Evaluated articles

eLife assessment

Serotonin is an important neurotransmitter and its synaptic concentration is controlled by re-uptake by the sodium-coupled serotonin transporter SERT. The manuscript by Chan et al reports results from a systematic deep mutagenesis approach to study the surface expression and APP+ (5HT analogue) transport mechanism of the human serotonin transporter. The authors complement this experimental evidence with large-scale molecular simulations of the transporter in the presence of APP+. The use of deep mutagenesis and large-scale adaptive sampling simulations is impressive, and could contribute to understanding the structural requirements for folding and how transporters evolve to recognize different substrates.

eLife assessment

This investigation marks an important advancement in our understanding of motor thalamus connectivity, illustrating a complex integration of inputs that reshapes previous models. The study utilizes compelling methodologies that expose a dynamic synaptic network, although the evidence of triple-input convergence on individual neurons and for multiple driver type inputs onto motor thalamic neurons remains incomplete. Despite this, the findings provide a persuasive rationale for revisiting our perceptions of the thalamic role in motor control, with a call for further studies to substantiate the breadth of these functional interactions.

eLife assessment

This fundamental work advances our understanding of the central coding and control mechanisms regulating sympathetic nervous system efferent signals to bone. The evidence supporting the conclusion is mostly convincing, although the inclusion of higher resolution images for certain data and further discussions would strengthen the study. This paper holds potential interest for skeletal biologists and neuroscientists who study the brain-bone sympathetic neural circuits.

eLife assessment

The study presents a valuable finding on quantifying the orientation and organization of chondrocyte columns in the prenatal and postnatal growth plate cartilage using advanced 3D imaging and a sophisticated image analysis pipeline. The evidence supporting the authors' conclusions regarding the lack of columns in the fetal growth plate is considered inadequate due to technical caveats, inconsistencies in the data and corresponding model, and failure to correctly put the findings in context.

eLife assessment

This paper is valuable in that it provides a critical missing link between measures of structural connectivity and rhythmic tapping abilities, pointing to some interesting possibilities for how tapping synchronization is carried out. The methodology and findings are solid, and of interest to those studying the neural mechanisms of timing.

eLife assessment

This paper presents a new method for separating organelles in an unbiased way. The method is applied to the separation of distinct subpopulations of insulin vesicles. There are concerns around whether the vesicles measured are in fact insulin vesicles and whether the observed changes in vesicle populations upon glucose stimulation are biologically meaningful, and thus it is difficult to assess at this stage how well the technique performs. This paper is likely to be of wide interest to cell biologists studying a variety of compartments, as well as to researchers in the beta cell field.

eLife assessment

This valuable study reports that actin-related proteins may be involved in transcriptional regulation during spermatogenesis. The supporting data remain incomplete, and more extensive disentanglement from the canonical role of these actin-related proteins and the experimental validation of in silico predictions are required. This work will be of interest to reproductive biologists and other researchers working on non-canonical roles of actin and actin-related proteins.

eLife assessment

This study uses numerical simulations to characterize and compare variants of two widely used mathematical models and then applies those models to inferring evolutionary parameters from breast cancer data. The copious numerical results will be of some interest to mathematical biologists working with similar models. The finding that many breast cancer mutations are mildly deleterious is valuable but the evidence supporting this claim is incomplete because the mathematical modelling and statistical methods are insufficiently justified and inadequately validated.

eLife Assessment

This important study significantly advances our understanding of the skeleton of cartilaginous fishes by using a range of state of the art and complementary approaches to compare the skeleton amongst three cartilagenous fishes (catshark, little skate and ratfish). The evidence presented is compelling and likely to impact several fields of study.

eLife Assessment

This study unveils important data describing cell states of olfactory ensheathing cells, and how these cell states may relate to repair after spinal cord injury. The framework used for characterizing these cells is solid. This work will be of interest to stem cell biologists and spinal cord injury researchers.

eLife Assessment

This valuable study provides a novel method to detect sleep cycles based on variations in the slope of the power spectrum from electroencephalography signals. The method, dispensing with time-consuming and potentially subjective manual identification of sleep cycles, is supported by solid evidence and analyses. This study will be of interest to researchers and clinicians working on sleep and brain dynamics.

eLife Assessment

This valuable study reports that epididymal proteins are required for embryogenesis after fertilization. The data presented are generally supportive of the conclusion and considered solid. This work will be of interest to reproductive biologists and andrologists.

eLife Assessment

This important study reports the developmental dynamics and molecular markers of the rete ovarii during ovarian development. The data supporting the main conclusions are convincing. This study will be of interest to developmental and reproductive biologists.

eLife assessment

This fundamental study reports the deep evolutionary conservation of a core genetic program regulating spermatogenesis in flies, mice, and humans. Convincing data were presented and supported the main conclusion. This work will be of interest to evolutionary and reproductive biologists.

eLife assessment

This important study shows how a combination of the latest generation of Oxford Nanopore Technology long reads with state-of-the art variant callers enables bacterial variant discovery at an accuracy that matches or exceeds the current "gold standard" with short reads. The work thus heralds a new era, in which Illumina short-read sequencing no longer rules supreme. While the inclusion of a larger number of reference genomes would have enabled an even more fine-grained analysis, the evidence as it is supports the claims of the authors convincingly. The work will be of interest to anyone performing sequencing for outbreak investigations, bacterial epidemiology, or similar studies.

eLife Assessment

Genetic variants have been strongly implicated in idiopathic scoliosis (IS), however, the list of variants that are causative of IS is not complete and the cellular and molecular mechanisms that underlie IS are poorly understood. These authors combined human genetic analysis with zebrafish experiments to produce valuable evidence that alleles that impair function of EPHA4 cause IS, thereby extending our understanding of the basis of IS. The human genetic data are quite convincing but the zebrafish work lacks some validations and details.

eLife assessment

This fundamental study provides a modeling regime that provides new insight into the energy-preservation parameters among schooling fish. The strength of the evidence supporting observations such as distilled dynamics between leading and lagging schooling fish which are derived from emergent properties is compelling. Overall, the study provides exciting insights into energetic coupling with respect to group swimming dynamics.

eLife assessment

This useful study describes the second earliest known winged ovule without a capule in the Famennian of Late Devonian. Using solid mathematical analysis, the authors demonstrate that three-winged seeds are more adapted to wind dispersal than one-, two- and four-winged seeds. The manuscript will help the scientific community to understand the origin and early evolutionary history of wind dispersal strategy of early land plants.

eLife Assessment

This work is important because it elucidates how immune cells migrate across the blood brain barrier. In the revised version of this study, the authors present a convincing framework to visualize, recognize and track the movement of different immune cells across primary human and mouse brain microvascular endothelial cells without the need for fluorescence-based imaging using microfluidic devices. This work will be of broad interest to the cancer biology, immunology and medical therapeutics fields.

eLife Assessment

This important study advances our understanding of the temporal dynamics and cortical mechanisms of eye movements and the cognitive process of attention. The evidence supporting the conclusions is convincing and based on measuring the time course of the eye movement-attention interaction in a novel, carefully-controlled experimental task. This study will be of broad interest to psychologists and neuroscientists interested in the dynamics of cognitive processes.