Evaluated articles

Exploring neurodevelopment via spatiotemporal collation of anatomical networks with NeuroSC

1. Noelle L Koonce
2. Sarah E Emerson
3. Dhananjay Bhaskar
4. Manik Kuchroo
5. Mark W Moyle
6. Pura Arroyo-Morales
7. Nabor Vázquez-Martínez
8. Jamie I Emerson
9. Smita Krishnaswamy
10. William A Mohler
11. Daniel A Colón-Ramos

• Curated by eLife

  eLife Assessment

  NeuroSC is an accessible and interactive tool for streamlined observation of neuronal morphology, membrane contact, and synaptic connectivity across developmental stages in the nematode C. elegans. This important tool relies on solid electron microscopy datasets. This resource will be of high interest to C. elegans researchers interested in nervous system wiring and circuit function.

Reviewed by eLife

Synergistic effect of inhibiting CHK2 and DNA replication on cancer cell growth

1. Flavie Coquel
2. Sing-Zong Ho
3. Keng-Chang Tsai
4. Chun-Yen Yang
5. Antoine Aze
6. Julie Devin
7. Ting-Hsiang Chang
8. Marie Kong-Hap
9. Audrey Bioteau
10. Jerome Moreaux
11. Domenico Maiorano
12. Philippe Pourquier
13. Wen-Chin Yang
14. Yea-Lih Lin
15. Philippe Pasero

• Curated by eLife

  eLife Assessment

  This study presents important findings on the activity of two compounds, BKC and IBC, isolated from Psoralea corylifolia, which act synergistically to inhibit cancer cell proliferation. Using a spectrum of methods, the authors characterized the mechanisms of action of both drugs, providing convincing evidence that BKC targets DNA polymerases and IBC selectively inhibits CHK2. The study opens the possibility of improving the effectiveness of the combination of BKC and other damaging agents with IBC in cancer treatment.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife

Chemotherapy resistance due to epithelial-to-mesenchymal transition is caused by abnormal lipid metabolic balance

1. Atsushi Matsumoto
2. Akihito Inoko
3. Takuya Tanaka
4. Gen-Ichi Konishi
5. Waki Hosoda
6. Takahiro Kojima
7. Koji Ohnishi
8. Junichi Ikenouchi

• Curated by eLife

  eLife Assessment

  This paper presents the fundamental discovery that lipid metabolic imbalance induced by Snail, an EMT-related transcription factor, contributes to the acquisition of chemoresistance in cancer cells. The evidence, supported by a wide range of methods and adequate quantification, provides a convincing mechanistic explanation of how Snail drives ectopic expression of the cholesterol- and drug-efflux transporter ABCA1. This work, which introduces a novel therapeutic concept targeting invasive cancer, will be of broad interest to researchers in cancer biology, lipid metabolism, and cell biology.

Reviewed by eLife

High-resolution deep mutational scanning of the melanocortin-4 receptor enables target characterization for drug discovery

1. Conor J Howard
2. Nathan S Abell
3. Beatriz A Osuna
4. Eric M Jones
5. Leon Y Chan
6. Henry Chan
7. Dean R Artis
8. Jonathan B Asfaha
9. Joshua S Bloom
10. Aaron R Cooper
11. Andrew Liao
12. Eden Mahdavi
13. Nabil Mohammed
14. Alan L Su
15. Giselle A Uribe
16. Sriram Kosuri
17. Diane E Dickel
18. Nathan B Lubock

• Curated by eLife

  eLife Assessment

  The authors use deep mutational scanning to assess the effect of ~6,600 protein-coding variants in MC4R, a G protein coupled receptor associated with obesity. They develop new, more precise approaches to deep mutational scanning, enabling them to probe molecular phenotypes directly relevant to the development of drugs that target this receptor. In this important work, the authors provide compelling evidence that variants impact signaling through MC4R in different ways, that some defective variants are amenable to a corrector drug and that deep mutational scanning data could guide compound optimization.

Reviewed by eLife

Myosin light chain 3 serves as a receptor for nervous necrosis virus entry into host cells via the macropinocytosis pathway

1. Lan Yao
2. Wanwan Zhang
3. Xiaogang Yang
4. Meisheng Yi
5. Kuntong Jia

• Curated by eLife

  eLife Assessment

  The findings in this manuscript are fundamental because they identify an entry receptor MYL3 that belongs to the myosin family as a possible target that could inhibit a virus that has a high impact on aquaculture. The evidence is convincing as it contains strong in vitro and in vivo data that support their conclusions; however, studies on the presence of MYL3 in NNV target tissues will further strengthen their claims

Reviewed by eLife

Therapeutic effects of PDGF-AB/BB against cellular senescence in human intervertebral disc

1. Changli Zhang
2. Martha Elena Diaz-Hernandez
3. Takanori Fukunaga
4. Sreekala Shenoy
5. Sangwook Tim Yoon
6. Lisbet Haglund
7. Hicham Drissi

• Curated by eLife

  eLife Assessment

  This work demonstrates the therapeutic potential of recombinant human PDGF-AB/BB proteins in alleviating the senescent signatures of primary human intervertebral disc cells. The study represents a fundamental, significant advance in the treatment of intervertebral disc degeneration through the suppression of senescence. The strength of evidence supporting these conclusions is compelling, as it is primarily based on transcriptomic analysis and direct protein measurements from relatively homogeneous cell populations. This work will be of interest to spine basic scientists and clinicians, as well as to musculoskeletal scientists more broadly. The revised manuscript adds greater clarity, and the impact of the study is greatly enhanced.

Reviewed by eLife

Nonlinear transcriptional responses to gradual modulation of transcription factor dosage

1. Júlia Domingo
2. Mariia Minaeva
3. John A Morris
4. Samuel Ghatan
5. Marcello Ziosi
6. Neville E Sanjana
7. Tuuli Lappalainen

• Curated by eLife

  eLife Assessment

  This important work develops a new protocol to experimentally perturb target genes across a quantitative range of expression levels in cell lines. The evidence supporting their new perturbation approach is convincing, and we propose that focusing on single modality (activation or inhibition) would be sufficient to draw their conclusions. The study will be of broad interest to scientists in the fields of functional genomics and biotechnology.

Reviewed by eLife

Harnessing AlphaFold to reveal hERG channel conformational state secrets

1. Khoa Ngo
2. Pei-Chi Yang
3. Vladimir Yarov-Yarovoy
4. Colleen E Clancy
5. Igor Vorobyov

• Curated by eLife

  eLife Assessment

  This valuable study uses AlphaFold2 to guide the structural modelling of different states of the human voltage-gated potassium channel KV11.1, a key pharmacological drug target. Follow-up molecular dynamics and drug-docking simulations, combined with experimental characterization, offer convincing evidence supporting the models. The work shows potential for improving drug potency predictions in ion channel pharmacology.

Reviewed by eLife

An unusual trafficking domain in MSRP6 defines a complex needed for Maurer’s clefts anchoring and maintenance in P. falciparum infected red blood cells

1. Alexandra Blancke Soares
2. Jan Stäcker
3. Svenja Schwald
4. Wieteke Hoijmakers
5. Nahla Galal Metwally
6. Jakob Cronshagen
7. Hanno Schoeler
8. Sven Flemming
9. Katharina Höhn
10. Ulrike Fröhlke
11. Paolo Mesén-Ramírez
12. Bärbel Bergmann
13. Melissa Khosh-Naucke
14. Iris Bruchhaus
15. Richárd Bártfai
16. Tobias Spielmann

• Curated by eLife

  eLife Assessment

  This study presents valuable data on the identification and function of a protein complex present at the Maurer's cleft organelles of Plasmodium falciparum-infected red blood cells. The evidence supporting the findings is solid, but would benefit from greater rigor in presentation and analysis.

Reviewed by eLife

Effects of residue substitutions on the cellular abundance of proteins

1. Thea K Schulze
2. Kresten Lindorff-Larsen

• Curated by eLife

  eLife Assessment

  This valuable study presents a thorough analysis of protein abundance changes caused by amino acid substitutions, using structural context to improve predictive accuracy. By deriving substitution response matrices based on solvent accessibility, the authors demonstrate that simple structural features can predict abundance effects with accuracy comparable to complex methods such as free energy calculations. The strength of the evidence is solid, supported by robust experimental design and comprehensive analyses. This work is expected to be of interest to broad audiences as it offers practical tools for analyzing mutational effects and insights into the structural basis of proteostasis.

Reviewed by eLife, PREreview

Recombination shapes the diversification of the wtf meiotic drivers

1. Yan Wang
2. Hao Xu
3. Qinliu He
4. Zhiwei Wu
5. Zhen Gong
6. Guan-Zhu Han

• Curated by eLife

  eLife Assessment

  This important study provides one mechanism that can explain the rapid diversification of poison-antidote pairs in fission yeast: recombination between existing pairs. The evidence is largely solid, but the study can benefit from demonstrating that the novel poison-antidote constructed by the authors can serve as a meiotic driver. The work is of interest to colleagues studying genetic incompatibilities.

Reviewed by eLife

Change point estimation by the mouse medial frontal cortex during probabilistic reward learning

1. Cayla E Murphy
2. Hongli Wang
3. Heather K Ortega
4. Alex C Kwan
5. Huriye Atilgan

• Curated by eLife

  eLife Assessment

  This study examined the role of the dorsal medial prefrontal cortex of mice in anticipating reward-value switch points in a two-armed bandit task. They demonstrate the dorsal medial prefrontal cortex is involved in task performance and use model-based methods to uncover the algorithmic processes affected by prefrontal cortex perturbations. If the claims were supported, this would be a valuable finding. Unfortunately, the reviewers recognised significant issues with the task design and analyses, making the evidence to support the role of the prefrontal cortex in anticipation of switches inadequate.

Reviewed by eLife

Glucocorticoids desensitize hypothalamic CRH neurons to norepinephrine and somatic stress activation via rapid nitrosylation-dependent regulation of α1 adrenoreceptor trafficking

1. Grant L Weiss
2. Laura M Harrison
3. Zhiying Jiang
4. Alyssa M Nielsen
5. Maximillian S Feygin
6. Sandy Nguyen
7. Parker S Tirrell
8. Jeffrey Tasker

• Curated by eLife

  eLife Assessment

  This manuscript describes work that is fundamental to our understanding of the mechanism of how stress regulates the noradrenergic system and the CRH system. Using a combination of ex vivo physiology and in vitro methods, the study provides compelling evidence as to the signaling mechanisms of how glucocorticoids impact adrenergic GPCRs in CRH cells via receptor trafficking. While the ex vivo work is specific to the hypothalamus, the mechanisms here could be extrapolated and investigated in other brain regions that may have similar signaling regulation.

Reviewed by eLife

Opposing roles for Bmp signalling during the development of electrosensory lateral line organs

1. Alexander S Campbell
2. Martin Minařík
3. Roman Franěk
4. Michaela Vazačová
5. Miloš Havelka
6. David Gela
7. Martin Pšenička
8. Clare VH Baker

• Curated by eLife

  eLife assessment

  This study reports analysis of the formation of electrosensory ampullary organs in non-model organisms, the sterlet sturgeon. By using a combination of targeted gene knock-out and inhibition, the study provides overall convincing evidence for differential roles of BMP signaling in lateral-line development, with few aspects that could be improved. The study is particularly valuable for understanding the development of a still-mysterious sensory system, and for its evolutionary implications.

Reviewed by eLife

Social experience shapes fighting strategies in Drosophila

1. Can Gao
2. Mingze Ma
3. Jie Chen
4. Xiaoxiao Ji
5. Qionglin Peng
6. Yufeng Pan

• Curated by eLife

  eLife Assessment

  The important paper presents a new behavioral assay for Drosophila aggression and demonstrates that social experience influences fighting strategies, with group-housed males favoring high-intensity but low-frequency tussling over aggressive lunging observed in isolated males. The experiments are solid and the conclusions are of interest to researchers studying the impact of social isolation on aggression.

Reviewed by eLife

Imaging of brain electric field networks with spatially resolved EEG

1. Lawrence R Frank
2. Vitaly L Galinsky
3. Olave Krigolson
4. Susan Tapert
5. Stephan Bickel
6. Antigona Martinez

Reviewed by eLife

Prefrontal working memory signal controls phase-coded information within extrastriate cortex

1. Mohsen Parto-Dezfouli
2. Isabel Vanegas
3. Mohammad Zarei
4. William H Nesse
5. Kelsey L Clark
6. Behrad Noudoost

• Curated by eLife

  eLife Assessment

  This study investigates how the maintenance of a spatial location in working memory affects the representation of visual information in area V4 of monkeys. As such, it is important not only for understanding vision but also for determining how working memory impacts perceptual signals and their underlying circuits. The data provide convincing evidence of a direct communication between prefrontal circuits that store spatial information and V4, which, under the current experimental conditions, manifests mainly as changes in temporal activity patterns (oscillations).

Reviewed by eLife

Experience shapes the transformation of olfactory representations along the cortico-hippocampal pathway

1. Eleonore Schiltz
2. Martijn Broux
3. Cagatay Aydin
4. Pedro Goncalves
5. Sebastian Haesler

• Curated by eLife

  eLife Assessment

  This important study describes the progressive transformation of olfactory information across five different brain regions in the olfactory pathway, including a comparison of responses to familiar and unfamiliar odors. This dataset is of broad interest for olfactory researchers and provides a solid analysis of a graded change in representations of odor identity and experience in different locations in the pathway.

Reviewed by eLife

An evolutionarily conserved Hox-Gbx segmentation code in the rice coral Montipora capitata

1. Shuonan He
2. Emma Rangel-Huerta
3. Eric Hill
4. Lacey Ellington
5. Shiyuan (Cynthia) Chen
6. Sofia Robb
7. Eva Majerová
8. Crawford Drury
9. Matthew C Gibson

• Curated by eLife

  eLife Assessment

  The authors studied the development of mesentery borders in the rice coral Montipora, a new experimental system, to complement existing data from the sea anemone Nematostella. They make a solid case that in Montipora, there is a sequence of Hox-Gbx genes whose staggered expression in the unsegmented larva is suggestive of their role in subdividing the gastric cavity into repeated units bordered by mesenteries, as in the sea anemone Nematostella. Pharmacological experiments also point to the involvement of the BMP pathway in this process, but additional experiments validating this are necessary. This is a valuable contribution to the field of cnidarian evolution, suggesting that BMP- and "Hox-Gbx code"-dependent patterning of the directive axis was ancestral for Anthozoa.

Reviewed by eLife