Evaluated articles

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

Regulation of defective mitochondrial DNA accumulation and transmission in C. elegans by the programmed cell death and aging pathways

1. Sagen Flowers
2. Rushali Kothari
3. Yamila N Torres Cleuren
4. Melissa R Alcorn
5. Chee Kiang Ewe
6. Geneva Alok
7. Samantha L Fiallo
8. Pradeep M Joshi
9. Joel H Rothman

• Curated by eLife

  eLife assessment

  This manuscript suggests a novel mechanism of purifying selection by which programmed cell death contributes to the selective removal of mtDNA deletion mutations in C. elegans. The evidence for this mechanism of removal is strong although questions remain regarding the underlying mechanism and the role of canonical ageing pathways. Because of the likely central role of mtDNA deletions in ageing and age-dependent diseases, this work will be of interest to scientists in the field of mitochondrial biology as well as ageing.

Reviewed by eLife

Cerebral chemoarchitecture shares organizational traits with brain structure and function

1. Benjamin Hänisch
2. Justine Y Hansen
3. Boris C Bernhardt
4. Simon B Eickhoff
5. Juergen Dukart
6. Bratislav Misic
7. Sofie Louise Valk

• Curated by eLife

  eLife assessment

  This work provides a valuable structural and functional characterization of the neurotransmitter's spatial distribution heterogeneity in cortical and subcortical regions. The authors report a systematic description and annotation of a new "layer" of brain organization that has been relatively poorly integrated with the wider neuroimaging literature to date. In sum, this paper has the potential to be of great interest to a wide audience in neurosciences.

Reviewed by eLife

Direct economic burden of mental health disorders associated with polycystic ovary syndrome: Systematic review and meta-analysis

1. Surabhi Yadav
2. Olivia Delau
3. Adam J Bonner
4. Daniela Markovic
5. William Patterson
6. Sasha Ottey
7. Richard P Buyalos
8. Ricardo Azziz

• Curated by eLife

  eLife assessment

  This important paper describes a valuable systematic review and meta-analysis of mental health problems in polycystic ovary syndrome (PCOS) that drive the excess economic burden associated with this common endocrine disorder. Interestingly, the cost of the diagnostic evaluation is only a relatively minor part of the total costs, but mental health disorders were identified as a significant component of the economic burden. These solid findings could not have been anticipated intuitively and are of considerable value for public health prioritization of PCOS.

Reviewed by eLife

The Axin scaffold protects the kinase GSK3β from cross-pathway inhibition

1. Maire Gavagan
2. Noel Jameson
3. Jesse G Zalatan

• Curated by eLife

  eLife assessment

  This study presents a valuable and elegant kinetic analysis of the GSKbeta activity as a function of phosphorylation and Axin binding - providing insights into critical steps of Wnt pathway signaling. The results will be of big use to the broader signaling community, however, the incomplete dissection of the mechanism by which Axin binding inhibits GSKbeta inhibitory phosphorylation remains a weakness of this study. The work will be of broad interest to cell biologists and biochemists.

Reviewed by eLife

Impact of inner ear malformation and cochlear nerve deficiency on the development of auditory-language network in children with profound sensorineural hearing loss

1. Yaoxuan Wang
2. Mengda Jiang
3. Yuting Zhu
4. Lu Xue
5. Wenying Shu
6. Xiang Li
7. Hongsai Chen
8. Yun Li
9. Ying Chen
10. Yongchuan Chai
11. Yu Zhang
12. Yinghua Chu
13. Yang Song
14. Xiaofeng Tao
15. Zhaoyan Wang
16. Hao Wu

• Curated by eLife

  eLife assessment

  This important study used high-resolution brain imaging methods to visualize and index non-invasively auditory and language pathways of young children born with inner ear malformations or cochlear nerve dysfunction resulting in profound hearing loss. Nerve fiber impairments were compellingly demonstrated in subcortical auditory and cortical language pathways relative to typically-hearing controls. The results suggested novel approaches for clinical assessment of central auditory and language pathways that may influence different intervention strategies, pending further evidence linking these structural findings with functional outcomes.

Reviewed by eLife

Sex-dependent noradrenergic modulation of premotor cortex during decision-making

1. Ellen M Rodberg
2. Carolina R den Hartog
3. Emma S Dauster
4. Elena M Vazey

• Curated by eLife

  eLife assessment

  Rodberg et al. show systemic β adrenergic antagonism reduces engagement in decision-making, particularly in female rats, and reduces task-related encoding in neural activity. This is a valuable finding that addresses a gap in the field, however, the understanding of the direct contribution of β adrenergic receptors to the observed effects is incomplete. Further, the theoretical grounds, data analyses, and results could be improved in several ways.

Reviewed by eLife

Functional imaging of conduction dynamics in cortical and spinal axons

1. Milos Radivojevic
2. Anna Rostedt Punga

• Curated by eLife

  eLife assessment

  This work provides fundamental new insight into fine axonal morphologies based solely on extracellular action potential recordings. They provide compelling evidence of fine resolution in mapping functional connections between neurons. The work may have broad use in neurobiology, bioengineering, stem cell biology, as well as tissue engineering in functional characterization.

Reviewed by eLife

Leveraging inter-individual transcriptional correlation structure to infer discrete signaling mechanisms across metabolic tissues

1. Mingqi Zhou
2. Ian Tamburini
3. Cassandra Van
4. Jeffrey Molendijk
5. Christy M Nguyen
6. Ivan Yao-Yi Chang
7. Casey Johnson
8. Leandro M Velez
9. Youngseo Cheon
10. Reichelle Yeo
11. Hosung Bae
12. Johnny Le
13. Natalie Larson
14. Ron Pulido
15. Carlos HV Nascimento-Filho
16. Cholsoon Jang
17. Ivan Marazzi
18. Jamie Justice
19. Nicholas Pannunzio
20. Andrea L Hevener
21. Lauren Sparks
22. Erin E Kershaw
23. Dequina Nicholas
24. Benjamin L Parker
25. Selma Masri
26. Marcus M Seldin

• Curated by eLife

  eLife assessment

  This important paper provides web based interface for cross-tissue analysis of omics datasets from – so far – two different human populations, with compelling evidence that the tool can be used to make meaningful scientific discoveries. Conceptually, these analyses are relevant for any systems biologist or bioinformatician who is interested in integrating large population datasets. Currently, the resource is already of use for scientists studying the HMDP or using GTEx data, and we hope to see updates in the coming years that incorporate more populations and more datatypes, which could make it a general tool for a wide community.

Reviewed by eLife

Mechanism of substrate binding and transport in BASS transporters

1. Patrick Becker
2. Fiona Naughton
3. Deborah Brotherton
4. Raul Pacheco-Gomez
5. Oliver Beckstein
6. Alexander D Cameron

• Curated by eLife

  eLife assessment

  The manuscript represents an important contribution to an ongoing discussion about the substrate binding site and mechanism of the Bile Acid Sodium Symporter (BASS) family of transporters. Structural and biochemical analysis of a bacterial homolog, ASTBnm, in complex with its native substrate (not bile acids, but a vitamin A precursor, pantoate) show a new binding site that is consistent with classical proposals for elevator-type transport mechanisms. Molecular dynamics (MD) simulations highlight the improved stability for the substrate in the active site when ions are present, suggesting a binding order during the transport cycle. The structural studies, binding assays, and MD simulations are convincing.

Reviewed by eLife

Molecular mechanism of complement inhibition by the trypanosome receptor ISG65

1. Alexander D Cook
2. Mark Carrington
3. Matthew K Higgins

• Curated by eLife

  eLife assessment

  This fundamental study significantly advances our understanding of how parasites evade the host complement immune system. The new cryo-EM structure of the trypanosome receptor ISG65 bound to complement component C3b is highly compelling and well-supported by biochemical experiments. This work will be of broad interest to parasitologists, immunologists, and structural biologists.

Reviewed by eLife