Evaluated articles

eLife Assessment

This study has fundamental findings that support the potential application of exogenous stem cell therapy as a viable therapeutic option for the management of intraocular pressure (IOP) and to increase outflow facility. The evidence supporting the clinical application of stem cells is compelling, using a combination of established in vivo and ex vivo experimental techniques. The work will be of interest to both basic stem cell biologists and clinical glaucoma specialists.

eLife Assessment

In this potentially valuable study, the authors employed in vivo experiments and theoretical modeling to study the growth dynamics of nuclear condensates. They observed that condensates can exhibit distinct growth modes, as dictated by the competition between condensate surface tension and local elasticity of chromatin. While the theoretical model appears to capture the experimental observations, the level of evidence supporting the proposed growth mechanism is incomplete due to, among other limitations, the multiple fitting parameters and poorly justified Neo-Hookean elasticity.

eLife Assessment

This interesting study presents important information on how human cytomegalovirus (HCMV) infection disrupts the activity of the TEAD1 transcription factor, leading to widespread chromatin alterations. The strength of evidence in revised manuscript is convincing, and includes additional functional data teasing out how TEAD1-driven chromatin changes might influence HCMV replication. This work will be of interest to the virology, chromosome biology and transcriptional co-regulation fields.

eLife Assessment

This study follows up on Arimura et al's powerful new method MagIC-Cryo-EM for imaging native complexes at high resolution. Using a clever design embedding protein spacers between the antibody and the nucleosomes purified, thereby minimizing interference from the beads, the authors concentrate linker histone variant H1.8 containing nucleosomes. From these samples, the authors obtain convincing atomic structures of the H1.8 bound chromatosome purified from interphase and metaphase cells, finding a NPM2 chaperone bound form exists as well. Caveats previously noted have been addressed nicely in the revision, strengthening the overall conclusions. This is an important new tool in the arsenal of single molecule biologists, permitting a deep dive into structure of native complexes, and will be of high interest to a broad swathe of scientists studying native macromolecules present at low concentrations in cells.

eLife Assessment

This valuable study tested the impact of DNA methylation on CTCF binding in two cancer cell lines. Increased CTCF binding sites are enriched in gene bodies, and associate with nuclear speckles, indicating a role in increased transcription. In the revised work, the inferred association with nuclear speckles has been supported with more solid data. These results will be of interest to the epigenetics field.

eLife Assessment

This is an important study that reports the mechanism by which Ankle2 (LEM4 in humans) interacts with and recruits PP2A and the ER protein Vap33 to promote BAF dephosphorylation and mediate nuclear membrane reformation, using Drosophila as their model. Using Ankle2 mutants, they find that the ER protein Vap33 is key for the normal interphase localisation of Ankle2/LEM4 and also impacts on the function of Ankle2/LEM4 during mitosis. The conclusions on the subcellular localization of Ankle2 are drawn from overexpression of constructs. Overall, the authors use a variety of complementary techniques and provide convincing evidence to support the claims and advance our knowledge in the field of mitosis and nuclear envelope biology.

eLife Assessment

This valuable study reports the first characterization of the CG14545 gene in Drosophila melanogaster, which the authors name "Sakura." Acting during germline stem cell fate and differentiation, Sakura is required for both oogenesis and female fertility, although some mechanistic details require further investigation. This solid study presents a wide-ranging and well-controlled characterization of Sakura, and accordingly the findings and associated reagents described will be of use to scientists interested in oogenesis and early development.

eLife Assessment

This valuable study presents findings on how prokaryotic antibiotics affect translation in mitochondrial ribosomes. Using mitoribosome profiling, the authors provide solid evidence that most tested antibiotics act similarly on bacterial and mitochondrial translation. Additionally, this work shows that alternative translation initiation events might exist in two specific mt-mRNAs (MT-ND1 and MT-ND5). However, additional biochemical and structural experiments are needed to support these findings.

eLife Assessment

The authors studied the relationship between structural and functional lateralization in the planum temporale region of the brain, whilst also considering the morphological presentation of a single or duplicated Heschl's gyrus. The analyses are compelling due to a large sample size, inter-rater reliability, and corrections for multiple comparisons. The associations in this important work might serve as a reference for future targeted-studies on brain lateralization.

eLife Assessment

This important work demonstrates the application of Pro-PRIME, a large language model, to engineer VHH antibodies with enhanced stability for extreme industrial environments. The evidence is convincing, showing through two rounds of design and experimental validation that AI-guided approaches can outperform traditional rational design methods. The solid methodology and results establish a foundation for further exploration of LLM-assisted protein engineering.

eLife Assessment

This important study investigates the signaling pathways regulating retinal regeneration. Convincing evidence shows that the sphingosine-1-phosphate (S1P) signaling pathway is inhibited following retinal injury. Small-molecule activators and inhibitors support a model in which S1P signaling must be inhibited to generate Müller glial progenitor cells-a key step in retinal regeneration. The presented results support the major conclusions. However, whether the drug treatments directly or indirectly affect the Müller cells remains unclear.

eLife Assessment

This important work investigates how orientation signals detected in higher brain areas may be transformed into motor responses in behaving animals. The authors characterize two types of descending neurons (DNs) that connect the brain to motor units and are involved in different aspects of turning control. They further show that orientation signals act by preferentially increasing relative stimulation onto left- or right-turn-inducing DNs. These compelling results, together with the independent work that they have inspired, represent significant progress in our understanding of mechanisms of animal navigation.

eLife Assessment

This important work advances our understanding of the impact of malnutrition on hematopoiesis and subsequently infection susceptibility. Support for the overall claims is convincing in some respects and incomplete in terms of identifying mechanism as highlighted by reviewers. This work will be of general interest to those in the fields of hematopoiesis, malnutrition, and dietary influence on immunity.

eLife Assessment

In this valuable study, the authors used rats to determine the receptor for a food-related perception that has been characterized in humans. The data are solid in terms of methods and analysis: the data show that this stimulus (ornithine) has some additive effects in terms of increasing preference and taste response in rats when it is mixed with other more common taste stimuli. Therefore, the combinations of experiments generally support (but do not conclusively prove) the hypothesis that the "kokumi" taste effect elicited by this stimulus in humans may be mediated by the specific receptor examined in the study.

eLife Assessment

This study proposes an important new approach to analyzing cell-count data, which are often undersampled and cannot be accurately assessed using traditional statistical methods. The case studies presented in the article provide compelling evidence of the superiority of the proposed methodology over existing approaches, which could promote the use of Bayesian statistics among neuroscientists. The authors have taken steps to make the methodology accessible, although some implementation difficulties are likely to remain.

eLife Assessment

This study utilizes an elegant approach to examine valence encoding of the mesolimbic dopamine system. The findings are valuable, demonstrating differential responses of dopamine to the same taste stimulus according to its valence (i.e., appetitive or aversive) and in alignment with distinct behavioral responses. The evidence supporting the claims is convincing, resulting from a well-controlled experimental design with minimal confounds and thorough reporting of the data.

eLife Assessment

This manuscript provides fundamental studies to gain insight into the mutations in the presenilin-1 (PSEN1) gene on proteolytic processing of the amyloid precursor protein (APP). The authors provide compelling evidence using mutations in PSEN to understand what drives alternative substrate turnover with convincing data and rigorous analysis. This deep mechanistic study provides a framework towards the development of small molecule inhibitors to treat AD.

eLife Assessment

This manuscript reports findings of fundamental significance on how bacteria might load helicase for DNA replication when normal DnaA-based loading pathway is defective. It provides convincing genetic and biochemical evidence that helicase loading at the E. coli oriC is not (as previously assumed) exclusively performed by the DnaA initiator protein but can also be executed by PriC (whether this occurs specifically at oriC has not been addressed in vivo). This is a significant step forward in our understanding of bacterial replication initiation.

eLife Assessment

This useful study provides incomplete evidence regarding the pathophysiological role of low estrogen levels post-menopause in hypertension, focusing on L-AABA as a key mediator. The results describe a novel hypothesis for the pathophysiology of hypertension in this population and are of interest to experts in hypertension and vascular biology.