A westerly wind dominated Puna Plateau during deposition of upper Pleistocene loessic sediments in the subtropical Andes, South America

The Tafí del Valle depression (~27° S) in the eastern Andes of Argentina provides a record of late Pleistocene dust deposition in the subtropics of South America. We present large-n U-Pb geochronology data for detrital zircons from upper Pleistocene loess-paleosol deposits. When compared to regional data, the age spectra from the Tafí del Valle samples are most like the southern Puna Plateau, supporting derivation largely from the west and northwest. This runs counter to hypotheses suggesting these loessic sediments were derived from the low elevation plains to the east or extra-Andean Patagonia. Mapping of linear wind erosion features on the Puna Plateau yield a mean orientation of 125.7° (1 s.d. = 12.4°). These new data and existing records are consistent with a westerly-northwesterly dominated (upper- and lower-level) wind system over the southern Puna Plateau (to at least ~27° S) during periods of high dust accumulation in Tafí del Valle

Global climate forcing on late Miocene establishment of the Pampean aeolian system in South America

Abstract Wind-blown dust from southern South America links the terrestrial, marine, atmospheric, and biological components of Earth’s climate system. The Pampas of central Argentina (~33°–39° S) contain a Miocene to Holocene aeolian record that spans an important interval of global cooling. Upper Miocene sediment provenance based on n = 3299 detrital-zircon U-Pb ages is consistent with the provenance of Pleistocene–Holocene deposits, indicating the Pampas are the site of a long-lived fluvial-aeolian system that has been operating since the late Miocene. Here, we show the establishment of aeolian sedimentation in the Pampas coincided with late Miocene cooling. These findings, combined with those from the Chinese Loess Plateau (~33°–39° N) underscore: (1) the role of fluvial transport in the development and maintenance of temporally persistent mid-latitude loess provinces; and (2) a global-climate forcing mechanism behind the establishment of large mid-latitude loess provinces during the late Miocene

Rates of water exchange for two cobalt(II) heteropolyoxotungstate compounds in aqueous solution

Polyoxometalate ions are used as ligands in water-oxidation processes related to solar energy production. An important step in these reactions is the association and dissociation of water from the catalytic sites, the rates of which are unknown. Here we report the exchange rates of water ligated to Co-II atoms in two polyoxotungstate sandwich molecules using the ¹⁷O-NMR-based Swift-Connick method. The compounds were the [Co₄(H₂O)₂(B-α-PW₉O₃₄)₂]¹⁰⁻ and the larger αββα-[Co₄(H₂O)₂(P₂W₁₅O₅₆)₂]¹⁶⁻ ions, each with two water molecules bound trans to one another in a Co-II sandwich between the tungstate ligands. The clusters, in both solid and solution state, were characterized by a range of methods, including NMR, EPR, FT-IR, UV-Vis, and EXAFS spectroscopy, ESI-MS, single-crystal Xray crystallography, and potentiometry. For [Co₄(H₂O)₂(B-α-PW₉O₃₄)₂]¹⁰⁻ at pH 5.4, we estimate: k²⁹⁸ = 1.5(5) ± 0.3 x 10(6) s⁻¹, ΔH≠ = 39.8 ± 0.4 kJ mol⁻¹, ΔS≠ = + 7.1 ± 1.2 J mol⁻¹K⁻¹ and ΔV≠ = 5.6 ± 1.6 cm³mol⁻¹. For the Wells-Dawson sandwich cluster (αββα-[Co₄(H₂O)₂₋(P₂W₁₅O₅₆)₂]¹⁶⁻) at pH 5.54, we find: k²⁹⁸ = 1.6(2) ± 0.3 x 10(6)s⁻¹, ΔH≠ = 27.6 ± 0.4 kJ mol⁻¹ ΔS≠ = -33 ± 1.3 J mol⁻¹K⁻¹ and ΔV≠ = 2.2 ± 1.4 cm³mol⁻¹ at pH 5.2. The molecules are clearly stable and monospecific in slightly acidic solutions, but dissociate in strongly acidic solutions. This dissociation is detectable by EPR spectroscopy as S=3/2 Co-II species (such as the [Co(H₂O)₆]²⁺ monomer ion) and by the significant reduction of the Co-Co vector in the XAS spectra

Mapping of HIV-1C Transmission Networks Reveals Extensive Spread of Viral Lineages Across Villages in Botswana Treatment-as-Prevention Trial

Abstract Background Phylogenetic mapping of HIV-1 lineages circulating across defined geographical locations is promising for better understanding HIV transmission networks to design optimal prevention interventions. Methods We obtained near full-length HIV-1 genome sequences from people living with HIV (PLWH), including participants on antiretroviral treatment in the Botswana Combination Prevention Project, conducted in 30 Botswana communities in 2013\textendash 2018. Phylogenetic relationships among viral sequences were estimated by maximum likelihood. Results We obtained 6078 near full-length HIV-1C genome sequences from 6075 PLWH. We identified 984 phylogenetically distinct HIV-1 lineages (molecular HIV clusters) circulating in Botswana by mid-2018, with 2\textendash 27 members per cluster. Of these, dyads accounted for 62%, approximately 32% (n\hspace0.25em=\hspace0.25em316) were found in single communities, and 68% (n\hspace0.25em=\hspace0.25em668) were spread across multiple communities. Men in clusters were approximately 3 years older than women (median age 42 years, vs 39 years; P\hspace0.25em<\hspace0.25em.0001). In 65% of clusters, men were older than women, while in 35% of clusters women were older than men. The majority of identified viral lineages were spread across multiple communities. Conclusions A large number of circulating phylogenetically distinct HIV-1C lineages (molecular HIV clusters) suggests highly diversified HIV transmission networks across Botswana communities by 2018

HIV-phyloTSI: Subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data

Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining duration of infection classify samples into recent and non-recent and are unable to give more granular TSI estimates. These binary classifications have a limited recency time window of several months, therefore requiring large sample sizes, and cannot assess the cumulative impact of an intervention. We developed a Random Forest Regression model, HIV-phyloTSI, that combines measures of within-host diversity and divergence to generate TSI estimates from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performed equally well for all major HIV subtypes based on data from African and European cohorts. We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis. Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting. Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis. Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries