Gray Matter Volumes Discriminate Cognitively Impaired and Unimpaired People with HIV

BACKGROUND: Current diagnostic criteria of HIV-associated neurocognitive disorders (HAND) rely on neuropsychological assessments. The aim of this study was to evaluate if gray matter volumes (GMV) can distinguish people with HAND, neurocognitively unimpaired people with HIV (unimpaired PWH), and uninfected controls using linear discriminant analyses. METHODS: A total of 231 participants, including 110 PWH and 121 uninfected controls, completed a neuropsychological assessment and an MRI protocol. Among PWH, HAND (n = 48) and unimpaired PWH (n = 62) designations were determined using the widely accepted Frascati criteria. We then assessed the extent to which GMV, corrected for intracranial volume, could accurately distinguish the three groups using linear discriminant analysis. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, area under the curve (AUC), and accuracy were computed for each model using the classification results based on GMV compared to the neuropsychological assessment. RESULTS: The best performing model was comprised of bilaterally combined GMV and was stratified by sex. Among males, sensitivity was 85.2% (95% CI: 66.3%-95.8%), specificity was 97.0% (95% CI: 91.6%-99.4%), and the AUC was 0.91 (95% CI: 0.83-0.99). Among females, sensitivity was 100.0% (95% CI: 83.9%-100.0%), specificity was 98.8% (95% CI: 93.4%-100.0%), and the AUC was 0.99 (95% CI: 0.98-1.00). CONCLUSIONS: GMV accurately discriminated HAND from unimpaired PWH and controls. Measures of GMV may be highly sensitive to HAND, and revisions to the Frascati criteria should consider including GMV in conjunction with a neuropsychological assessment to diagnose HAND

GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment

The antileukemic agent asparaginase triggers the amino acid response (AAR) in the liver by activating the eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2). To explore the mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation and prevent liver dysfunction during continued asparaginase treatment, wild-type and Gcn2 null mice were injected once daily with asparaginase or phosphate buffered saline for up to 14 days. Asparaginase induced mRNA expression of multiple AAR genes and greatly increased circulating concentrations of the metabolic hormone fibroblast growth factor 21 (FGF21) independent of food intake. Loss of Gcn2 precluded mRNA expression and circulating levels of FGF21 and blocked mRNA expression of multiple genes regulating lipid synthesis and metabolism including Fas, Ppara, Pparg, Acadm, and Scd1 in both liver and white adipose tissue. Furthermore, rates of triglyceride export and protein expression of apolipoproteinB-100 were significantly reduced in the livers of Gcn2 null mice treated with asparaginase, providing a mechanistic basis for the increase in hepatic lipid content. Loss of AAR-regulated antioxidant defenses in Gcn2 null livers was signified by reduced Gpx1 gene expression alongside increased lipid peroxidation. Substantial reductions in antithrombin III hepatic expression and activity in the blood of asparaginase-treated Gcn2 null mice indicated liver dysfunction. These results suggest that the ability of the liver to adapt to prolonged asparaginase treatment is influenced by GCN2-directed regulation of FGF21 and oxidative defenses, which, when lost, corresponds with maladaptive effects on lipid metabolism and hemostasis

The Atacama Cosmology Telescope: Cosmological parameters from three seasons of data

We present constraints on cosmological and astrophysical parameters from high-resolution microwave background maps at 148 GHz and 218 GHz made by the Atacama Cosmology Telescope (ACT) in three seasons of observations from 2008 to 2010. A model of primary cosmological and secondary foreground parameters is fit to the map power spectra and lensing deflection power spectrum, including contributions from both the thermal Sunyaev-Zeldovich (tSZ) effect and the kinematic Sunyaev-Zeldovich (kSZ) effect, Poisson and correlated anisotropy from unresolved infrared sources, radio sources, and the correlation between the tSZ effect and infrared sources. The power ell^2 C_ell/2pi of the thermal SZ power spectrum at 148 GHz is measured to be 3.4 +\- 1.4 muK^2 at ell=3000, while the corresponding amplitude of the kinematic SZ power spectrum has a 95% confidence level upper limit of 8.6 muK^2. Combining ACT power spectra with the WMAP 7-year temperature and polarization power spectra, we find excellent consistency with the LCDM model. We constrain the number of effective relativistic degrees of freedom in the early universe to be Neff=2.79 +\- 0.56, in agreement with the canonical value of Neff=3.046 for three massless neutrinos. We constrain the sum of the neutrino masses to be Sigma m_nu < 0.39 eV at 95% confidence when combining ACT and WMAP 7-year data with BAO and Hubble constant measurements. We constrain the amount of primordial helium to be Yp = 0.225 +\- 0.034, and measure no variation in the fine structure constant alpha since recombination, with alpha/alpha0 = 1.004 +/- 0.005. We also find no evidence for any running of the scalar spectral index, dns/dlnk = -0.004 +\- 0.012.Comment: 26 pages, 22 figures. This paper is a companion to Das et al. (2013) and Dunkley et al. (2013). Matches published JCAP versio

Global online trade in primates for pets

The trade in primates as pets is a global enterprise and as access to the Internet has increased, so too has the trade of live primates online. While quantifying primate trade in physical markets is relatively straightforward, limited insights have been made into trade via the Internet. Here we followed a three-pronged approach to estimate the prevalence and ease of purchasing primates online in countries with different socioeconomic characteristics. We first conducted a literature review, in which we found that Malaysia, Thailand, the USA, Ukraine, South Africa, and Russia stood out in terms of the number of primate individuals being offered for sale as pets in the online trade. Then, we assessed the perceived ease of purchasing pet primates online in 77 countries, for which we found a positive relationship with the Internet Penetration Rate, total human population and Human Development Index, but not to Gross Domestic Product per capita or corruption levels of the countries. Using these results, we then predicted the levels of online primate trade in countries for which we did not have first-hand data. From this we created a global map of potential prevalence of primate trade online. Finally, we analysed price data of the two primate taxa most consistently offered for sale, marmosets and capuchins. We found that prices increased with the ease of purchasing primates online and the Gross Domestic Product per capita. This overview provides insight into the nature and intricacies of the online primate pet trade and advocates for increased trade regulation and monitoring in both primate range and non-range countries where trade has been substantially reported. © 2023 The Author

Nitrogen Fixation in Mesoscale Eddies of the North Pacific Subtropical Gyre: Patterns and Mechanisms

Mesoscale eddies have been shown to support elevated dinitrogen (N2) fixation rates (NFRs) and abundances of N2-fixing microorganisms (diazotrophs), but the mechanisms underlying these observations are not well understood. We sampled two pairs of mesoscale cyclones and anticyclones in the North Pacific Subtropical Gyre in 2017 and 2018 and compared our observations with seasonal patterns from the Hawaii Ocean Time-series (HOT) program. Consistent with previous reports, we found that NFRs were anomalously high for this region (up to 3.7-fold above previous monthly HOT observations) in the centers of both sampled anticyclones. In 2017, these elevated rates coincided with high concentrations of the diazotroph Crocosphaera. We then coupled our field-based observations, together with transcriptomic analyses of nutrient stress marker genes and ecological models, to evaluate the role of biological (via estimates of growth and grazing rates) and physical controls on populations of Crocosphaera, Trichodesmium, and diatom symbionts at the mesoscale. Our results suggest that increased Crocosphaera abundances in the 2017 anticyclone resulted from the alleviation of phosphate limitation, allowing cells to grow at rates exceeding grazing losses. In contrast, distributions of larger, buoyant taxa (Trichodesmium and diatom symbionts) appeared less affected by eddy-driven biological controls. Instead, they appeared driven by physical dynamics along frontal boundaries that separate cyclonic and anticyclonic eddies. No examined controls were able to explain our 2018 findings of higher NFRs in the anticyclone. A generalized explanation of elevated NFRs in mesoscale eddies remains challenging due to the interplay of eddy-driven bottom-up, top-down, and physical control mechanisms.This work was funded by the Simons Foundation (Award # 721252 to DMK, 721256 to AEW, 721223 to EFD, 721221 to MJC, 721244 to EVA, 721225 to STD, 329108 to SJ, and 724220 to JPZ) and expedition funding from the Schmidt Ocean Institute for R/V Falkor Cruise FK180310 in 2018.Peer reviewe

Data from a pre-publication independent replication initiative examining ten moral judgement effects

We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires. Results revealed a mix of reliable, unreliable, and culturally moderated findings. Unlike any previous replication project, this dataset includes the data from not only the replications but also from the original studies, creating a unique corpus that researchers can use to better understand reproducibility and irreproducibility in science

The pipeline project: Pre-publication independent replications of a single laboratory's research pipeline

This crowdsourced project introduces a collaborative approach to improving the reproducibility of scientific research, in which findings are replicated in qualified independent laboratories before (rather than after) they are published. Our goal is to establish a non-adversarial replication process with highly informative final results. To illustrate the Pre-Publication Independent Replication (PPIR) approach, 25 research groups conducted replications of all ten moral judgment effects which the last author and his collaborators had “in the pipeline” as of August 2014. Six findings replicated according to all replication criteria, one finding replicated but with a significantly smaller effect size than the original, one finding replicated consistently in the original culture but not outside of it, and two findings failed to find support. In total, 40% of the original findings failed at least one major replication criterion. Potential ways to implement and incentivize pre-publication independent replication on a large scale are discussed

A Computational Investigation on the Connection between Dynamics Properties of Ribosomal Proteins and Ribosome Assembly

Assembly of the ribosome from its protein and RNA constituents has been studied extensively over the past 50 years, and experimental evidence suggests that prokaryotic ribosomal proteins undergo conformational changes during assembly. However, to date, no studies have attempted to elucidate these conformational changes. The present work utilizes computational methods to analyze protein dynamics and to investigate the linkage between dynamics and binding of these proteins during the assembly of the ribosome. Ribosomal proteins are known to be positively charged and we find the percentage of positive residues in r-proteins to be about twice that of the average protein: Lys+Arg is 18.7% for E. coli and 21.2% for T. thermophilus. Also, positive residues constitute a large proportion of RNA contacting residues: 39% for E. coli and 46% for T. thermophilus. This affirms the known importance of charge-charge interactions in the assembly of the ribosome. We studied the dynamics of three primary proteins from E. coli and T. thermophilus 30S subunits that bind early in the assembly (S15, S17, and S20) with atomic molecular dynamic simulations, followed by a study of all r-proteins using elastic network models. Molecular dynamics simulations show that solvent-exposed proteins (S15 and S17) tend to adopt more stable solution conformations than an RNA-embedded protein (S20). We also find protein residues that contact the 16S rRNA are generally more mobile in comparison with the other residues. This is because there is a larger proportion of contacting residues located in flexible loop regions. By the use of elastic network models, which are computationally more efficient, we show that this trend holds for most of the 30S r-proteins

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe