The link between volcanism and plutonism in epizonal magma systems; high-precision U–Pb zircon geochronology from the Organ Mountains caldera and batholith, New Mexico

The Organ Mountains caldera and batholith expose the volcanic and epizonal plutonic record of an Eocene caldera complex. The caldera and batholith are well exposed, and extensive previous mapping and geochemical analyses have suggested a clear link between the volcanic and plutonic sections, making this an ideal location to study magmatic processes associated with caldera volcanism. Here we present high-precision thermal ionization mass spectrometry U–Pb zircon dates from throughout the caldera and batholith, and use these dates to test and improve existing petrogenetic models. The new dates indicate that Eocene volcanic and plutonic rocks in the Organ Mountains formed from ~44 to 34 Ma. The three largest caldera-related tuff units yielded weighted mean [superscript 206]Pb/[superscript 238]U dates of 36.441 ± 0.020 Ma (Cueva Tuff), 36.259 ± 0.016 Ma (Achenback Park tuff), and 36.215 ± 0.016 Ma (Squaw Mountain tuff). An alkali feldspar granite, which is chemically similar to the erupted tuffs, yielded a synchronous weighted mean [superscript 206]Pb/[superscript 238]U date of 36.259 ± 0.021 Ma. Weighted mean [superscript 206]Pb/[superscript 238]U dates from the larger volume syenitic phase of the underlying Organ Needle pluton range from 36.130 ± 0.031 to 36.071 ± 0.012 Ma, and the youngest sample is 144 ± 20 to 188 ± 20 ka younger than the Squaw Mountain and Achenback Park tuffs, respectively. Younger plutonism in the batholith continued through at least 34.051 ± 0.029 Ma. We propose that the Achenback Park tuff, Squaw Mountain tuff, alkali feldspar granite and Organ Needle pluton formed from a single, long-lived magma chamber/mush zone. Early silicic magmas generated by partial melting of the lower crust rose to form an epizonal magma chamber. Underplating of the resulting mush zone led to partial melting and generation of a high-silica alkali feldspar granite cap, which erupted to form the tuffs. The deeper parts of the chamber underwent continued recharge and crystallization for 144 ± 20 ka after the final eruption. Calculated magmatic fluxes for the Organ Needle pluton range from 0.0006 to 0.0030 km3/year, in agreement with estimates from other well-studied plutons. The petrogenetic evolution proposed here may be common to many small-volume silicic volcanic systems

Phase Change Material for Thermotherapy of Buruli Ulcer: A Prospective Observational Single Centre Proof-of-Principle Trial

Buruli ulcer is an infection of the subcutaneous tissue leading to chronic necrotizing skin ulcers. The causative pathogen, Mycobacterium ulcerans, grows best at 30°C–33°C and not above 37°C, and this property makes the application of heat a treatment option. We achieved a breakthrough in heat treatment of Buruli ulcer by employing the phase change material sodium acetate trihydrate as a heat application system for thermotherapy, which is widely used in commercial pocket heat pads. It is easy to apply, rechargeable in hot water, non-toxic and non-hazardous to the environment. Six laboratory reconfirmed patients with ulcerative Buruli lesions were included in the proof-of-principle study and treated for four to six weeks. In patients with small ulcers, wounds healed completely without further intervention. Patients with large defects had skin grafting after successful heat treatment. Heat treatment was not associated with marked increases in local inflammation or the development of ectopic lymphoid tissue. One and a half years after completion of treatment, all patients are relapse-free. The reusable phase change material–based heat application device appears perfectly suited for use in remote Buruli ulcer–endemic areas of countries with limited resources and infrastructure

Measuring Global Credibility with Application to Local Sequence Alignment

Computational biology is replete with high-dimensional (high-D) discrete prediction and inference problems, including sequence alignment, RNA structure prediction, phylogenetic inference, motif finding, prediction of pathways, and model selection problems in statistical genetics. Even though prediction and inference in these settings are uncertain, little attention has been focused on the development of global measures of uncertainty. Regardless of the procedure employed to produce a prediction, when a procedure delivers a single answer, that answer is a point estimate selected from the solution ensemble, the set of all possible solutions. For high-D discrete space, these ensembles are immense, and thus there is considerable uncertainty. We recommend the use of Bayesian credibility limits to describe this uncertainty, where a (1−α)%, 0≤α≤1, credibility limit is the minimum Hamming distance radius of a hyper-sphere containing (1−α)% of the posterior distribution. Because sequence alignment is arguably the most extensively used procedure in computational biology, we employ it here to make these general concepts more concrete. The maximum similarity estimator (i.e., the alignment that maximizes the likelihood) and the centroid estimator (i.e., the alignment that minimizes the mean Hamming distance from the posterior weighted ensemble of alignments) are used to demonstrate the application of Bayesian credibility limits to alignment estimators. Application of Bayesian credibility limits to the alignment of 20 human/rodent orthologous sequence pairs and 125 orthologous sequence pairs from six Shewanella species shows that credibility limits of the alignments of promoter sequences of these species vary widely, and that centroid alignments dependably have tighter credibility limits than traditional maximum similarity alignments

Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag

The Pr55(gag) (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA) and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs). In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release.Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol) (Gag-Pol) levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells.This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

Protective Mechanisms for Depression among Racial/Ethnic Minority Youth: Empirical Findings, Issues, and Recommendations

We (1) review empirical studies that report findings regarding putative protective mechanisms when exposed to risk of depression in African American and Hispanic adolescents; (2) identify key protective mechanisms for different risk contexts that garner empirical support; (3) synthesize the mechanisms identified as protective against depression among racial/ethnic minority adolescents; and (4) discuss improved methods for advancing understanding of resilience against depression in minority youth. The studies were selected from PsycINFO searches that met the following inclusion criteria: participants between 12 and 21 years of age, inclusions of racial/ethnic minority members, examining protection through an interaction with a risk factor, and outcome measures of depression, depressed mood, or depressive symptomatology. We found 39 eligible studies; 13 of which included multiple racial/ethnic groups. The following were supported as protective mechanisms, at least preliminarily, for at least one racial/ethnic group and in at least one risk context: employment, extracurricular activities, father–adolescent closeness, familism, maternal support, attending predominately minority schools, neighborhood composition, non-parent support, parental inductive reasoning, religiosity, self-esteem, social activities, and positive early teacher relationships. To investigate protective mechanisms more comprehensively and accurately across individual, social, and community levels of influence, we recommend incorporating multilevel modeling or multilevel growth curve analyses and large diverse samples