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Motamedi, S.

Publications and source records attributed to Motamedi, S..

3 recordsLinked to original sources

Multiscale networks in multiple sclerosis

Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phosphoproteomics and cytomics), brain and retinal imaging, and clinical data, obtained from a multicenter prospective cohort of 328 patients and 90 healthy controls. Multilayer networks were constructed using mutual information, and Boolean simulations identified paths within and among all layers. The path more commonly found from the boolean simulations connects MP2K, with Th17 cells, the retinal nerve fiber layer (RNFL) thickness and the age related MS severity score (ARMSS). Combinations of several proteins (HSPB1, MP2K1, SR6, KS6B1, SRC, MK03, LCK and STAT6)) and immune cells (Th17, Th1 non-classic, CD8, CD8 Treg, CD56 neg, and B memory) were part of the paths explaining the clinical phenotype. Specific paths identified were subsequently analyzed by flow cytometry at the single-cell level. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/530153v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@7dd26org.highwire.dtl.DTLVardef@482239org.highwire.dtl.DTLVardef@1bef03borg.highwire.dtl.DTLVardef@8dc6e6_HPS_FORMAT_FIGEXP M_FIG C_FIG Author SummaryComplex diseases such as Multiple Sclerosis (MS) involve the contribution of a wide range of biological processes. We conducted a systems biology study of MS based on network analysis and deep phenotyping in a prospective cohort of patients with clinical, imaging, genetics, and omics assessments. The gene, proteins and cell paths explained variation in central nervous system damage, and in metrics of disease severity. Such multilayer paths explain the different phenotypes of the disease and can be developed as biomarkers of MS.

systems biology↗

Metabolic strategies shared by basement residents of the Lost City hydrothermal field

Alkaline fluids venting from chimneys of the Lost City hydrothermal field flow from a potentially vast microbial habitat within the seafloor where energy and organic molecules are released by chemical reactions within rocks uplifted from Earths mantle. In this study, we investigated hydrothermal fluids venting from Lost City chimneys as windows into subseafloor environments where the products of geochemical reactions, such as hydrogen (H2), formate, and methane, may be the only available sources of energy for biological activity. Our deep sequencing of metagenomes and metatranscriptomes from these hydrothermal fluids revealed a few key species of archaea and bacteria that are likely to play critical roles in the subseafloor microbial ecosystem. We identified a population of Thermodesulfovibrionales (belonging to phylum Nitrospirae) as a prevalent sulfate-reducing bacterium that may be responsible for much of the consumption of H2 and sulfate in Lost City fluids. Metagenome-assembled genomes (MAGs) classified as Methanosarcinaceae and Candidatus Bipolaricaulota were also recovered from venting fluids and represent potential methanogenic and acetogenic members of the subseafloor ecosystem. These genomes share novel hydrogenases and formate dehydrogenase-like sequences that may be unique to hydrothermal and subsurface alkaline environments where hydrogen and formate are much more abundant than carbon dioxide. The results of this study include multiple examples of metabolic strategies that appear to be advantageous in hydrothermal and subsurface environments where energy and carbon are provided by geochemical reactions. IMPORTANCEThe Lost City hydrothermal field is an iconic example of a microbial ecosystem fueled by energy and carbon from Earths mantle. Uplift of mantle rocks into the seafloor can trigger a process known as serpentinization that releases hydrogen and creates unusual environmental conditions where simple organic carbon molecules are more stable than dissolved inorganic carbon. This study provides an initial glimpse into the kinds of microbes that live deep within the seafloor where serpentinization takes place, by sampling hydrothermal fluids exiting from the Lost City chimneys. The metabolic strategies that these microbes appear to be using are also shared by microbes that inhabit other sites of serpentinization, including continental subsurface environments and natural springs. Therefore, the results of this study contribute to a broader, interdisciplinary effort to understand the general principles and mechanisms by which serpentinization-associated processes can support life on Earth and perhaps other worlds.

microbiology↗

Microbial residents of the Atlantis Massif's shallow serpentinite subsurface

The Atlantis Massif rises 4,000 m above the seafloor near the Mid-Atlantic Ridge and consists of rocks uplifted from Earths upper mantle. Exposure of the mantle rocks to seawater leads to their alteration into serpentinites. These aqueous geochemical reactions, collectively known as the process of serpentinization, are exothermic and are associated with the release of hydrogen gas (H2), methane (CH4), and small organic molecules. The biological consequences of this flux of energy and organic compounds from the Atlantis Massif were explored by International Ocean Discovery Program (IODP) Expedition 357, which used seabed drills to collect continuous sequences of shallow (<16 meters below seafloor) marine serpentinites and mafic assemblages. Here, we report the first census of microbial diversity in samples of the drill cores, as measured by environmental 16S rRNA gene amplicon sequencing. The problem of contamination of subsurface samples was a primary concern during all stages of this project, starting from the initial study design, continuing to the collection of samples from the seafloor, handling the samples shipboard and in the lab, preparing the samples for DNA extraction, and analyzing the DNA sequence data. To distinguish endemic microbial taxa of serpentinite subsurface rocks from seawater residents and other potential contaminants, the distributions of individual 16S rRNA gene sequences among all samples were evaluated, taking into consideration both presence/absence as well as relative abundances. Our results highlight a few candidate residents of the shallow serpentinite subsurface, including uncultured representatives of the Thermoplasmata, Acidobacteria, Acidimicrobiia, and Chloroflexi. ImportanceInternational Ocean Discovery Program Expedition 357: "Serpentinization and Life" utilized seabed drills for the first time to collect rocks from the oceanic crust. The recovered rock cores represent the shallow serpentinite subsurface of the Atlantis Massif, where reactions between uplifted mantle rocks and water, collectively known as serpentinization, produce environmental conditions that can stimulate biological activity and are thought to be analogous to environments that were prevalent on the early Earth and perhaps other planets. The methodology and results of this project have implications for life detection experiments, including sample return missions, and provide the first window into the diversity of microbial communities inhabiting subseafloor serpentinites.

microbiology↗