Lunar resources: a review

There is growing interest in the possibility that the resource base of the Solar System might in future be used to supplement the economic resources of our own planet. As the Earth’s closest celestial neighbour, the Moon is sure to feature prominently in these developments. In this paper I review what is currently known about economically exploitable resources on the Moon, while also stressing the need for continued lunar exploration. I find that, although it is difficult to identify any single lunar resource that will be sufficiently valuable to drive a lunar resource extraction industry on its own (notwithstanding claims sometimes made for the 3He isotope, which are found to be exaggerated), the Moon nevertheless does possess abundant raw materials that are of potential economic interest. These are relevant to a hierarchy of future applications, beginning with the use of lunar materials to facilitate human activities on the Moon itself, and progressing to the use of lunar resources to underpin a future industrial capability within the Earth-Moon system. In this way, gradually increasing access to lunar resources may help ‘bootstrap’ a space-based economy from which the world economy, and possibly also the world’s environment, will ultimately benefit

Matrix metalloproteinases in lung biology

Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs) do in tissues. The catalytic activity of these enzymes has been implicated to function in normal lung biology by participating in branching morphogenesis, homeostasis, and repair, among other events. Overexpression of MMPs, however, has also been blamed for much of the tissue destruction associated with lung inflammation and disease. Beyond their role in the turnover and degradation of extracellular matrix proteins, MMPs also process, activate, and deactivate a variety of soluble factors, and seldom is it readily apparent by presence alone if a specific proteinase in an inflammatory setting is contributing to a reparative or disease process. An important goal of MMP research will be to identify the actual substrates upon which specific enzymes act. This information, in turn, will lead to a clearer understanding of how these extracellular proteinases function in lung development, repair, and disease

A Novel Secretion Pathway of Salmonella enterica Acts as an Antivirulence Modulator during Salmonellosis

Salmonella spp. are Gram-negative enteropathogenic bacteria that infect a variety of vertebrate hosts. Like any other living organism, protein secretion is a fundamental process essential for various aspects of Salmonella biology. Herein we report the identification and characterization of a horizontally acquired, autonomous and previously unreported secretion pathway. In Salmonella enterica serovar Typhimurium, this novel secretion pathway is encoded by STM1669 and STM1668, designated zirT and zirS, respectively. We show that ZirT is localized to the bacterial outer membrane, expected to adopt a compact β-barrel conformation, and functions as a translocator for ZirS. ZirS is an exoprotein, which is secreted into the extracellular environment in a ZirT-dependent manner. The ZirTS secretion pathway was found to share several important features with two-partner secretion (TPS) systems and members of the intimin/invasin family of adhesions. We show that zirTS expression is affected by zinc; and that in vivo, induction of zirT occurs distinctively in Salmonella colonizing the small intestine, but not in systemic sites. Additionally, strong expression of zirT takes place in Salmonella shed in fecal pellets during acute and persistent infections of mice. Inactivation of ZirTS results in a hypervirulence phenotype of Salmonella during oral infection of mice. Cumulatively, these results indicate that the ZirTS pathway plays a unique role as an antivirulence modulator during systemic disease and is involved in fine-tuning a host–pathogen balance during salmonellosis

Hydrogen Peroxide Acts on Sensitive Mitochondrial Proteins to Induce Death of a Fungal Pathogen Revealed by Proteomic Analysis

How the host cells of plants and animals protect themselves against fungal invasion is a biologically interesting and economically important problem. Here we investigate the mechanistic process that leads to death of Penicillium expansum, a widespread phytopathogenic fungus, by identifying the cellular compounds affected by hydrogen peroxide (H2O2) that is frequently produced as a response of the host cells. We show that plasma membrane damage was not the main reason for H2O2-induced death of the fungal pathogen. Proteomic analysis of the changes of total cellular proteins in P. expansum showed that a large proportion of the differentially expressed proteins appeared to be of mitochondrial origin, implying that mitochondria may be involved in this process. We then performed mitochondrial sub-proteomic analysis to seek the H2O2-sensitive proteins in P. expansum. A set of mitochondrial proteins were identified, including respiratory chain complexes I and III, F1F0 ATP synthase, and mitochondrial phosphate carrier protein. The functions of several proteins were further investigated to determine their effects on the H2O2-induced fungal death. Through fluorescent co-localization and the use of specific inhibitor, we provide evidence that complex III of the mitochondrial respiratory chain contributes to ROS generation in fungal mitochondria under H2O2 stress. The undesirable accumulation of ROS caused oxidative damage of mitochondrial proteins and led to the collapse of mitochondrial membrane potential. Meanwhile, we demonstrate that ATP synthase is involved in the response of fungal pathogen to oxidative stress, because inhibition of ATP synthase by oligomycin decreases survival. Our data suggest that mitochondrial impairment due to functional alteration of oxidative stress-sensitive proteins is associated with fungal death caused by H2O2

Nephronophthisis

Nephronophthisis (NPH) is an autosomal recessive disease characterized by a chronic tubulointerstitial nephritis that progress to terminal renal failure during the second decade (juvenile form) or before the age of 5 years (infantile form). In the juvenile form, a urine concentration defect starts during the first decade, and a progressive deterioration of renal function is observed in the following years. Kidney size may be normal, but loss of corticomedullary differentiation is often observed, and cysts occur usually after patients have progressed to end-stage renal failure. Histologic lesions are characterized by tubular basement membrane anomalies, tubular atrophy, and interstitial fibrosis. The infantile form is characterized by cortical microcysts and progression to end-stage renal failure before 5 years of age. Some children present with extrarenal symptoms: retinitis pigmentosa (Senior-Løken syndrome), mental retardation, cerebellar ataxia, bone anomalies, or liver fibrosis. Positional cloning and candidate gene approaches led to the identification of eight causative genes (NPHP1, 3, 4, 5, 6, 7, 8, and 9) responsible for the juvenile NPH and one gene NPHP2 for the infantile form. NPH and associated disorders are considered as ciliopathies, as all NPHP gene products are expressed in the primary cilia, similarly to the polycystic kidney disease (PKD) proteins

Contemporary review of stress echocardiography workforce within the UK: an EVAREST/BSE NSTEP study

Background Stress echocardiography is a key imaging modality for assessing coronary artery disease in the UK. Traditionally, stress echo services were led by consultant cardiologists, but evolving workforce models have increased the involvement of cardiac physiologists and scientists. This study, as part of the National Review of Stress Echocardiography Practice (BSE N-STEP), aimed to evaluate current stress echo workforce structures and test outcomes across a group of UK hospitals to inform future workforce planning. Results Data were analysed from 8506 stress echocardiograms, conducted between September 2020 and June 2023 across 34 UK hospitals. Based on the supervising workforce, stress echocardiograms were allocated into either a doctor-led (DL) or cardiac physiologist/scientist and nurse-led (CNL) model. 56.9% of stress echocardiograms were DL, while 42.7% were conducted under a CNL model. Physiologists/scientists were the most frequently involved staff (81.9%). The primary indication for stress echocardiography was ischaemia evaluation (89.4%). Dobutamine stress echocardiography was more common in DL services (63.0 vs. 56.3%, p < 0.001), while CNL services performed more exercise stress echocardiography (42.8 vs. 36.4%, p < 0.001). Test positivity rates were similar between DL and CNL models (17.1 vs. 17.7%, p = ns), though the CNL group had a lower complication rate (2.2 vs. 5.3%, p < 0.001). Reporting of stress echocardiograms remained consultant-led in 82% of cases, but physiologist/scientist-led reporting showed an increase over time. Training was primarily provided to registrars/fellows (60.2%), with physiologist/scientist trainees accounting for 32.4%. Conclusions This study provides a contemporary overview of stress echocardiography workforce models in the UK, highlighting the increasing role of cardiac physiologists and scientists in supervising and reporting stress echocardiography. Despite these shifts, consultant cardiologists remain central to stress echo reporting. The findings support the integration of multidisciplinary workforce models to enhance service efficiency. These insights will aid in future workforce planning and training strategies to optimise stress echocardiography service provision across the NHS

Changes in Coronary Disease Management Decisions in Real World Practice between 2015 and 2023: Insights from the Evarest/BSE-NSTEP observational study

Aims To assess the real world impact of updated clinical guidelines and literature on the management of patients undergoing stress echocardiography for the assessment of inducible ischaemia across a national health service. Methods and Results A total of 13,819 patients from 32 UK hospitals, referred for stress echocardiography between 2015-2023, were analysed across two phases: phase 1 (2015-2020) and phase 2 (2020-2023). Follow-up data for one year was available for 4,920 participants through NHS Digital. Patients in phase 2 were younger, and presented with a higher cardiovascular risk profile, although sex distribution remained similar across phases. There was an observed reduction in invasive angiography referrals within one year following a positive stress echocardiogram (p<0.01), which appeared to be attributed to changes in management of patients with moderate ischaemia (3-4 segments; p<0.01). For those who did receive invasive assessment, there were no changes in intervention rate (p=0.27), regardless of ischaemic burden. This trend was most evident in centres performing a higher volume of stress echocardiograms. Conclusion Coronary disease management pathways have changed within the UK and fewer patients with moderate ischaemia are undergoing invasive coronary angiography. However, coronary intervention rates are unchanged, suggesting stress echocardiography is being used to improve patient selection for invasive procedures, while minimising unnecessary referrals. Future work will assess if this reduction in angiography referrals is maintained long term, and if there are any effects on patient outcomes

An Overview of Three Promising Mechanical, Optical, and Biochemical Engineering Approaches to Improve Selective Photothermolysis of Refractory Port Wine Stains

During the last three decades, several laser systems, ancillary technologies, and treatment modalities have been developed for the treatment of port wine stains (PWSs). However, approximately half of the PWS patient population responds suboptimally to laser treatment. Consequently, novel treatment modalities and therapeutic techniques/strategies are required to improve PWS treatment efficacy. This overview therefore focuses on three distinct experimental approaches for the optimization of PWS laser treatment. The approaches are addressed from the perspective of mechanical engineering (the use of local hypobaric pressure to induce vasodilation in the laser-irradiated dermal microcirculation), optical engineering (laser-speckle imaging of post-treatment flow in laser-treated PWS skin), and biochemical engineering (light- and heat-activatable liposomal drug delivery systems to enhance the extent of post-irradiation vascular occlusion)