Evaluated articles

Unveiling the domain-specific and RAS isoform-specific details of BRAF kinase regulation

1. Tarah Elizabeth Trebino
2. Borna Markusic
3. Haihan Nan
4. Shrhea Banerjee
5. Zhihong Wang

• Curated by eLife

  eLife assessment

  This manuscript describes useful information on the interactions of the BRAF N-terminal regulatory regions (CRD, RBD and BSR) with the C-terminal kinase domain and with the upstream regulators HRAS and KRAS. The authors provide solid evidence that the BRAF BSR domain may negatively regulate RAS binding and propose that the presence of the BSR domain in BRAF provides an additional layer of autoinhibitory constraints. The data will be of interest for researchers in the RAS/RAF and general kinase regulation fields.

Reviewed by eLife

Ca2+ channel and active zone protein abundance intersects with input-specific synapse organization to shape functional synaptic diversity

1. Audrey T Medeiros
2. Scott J Gratz
3. Ambar Delgado
4. Jason T Ritt
5. Kate M O'Connor-Giles

• Curated by eLife

  eLife assessment

  Calcium channels are key regulators of synaptic strength and plasticity. The authors generate new endogenous tags of the Drosophila channel Cac as well as auxiliary subunits to investigate distinct calcium channel functions at the fly NMJ, Is and Ib. They demonstrate functions for voltage-gated calcium channel subunits in promoting synaptic strength, diversity, and plasticity with a series of convincing analyses. The work is important and has broad implications. In addition, the newly developed tools should be quite beneficial for fly biologists.

Reviewed by eLife

Meaning-making behavior in a small-brained hominin, Homo naledi, from the late Pleistocene: contexts and evolutionary implications

1. Agustín Fuentes
2. Marc Kissel
3. Penny Spikins
4. Keneiloe Molopyane
5. John Hawks
6. Lee R Berger

• Curated by eLife

  eLife Assessment

  This paper discusses the cognitive implications of potential intentional burial, wall engraving creation, and fire as light source use behaviors by relatively small-brained Homo naledi hominins. The discussion presented in the paper is valuable theoretically in its healthy questioning of prior assumptions concerning the socio-biological constraints of hominin meaning-making behavior. The discussion also contributes practically given that these behaviors have been ascribed to Homo naledi in two associated papers. Still, the strength of evidence in this contribution relies on the validity of the conclusions from the two associated papers, which remain actively questioned. The ultimate assessment of this work will vary among individual readers depending on how they view this debate, but if the conclusions from the associated papers hold up, the conclusions in the current paper can be considered solid.

Reviewed by eLife

An initial report of circa 241,000- to 335,000-year-old rock engravings and their relation to Homo naledi in the Rising Star cave system, South Africa

1. Lee R Berger
2. John Hawks
3. Agustín Fuentes
4. Dirk Van Rooyen
5. Mathabela Tsikoane
6. Maropeng Mpete
7. Samuel Nkwe
8. Keneiloe Molopyane

• Curated by eLife

  eLife Assessment

  This paper presents important information about potential Homo naledi-associated markings discovered on the walls of the Hill Antechamber of the Rising Star Cave system, South Africa. If confirmed, the antiquity, intentionality, and authorship of the reported markings will have profound archaeological implications, as such behaviors are otherwise widely considered to be unique to our species, Homo sapiens. This report concerns preliminary findings and as it stands the study is incomplete, with further work needed in the future to support the claims about the anthropogenic nature, age, and author of the engravings.

Reviewed by eLife

Evidence for deliberate burial of the dead by Homo naledi

1. Lee R Berger
2. Tebogo Vincent Makhubela
3. Keneiloe Molopyane
4. Ashley Krüger
5. Patrick Randolph-Quinney
6. Marina Elliott
7. Becca Peixotto
8. Agustín Fuentes
9. Paul Tafforeau
10. Vincent Beyrand
11. Kathleen Dollman
12. Zubair Jinnah
13. Angharad Brewer Gillham
14. Kenneth Broad
15. Juliet Brophy
16. Gideon Chinamatira
17. Paul HGM Dirks
18. Elen Feuerriegel
19. Alia Gurtov
20. Nompumelelo Hlophe
21. Lindsay Hunter
22. Rick Hunter
23. Kudakwashe Jakata
24. Corey Jaskolski
25. Hannah Morris
26. Ellie Pryor
27. Maropeng Mpete
28. Eric M Roberts
29. Jacqueline S Smilg
30. Mathabela Tsikoane
31. Steven Tucker
32. Dirk Van Rooyen
33. Kerryn Warren
34. Colin D Wren
35. Marc Kissel
36. Penny Spikins
37. John Hawks

• Curated by eLife

  eLife Assessment

  The authors study the context of the skeletal remains of three individuals and associated sediment samples to conclude that the hominin species Homo naledi intentionally buried their dead. Demonstration of the earliest known instance of intentional funerary practice – with a relatively small-brained hominin engaging in a highly complex behavior that has otherwise been observed from Homo sapiens and Homo neanderthalensis – would represent a landmark finding. The authors have revised their manuscript extensively in light of the reviews of their initial submission, with improved illustration, context, discussion, and theoretical frameworks, leading to an improved case supporting their conclusion that Homo naledi intentionally buried their dead. One of the reviewers concludes that the findings convincingly demonstrate intentional burial practices, while another considers evidence for such an unambiguous conclusion to be incomplete given a lack of definitive knowledge around how the hominins got into the chamber. We look forward to seeing the continued development and assessment of this hypothesis. It is worth noting that the detailed reviews (both rounds) and comprehensive author response are commendable and consequential parts of the scientific record of this study. The editors note that the authors' response repeatedly invokes precedent from previous publications to help justify the conclusions in this paper. While doing so is helpful, the editors also note that scientific norms and knowledge are constantly evolving, and that any study has to rest on its own scientific merit.

Reviewed by eLife

Whole genomes from the extinct Xerces Blue butterfly can help identify declining insect species

1. Toni de-Dios
2. Claudia Fontsere
3. Pere Renom
4. Josefin Stiller
5. Laia Llovera
6. Marcela Uliano-Silva
7. Alejandro Sánchez-Gracia
8. Charlotte Wright
9. Esther Lizano
10. Berta Caballero
11. Arcadi Navarro
12. Sergi Civit
13. Robert K Robbins
14. Mark Blaxter
15. Tomàs Marquès
16. Roger Vila
17. Carles Lalueza-Fox

• Curated by eLife

  eLife assessment

  This important study illustrates the value of museum samples for understanding past genetic variability in the genomes of populations and species, including those that no longer exist. The authors present genomic sequencing data for the extinct Xerces Blue butterfly and report convincing evidence of declining population sizes and increases in inbreeding beginning 75,000 years ago, which strongly contrasts to the patterns observed in similar data from its closest relative, the extant Silvery Blue butterfly. Such long-term population health indicators may be used to highlight still extant but especially vulnerable-to-extinction insect species – irrespective of their current census population size abundance.

Reviewed by eLife

Spatial transcriptomics of meningeal inflammation reveals inflammatory gene signatures in adjacent brain parenchyma

1. Sachin P Gadani
2. Saumitra Singh
3. Sophia Kim
4. Jingwen Hu
5. Matthew D Smith
6. Peter A Calabresi
7. Pavan Bhargava

• Curated by eLife

  eLife Assessment

  Brain inflammation is a hallmark of multiple sclerosis. Using novel spatial transcriptomics methods, the authors provide solid evidence for a gradient of immune genes and inflammatory markers from the meninges toward the adjacent brain parenchyma in a mouse model. This important study advances our understanding of the mechanisms of brain damage in this autoimmune disease.

Reviewed by eLife

Automated cell annotation in multi-cell images using an improved CRF_ID algorithm

1. Hyun Jee Lee
2. Jingting Liang
3. Shivesh Chaudhary
4. Sihoon Moon
5. Zikai Yu
6. Taihong Wu
7. He Liu
8. Myung-Kyu Choi
9. Yun Zhang
10. Hang Lu

• Curated by eLife

  eLife Assessment

  This Research Advance describes a valuable image analysis method to identify individual neurons within a ‎population of fluorescently labeled cells in the nematode C. elegans. The findings are solid and the method succeeds to identify cells with high precision. The method will be be of interest to the C. elegans research community.

Reviewed by eLife

Condensin positioning at telomeres by shelterin proteins drives sister-telomere disjunction in anaphase

1. Léonard Colin
2. Celine Reyes
3. Julien Berthezene
4. Laetitia Maestroni
5. Laurent Modolo
6. Esther Toselli
7. Nicolas Chanard
8. Stephane Schaak
9. Olivier Cuvier
10. Yannick Gachet
11. Stephane Coulon
12. Pascal Bernard
13. Sylvie Tournier

• Curated by eLife

  eLife assessment

  This is an important study that characterises the involvement of condensin complexes in the segregation of telomeres in fission yeast. The authors present convincing evidence to support their claims, employing a diverse range of complementary techniques. This research will be of interest to cell biologists working on chromosome biology and cell division.

Reviewed by eLife

Evolution of a functionally intact but antigenically distinct DENV fusion loop

1. Rita M Meganck
2. Deanna Zhu
3. Stephanie Dong
4. Lisa J Snoderly-Foster
5. Yago R Dalben
6. Devina Thiono
7. Laura J White
8. Arivianda M DeSilva
9. Ralph S Baric
10. Longping V Tse

• Curated by eLife

  eLife assessment

  This valuable study describes engineered dengue virus variants that can be used to dissect epitope specificities in polyclonal sera, and to design candidate vaccine antigens that dampen antibody responses against undesirable epitopes. While the major claims are supported by solid evidence, experiments to distinguish the impact on antibody binding from neutralizing activities would have strengthened the study. This work will be of interest to virologists and structural biologists working on antibody responses to flaviviruses.

Reviewed by eLife

FSHβ links photoperiodic signaling to seasonal reproduction in Japanese quail

1. Gaurav Majumdar
2. Timothy A Liddle
3. Calum Stewart
4. Christopher J Marshall
5. Maureen Bain
6. Tyler Stevenson

• Curated by eLife

  eLife assessment

  This important article provides insights into the neural centers and hormonal modulations underlying seasonal changes associated with photoperiod-induced life-history states in birds. The physiological and transcriptomic analyses of the mediobasal hypothalamus and pituitary gland offer convincing evidence for a timing mechanism for measuring day length, which is relevant for the field of seasonal biology. The study's experiments and findings have the potential to captivate the attention of molecular and organismal endocrinologists and chronobiologists.

Reviewed by eLife

Analysis of RNA processing directly from spatial transcriptomics data reveals previously unknown regulation

1. Julia Olivieri
2. Julia Salzman

• Curated by eLife

  eLife assessment:

  This important study describes spatial RNA processing events by combining methods for single-cell transcriptomics data with spatial transcriptomics data. The evidence supporting the claims of the authors is solid, although the analysis could be further strengthened by including a broader range of samples as well as orthogonal validation either by experimental methods or simulated data. The work will be of general interest to researchers in the spatial transcriptomics field as well as researchers investigating alternative pre-mRNA processing across diverse tissues.

Reviewed by eLife

PI(3,4,5)P3 allosteric regulation of repressor activator protein 1 controls antigenic variation in trypanosomes

1. Abdoulie O Touray
2. Rishi Rajesh
3. Tony Isebe
4. Tamara Sternlieb
5. Mira Loock
6. Oksana Kutova
7. Igor Cestari

Reviewed by eLife

Statistical analysis supports pervasive RNA subcellular localization and alternative 3' UTR regulation

1. Rob Bierman
2. Jui M Dave
3. Daniel M Greif
4. Julia Salzman

• Curated by eLife

  eLife assessment

  This paper describes an important, well-organized study into an under-exploited area of spatial transcriptomics. The limitations of the approach are generally made clear, but there is insufficient orthogonal validation to demonstrate the biological significance of the results, which leads to the evidence for the claims being currently incomplete. Nevertheless, the tools presented will provide a resource to researchers wishing to characterise spatial patterning of mRNAs, and the paper will be of interest to researchers studying cell biology, RNA biology, and method development for spatial transcriptomics/proteomics.

Reviewed by eLife

Influenza virus transcription and progeny production are poorly correlated in single cells

1. David J Bacsik
2. Bernadeta Dadonaite
3. Andrew Butler
4. Allison J Greaney
5. Nicholas S Heaton
6. Jesse D Bloom

• Curated by eLife

  eLife assessment

  This important paper reports a novel, compelling method, based on barcoding viral genes and next-generation sequencing, to quantify both viral transcription levels and progeny virus production in influenza virus-infected cells at the single-cell level. The authors show that viral transcription and progeny virus production are unexpectedly poorly correlated, and that cells in which viral RNAs are transcribed at high levels are not necessarily those producing the most progeny virions. Because of its novelty, the study will be of interest to the broader virology community.

Reviewed by eLife

Two RNA-binding proteins mediate the sorting of miR223 from mitochondria into exosomes

1. Liang Ma
2. Jasleen Singh
3. Randy Schekman

• Curated by eLife

  eLife assessment

  This is an important study that reports the discovery of a new pathway of miRNA sorting to exosomes, involving a mitochondrially-localized protein. The evidence provided by some of the biochemical data is convincing. However, the major body of evidence is still incomplete.

Reviewed by eLife

Treatment with tumor-treating fields (TTFields) suppresses intercellular tunneling nanotube formation in vitro and upregulates immuno-oncologic biomarkers in vivo in malignant mesothelioma

1. Akshat Sarkari
2. Sophie Korenfeld
3. Karina Deniz
4. Katherine Ladner
5. Phillip Wong
6. Sanyukta Padmanabhan
7. Rachel I Vogel
8. Laura A Sherer
9. Naomi Courtemanche
10. Clifford Steer
11. Kerem Wainer-Katsir
12. Emil Lou

• Curated by eLife

  eLife assessment

  Overall, this is an interesting topic of study, and the conclusions could be of relevance more broadly. However, mechanistic support, limited TTF frequencies/timing, and visual support of the quantitative data would be critical in order to provide convincing and rigorous support for this interesting concept.

Reviewed by eLife

Inhibition of DNMT1 methyltransferase activity via glucose-regulated O-GlcNAcylation alters the epigenome

1. Heon Shin
2. Amy Leung
3. Kevin R Costello
4. Parijat Senapati
5. Hiroyuki Kato
6. Roger E Moore
7. Michael Lee
8. Dimitri Lin
9. Xiaofang Tang
10. Patrick Pirrotte
11. Zhen Bouman Chen
12. Dustin E Schones

• Curated by eLife

  eLife assessment

  This study explores the regulatory function of O-GlcNAcylation on DNA methyltransferase 1 and identifies serine 878 as the main target. This study is of interest to those in epigenetics and metabolism. The significance is important and the strength of the evidence is convincing.

Reviewed by eLife

Examining the perceived impact of the COVID-19 pandemic on cervical cancer screening practices among clinicians practicing in Federally Qualified Health Centers: A mixed methods study

1. Lindsay Fuzzell
2. Paige Lake
3. Naomi C Brownstein
4. Holly B Fontenot
5. Ashley Whitmer
6. Alexandra Michel
7. McKenzie McIntyre
8. Sarah L Rossi
9. Sidika Kajtezovic
10. Susan T Vadaparampil
11. Rebecca Perkins

• Curated by eLife

  eLife assessment

  This US study presents findings from an online survey and in-person interviews of healthcare providers in areas associated with cervical screening provision during the post-acute phase of the pandemic. The findings are valuable as they provide insights into a range of areas, from healthcare characteristics to screening barriers and HPV self-sampling. The evidence supporting the claims of the authors is solid, although the inclusion of a nationally-representative sample of healthcare providers and a greater gender/ethnicity/racial mix of interviewees would have strengthened the study. The work will be of interest to public health scientists and a cancer prevention and control audience.

Reviewed by eLife