eLife

Latest preprint reviews

1. Zebrafish Rif1 impacts zygotic genome activation, replication timing, and sex determination

   This article has 6 authors:

   1. Emily A. Masser
   2. Tyler D. Noble
   3. Joseph C. Siefert
   4. Duane Goins
   5. Courtney G. Sansam
   6. Christopher L. Sansam

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This paper reports on the role of RIF1 during early stages of zebrafish embryonic development, with the important finding that Rif1 seems to be required predominantly to establish the correct embryonic transcriptional program first, followed by a switch to a more replication-timing centered later function. The evidence is convincing, with the major strength being the elegant system and the possibility to also address the problem of the maternal pool of Rif1. A weakness is that the study remains descriptive and the presentation slightly disconnected, with limited mechanistic insight. The work will be of interest for researchers both in the transcription and the replication field, especially for scientists investigating the interplay between the two processes.

   Reviewed by eLife

2. DHODH inhibition enhances the efficacy of immune checkpoint blockade by increasing cancer cell antigen presentation

   This article has 16 authors:

   1. Nicholas J Mullen
   2. Surendra K Shukla
   3. Ravi Thakur
   4. Sai Sundeep Kollala
   5. Dezhen Wang
   6. Nina Chaika
   7. Juan F Santana
   8. William R Miklavcic
   9. Drew A LaBreck
   10. Jayapal Reddy Mallareddy
   11. David H Price
   12. Amarnath Natarajan
   13. Kamiya Mehla
   14. David B Sykes
   15. Michael A Hollingsworth
   16. Pankaj K Singh

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This important study reports a novel mechanism linking DHODH inhibition and subsequent pyrimidine nucleotide depletion with upregulation of cell surface MHC I in cancer cells. The in vitro mechanistic data are compelling, with rigorous methodology and validation across multiple cell lines. The authors also provide in vivo evidence for additive effects of DHODH inhibitors and immune checkpoint blockade. However, the in vivo assessments of the functional relevance of this mechanism remain incomplete, requiring additional analyses to fully substantiate the conclusions made.

   Reviewed by eLife

3. Structure of the connexin-43 gap junction channel in a putative closed state

   This article has 12 authors:

   1. Chao Qi
   2. Silvia Acosta Gutierrez
   3. Pia Lavriha
   4. Alaa Othman
   5. Diego Lopez-Pigozzi
   6. Erva Bayraktar
   7. Dina Schuster
   8. Paola Picotti
   9. Nicola Zamboni
   10. Mario Bortolozzi
   11. Francesco Luigi Gervasio
   12. Volodymyr M Korkhov

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     Gap junctions, formed from connexins, are important in cell communication, allowing ions and small molecules to move directly between cells. By determining the Cryo EM structure of the structure of connexin 43 in a putative closed state involving lipids, the study makes an important contribution to the development of a mechanistic model for connexin activation. The connexin 43 structure is solid and its presentation will appeal to the channel and membrane protein communities.

   Reviewed by eLife

4. Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain

   This article has 12 authors:

   1. Noah J Harris
   2. Meredith L Jenkins
   3. Sung-Eun Nam
   4. Manoj K Rathinaswamy
   5. Matthew AH Parson
   6. Harish Ranga-Prasad
   7. Udit Dalwadi
   8. Brandon E Moeller
   9. Eleanor Sheeky
   10. Scott D Hansen
   11. Calvin K Yip
   12. John E Burke

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This study presents fundamental new insight into the regulatory apparatus of PI3Kγ, a kinase in signaling pathways that control the immune response and cancer. A suite of biophysical and biochemical approaches provide convincing evidence for new sites of allosteric control over enzyme activity. The rigorous findings provide structure and dynamic information that may be exploited in efforts to control PI3Kγ activity in a therapeutic setting.

   Reviewed by eLife

5. Atlas of Plasmodium falciparum intraerythrocytic development using expansion microscopy

   This article has 9 authors:

   1. Benjamin Liffner
   2. Ana Karla Cepeda Diaz
   3. James Blauwkamp
   4. David Anaguano
   5. Sonja Frolich
   6. Vasant Muralidharan
   7. Danny W Wilson
   8. Jeffrey D Dvorin
   9. Sabrina Absalon

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This important study provides an unprecedented overview of the subcellular organization of proliferative blood stage malaria parasites using expansion microscopy. The localization of multiple parasite organelles is comprehensively probed using three-dimensional super-resolution microscopy throughout the entire intraerythrocytic development cycle. This work provides a compelling framework to investigate in future more deeply the unconventional cell biology of malaria-causing parasites.

   Reviewed by eLife, preLights, Life Science Editors

6. Spatial chromatin accessibility sequencing resolves high-order spatial interactions of epigenomic markers

   This article has 17 authors:

   1. Yeming Xie
   2. Fengying Ruan
   3. Yaning Li
   4. Meng Luo
   5. Chen Zhang
   6. Zhichao Chen
   7. Zhe Xie
   8. Zhe Weng
   9. Weitian Chen
   10. Wenfang Chen
   11. Yitong Fang
   12. Yuxin Sun
   13. Mei Guo
   14. Juan Wang
   15. Shouping Xu
   16. Hongqi Wang
   17. Chong Tang

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This paper reports the development of SCA-seq, a new method derived from PORE-C for simultaneously measuring chromatin accessibility, genome 3D and CpG DNA methylation. Most of the conclusions are supported by convincing data. SCA-seq has the potential to become a useful tool to the scientific communities to interrogate genome structure-function relationships.

   Reviewed by eLife

7. Cancers adapt to their mutational load by buffering protein misfolding stress

   This article has 4 authors:

   1. Susanne Tilk
   2. Judith Frydman
   3. Christina Curtis
   4. Dmitri A Petrov

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     Tilk and colleagues present a computational analysis of tumor transcriptomes to investigate the hypothesis that the large number of somatic mutations in some tumors is detrimental such that these detrimental effects are mitigated by an up-regulation by pathways and mechanisms that prevent protein misfolding. The authors address this question by fitting a model that explains the log expression of a gene as a linear function of the log number of mutations in the tumor and show that specific categories of genes (proteasome, chaperones, ...) tend to be upregulated in tumors with a large number of somatic mutations. Some of the associations presented could arise through confounding, but overall the authors present solid evidence that mutational load is associated with higher expression of genes involved in mitigation of protein misfolding – an important finding with general implications for our understanding of cancer evolution.

   Reviewed by eLife

8. High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen

   This article has 9 authors:

   1. Wan-ping Yang
   2. Mei-qi Li
   3. Jie Ding
   4. Jia-yan Li
   5. Gang Wu
   6. Bao Liu
   7. Yu-qi Gao
   8. Guo-hua Wang
   9. Qian-qian Luo

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This useful study reports that a week or more of hypoxia exposure in mice increases erythropoiesis and decreases the number of iron-recycling macrophages in the spleen, compromising their capacity for red blood cell phagocytosis – reflected by increased mature erythrocyte retention in the spleen. Compared to an earlier version, the study has been strengthened with mouse experiments under hypobaric hypoxia and complemented by extensive ex vivo analyses. Unfortunately, while some of the evidence is solid, the work as it currently stands only incompletely supports the authors' hypotheses. While the study would benefit from additional experiments that more directly buttress the central claims, it should be of interest to the fields of hemopoiesis and bone marrow biology and possibly also blood cancer.

   Reviewed by eLife

9. A local ATR-dependent checkpoint pathway is activated by a site-specific replication fork block in human cells

   This article has 9 authors:

   1. Sana Ahmed-Seghir
   2. Manisha Jalan
   3. Helen E Grimsley
   4. Aman Sharma
   5. Shyam Twayana
   6. Settapong T Kosiyatrakul
   7. Christopher Thompson
   8. Carl L Schildkraut
   9. Simon N Powell

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This manuscript reports important data on the cellular response to a single site-specific replication fork block in human MCF7 cells. Compelling evidence shows the efficacy of the bacterial Tus-Ter system to stall replication forks in human cells. Fork stalling let to lasting ATR-dependent phosphorylation of histone H2AX but not of ATR itself and its downstream targets RPA and CHK1.

   Reviewed by eLife

10. Rubella virus tropism and single-cell responses in human primary tissue and microglia-containing organoids

    This article has 7 authors:

    1. Galina Popova
    2. Hanna Retallack
    3. Chang N Kim
    4. Albert Wang
    5. David Shin
    6. Joseph L DeRisi
    7. Tomasz Nowakowski

    This article has been curated by 1 group:

    • Curated by eLife

      eLife assessment

      The manuscript represents an important study on the pathogenesis of rubella virus tropism and neuropathology in human microglia-containing human stem cell derived organoids and human fetal brain slices. The strength of evidence is compelling, employing two different human-relevant models. The findings will be of broad interest to virologists and infectious disease experts, as well as neurodevelopmental biologists. The findings could also be of interest to pediatrics and obstetrics clinical colleagues.

    Reviewed by eLife