The core metabolome and root exudation dynamics of three phylogenetically distinct plant species

Root exudates are plant-derived, exported metabolites likely shaping root-associated microbiomes by acting as nutrients and signals. However, root exudation dynamics are unclear and thus also, if changes in exudation are reflected in changes in microbiome structure. Here, we assess commonalities and differences between exudates of different plant species, diurnal exudation dynamics, as well as the accompanying methodological aspects of exudate sampling. We find that exudates should be collected for hours rather than days as many metabolite abundances saturate over time. Plant growth in sterile, nonsterile, or sugar-supplemented environments significantly alters exudate profiles. A comparison of Arabidopsis thaliana, Brachypodium distachyon, and Medicago truncatula shoot, root, and root exudate metabolite profiles reveals clear differences between these species, but also a core metabolome for tissues and exudates. Exudate profiles also exhibit a diurnal signature. These findings add to the methodological and conceptual groundwork for future exudate studies to improve understanding of plant-microbe interactions

Global health learning outcomes in pharmacy students completing international advanced pharmacy practice experiences

© 2020, American Association of Colleges of Pharmacy. All rights reserved. Objective. To examine the global health learning outcomes of Doctor of Pharmacy (PharmD) students from three US schools who participated in international advanced pharmacy practice experiences (APPEs). Methods. A mixed-methods, prospective study was used to assess fourth-year PharmD students at three US pharmacy schools who participated in an international APPE during the 2017-2018 academic year and a matched cohort (control group) of PharmD students who did not participate in an international APPE. To evaluate students’ self-perceived growth in the Consortium of Universities for Global Health (CUGH) competencies, all students completed a 13-item retrospective pre-post instrument using a five-point Likert scale. The students who had completed an international APPE were invited to participate in a focus group (N522). Paired and independent t tests and multiple linear regression were used to analyze data. Qualitative open-ended questions and focus group data were mapped to knowledge, skills, and attitudes themes. Results. The students who completed an international APPE (N581) showed significantly more growth in CUGH competencies than students who did not (mean improvement in total score of 10.3 [7.0] vs 2.4 [6.0]). International APPE participation was the only significant predictor of growth in CUGH competencies. The international APPE students reported improvements in cultural awareness and appreciation, communication skills, problem-solving skills, adaptability, self-awareness, personal and professional outlook, and global health perspective. Conclusion. Pharmacy students’ participation in international APPEs led to significant improvement in all CUGH competencies. The CUGH competency framework appears to be a suitable instrument to assess pharmacy students’ global health learning outcomes

Global health learning outcomes by country location and duration for international experiences

© 2020 American Association of Colleges of Pharmacy. Objective. To determine the impact of country income classification and experience duration on learning outcomes for student pharmacists participating in international advanced pharmacy practice experiences (APPEs). Methods. A mixed-methods, longitudinal study evaluated 81 fourth-year student pharmacists participating in an international APPE through one of three US universities. A pre-post survey was administered to evaluate students’ self-perceived growth across 13 competencies established by the Consortium of Universities for Global Health (CUGH). The survey included four additional open-ended questions. Student pharmacists were also invited to participate in a focus group. Paired and independent t tests and multiple linear regression were conducted. Qualitative survey and focus group data underwent a two-cycle, open-coding process using conventional content analysis. Results. Students who completed their APPE in a low-to middle-income country had greater growth in all CUGH competency statements compared to those who completed their APPE in a high-income country. Completing the APPE in a low-to middle-income country and prior travel for non-vacation purposes were significant predictors of student growth. Students who went to a low-to middle-income country demonstrated increased cultural sensitivity, more patient-centered care, and skill development, while students who went to a high-income country displayed increased knowledge regarding differ-ences in health care system components, pharmacy practice, pharmacy education, and an appreciation for alternative patient care approaches. Conclusion. Learning outcomes differed between students who completed an APPE in a high-income rather than a low-to middle-income country, with both types of locations providing valuable educational opportunities and professional and personal development

Formation of ER-lumenal intermediates during export of Plasmodium proteins containing transmembrane-like hydrophobic sequences

During the blood stage of a malaria infection, malaria parasites export both soluble and membrane proteins into the erythrocytes in which they reside. Exported proteins are trafficked via the parasite endoplasmic reticulum and secretory pathway, before being exported across the parasitophorous vacuole membrane into the erythrocyte. Transport across the parasitophorous vacuole membrane requires protein unfolding, and in the case of membrane proteins, extraction from the parasite plasma membrane. We show that trafficking of the exported Plasmodium protein, Pf332, differs from that of canonical eukaryotic soluble-secreted and transmembrane proteins. Pf332 is initially ER-targeted by an internal hydrophobic sequence that unlike a signal peptide, is not proteolytically removed, and unlike a transmembrane segment, does not span the ER membrane. Rather, both termini of the hydrophobic sequence enter the ER-lumen and the ER-lumenal species is a productive intermediate for protein export. Furthermore, we show in intact cells, that two other exported membrane proteins, SBP1 and MAHRP2, assume a lumenal topology within the parasite secretory pathway. Although the addition of a C-terminal ER-retention sequence, recognised by the lumenal domain of the KDEL receptor, does not completely block export of SBP1 and MAHRP2, it does enhance their retention in the parasite ER. This indicates that a sub-population of each protein adopts an ER-lumenal state that is an intermediate in the export process. Overall, this suggests that although many exported proteins traverse the parasite secretory pathway as typical soluble or membrane proteins, some exported proteins that are ER-targeted by a transmembrane segment-like, internal, non-cleaved hydrophobic segment, do not integrate into the ER membrane, and form an ER-lumenal species that is a productive export intermediate. This represents a novel means, not seen in typical membrane proteins found in model systems, by which exported transmembrane-like proteins can be targeted and trafficked within the lumen of the secretory pathway

Your: Your Unified Reader

The advancement in signal processing and GPU based systems has enabled new transient detectors at various telescopes to perform much more sensitive searches than their predecessors. Typically the data output from the telescopes is in one of the two commonly used formats: psrfits and Sigproc filterbank. Software developed for transient searches often only works with one of these two formats, limiting their general applicability. Therefore, researchers have to write custom scripts to read/write the data in their format of choice before they can begin any data analysis relevant for their research. \textsc{Your} (Your Unified Reader) is a python-based library that unifies the data processing across multiple commonly used formats. \textsc{Your} implements a user-friendly interface to read and write in the data format of choice. It also generates unified metadata corresponding to the input data file for a quick understanding of observation parameters and provides utilities to perform common data analysis operations. \textsc{Your} also provides several state-of-the-art radio frequency interference mitigation (RFI) algorithms, which can now be used during any stage of data processing (reading, writing, etc.) to filter out artificial signals.Comment: 3 pages, Published in JOSS, Github: https://github.com/thepetabyteproject/you

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Fresolimumab Treatment Decreases Biomarkers and Improves Clinical Symptoms in Systemic Sclerosis Patients

BACKGROUND. TGF-β has potent profibrotic activity in vitro and has long been implicated in systemic sclerosis (SSc), as expression of TGF-β–regulated genes is increased in the skin and lungs of patients with SSc. Therefore, inhibition of TGF-β may benefit these patients. METHODS. Patients with early, diffuse cutaneous SSc were enrolled in an open-label trial of fresolimumab, a high-affinity neutralizing antibody that targets all 3 TGF-β isoforms. Seven patients received two 1 mg/kg doses of fresolimumab, and eight patients received one 5 mg/kg dose of fresolimumab. Serial mid-forearm skin biopsies, performed before and after treatment, were analyzed for expression of the TGF-β–regulated biomarker genes thrombospondin-1 (THBS1) and cartilage oligomeric protein (COMP) and stained for myofibroblasts. Clinical skin disease was assessed using the modified Rodnan skin score (MRSS). RESULTS. In patient skin, THBS1 expression rapidly declined after fresolimumab treatment in both groups (P = 0.0313 at 7 weeks and P = 0.0156 at 3 weeks), and skin expression of COMP exhibited a strong downward trend in both groups. Clinical skin disease dramatically and rapidly decreased (P \u3c 0.001 at all time points). Expression levels of other TGF-β–regulated genes, including SERPINE1 and CTGF, declined (P = 0.049 and P = 0.012, respectively), and a 2-gene, longitudinal pharmacodynamic biomarker of SSc skin disease decreased after fresolimumab treatment (P = 0.0067). Dermal myofibroblast infiltration also declined in patient skin after fresolimumab (P \u3c 0.05). Baseline levels of THBS1 were predictive of reduced THBS1 expression and improved MRSS after fresolimumab treatment. CONCLUSION. The rapid inhibition of TGF-β–regulated gene expression in response to fresolimumab strongly implicates TGF-β in the pathogenesis of fibrosis in SSc. Parallel improvement in the MRSS indicates that fresolimumab rapidly reverses markers of skin fibrosis

Author Correction:SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland

Population-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. We describe COVID-19 vaccine uptake and SARS-CoV-2 infection in pregnant women in Scotland, using whole-population data from a national, prospective cohort. Between the start of a COVID-19 vaccine program in Scotland, on 8 December 2020 and 31 October 2021, 25,917 COVID-19 vaccinations were given to 18,457 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of 18−44 years; 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 d of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9−38.5; pandemic background rate 5.6 per 1,000 births; 452 out of 80,456; 95% CI 5.1−6.2). Overall, 77.4% (3,833 out of 4,950; 95% CI 76.2−78.6) of SARS-CoV-2 infections, 90.9% (748 out of 823; 95% CI 88.7−92.7) of SARS-CoV-2 associated with hospital admission and 98% (102 out of 104; 95% CI 92.5−99.7) of SARS-CoV-2 associated with critical care admission, as well as all baby deaths, occurred in pregnant women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic

SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland

Population-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. We describe COVID-19 vaccine uptake and SARS-CoV-2 infection in pregnant women in Scotland, using whole-population data from a national, prospective cohort. Between the start of a COVID-19 vaccine program in Scotland, on 8 December 2020 and 31 October 2021, 25,917 COVID-19 vaccinations were given to 18,457 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of 18-44 years; 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 d of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9-38.5; pandemic background rate 5.6 per 1,000 births; 452 out of 80,456; 95% CI 5.1-6.2). Overall, 77.4% (3,833 out of 4,950; 95% CI 76.2-78.6) of SARS-CoV-2 infections, 90.9% (748 out of 823; 95% CI 88.7-92.7) of SARS-CoV-2 associated with hospital admission and 98% (102 out of 104; 95% CI 92.5-99.7) of SARS-CoV-2 associated with critical care admission, as well as all baby deaths, occurred in pregnant women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic. [Abstract copyright: © 2022. The Author(s).

Upper Palaeolithic genomes reveal deep roots of modern Eurasians.

We extend the scope of European palaeogenomics by sequencing the genomes of Late Upper Palaeolithic (13,300 years old, 1.4-fold coverage) and Mesolithic (9,700 years old, 15.4-fold) males from western Georgia in the Caucasus and a Late Upper Palaeolithic (13,700 years old, 9.5-fold) male from Switzerland. While we detect Late Palaeolithic-Mesolithic genomic continuity in both regions, we find that Caucasus hunter-gatherers (CHG) belong to a distinct ancient clade that split from western hunter-gatherers ∼45 kya, shortly after the expansion of anatomically modern humans into Europe and from the ancestors of Neolithic farmers ∼25 kya, around the Last Glacial Maximum. CHG genomes significantly contributed to the Yamnaya steppe herders who migrated into Europe ∼3,000 BC, supporting a formative Caucasus influence on this important Early Bronze age culture. CHG left their imprint on modern populations from the Caucasus and also central and south Asia possibly marking the arrival of Indo-Aryan languages.This research was supported by the European Research Council (ERC) Starting Grant to R.P. (ERC-2010-StG 263441). D.B., M.H and AM. were also supported by the ERC (295729-CodeX, 310763-GeneFlow and 647787-LocalAdaptation respectively). The National Geographic Global Exploration Fund funded fieldwork in Satsurblia Cave l from April 2013 to February 2014 (grant- GEFNE78–13). V.S. was supported by a scholarship from the Gates Cambridge Trust and M.G.L. by a BBSRC DTP studentship. C.G. was supported by the Irish Research Council for Humanities and Social Sciences (IRCHSS) ERC Support Programme and the Marie-Curie Intra-European Fellowships (FP7-IEF-328024). R.M. was funded by the BEAN project of the Marie Curie ITN (289966) and L.C. by the Irish Research Council (GOIPG/2013/1219). R.L.M. was funded by the ALS Association of America (2284) and Fondation Thierry Latran (ALSIBD). M.C. was supported by Swiss NSF grant 31003A_156853. We acknowledge Shota Rusataveli Georgian National Science Foundation as well as the DJEI/DES/SFI/HEA Irish Centre for High-End Computing (ICHEC) for the provision of computational facilities and Science Foundation Ireland (12/ERC/B2227) for provision of sequencing facilities. We thank Valeria Mattiangeli and Matthew D. Teasdale for their assistance.This is the final version of the article. It was first available from NPG via http://dx.doi.org/10.1038/ncomms991