Pathway-centric analysis of microbial metabolic potential and expression along nutrient and energy gradients in the western Atlantic Ocean

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Cavaco, M. A., Bhatia, M. P., Hawley, A. K., Torres-Beltran, M., Johnson, W. M., Longnecker, K., Konwar, K., Kujawinski, E. B., & Hallam, S. J. Pathway-centric analysis of microbial metabolic potential and expression along nutrient and energy gradients in the western Atlantic Ocean. Frontiers in Marine Science, 9, (2022): 867310, https://doi.org/10.3389/fmars.2022.867310.Microbial communities play integral roles in driving nutrient and energy transformations in the ocean, collectively contributing to fundamental biogeochemical cycles. Although it is well known that these communities are stratified within the water column, there remains limited knowledge of how metabolic pathways are distributed and expressed. Here, we investigate pathway distribution and expression patterns from surface (5 m) to deep dark ocean (4000 m) at three stations along a 2765 km transect in the western South Atlantic Ocean. This study is based on new data, consisting of 43 samples for 16S rRNA gene sequencing, 20 samples for metagenomics and 19 samples for metatranscriptomics. Consistent with previous observations, we observed vertical zonation of microbial community structure largely partitioned between light and dark ocean waters. The metabolic pathways inferred from genomic sequence information and gene expression stratified with depth. For example, expression of photosynthetic pathways increased in sunlit waters. Conversely, expression of pathways related to carbon conversion processes, particularly those involving recalcitrant and organic carbon degradation pathways (i.e., oxidation of formaldehyde) increased in dark ocean waters. We also observed correlations between indicator taxa for specific depths with the selective expression of metabolic pathways. For example, SAR202, prevalent in deep waters, was strongly correlated with expression of the methanol oxidation pathway. From a biogeographic perspective, microbial communities along the transect encoded similar metabolic potential with some latitudinal stratification in gene expression. For example, at a station influenced by input from the Amazon River, expression of pathways related to oxidative stress was increased. Finally, when pairing distinct correlations between specific particulate metabolites (e.g., DMSP, AMP and MTA) and both the taxonomic microbial community and metatranscriptomic pathways across depth and space, we were able to observe how changes in the marine metabolite pool may be influenced by microbial function and vice versa. Taken together, these results indicate that marine microbial communities encode a core repertoire of widely distributed metabolic pathways that are differentially regulated along nutrient and energy gradients. Such pathway distribution patterns are consistent with robustness in microbial food webs and indicate a high degree of functional redundancy.This work was funded by the NSF Division of Ocean Sciences (Grant no. OCE-1154320 to EK and KL) and a small (“Microbial controls on marine organic carbon cycling”) and large (“Marine microbial communities from the Southern Atlantic Ocean transect to study dissolved organic matter and carbon cycling”) community sequencing grants from the Joint Genome Institute (US Department of Energy, Walnut Creek, CA) to SH and MB. MB was supported by an NSERC post-doctoral fellowship and a CIFAR Global Scholars fellowship. MC was supported by a Campus Alberta Innovates Program (CAIP) chair to MB

The “Connection” Between HIV Drug Resistance and RNase H

Currently, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) are two classes of antiretroviral agents that are approved for treatment of HIV-1 infection. Since both NRTIs and NNRTIs target the polymerase (pol) domain of reverse transcriptase (RT), most genotypic analysis for drug resistance is limited to the first ∼300 amino acids of RT. However, recent studies have demonstrated that mutations in the C-terminal domain of RT, specifically the connection subdomain and RNase H domain, can also increase resistance to both NRTIs and NNRTIs. In this review we will present the potential mechanisms by which mutations in the C-terminal domain of RT influence NRTI and NNRTI susceptibility, summarize the prevalence of the mutations in these regions of RT identified to date, and discuss their importance to clinical drug resistance

Screen-based identification and validation of four new ion channels as regulators of renal ciliogenesis

©2015. To investigate the contribution of ion channels to ciliogenesis, we carried out a small interfering RNA (siRNA)-based reverse genetics screen of all ion channels in the mouse genome in murine inner medullary collecting duct kidney cells. This screen revealed four candidate ion channel genes: Kcnq1, Kcnj10, Kcnf1 and Clcn4. We show that these four ion channels localize to renal tubules, specifically to the base of primary cilia. We report that human KCNQ1 Long QT syndrome disease alleles regulate renal ciliogenesis; KCNQ1-p. R518X, -p.A178T and -p.K362R could not rescue ciliogenesis after Kcnq1-siRNA-mediated depletion in contrast to wild-type KCNQ1 and benign KCNQ1-p.R518Q, suggesting that the ion channel function of KCNQ1 regulates ciliogenesis. In contrast, we demonstrate that the ion channel function ofKCNJ10 is independent of its effect on ciliogenesis. Our data suggest that these four ion channels regulate renal ciliogenesis through the periciliary diffusion barrier or the ciliary pocket, with potential implication as genetic contributors to ciliopathy pathophysiology. The new functional roles of a subset of ion channels provide new insights into the disease pathogenesis of channelopathies, which might suggest future therapeutic approaches

Teaching Domestic Violence in the New Millennium: Intersectionality as a Framework for Social Change

This article describes an intersectional approach to teaching about domestic violence (DV), which aims to empower students as critical thinkers and agents of change by merging theory, service learning, self-reflection, and activism. Three intersectional strategies and techniques for teaching about DV are discussed: promoting difference-consciousness, complicating gender-only power frameworks, and organizing for change. The author argues that to empower future generations to end violence, educators should put intersectionality into action through their use of scholarship, teaching methods, and pedagogical authority. Finally, the benefits and challenges of intersectional pedagogy for social justice education are considered

Spatiotemporal scaling changes in gait in a progressive model of Parkinson's disease

ObjectiveGait dysfunction is one of the most difficult motor signs to treat in patients with Parkinson's disease (PD). Understanding its pathophysiology and developing more effective therapies for parkinsonian gait dysfunction will require preclinical studies that can quantitatively and objectively assess the spatial and temporal features of gait.DesignWe developed a novel system for measuring volitional, naturalistic gait patterns in non-human primates, and then applied the approach to characterize the progression of parkinsonian gait dysfunction across a sequence of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatments that allowed for intrasubject comparisons across mild, moderate, and severe stages.ResultsParkinsonian gait dysfunction was characterized across treatment levels by a slower stride speed, increased time in both the stance and swing phase of the stride cycle, and decreased cadence that progressively worsened with overall parkinsonian severity. In contrast, decreased stride length occurred most notably in the moderate to severe parkinsonian state.ConclusionThe results suggest that mild parkinsonism in the primate model of PD starts with temporal gait deficits, whereas spatial gait deficits manifest after reaching a more severe parkinsonian state overall. This study provides important context for preclinical studies in non-human primates studying the neurophysiology of and treatments for parkinsonian gait

Social contact patterns during the COVID-19 pandemic in 21 European countries - evidence from a two-year study

CoMix Europe Working Group: Daniela Paolotti, Michele Tizzani, Ciro Cattuto, Andrea Schmidt, Gerald Gredinger, Sophie Stumpfl, Joaquin Baruch, Tanya Melillo, Henrieta Hudeckova, Jana Zibolenova, Zuzana Chladna, Magdalena Rosinska, Marta Niedzwiedzka-Stadnik, Krista Fischer, Sigrid Vorobjov, Hanna Sõnajalg, Christian Althaus, Nicola Low, Martina Reichmuth, Kari Auranen, Markku Nurhonen, Goranka Petrović, Zvjezdana Lovric Makaric, Sónia Namorado, Constantino Caetano, Ana João Santos, Gergely Röst, Beatrix Oroszi, Márton Karsai, Mario Fafangel, Petra Klepac, Natalija Kranjec, Cristina Vilaplana, Jordi Casabona.Sónia Namorado, Constantino Caetano, and Ana João Santos (Department of Epidemiology, National Institute of Health Dr Ricardo Jorge, Portugal).Background: Most countries have enacted some restrictions to reduce social contacts to slow down disease transmission during the COVID-19 pandemic. For nearly two years, individuals likely also adopted new behaviours to avoid pathogen exposure based on personal circumstances. We aimed to understand the way in which different factors affect social contacts - a critical step to improving future pandemic responses. Methods: The analysis was based on repeated cross-sectional contact survey data collected in a standardized international study from 21 European countries between March 2020 and March 2022. We calculated the mean daily contacts reported using a clustered bootstrap by country and by settings (at home, at work, or in other settings). Where data were available, contact rates during the study period were compared with rates recorded prior to the pandemic. We fitted censored individual-level generalized additive mixed models to examine the effects of various factors on the number of social contacts. Results: The survey recorded 463,336 observations from 96,456 participants. In all countries where comparison data were available, contact rates over the previous two years were substantially lower than those seen prior to the pandemic (approximately from over 10 to < 5), predominantly due to fewer contacts outside the home. Government restrictions imposed immediate effect on contacts, and these effects lingered after the restrictions were lifted. Across countries, the relationships between national policy, individual perceptions, or personal circumstances determining contacts varied. Conclusions: Our study, coordinated at the regional level, provides important insights into the understanding of the factors associated with social contacts to support future infectious disease outbreak responses.The following funding sources are acknowledged as providing funding for the named authors. HPRU in Modelling & Health Economics (NIHR200908: KLMW); European Union Horizon 2020 research and innovation programme (EpiPose 101003688: AG, WJE); European Research Council under the European Union Horizon 2020 research and innovation programme (TransMID 682540: CF, PB, NH) This research was partly funded by the Global Challenges Research Fund (GCRF) project RECAP managed through RCUK and ESRC (ES/P010873/1: CIJ) NIHR (PR_OD_1017_20002: WJE) UK MRC (MC_PC_19065—Covid 19: Under standing the dynamics and drivers of the COVID-19 epidemic using real-time outbreak analytics: WJE). In Belgium, CoMix data collection in Belgium was made possible with fnancial support of Janssen Pharmaceuticals and the national public health institute of Belgium, Sciensano. In Germany, the COVIMOD project is funded by intramural funds of the Institute of Epidemiology and Social Medicine, University of Münster, and of the Institute of Medical Epidemiology, Biometry and Informatics, Martin Luther University Halle-Wittenberg, as well as by funds provided by the Robert Koch Institute, Berlin, the Helmholtz-Gemeinschaft Deutscher Forschungszentren e.V. via the HZEpiAdHoc "The Helmholtz Epidemiologic Response against the COVID-19 Pandemic" project, the Saxonian COVID-19 Research Consortium SaxoCOV (co-fnanced with tax funds on the basis of the budget passed by the Saxon state parliament), the Federal Ministry of Education and Research (BMBF) as part of the Network University Medicine (NUM) via the egePan Unimed project (funding code: 01KX2021) and the Deutsche Forschungsge meinschaft (DFG, German Research Foundation, project number 458526380)info:eu-repo/semantics/publishedVersio