Evaluated articles

Evaluation Summary:

This paper is of interest to neuroscientists studying the interaction between working memory, decision making, cell types, and neural oscillations. It introduces a detailed model of different brain areas which interact giving rise to the complex pattern of oscillations that are observed during a visual attention task. Additionally, the model reproduces the phase-dependent behavioral performance observed experimentally during such a task. This provides a new level of precision in our understanding of how rhythmic attention works in the brain.

(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 manuscript presents a creative, unique, and well-explained theoretical analysis of the shapes adopted by chromosome-attached microtubule bundles during manipulation with glass microneedles inside dividing cells. The overall conclusion is that the bundles are laterally anchored to other structures in the mitotic apparatus within several micrometers of their chromosome-attached ends, but relatively freer at their pole-proximal ends. This interesting work should appeal broadly to cell biologists and biophysicists.

(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:

Through the use of multiplexed in situ hybridization with careful embryo staging, this manuscript represents exemplary documentation of dynamic gene expression patterns in early fly development. By comparison of these patterns in various mutant combinations, a simple logical model for specification of expression is proposed. This manuscript will be of broad significance to developmental biologists interested in embryo segmentation and gene regulatory networks underpinning patterning.

(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 is of interest to scientists interested in the functions of the hippocampus, as well as those in the field of sensorimotor timing. The reported data and findings point towards the possibility that the hippocampus supports specific and generalized learning of short time intervals relevant to behavior. While the conclusions are mostly supported by the evidence, further clarification of methodology as well as additional analyses and discussion would strengthen the authors' conclusions.

(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 combination of proteome-specific protein complex structures and publicly available ribosome profiling data to show that cotranslational assembly is favored by large N-terminal intermolecular interfaces. The manuscript represents an important contribution to the field of protein biosynthesis pathways by suggesting an intuitive evolutionary mechanism that can promote co-translational assembly pathways in mammalians, yeast, and bacteria.

(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:

Second order conditioning is a higher form of learning where a previously conditioned stimulus (e.g. odor A by food) is used to condition the perception of another stimulus (e.g. odor B by odor A). Yamada et al. have used the fly to identify a neural circuit in the insect mushroom body underpinning second order conditioning. This work elegantly combines neural circuit mapping, electrophysiology and modeling to put forward a mechanistic model for this highly conserved form of learning.

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 measured the heartbeat and touch perception while people touched a variety of surfaces. The results indicate that people's heart rates and heartbeats vary systematically according to the type of touch performed and how difficult it was to perceive the grooved surfaces. The paradigm and the results appear very interesting though the specific analyses of choice and their presentation require some improvement to make a more convincing case.

(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 name with the authors.)

Evaluation Summary:

This paper is mainly for an audience of genetic epidemiologists interested in the evaluation and portability of polygenic scores. The authors show that a polygenic risk score to predict prostate cancer risk is very informative for individuals that are classified on three different ancestry categories. The authors show that the polygenic risk score can be used to predict the risk to develop prostate cancer as a function of age. This paper provides evidence that genetic information could be used to provide guidance to clinicians on when to perform screenings to detect prostate cancer in patients.

(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 paper is an impressive and deep look at a very important problem: understanding the genetic underpinnings of evolution acting on a quantitative trait. The authors analytically study the response to an abrupt shift in phenotypic optimum, in terms of both phenotype and genetic basis (how various alleles/loci contribute to this response). The basic assumptions are classic, but the methods and findings are new (especially finite population effects) and well supported by clear analytical approximations and extensive simulation checks. The main finding is that the relative contribution of large vs moderate effect alleles changes substantially and predictably over a long-term period after the shift, even though the phenotypic changes are already undetectable over this period.

(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 name with the authors.)

Evaluation Summary:

This manuscript contributes to a circuit-based understanding of how sweet and bitter tastes are integrated with hunger state to drive feeding initiation in Drosophila. Anatomical, behavioral, and neuronal activity data support a multi-step pathway from sensory input to motor output. This manuscript, thus, contributes to our understanding of how multiple sensory cues are integrated with an internal state to reach a behavioral decision.

(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 study investigates on how weight loss by bariatric surgery or weight-matched dietary intervention impairs breast cancer growth as well as immunotherapy. This study can potentially provide some therapeutic intervention strategies on combining vertical sleeve gastrectomy and immunotherapy in treating 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 agreed to share their name with the authors.)

Evaluation Summary:

This is an exemplary manuscript describing the creation of a novel mouse model to study bone marrow adipocytes. The authors demonstrate that these cells play a critical role in the pathophysiology of myeloid cell lineage regeneration as well as the maintenance of bone mass and hematopoietic progenitors during times of limited energy (e.g. caloric restriction).

(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:

In this paper, Ekman and colleagues present novel evidence, using a visual sequence task in fMRI, that the early visual cortex (V1) and the hippocampus both represent perceptual sequences in the form of a predictive "successor" representation, where the current state is represented in terms of its future (successor) states in a temporally discounted fashion. In both brain structures, there was evidence for upcoming, but not preceding steps in the sequence, and these results were found only in the temporal but not spatial domain. This study suggests that the hippocampus and V1 represent temporally structured information in a predictive, future-oriented manner.

(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 study provides evidence that murine acid ceramidase (Ac) is required for normal erythropoiesis and development of rodent malaria. The findings are of interest in understanding molecular processes involved in regulating erythropoiesis, as well as the potential to develop host-directed therapies for malarial parasites that target human reticulocytes.

(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:

Haggerty et al. reported findings examining how changes in brain function are involved in alcohol binge drinking, with a selective focus on the synaptic and circuit alterations that occur in the anterior insular cortex inputs within the dorsolateral striatum. They show that chronic alcohol drinking produces glutamatergic synaptic adaptations and by stimulating this circuit, binge drinking could be reduced without altering either water consumption or general performance for select reinforcing, anxiogenic or locomotor behaviors. The results of this study may specifically improve our understanding of the neurocircuitry mediating a common alcohol use disorder associated behavior referred to as "front-loading" or excessive drinking during the very beginning of the session.

(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 manuscript reports the complex interactions that take place in the uterus between the endometrium and the blastocyst during and after embryonic diapause, a period of suspended animation that occurs in some mammals including the mouse, the model used here. The authors showed that one gene, Foxa2, interacts with two other genes, Msx1 and LIF, to control the success and duration of diapause. This will be of broad interest to researchers in the field of developmental biology and reproduction. It is a carefully done study, providing new information on the complex process that is diapause in which an embryo goes into suspended animation until it receives appropriate signaling from the uterine endometrial secretions to reactivate.

(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 study intergenerational adaptation patterns in four relatively closely related nematode species, using previously established experimental procedures. Phenotypic and transcriptomic data are used to compare responses to stress triggers in the offspring generation between the species. The authors conclude that at least some of the responses are evolutionary conserved.

(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 paper is of interest for scientists studying human genetic adaptation and disease. The work improves on previous studies addressing the question of recent positive selection on genes underlying Mendelian diseases, by examining larger datasets of disease genes as well as carefully controlling for confounding factors that could result in disease genes and non-disease genes showing different patterns of genetic variation. The authors suggest that interference between strongly deleterious recessive mutations can reduce adaptation at disease genes, although this conclusion is weakened by the fact that the signal is only observed in Africa.

(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 is of interest to a broad range of neuroscientists, particularly those interested in ApoE biology and Alzheimer's disease (AD), as it reveals a novel mechanism that counteracts AD-linked amyloid plaque burden and synapse dysfunction in mice. Overall, the methodology is sound, sophisticated, and employs animal models that more closely mimic human diseases, and the results are interesting and compelling. Whilst the mechanistic hypothesis proposed by the authors is consistent with the data, plausible alternative explanations remain.

(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 manuscript presents a method to characterize diverse neural activity patterns arising from a small invertebrate circuit. This is of practical interest to invertebrate neuroscientists. The application of unsupervised methods to characterize qualitatively distinct regimes of spiking neural circuits is very interesting. The challenges and lessons learned in this study are therefore of broader interest to those seeking to quantitatively characterize large sets of neural data across many subjects. The survey could be improved by further validation of the derived clusters.

(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.)