Evolutionary origins and innovations sculpting the mammalian PRPS enzyme complex.

The phosphoribosyl pyrophosphate synthetase (PRPS) enzyme conducts a chokepoint reaction connecting central carbon metabolism and nucleotide production pathways, making it essential for life. Here, we show that the presence of multiple PRPS-encoding genes is a hallmark trait of eukaryotes, and we trace the evolutionary origins and define the individual functions of each of the five mammalian PRPS homologs - three isozymes (one testis-restricted) and two non-enzymatic associated proteins (APs) - which we demonstrate operate together as a large molecular weight complex capable of attaining a heterogeneous array of functional multimeric configurations. Employing a repertoire of isogenic fibroblast clones in all viable individual or combinatorial assembly states, we define preferential interactions between subunits, and we show that cells lacking PRPS2, PRPSAP1, and PRPSAP2 render PRPS1 into aberrant homo-oligomeric assemblies with diminished metabolic flux and impaired proliferative capacity.

Structural modeling and characterization of the Mycobacterium tuberculosis MmpL3 C-terminal domain.

The Mycobacterium tuberculosis (Mtb) cell envelope provides a protective barrier against the immune response and antibiotics. The mycobacterial membrane protein large (MmpL) family of proteins export cell envelope lipids and siderophores; therefore, these proteins are important for the basic biology and pathogenicity of Mtb. In particular, MmpL3 is essential and a known drug target.

Cationic Polysaccharides Bind to the Endothelial Cell Surface Extracellular Matrix Involving Heparan Sulfate.

Cationic polysaccharides have been extensively studied for drug delivery via the bloodstream, yet few have progressed to clinical use. Endothelial cells lining the blood vessel wall are coated in an anionic extracellular matrix called the glycocalyx. However, we do not fully comprehend the charged polysaccharide interactions with the glycocalyx.

Overcoming barriers to equality, diversity, inclusivity, and sense of belonging in healthcare education: the Underrepresented Groups' Experiences in Osteopathic Training (UrGEnT) mixed methods study.

Background: Individuals from minority groups have historically faced social injustices. Those from underrepresented groups have been less likely to access both healthcare services and higher education. Little is known about the experiences of underrepresented students during their undergraduate studies in osteopathy in the UK.

Teaching an Old Dog New Tricks: A Global Approach to Enhancing the Cytotoxicity of Drug-Loaded, Non-responsive Micelles Using Oligoelectrolytes.

Polymeric micelles have been extensively studied as vectors for the delivery of hydrophobic drugs for the treatment of cancers and other diseases. Despite intensive research, few formulations provide significant benefits, and even fewer have been clinically approved. While many traditional non-responsive micelles have excellent safety profiles, they lack the ability to respond to the intracellular environment and release their cargo in a spatiotemporally defined manner to effectively deliver large doses of cytotoxic drugs into the cytosol of cells that overwhelm efflux pumps.

Characterising the interventions designed to affect the reporting of musculoskeletal imaging: a scoping review protocol using the COM-B model.

Introduction: Attributing musculoskeletal (MSK) pain to normal and commonly occurring imaging findings, such as tendon, cartilage and spinal disc degeneration, has been shown to increase people's fear of movement, reduce their optimism about recovery and increase healthcare costs. Interventions seeking to reduce the negative effects of MSK imaging reporting have had little effect. To understand the ineffectiveness of these interventions, this study seeks to scope their behavioural targets, intended mechanisms of action and theoretical underpinnings.

Transdisciplinary stakeholder understandings of antimicrobial resistance: An integrative approach in Aotearoa New Zealand.

Objective: Antimicrobial resistance (AMR) is a complex public health issue, with a range of influences across human, animal, and environmental health. Given the complexity of the problem, the diversity of stakeholders, and the failure of current policies to curb AMR worldwide, integrative approaches are needed to identify effective actions. Underpinned by systems thinking and One Health principles, this qualitative study explored how diverse AMR experts in Aotearoa New Zealand perceive the main drivers and effects of AMR.

Correlative Fluorescence and Transmission Electron Microscopy Assisted by 3D Machine Learning Reveals Thin Nanodiamonds Fluoresce Brighter.

Nitrogen vacancy (NV) centers in fluorescent nanodiamonds (FNDs) draw widespread attention as quantum sensors due to their room-temperature luminescence, exceptional photo- and chemical stability, and biocompatibility. For bioscience applications, NV centers in FNDs offer high-spatial-resolution capabilities that are unparalleled by other solid-state nanoparticle emitters. On the other hand, pursuits to further improve the optical properties of FNDs have reached a bottleneck, with intense debate in the literature over which of the many factors are most pertinent.

Long-term health care use and diagnosis after hospitalization for COVID-19: a retrospective matched cohort study.

Background: Knowledge pertaining to the health and health care utilization of patients after recovery from acute COVID-19 is limited. We sought to assess the frequency of new diagnoses of disease and health care use after hospitalization with COVID-19.

Methods: We included all patients hospitalized with COVID-19 in Alberta between Mar.

Superheated storms: climate drivers, health effects and responses.

Nil.

Spliceosome assembly and regulation: insights from analysis of highly reduced spliceosomes.

Premessenger RNA splicing is catalyzed by the spliceosome, a multimegadalton RNA-protein complex that assembles in a highly regulated process on each intronic substrate. Most studies of splicing and spliceosomes have been carried out in human or model systems. There exists, however, a large diversity of spliceosomes, particularly in organisms with reduced genomes, that suggests a means of analyzing the essential elements of spliceosome assembly and regulation.

Structural basis for recognition of transcriptional terminator structures by ProQ/FinO domain RNA chaperones.

The ProQ/FinO family of RNA binding proteins mediate sRNA-directed gene regulation throughout gram-negative bacteria. Here, we investigate the structural basis for RNA recognition by ProQ/FinO proteins, through the crystal structure of the ProQ/FinO domain of the Legionella pneumophila DNA uptake regulator, RocC, bound to the transcriptional terminator of its primary partner, the sRNA RocR. The structure reveals specific recognition of the 3' nucleotide of the terminator by a conserved pocket involving a β-turn-α-helix motif, while the hairpin portion of the terminator is recognized by a conserved α-helical N-cap motif.

Blinding and sham control methods in trials of physical, psychological, and self-management interventions for pain (article II): a meta-analysis relating methods to trial results.

Sham interventions in randomized clinical trials (RCTs) of physical, psychological, and self-management (PPS) therapies for pain are highly variable in design and believed to contribute to poor internal validity. However, it has not been formally tested whether the extent to which sham controls resemble the treatment under investigation consistently affects trial outcomes, such as effect sizes, differential attrition, participant expectancy, and blinding effectiveness. Placebo- or sham-controlled RCTs of PPS interventions of clinical pain populations were searched in 12 databases.

Navigating fundamental tensions towards a decolonial relational vision of planetary health.

Planetary health has an important role to play in guiding humanity towards a healthy, equitable, and sustainable future. However, given planetary health's dominant colonial and capitalist underpinning ideologies, it risks reinscribing the same exploitative power dynamics that are fundamental drivers of global ecological collapse. In this Personal View, we reaffirm the need for a vision of planetary health grounded in Indigenous epistemologies, which centre relational ecocentric norms and values.

Understanding and experience of climate change in rural general practice in Aotearoa-New Zealand.

Background: Climate change is already affecting Aotearoa New Zealand (Aotearoa-NZ). The public health effects are varied and complex, and rural primary care staff will be at the front line of effects and responses. However, little is known about their understanding and experience.

Laparoscopic Lumen-guided cholecystectomy in face of the difficult gallbladder.

Background: Where the critical view of safety cannot be established during cholecystectomy, certain salvage techniques are indicated to reduce the likelihood of bile duct injury. The present study describes a salvage technique termed the "laparoscopic lumen-guided cholecystectomy" (LLC) and reports its peri-operative outcomes.

Method: A summary of the technique is as follows: (1) Hartmann's pouch is incised and stones are evacuated; (2) the cystic anatomy is inspected from the inside of the gallbladder; (3) the lumen is used to guide retrograde dissection towards the cystic pedicle; (4) cystic duct control is achieved if deemed safe.

Subtle changes in pH affect the packing and robustness of fatty acid bilayers.

Connecting molecular interactions to emergent properties is a goal of physical chemistry, self-assembly, and soft matter science. We show that for fatty acid bilayers, vesicle rupture tension, and permeability to water and ions are coupled to pH alterations to lipid packing. A change in pH of one, for example, can halve the rupture tension of oleic acid membranes, an effect that is comparable to increasing lipid unsaturation in phospholipid systems.

Can a Greenhouse Gas Emissions Tax on Food also Be Healthy and Equitable? A Systemised Review and Modelling Study from Aotearoa New Zealand.

Policies to mitigate climate change are essential. The objective of this paper was to estimate the impact of greenhouse gas (GHG) food taxes and assess whether such a tax could also have health benefits in Aotearoa NZ. We undertook a systemised review on GHG food taxes to inform four tax scenarios, including one combined with a subsidy.

Lifetime based axial contrast enable simple 3D-STED imaging.

Stimulated Emission Depletion (STED) microscopy increase spatial image resolution by laterally sharpening the illumination profile of the confocal microscope. However, it remains compromised in axial resolution. To improve axial STED resolution, constructive interference of the STED depletion beam must be formed surrounding the focal plane to turn off the fluorophores beyond the focal plane.

Lanthanide-based β-Tricalcium Phosphate Upconversion Nanoparticles as an Effective Theranostic Nonviral Vectors for Image-Guided Gene Therapy.

Lanthanide-based beta-tricalcium phosphate (β-TCP) upconversion nanoparticles are exploited as a non-viral vector for imaging guided-gene therapy by virtue of their unique optical properties and multi-modality imaging ability, high transfection efficiency, high biocompatibility, dispersibility, simplicity of synthesis and surface modification. Ytterbium and thulium-doped β-TCP nanoparticles (βTCPYbTm) are synthesized via co-precipitation method, coated with polyethylenimine (PEI) and functionalized with a nuclear-targeting peptide (TAT). Further, studies revealed that the nanotheranostic carriers are able to transfect cells with the plasmid eGFP at a high efficiency, with approximately 60% of total cells producing the fluorescent green protein.