Evaluated articles

Evaluation Summary:

There has been a great deal of recent interest in the neural basis for offset responses given their hypothesised importance to perception. This tests the relevance of offset responses to duration perception in a mouse model in addition to examining the brain basis. The work is thorough and well executed. The work demonstrates offset responses that occurs for the first time in auditory cortex distinct from A1 where prevention of offsets by activating cells causes worsening of behavioural performance.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

The manuscript addresses an important question with broad relevance to the fields of virology, reproductive biology and immunology, and cell death. The primary conclusion of viral-induced cell death is well supported. Some mechanistic details of the pathway remain unclear.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This paper documents in wild bonobos significant physiological changes in response to becoming a sibling for the first time. The authors find that new siblings' cortisol increases dramatically, while their neopterin (a marker of immune function) decreases. This paper will be of interest to those who study development, life history transitions, and colleagues at the intersection of physiology and behavior, in particular in primates and other mammals with slow life histories.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This is an interesting study, conducted in mice, that demonstrates for the first time the presence of a large population of cytotoxic CD4+ T lymphocytes in infection with Trypanosoma cruzi, a relevant human pathogen. At present, the relevance of these cells in protective immunity engendered by the host remains unclear. Additional experiments are needed to characterize the functionality of these cytotoxic CD4 T cells vis-a-vis the canonical Th1 T cells. This paper can be of interest to scientists interested in immune responses to parasitic infections.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

The manuscript will be of interest to a broad audience in structural biology, biochemistry, and enzymology. The work demonstrates the use of a cutting-edge approach in protein crystallography to investigate and visualize the complex mechanism of an enzyme, the paradigm being Mn-dependent ribonucleotide reductase R2b in complex with flavin-bound NrdI at different redox states. The work is timely and has implications for future investigation of complex biochemical processes.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Using an impressive experimental design, Tang et al. analyzed the effects of intraspecific (genetic) and interspecific (species) diversity in ecosystem processes carried out by forest communities. The results show that both species and genotype diversity influence productivity via changes in overall functional diversity, herbivory, and soil fungal diversity. This study will be important to ecologists and environmentalists interested in ecosystem processes and restoration efforts.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

The manuscript shows an important role for Cav2.3 channels in SNI-mediated allodynia and firing properties of PV-expressing APT neurons. Mechanisms that underlie adaptations in chronic pain models are extremely important for the development of novel therapeutics for chronic pain and this could be a significant contribution in that regard. However, the discussion asserts that these studies are the "first direct evidence that supra-spinal Cav3.2 channels play a fundamental role in pain pathophysiology." This is an overstatement as Chen and colleagues examined the role of these channels in the anterior cingulate cortex in CCI-mediated neuropathic pain (Shen, et al., 2015, Molecular Pain).

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

Ribeiro M et al investigate the ability of a novel bispecific CD19-CD47 antibody to enhance the cell mediated killing mediated by existing drug combinations - anti-CD20 plus PIK3d/CK1E inhibitor. The novelty of this study is the restriction to CD19 positive lymphoma cells, thus potentially avoiding toxicity to non-lymphoma lineages, and the gene expression profiling to identify up regulation of GPR183 after combined treatment of CD19/47 plus CD20/PI3K/CK1E vs CD19/47 alone. Genetic and drug studies suggest that GPR183 is essential for the full activity of the triplet drug combination.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Evaluation summary:

This study investigates the neural basis of the hidden causal structure between visual and proprioceptive signals in the primate premotor and parietal circuit during reaching tasks executed in a virtual reality environment, where information between the two modalities can be dissociated. Modelling is used to characterize the proprioceptive drift of the monkeys when integrating bimodal information. The key novel result is that premotor neurons represent the integration of bimodal information for small disparities and the segregation for large disparities between the proprioceptive and visual information, while parietal cells show reaching tuning changes that support the updating sensory uncertainty between tasks. Overall, the experiments are technically sound, and the conclusions are mostly well supported. However, a simpler framing of the paper could make the main message easier to grasp, the analysis of Bayesian models seems to lack major details, the statistical reporting is below standard, and a large part of the extensive literature on the role of premotor and parietal cortex in visuomotor behavior is lacking.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This paper suggests that assembly of CaV2.3 with b2a/b2e splice variants confers biophysical properties that enable these channels to contribute to calcium-dependent pacemaking in dopaminergic neurons. The findings could have implications for why these neurons are vulnerable to degeneration in Parkinson's disease. The work will be of interest to ion channel biophysicists and neuroscientists.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

The authors use a comparative genomics approach to predict gene function, in particular genes that have a role in eye development. After identifying the convergent loss of SERPINE3 with vision loss across mammals, the authors confirmed its involvement in eye development by characterizing zebrafish knockouts. This work highlights the power of comparative genomics to generate hypotheses that can be experimentally validated. This work is relevant to a broad audience interested in evolution and adaptation as well as for those studying eye development and eye pathologies.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

The authors provide evidence suggesting the gene expression profile of a specific subset of dendritic cells define features of specific forms of non-infectious uveitis. This work suggests specific pathways in these cells that may have mechanistic import in inflammatory eye disease. This manuscript is of interested to immunologists studying autoimmunity and ocular immunity. While the paper is largely descriptive, the data it presents should serve as a valuable resource for generating hypotheses about the pathogenesis of ocular autoimmune disease.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This article proposes methodology and accompanying software for robustly fitting dose-response curves where response is a number between 0 and 1. When response is transformed using the common logistic transformation, values close to 0 or 1 become large in magnitude, unduly influencing the fitted curve after back-transformation and introducing bias in the estimate of certain parameters. The proposed approach, called Robust and Efficient Assessment of Potency, is less perturbed by these extreme measurements.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This paper combines new and previously generated data on hand preference to show that hand preference strength, but not direction, is predicted by ecology and phylogeny across primates. By drawing on the most expansive data set to date on experimentally determined hand preference, it calls existing hypotheses on the evolution of hand preference into question and shows that the strength of lateralization in humans is uniquely extreme. Its results are of interest to evolutionary anthropologists, primatologists, and evolutionary morphologists. However, concerns about intraspecific variation and the accuracy of handedness estimates for poorly sampled species are incompletely addressed by the manuscript in its current form.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

The authors of this manuscript, which is of interest to the cancer community, identify the chromatin regulator WDR5 as a possible new drug target in triple negative breast cancer. Targeted therapeutics for this patient population are of high scientific and clinical interest, and the authors provide a compelling case that co-targeting WDR5 along with mTOR provides a promising new therapeutic strategy.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

This manuscript provides a detailed structural and biophysical characterization of several complexes of the p52 homodimer of NF kB and different DNA binding sites. The main topic is the investigation of why the central base pair(s) have a strong influence on the transcriptional activity of the homodimer. The authors correlate structural changes with measurements of kinetic on and off rates to develop a model that explains the differences in activity. The paper is of interest to all working on understanding how transcriptional activity is regulated.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

The long non-coding RNA HOTAIR has been widely reported to be overexpressed in many cancers, including breast cancer, and is strongly associated with disease progression and poor patient outcomes. A valuable new mouse model was developed for studying the functional effects of overexpressing HOTAIR and the mechanism of action of HOTAIR and used to demonstrate overexpression of HOTAIR promoted breast cancer metastasis to the lung. The mouse model and the conclusions will be of interest to researchers interested in improving treatment for breast cancer.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This paper proposes that specializations in the outer hair cells' biophysical properties along the cochlea may allow them to amplify the reduced receptor potentials in a manner sufficient to explain all present experimental results. Moreover, the filtering provided by the hair cells may be beneficial for hearing soft high-frequency sounds because it decreases noise and harmonic distortions. Importantly, the amplitude of the relevant motions, even with the low-pass-filtered attenuation, are as large as those measured in the high frequency regions of the cochlea. The authors provide insights and suggestions but the paper lacks strong supportive experimental data to definitively resolve the claimed "apparent" membrane time constant conundrum.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

The manuscript describes several optimizations of classic DNA reporter constructs to monitor closely the dynamics of Wnt/β-catenin signalling during development using transgenic avian lines. As Wnt signalling pathway is essential in the homeostasis of vertebrate and invertebrate organisms, a robust tool to analyse finely the dynamics of Wnt/β-catenin pathway is of broad interest for the biology/biomedicine scientific communities.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

The authors describe the reconstitution of axonemal bending using polymerized microtubules, purified outer-arm dyneins, and synthesized DNA origami to cross-link two microtubules. The work is of interest for the field as it shows that bidirectional sliding and bending of microtubules can be generated by a minimal set of elements.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)