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1.
Adv Microb Physiol ; 84: 51-82, 2024.
Article in English | MEDLINE | ID: mdl-38821634

ABSTRACT

Formic acid (HCOOH) and dihydrogen (H2) are characteristic products of enterobacterial mixed-acid fermentation, with H2 generation increasing in conjunction with a decrease in extracellular pH. Formate and acetyl-CoA are generated by radical-based and coenzyme A-dependent cleavage of pyruvate catalysed by pyruvate formate-lyase (PflB). Formate is also the source of H2, which is generated along with carbon dioxide through the action of the membrane-associated, cytoplasmically-oriented formate hydrogenlyase (FHL-1) complex. Synthesis of the FHL-1 complex is completely dependent on the cytoplasmic accumulation of formate. Consequently, formate determines its own disproportionation into H2 and CO2 by the FHL-1 complex. Cytoplasmic formate levels are controlled by FocA, a pentameric channel that translocates formic acid/formate bidirectionally between the cytoplasm and periplasm. Each protomer of FocA has a narrow hydrophobic pore through which neutral formic acid can pass. Two conserved amino acid residues, a histidine and a threonine, at the center of the pore control directionality of translocation. The histidine residue is essential for pH-dependent influx of formic acid. Studies with the formate analogue hypophosphite and amino acid variants of FocA suggest that the mechanisms of formic acid efflux and influx differ. Indeed, current data suggest, depending on extracellular formate levels, two separate uptake mechanisms exist, both likely contributing to maintain pH homeostasis. Bidirectional formate/formic acid translocation is dependent on PflB and influx requires an active FHL-1 complex. This review describes the coupling of formate and H2 production in enterobacteria.


Subject(s)
Enterobacteriaceae , Fermentation , Formates , Hydrogen , Formates/metabolism , Hydrogen/metabolism , Enterobacteriaceae/metabolism , Enterobacteriaceae/genetics , Enterobacteriaceae/enzymology , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Formate Dehydrogenases , Hydrogenase , Multienzyme Complexes
3.
J Am Med Inform Assoc ; 30(7): 1293-1300, 2023 06 20.
Article in English | MEDLINE | ID: mdl-37192819

ABSTRACT

Research increasingly relies on interrogating large-scale data resources. The NIH National Heart, Lung, and Blood Institute developed the NHLBI BioData CatalystⓇ (BDC), a community-driven ecosystem where researchers, including bench and clinical scientists, statisticians, and algorithm developers, find, access, share, store, and compute on large-scale datasets. This ecosystem provides secure, cloud-based workspaces, user authentication and authorization, search, tools and workflows, applications, and new innovative features to address community needs, including exploratory data analysis, genomic and imaging tools, tools for reproducibility, and improved interoperability with other NIH data science platforms. BDC offers straightforward access to large-scale datasets and computational resources that support precision medicine for heart, lung, blood, and sleep conditions, leveraging separately developed and managed platforms to maximize flexibility based on researcher needs, expertise, and backgrounds. Through the NHLBI BioData Catalyst Fellows Program, BDC facilitates scientific discoveries and technological advances. BDC also facilitated accelerated research on the coronavirus disease-2019 (COVID-19) pandemic.


Subject(s)
COVID-19 , Cloud Computing , Humans , Ecosystem , Reproducibility of Results , Lung , Software
4.
PLoS One ; 9(8): e104798, 2014.
Article in English | MEDLINE | ID: mdl-25165807

ABSTRACT

We analyze data sharing practices of astronomers over the past fifteen years. An analysis of URL links embedded in papers published by the American Astronomical Society reveals that the total number of links included in the literature rose dramatically from 1997 until 2005, when it leveled off at around 1500 per year. The analysis also shows that the availability of linked material decays with time: in 2011, 44% of links published a decade earlier, in 2001, were broken. A rough analysis of link types reveals that links to data hosted on astronomers' personal websites become unreachable much faster than links to datasets on curated institutional sites. To gauge astronomers' current data sharing practices and preferences further, we performed in-depth interviews with 12 scientists and online surveys with 173 scientists, all at a large astrophysical research institute in the United States: the Harvard-Smithsonian Center for Astrophysics, in Cambridge, MA. Both the in-depth interviews and the online survey indicate that, in principle, there is no philosophical objection to data-sharing among astronomers at this institution. Key reasons that more data are not presently shared more efficiently in astronomy include: the difficulty of sharing large data sets; over reliance on non-robust, non-reproducible mechanisms for sharing data (e.g. emailing it); unfamiliarity with options that make data-sharing easier (faster) and/or more robust; and, lastly, a sense that other researchers would not want the data to be shared. We conclude with a short discussion of a new effort to implement an easy-to-use, robust, system for data sharing in astronomy, at theastrodata.org, and we analyze the uptake of that system to-date.


Subject(s)
Astronomy/methods , Datasets as Topic , Information Dissemination/methods , Humans , Qualitative Research , United States
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