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  <front>
    <journal-meta>
      <journal-title-group>
        <journal-title>Cosmological and Astrobiological Review</journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0000-0000</issn>
      <issn pub-type="epub">0000-0000</issn>
      <publisher>
        <publisher-name>SAPCRAA</publisher-name>
        <publisher-loc>Banja Luka, Bosnia and Herzegovina</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">1513</article-id>
      <article-id pub-id-type="doi">https://doi.org/10.65932/CAR-2023-1-2</article-id>
      <title-group>
        <article-title>Cryo-electron tomography in native cells: atomic resolution in context</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Cardoso</surname>
            <given-names>Juliana Barbosa</given-names>
          </name>
          <contrib-id contrib-id-type="orcid">https://orcid.org/0009-0003-0316-7930</contrib-id>
        </contrib>
      </contrib-group>
      <pub-date pub-type="epub">
        <day>30</day>
        <month>12</month>
        <year>2023</year>
      </pub-date>
      <volume>1</volume>
      <issue>1</issue>
      <fpage>23</fpage>
      <lpage>35</lpage>
      <self-uri xlink:href="https://www.sapcraa.com/article-preview/1513"/>
      <abstract>
        <p>Between 2016 and 2022, cryo-electron tomography (cryo-ET) underwent a generational transition from a method that produced informative but resolution-limited images of vitrified cells to one that produced, on a growing subset of targets, atomic-resolution structures inside intact bacterial and eukaryotic cells without recourse to purification. The transition was the consequence of four converging technical developments: routine cryo-focused-ion-beam (cryoFIB) milling that produced electron-transparent lamellae of 100-300 nm thickness from vitrified cells, the Volta phase plate that improved low-defocus image contrast, direct-detection cameras whose dose-fractionated frames preserved high-resolution information, and a suite of imageprocessing developments (Warp, M, emClarity, AreTomo, SPHIRE-crYOLO) that enabled tiltseries alignment, subtomogram averaging and multi-particle refinement at sub-nanometer resolutions. The cumulative empirical demonstration that ribosomes inside intact bacterial cells can be resolved to 3.5 Å — the Tegunov-Xue-Cramer-Mahamid 2021 multi-particle-M result — established that the field&apos;s long-standing goal of “atomic resolution in context” was achievable, not merely aspirational. The accelerating pace of in situ structural studies has, however, made cross-study comparison increasingly difficult: the relevant figure of merit is not resolution alone, but resolution-in-context, and no single metric currently captures the tradeoff between achievable resolution, preservation of native cellular context, and spatial localisation specificity. In this article I review the technical landscape of in situ cryo-ET from 2016 to 2022 and propose, as the original contribution, the In Situ Resolution-in-Context Index (IRiCI) — a single normalised composite metric, bounded on [0,1], that integrates five performance dimensions (achieved resolution, native-context preservation, spatial localisation specificity, throughput per tomogram, and intercell reproducibility) and returns a quantitative ranking of in situ cryo-ET studies on a metric explicitly designed to reward atomic resolution and intact cellular context simultaneously. Applied to ten landmark studies from the 2016-2022 window, IRiCI returns a ranking that identifies the Tegunov et al. (2021) in-cell ribosome-antibiotic structure and the Allegretti et al. (2020) in-cell nuclear pore complex study as the joint leaders, with the Mahamid et al. (2016) nuclear-periphery work as the foundational precursor.</p>
      </abstract>
      <kwd-group kwd-group-type="author">
        <kwd>krio-elektronska tomografija</kwd>
        <kwd>cryo-FIB glodanje</kwd>
        <kwd>prosjek subtomograma</kwd>
        <kwd>in situ strukturna biologija</kwd>
        <kwd>atomska rezolucija</kwd>
        <kwd>Volta fazna ploča</kwd>
        <kwd>nuklearni kompleks pora</kwd>
        <kwd>ribosom</kwd>
        <kwd>Warp/M softver</kwd>
        <kwd>nativni ćelijski kontekst</kwd>
      </kwd-group>
    </article-meta>
  </front>
</article>
