Evaluated articles

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

The Toxoplasma monocarboxylate transporters are involved in the metabolism within the apicoplast and are linked to parasite survival

1. Hui Dong
2. Jiong Yang
3. Kai He
4. Wen-Bin Zheng
5. De-Hua Lai
6. Jing Liu
7. Hui-Yong Ding
8. Rui-Bin Wu
9. Kevin M Brown
10. Geoff Hide
11. Zhao-Rong Lun
12. Xing-Quan Zhu
13. Shaojun Long

• Curated by eLife

  eLife assessment

  This study identifies two new transporters in the apicoplast, a non-photosynthetic organelle of apicomplexan parasites. While this is important work, it only partially reveals how essential these transporters are, as it does not address the metabolic function of the transporters for the parasite. Although the evidence is still incomplete, the results should be of interest to parasitologists and eukaryotic cell biologists.

Reviewed by eLife

Epistasis facilitates functional evolution in an ancient transcription factor

1. Brian PH Metzger
2. Yeonwoo Park
3. Tyler N Starr
4. Joseph W Thornton

• Curated by eLife

  eLife assessment

  This study includes fundamental findings on protein evolution, namely that changes in function are largely attributable to pairwise rather than higher-order interactions, and that epistasis potentiates rather than constrains evolutionary paths. Compelling evidence supporting the conclusions is provided by applying a new model to a previously generated experimental dataset on deep mutational scanning of the DNA-binding domain (DBD) of steroid hormone receptor. The implications of this work are of considerable interest to protein biochemistry, evolutionary biology, and numerous other fields.

Reviewed by eLife

Delayed postglacial colonization of Betula in Iceland and the circum North Atlantic

1. David J Harning
2. Samuel Sacco
3. Kesara Anamthawat-Jónsson
4. Nicolò Ardenghi
5. Thor Thordarson
6. Jonathan H Raberg
7. Julio Sepúlveda
8. Áslaug Geirsdóttir
9. Beth Shapiro
10. Gifford H Miller

• Curated by eLife

  eLife assessment

  This valuable work on the paleovegetation history of Iceland has implications for the field of paleoecology, and the deglaciation history of Iceland and additional localities in Northern America and Europe via woody shrub colonization. The study uses a sedimentary ancient DNA metabarcoding approach to study this historic process. The strength of evidence is solid, with the methods (analysis of sedimentary DNA) and data analyses broadly supporting the claims.

Reviewed by eLife

Ryanodine receptor 2 inhibition reduces dispersion of cardiac repolarization, improves contractile function, and prevents sudden arrhythmic death in failing hearts

1. Pooja Joshi
2. Shanea Estes
3. Deeptankar DeMazumder
4. Bjorn C Knollmann
5. Swati Dey

• Curated by eLife

  eLife assessment

  This important study examined the use of dantrolene, a Ryanodine Receptor stabilizer, in slowing pathological progression of pressure-overload heart failure in a guinea pig model and reducing arrhythmias. Convincing data were collected and analyzed using validated methodology and can be used as a starting point for future studies of dantrolene in Ca2+ handling in ROS production and further deterioration of cardiac function in chronic heart failure.

Reviewed by eLife

Recursive self-embedded vocal motifs in wild orangutans

1. Adriano R Lameira
2. Madeleine E Hardus
3. Andrea Ravignani
4. Teresa Raimondi
5. Marco Gamba

• Curated by eLife

  eLife assessment

  The paper represents a novel application of recursion theory to the long call vocalisations of orangutans to demonstrate repetitive, rhythmic sub-structuring. The authors use detailed acoustic analyses to show compelling evidence for self-embedded and nested isochronic motifs. These fundamental results have the potential to significantly advance current approaches used to compare nonhuman communication systems with human language.

Reviewed by eLife

DYRK1A interacts with the tuberous sclerosis complex and promotes mTORC1 activity

1. Pinhua Wang
2. Sunayana Sarkar
3. Menghuan Zhang
4. Tingting Xiao
5. Fenhua Kong
6. Zhe Zhang
7. Deepa Balasubramanian
8. Nandan Jayaram
9. Sayantan Datta
10. Ruyu He
11. Ping Wu
12. Peng Chao
13. Ying Zhang
14. Michael Washburn
15. Laurence A Florens
16. Sonal Nagarkar-Jaiswal
17. Manish Jaiswal
18. Man Mohan

• Curated by eLife

  eLife assessment

  This fundamental study identifies the kinase DYRK1A as a novel component of the tuberous sclerosis complex (TSC) protein complex, which is central to cellular growth and cell size. The findings presented here have broad implications for how cell size and growth is regulated. The methodology and analysis are convincing and support the findings.

Reviewed by eLife

Optical mapping of ground reaction force dynamics in freely behaving Drosophila melanogaster larvae

1. Jonathan H Booth
2. Andrew T Meek
3. Nils M Kronenberg
4. Stefan R Pulver
5. Malte C Gather

• Curated by eLife

  eLife assessment

  This study reports important findings about new locomotory dynamics of crawling Drosophila larva based on imaging the reaction forces during larval crawling. The evidence with the new high-resolution microscopy method is compelling, as it significantly improves the spatial, temporal, and force resolution compared to previous methods for studying Drosophila larva and could be applied to other crawling organisms. The manuscript explains the new technology, WARP microscopy, and provides analysis of the data to characterize small animal behavior and discover new crawling-associated anatomical features and motor patterns. The work will be of interest to the broad neuroscience community interested in the mechanisms of locomotion in a highly tractable model.

Reviewed by eLife

Intra- and interspecific diversity in a tropical plant clade alter herbivory and ecosystem resilience

1. Ari Grele
2. Tara J Massad
3. Kathryn A Uckele
4. Lee A Dyer
5. Yasmine Antonini
6. Laura Braga
7. Matthew L Forister
8. Lidia Sulca
9. Massuo Kato
10. Humberto G Lopez
11. André R Nascimento
12. Thomas Parchman
13. Wilmer R Simbaña
14. Angela M Smilanich
15. John O Stireman
16. Eric J Tepe
17. Thomas Walla
18. Lora A Richards

• Curated by eLife

  eLife assessment

  This important, large experimental study examines the effects of plant species richness, plant genotypic richness, and soil water availability on herbivory patterns for Piper species in several tropical sites. The authors find solid evidence that water availability, as well as intra- and interspecific plant diversity, influence herbivory and herbivore diversity, but that the effects differ geographically.

Reviewed by eLife

Functional ultrasound imaging of stroke in awake rats

1. Clément Brunner
2. Gabriel Montaldo
3. Alan Urban

• Curated by eLife

  eLife assessment

  This important proof-of-concept study strongly supports the utility of functional ultrasound imaging for evaluating cerebral hemodynamics in rat models of brain injury. Functional ultrasound affords a distinct coverage/spatial/temporal resolution tradeoff when compared to other modalities for studying brain hemodynamics. The solid data presented indicate high fidelity of the recordings, a particular feat given that the rats were awake. On the other hand, single slice imaging and complexity of registration of subsequent imaging sessions limit the usefulness of the approach, particularly for quantitative imaging, and the small sample size will need to be followed up with and verified by future studies. This work will be of interest to researchers working in functional neuroimaging and more precisely with preclinical models of stroke in rodents.

Reviewed by eLife

I-Spin live, an open-source software based on blind-source separation for real-time decoding of motor unit activity in humans

1. Julien Rossato
2. François Hug
3. Kylie Tucker
4. Ciara Gibbs
5. Lilian Lacourpaille
6. Dario Farina
7. Simon Avrillon

Reviewed by eLife