ALBERT

Description: Tuberculosis (TB) remains the single biggest infectious cause of death globally, claiming almost two million lives and causing disease in over 10 million individuals annually. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes with various physiological roles implicated as key factors contributing to the spread of TB. They are involved in the breakdown of lung extracellular matrix and the consequent release of Mycobacterium tuberculosis bacilli into the airways. Evidence demonstrates that MMPs also play a role in central nervous system (CNS) tuberculosis, as they contribute to the breakdown of the blood brain barrier and are associated with poor outcome in adults with tuberculous meningitis (TBM). However, in pediatric TBM, data indicate that MMPs may play a role in both pathology and recovery of the developing brain. MMPs also have a significant role in HIV-TB-associated immune reconstitution inflammatory syndrome in the lungs and the brain, and their modulation offers potential novel therapeutic avenues. This is a review of recent research on MMPs in pulmonary and CNS TB in adults and children and in the context of co-infection with HIV. We summarize different methods of MMP investigation and discuss the translational implications of MMP inhibition to reduce immunopathology.

Description: The Bingham Canyon porphyry deposit is one of the world’s largest Cu-Mo-Au resources. Elevated concentrations of thallium (Tl) compared to average continental crust have been found in some brecciated and igneous samples in this area, which likely result from mobilization of Tl by relatively low temperature hydrothermal fluids. The Tl-enrichment at Bingham Canyon therefore provides an opportunity to investigate if Tl isotope ratios reflect hydrothermal enrichment and whether there are systematic Tl isotope fractionations that could provide an exploration tool. We present a reconnaissance study of nineteen samples spanning a range of lithologies from the Bingham district which were analysed for their Tl content and Tl isotope ratios, reported as parts per ten thousand (ε205Tl) relative to the NIST SRM997 international standard. The range of ε205Tl reported in this study (−16.4 to +7.2) is the largest observed in a hydrothermal ore deposit to date. Unbrecciated samples collected relatively proximal to the Bingham Canyon porphyry system have ε205Tl of −4.2 to +0.9, similar to observations in a previous study of porphyry deposits. This relatively narrow range suggests that high-temperature (〉300 °C) hydrothermal alteration does not result in significant Tl isotope fractionation. However, two samples ~3–4 km away from Bingham Canyon have higher ε205Tl values (+1.3 and +7.2), and samples from more distal (~7 km) disseminated gold deposits at Melco and Barneys Canyon display an even wider range in ε205Tl (−16.4 to +6.0). The observation of large positive and negative excursions in ε205Tl relative to the mantle value (ε205Tl = −2.0 ± 1.0) contrasts with previous investigations of hydrothermal systems. Samples displaying the most extreme positive and negative ε205Tl values also contain elevated concentrations of Tl-Sb-As. Furthermore, with the exception of one sample, all of the Tl isotopic anomalies occur in hydrothermal breccia samples. This suggests that ε205Tl excursions are most extreme during the migration of low-temperature hydrothermal fluids potentially related to sediment-hosted gold mineralization. Future investigation to determine the host phase(s) for Tl in breccias displaying both chalcophile element enrichment and ε205Tl excursions can potentially provide new information about hydrothermal fluid composition and could be used to locate sites for future porphyry exploration.

Description: In the response to this pandemic, two vital, but controversial ethical questions are we should allocate ventilators to patients with severe respiratory failure, and how we should distribute vaccines to people at risk of contracting coronavirus. There There are opposing ethical views about how to prioritise, and countries have taken different different differentdifferentapproaches. There There is a strong ethical argument that policies should take a pluralistic approach to allocation that reflectsreflects reflectsreflectsreflectsmultiple ethical values - both because of the diversity of viewpoints within communities and the recognition that there are competing relevant ethical values. In this chapter, I look at the epistemic and normative problems raised by pluralistic allocation in this pandemic and suggest implications for future pandemics. I summarise some of the relevant evidence about the public’s views and values relating to prioritisation. I also explore some practical approaches to prioritisation of scarce resources in the face of contrasting and competing ethical values

Description: The COVID-19 pandemic has been a defining defining event of the 21st century. Global estimates of excess mortality indicate that it has taken fifteen fifteen million lives over 2020-21 (Knutson et al. 2022). It has closed national borders, put whole populations into quarantine and devastated economies. Almost half of workers in low or middle income countries lost a job or business due to the pandemic (Anonymous 2021). The International Monetary Fund has estimated a global loss to the world economy of US$12trillion by the end of 2021 (Bill and Melinda Gates Foundation 2020). It led to a rise in rates of extreme poverty for the first firstfirst time in 25 years, with 37 million additional people experiencing this in 2020. The pandemic toll and the cost of measures taken to combat it—both effective effectiveeffectiveeffectiveeffectiveeffective and ineffective—has ineffective—has ineffective—hasineffective—hasineffective—hasineffective—hasineffective—has ineffective—has been paid in human lives, mental and physical suffering,suffering, suffering, suffering,suffering, and economic hardship. The costs will continue to be paid by individuals and societies for decades to come. While the COVID-19 pandemic has been catastrophic, it is not unique. It is not as severe as Spanish influenza, estimated to have killed between 50-100 million people. Recent MERS and SARS epidemics were more deadly to those infected, but less contagious. Future influenza pandemics, perhaps like the hypothetical example above, undoubtedly lie ahead. We await ‘Disease X’, the World Health Organisation’s placeholder name for “a serious international epidemic … caused by a pathogen currently unknown to cause human disease.” In some ways, the COVID-19 pandemic has been a wake up-call. Children who have been home-schooled during the COVID pandemic will almost certainly face another pandemic in their lifetime – one at least as bad—and potentially much worse—than this one.

Description: This chapter examines whether and when the experience of inner speech can be inaccurate and thereby mislead the subject. It presents a view about the representational content of speech experience generally and then applies it to inner speech in particular. On such a view, speech experience typically presents us with far more than simply the low-level acoustic properties of speech: it conveys the relevant mental states of the (actual or hypothetical) speaker. Similarly, inner speech presents inner speakers with their own mental states. In light of this, inner speech can mislead either by presenting the subject with mental states they do not in fact have, or by presenting these mental states as belonging to another agent. The chapter reflects on the sorts of contexts in which either of these could occur.

Description: CerealsDB (www.cerealsdb.uk.net) is an online repository of mainly hexaploid wheat (Triticum aestivum) single nucleotide polymorphisms (SNPs) and genotyping data. The CerealsDB website has been designed to enable wheat breeders and scientists to select the appropriate markers for research breeding tasks, such as marker-assisted selection. We report a large update of genotyping information for over 6000 wheat accessions and describe new webtools for exploring and visualizing the data. We also describe a new database of quantitative trait loci that links phenotypic traits to CerealsDB SNP markers and allelic scores for each of those markers. CerealsDB is an open-access website that hosts information on wheat SNPs considered useful for both plant breeders and research scientists. The latest CerealsDB database is available at https://www.cerealsdb.uk.net/cerealgenomics/CerealsDB/indexNEW.php.

Description: Certain phosphorous solubilizing (PSB) and phosphorous mineralizing (PMB) bacteria may improve plant growth by improving nutrient availability. The aim of this work was to evaluate the effect of inoculation with two Bacillus spp. strains, 12A and 25A, on wheat seedlings growth. To this aim, a durum and a bread wheat genotype were grown under controlled conditions in a low P compost medium to evaluate: (i) the effect of the bacterial isolates on plant growth and root system architecture; (ii) the expression of two key genes indicative of the P-starvation response and phosphate (Pi) uptake, TaIPS1 and TaPHT1.6-B1. The results showed that 12A Bacillus sp. significantly increased root length, surface area and biomass. Furthermore, an enhanced shoot dry weight and P content were observed. This might be explained by the capacity of strain 12A to produce indole-3-acetic acid (IAA) in addition to P mineralizing and P solubilizing capability. No effect on plant growth was observed for 25A strain. The semi-quantitative gene expression analysis showed an overall lower expression of TaIPS1 in the inoculated plants and highest expression of TaPHT1.6-B1 in 12A inoculated plants. This suggests that Pi-responsive genes might be useful molecular indicators for the effectiveness of PSB and PMB.

Description: Dwarf spheroidal (dSph) galaxies are prime targets for present and future -ray telescopes hunting for indirect signals of particle dark matter. The interpretation of the data requires careful assessment of their dark matter content in order to derive robust constraints on candidate relic particles. Here, we use an optimized spherical Jeans analysis to reconstruct the ‘astrophysical factor’ for both annihilating and decaying dark matter in 21 known dSphs. Improvements with respect to previous works are: (i) the use of more flexible luminosity and anisotropy profiles to minimize biases, (ii) the use of weak priors tailored on extensive sets of contamination-free mock data to improve the confidence intervals, (iii) systematic cross-checks of binned and unbinned analyses on mock and real data, and (iv) the use of mock data including stellar contamination to test the impact on reconstructed signals. Our analysis provides updated values for the dark matter content of 8 ‘classical’ and 13 ‘ultrafaint’ dSphs, with the quoted uncertainties directly linked to the sample size; the more flexible parametrization we use results in changes compared to previous calculations. This translates into our ranking of potentially-brightest and most robust targets – namely Ursa Minor, Draco, Sculptor – and of the more promising, but uncertain targets – namely Ursa Major 2, Coma – for annihilating dark matter. Our analysis of Segue 1 is extremely sensitive to whether we include or exclude a few marginal member stars, making this target one of the most uncertain. Our analysis illustrates challenges that will need to be addressed when inferring the dark matter content of new ‘ultrafaint’ satellites that are beginning to be discovered in southern sky surveys.

Description: In the thermal dark matter (DM) paradigm, primordial interactions between DM and Standard Model particles are responsible for the observed DM relic density. In Bœhm et al., we showed that weak-strength interactions between DM and radiation (photons or neutrinos) can erase small-scale density fluctuations, leading to a suppression of the matter power spectrum compared to the collisionless cold DM (CDM) model. This results in fewer DM subhaloes within Milky Way-like DM haloes, implying a reduction in the abundance of satellite galaxies. Here we use very high-resolution N -body simulations to measure the dynamics of these subhaloes. We find that when interactions are included, the largest subhaloes are less concentrated than their counterparts in the collisionless CDM model and have rotation curves that match observational data, providing a new solution to the ‘too big to fail’ problem.