of Nebular Shells in Planetary Nebulae in the Milky Way Bulge

We study the line widths in the [\ion{O}{3}]$\lambda$5007 and H$\alpha$ lines for two groups of planetary nebulae in the Milky Way bulge based upon spectroscopy obtained at the Observatorio Astron\'omico Nacional in the Sierra San Pedro M\'artir (OAN-SPM) using the Manchester Echelle Spectrograph. The first sample includes objects early in their evolution, having high H$\beta$ luminosities, but [\ion{O}{3}]$\lambda 5007/\mathrm H\beta < 3$. The second sample comprises objects late in their evolution, with \ion{He}{2} $\lambda 4686/\mathrm H\beta > 0.5$. These planetary nebulae represent evolutionary phases preceeding and following those of the objects studied by Richer et al. (2008). Our sample of planetary nebulae with weak [\ion{O}{3}]$\lambda$5007 has a line width distribution similar to that of the expansion velocities of the envelopes of AGB stars, and shifted to systematically lower values as compared to the less evolved objects studied by Richer et al. (2008). The sample with strong \ion{He}{2} $\lambda 4686$ has a line width distribution indistinguishable from that of the more evolved objects from Richer et al. (2008), but a distribution in angular size that is systematically larger and so they are clearly more evolved. These data and those of Richer et al. (2008) form a homogeneous sample from a single Galactic population of planetary nebulae, from the earliest evolutionary stages until the cessation of nuclear burning in the central star. They confirm the long-standing predictions of hydrodynamical models of planetary nebulae, where the kinematics of the nebular shell are driven by the evolution of the central star.Comment: accepted for publication in the Astrophysical Journa

Muscle injury and impaired function, and insulin resistance in Chromogranin A knockout mice

Chromogranin A (CgA) is widely expressed in endocrine and neuroendocrine tissues as well as in the central nervous system. We observed CgA expression (mRNA and protein) in the gastrocnemius (GAS) muscle and found that performance of CgA-deficient Chga-KO mice in treadmill exercise was impaired. Supplementation with CgA in Chga-KO mice restored exercise ability suggesting a novel role for endogenous CgA in skeletal muscle function. Chga-KO mice display (i) lack of exercise-induced stimulation of pAKT, pTBC1D1 and phospho-p38 kinase signaling, (ii) loss of GAS muscle mass, (iii) extensive formation of tubular aggregates (TA), (iv) disorganized cristae architecture in mitochondria, (v) increased expression of the inflammatory cytokines Tnfα, Il6 and Ifnɣ, and fibrosis. The impaired maximum running speed and endurance in the treadmill exercise in Chga-KO mice correlated with decreased glucose uptake and glycolysis, defects in glucose oxidation and decreased mitochondrial cytochrome C oxidase activity. The lack of adaptation to endurance training correlated with the lack of stimulation of p38MAPK that is known to mediate the response to tissue damage. Since CgA sorts proteins to the regulated secretory pathway, we speculate that lack of CgA could cause misfolding of membrane proteins inducing aggregation of sarcoplasmic reticulum (SR) membranes and formation of tubular aggregates that is observed in Chga-KO mice. In conclusion, CgA deficiency renders the muscle energy deficient, impairs performance in treadmill exercise and prevents regeneration after exercise-induced tissue damage

RTS,S/AS01 malaria vaccine pilot implementation in western Kenya: a qualitative longitudinal study to understand immunisation barriers and optimise uptake

Background: Malaria is a significant public health threat in sub-Saharan Africa, particularly among children. The RTS,S/AS01 malaria vaccine reduces the risk and severity of malaria in children. RTS,S/AS01 was piloted in three African countries, Ghana, Kenya and Malawi, to assess safety, feasibility and cost-effectiveness in real-world settings. A qualitative longitudinal study was conducted as part of the feasibility assessment. This analysis explores RTS,S/AS01 vaccination barriers and identifies potential motivators among caregivers in three sub-counties in western Kenya. Methods: A cohort of 63 caregivers with a malaria vaccine eligible child was interviewed at three time points over 24 months. A sub-set of 11 caregivers whose eligible children were either partially or non-vaccinated were selected for this sub-analysis. The 5A Taxonomy for root causes of under-vaccination was used to organise the inductively-coded data into categories (awareness, acceptance, access, affordability, and activation) and identify the factors influencing uptake across caregivers. A trajectory analysis was conducted to understand changes in factors over time within each caregiver experience. Caregiver narratives are used to illustrate how the factors influencing uptake were interrelated and changed over time. Results: Lack of awareness, previous negative experiences with routine childhood immunisations and the burden of getting to the health facility contributed to caregivers initially delaying uptake of the vaccine. Over time concerns about vaccine side effects diminished and anticipated vaccination benefits strongly motivated caregivers to vaccinate their children. Persistent health system barriers (e.g., healthcare provider strikes, vaccine stockouts, negative provider attitudes) meant some children missed the first-dose eligibility window by aging-out. Conclusions: Caregivers in this study believed the RTS,S/AS01 to be effective and were motivated to have their children vaccinated. Despite these positive perceptions of the malaria vaccine, uptake was substantially hindered by persistent health system constraints. Negative provider attitudes emerged as a powerful deterrent to attending immunisation services and hampered uptake of the vaccine. Strategies that focus on improving interpersonal communication skills among healthcare providers are needed

Integration of the RTS,S/AS01 malaria vaccine into the Essential Programme on Immunisation in western Kenya: a qualitative longitudinal study from the health system perspective.

Background Malaria accounts for over half a million child deaths annually. WHO recommends RTS,S/AS01 to prevent malaria in children living in moderate-to-high malaria transmission regions. We conducted a qualitative longitudinal study to investigate the contextual and dynamic factors shaping vaccine delivery and uptake during a pilot introduction in western Kenya. Methods The study was conducted between Oct 3, 2019, and Mar 24, 2022. We conducted participant and non-participant observations and in-depth interviews with health-care providers, health managers, and national policymakers at three timepoints using an iterative approach and observations of practices and processes of malaria vaccine delivery. Transcripts were coded by content analysis using the consolidated framework for implementation research, to which emerging themes were added deductively and categorised into challenges and opportunities. Findings We conducted 112 in-depth interviews with 60 participants (25 health-care providers, 27 managers, and eight policy makers). Health-care providers highlighted limitations in RTS,S/AS01 integration into routine immunisation services due to the concurrent pilot evaluation and temporary adaptations for health reporting. Initial challenges related to the complexity of the four-dose schedule (up to 24-months); however, self-efficacy increased over time as the health-care providers gained experience in vaccine delivery. Low uptake of the fourth dose remained a challenge. Health managers cited insufficient trained immunisation staff and inadequate funding for supervision. Confidence in the vaccine increased among all participant groups owing to reductions in malaria frequency and severity. Interpretation Integration of RTS,S/AS01 into immunisation services in western Kenya presented substantial operational challenges most of which were overcome in the first 2 years, providing important lessons for other countries. Programme expansion is feasible with intensive staff training and retention, enhanced supervision, and defaulter-tracing to ensure uptake of all doses