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  1. Single-cell and single-nucleus RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates, and humans

    This article has 29 authors:
    1. Trygve E Bakken
    2. Cindy TJ van Velthoven
    3. Vilas Menon
    4. Rebecca D Hodge
    5. Zizhen Yao
    6. Thuc Nghi Nguyen
    7. Lucas T Graybuck
    8. Gregory D Horwitz
    9. Darren Bertagnolli
    10. Jeff Goldy
    11. Anna Marie Yanny
    12. Emma Garren
    13. Sheana Parry
    14. Tamara Casper
    15. Soraya I Shehata
    16. Eliza R Barkan
    17. Aaron Szafer
    18. Boaz P Levi
    19. Nick Dee
    20. Kimberly A Smith
    21. Susan M Sunkin
    22. Amy Bernard
    23. John Phillips
    24. Michael J Hawrylycz
    25. Christof Koch
    26. Gabe J Murphy
    27. Ed Lein
    28. Hongkui Zeng
    29. Bosiljka Tasic
    This article has been curated by 1 group:
    • Curated by eLife

      Summary: This manuscript provides a comparative analysis of the cell variety present in the dorsal lateral geniculate nucleus (dLGN) of mice, non-human primates, and humans using single-cell/single-nucleus RNA-sequencing (Smart-seq). The study identifies excitatory and inhibitory dLGN cell types in the three species and shows that the different subclasses of inhibitory neurons are relatively similar across species. In contrast, excitatory neurons appear to bear cross-species differences particularly between mouse and primates. The study provides an extensive description of the dLGN neurons, an important visual relay nucleus that has been so far poorly studied. As such, these data are very welcomed and will likely attract the interest of researchers working in visual function and beyond. The strong and creative bioinformatics analysis has uncovered interesting and subtle cross species links between different types of neurons.

      Reviewer #1, Reviewer #2 and Reviewer #3 opted to reveal their name to the authors in the decision letter after review.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  2. Computational modeling identifies embolic stroke of undetermined source patients with potential arrhythmic substrate

    This article has 13 authors:
    1. Savannah F Bifulco
    2. Griffin D Scott
    3. Sakher Sarairah
    4. Zeinab Birjandian
    5. Caroline H Roney
    6. Steven A Niederer
    7. Christian Mahnkopf
    8. Peter Kuhnlein
    9. Marcel Mitlacher
    10. David Tirschwell
    11. WT Longstreth
    12. Nazem Akoum
    13. Patrick M Boyle
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      In this manuscript, the authors try to answer an important clinical question about the previously observed connection between embolic stroke of undetermined source (ESUS) and atrial fibrillation (AF). Using cutting-edge personalized computational modeling of left atrium from both ESUS and AFib patients, the researchers try to understand why the fibrotic substrate found in both ESUS and AFib patients causes arrhythmia in the latter group but not the former. Their study concludes that the intrinsic capacity to sustain arrhythmias of fibrosis found in ESUS and AFib atrium are identical. The key claims of the manuscript are well supported by the data, and the modeling methodology is largely appropriate.

      (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 and Reviewer #3 agreed to share their names with the authors.)

    Reviewed by eLife

    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  3. Perinatal granulopoiesis and risk of pediatric asthma

    This article has 10 authors:
    1. Benjamin A Turturice
    2. Juliana Theorell
    3. Mary Dawn Koenig
    4. Lisa Tussing-Humphreys
    5. Diane R Gold
    6. Augusto A Litonjua
    7. Emily Oken
    8. Sheryl L Rifas-Shiman
    9. David L Perkins
    10. Patricia W Finn
    This article has been curated by 1 group:
    • Curated by eLife

      Summary: This is a nice study that is clearly written and makes use of several datasets. It attempts to explain perinatal risk factors and the associated risk of developing pediatric asthma in the mid-childhood and early teenage years. Identified among maternal characteristics that were associated with risks of subsequent asthma development included atopy, BMI, race/ethnicity and demographics, birth characteristics, and mode of delivery. The paper then goes on to demonstrate the differences in immune response during the different time frames of pregnancy. Most notably, a gene signature associated with increased myelopoiesis in utero is associated with increased risk of pediatric asthma. Furthermore they show that cord blood serum PGLYRP -1 is associated with reduced risk of pediatric asthma and increased FEV1/FVC. Interestingly sIL6ra which is derived from neutrophils but not associated with neutrophil granules did not show any association with pulmonary outcomes. This suggests that it is the neutrophil granules rather than the neutrophils per se that are the problem association.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  4. Anticipation of temporally structured events in the brain

    This article has 3 authors:
    1. Caroline S Lee
    2. Mariam Aly
    3. Christopher Baldassano
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      The study addresses a topic that is timely and of general interest. The findings represent a potentially very interesting contribution to the important question of how the brain comes to predict the future, in particular lifelike sequences of events. However, some of the main conclusions would require further statistical support.

      (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.)

    Reviewed by eLife

    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  5. Fate mapping analysis reveals a novel murine dermal migratory Langerhans-like cell population

    This article has 13 authors:
    1. Jianpeng Sheng
    2. Qi Chen
    3. Xiaoting Wu
    4. Yu Wen Dong
    5. Johannes Mayer
    6. Junlei Zhang
    7. Lin Wang
    8. Xueli Bai
    9. Tingbo Liang
    10. Yang Ho Sung
    11. Wilson Wen Bin Goh
    12. Franca Ronchese
    13. Christiane Ruedl
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      The present study uses innovative approaches to further our knowledge of skin immunobiology. The corresponding results explain the expression of langerin on two fractions of dermal DC (CD103+ and CD103-) observed several years ago. The demonstration that epidermal LC do not contribute to LN populations in the steady state is completely unexpected and raises important questions about the in vivo function of the LC-like subset unveiled in the present study.

      (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.)

    Reviewed by eLife

    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  6. Confinement discerns swarmers from planktonic bacteria

    This article has 6 authors:
    1. Weijie Chen
    2. Neha Mani
    3. Hamid Karani
    4. Hao Li
    5. Sridhar Mani
    6. Jay X Tang
    This article has been curated by 1 group:
    • Curated by eLife

      Summary: In this paper, the authors proposed a new approach by mounting a PDMS microwells of specific sizes on agar surface to confine swarming and planktonic SM3 cells. They found swarming bacteria exhibit a "single-swirl" motion pattern and concentrated planktonic bacteria exhibit "multi-swirls" motion pattern in the diameter range of 31-90 μm. The phase diagram shows that in smaller wells concentrated planktonic SM3 forms a single vortex and in larger wells swarming SM3 also breaks into mesoscale vortices.

      In addition, they conducted systematic experiments to explore parameters defining the divergence of motion patterns in confinement including cell density, cell length, cell speed and surfactant. They concluded that the single swirl pattern depends on cohesive cell-cell interaction mediated by biochemical factors removable through matrix dilution.

      This paper gives a new method to discern swarmers from planktonic bacteria and carefully studies the factors that influence the formation of bacterial vortices under restriction.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  7. Loss of MGA repression mediated by an atypical polycomb complex promotes tumor progression and invasiveness

    This article has 19 authors:
    1. Haritha Mathsyaraja
    2. Jonathen Catchpole
    3. Brian Freie
    4. Emily Eastwood
    5. Ekaterina Babaeva
    6. Michael Geuenich
    7. Pei Feng Cheng
    8. Jessica Ayers
    9. Ming Yu
    10. Nan Wu
    11. Sitapriya Moorthi
    12. Kumud R Poudel
    13. Amanda Koehne
    14. William Grady
    15. A McGarry Houghton
    16. Alice H Berger
    17. Yuzuru Shiio
    18. David MacPherson
    19. Robert N Eisenman
    This article has been curated by 1 group:
    • Curated by eLife

      Summary:

      The reviewers agreed that the paper provides strong in vivo data for a tumor-suppressive role for Mga in lung carcinogenesis. The authors convincingly show that MGA is important in oncogenesis. We note here that MGA is highly understudied (~200 publications) in and of itself despite its involvement with the MYC network for oncogenesis (~41,000 publications at the current time). Given a protein of 3000 amino acids, the number of potential protein partners and PTMs that might modify its tumor suppressor functions are staggering. However, the reviewers also noted that a previous paper has addressed the same topic and the novelty of the data presented here needs to be better explained and additional experiments are needed to strengthen and expand the new aspects.

      Reviewer #1 opted to reveal their name to the authors in the decision letter after review.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  8. Probing the decision-making mechanisms underlying choice between drug and nondrug rewards in rats

    This article has 5 authors:
    1. Youna Vandaele
    2. Magalie Lenoir
    3. Caroline Vouillac-Mendoza
    4. Karine Guillem
    5. Serge H Ahmed
    This article has been curated by 1 group:
    • Curated by eLife

      Summary:

      In this manuscript the authors perform a retrospective analysis in attempt to delineate the role of goal-directed versus habitual mechanisms underlying choice between drug and non-drug rewards. Specifically, the authors utilized data generated in their laboratory to assess cocaine-versus-saccharin choice following limited and extended training paradigms. A sequential choice model was used to assess the prediction that increased latencies during choice reflect goal-directed control; whereas no change in latencies reflects habitual control. Based on this model, the authors report that rats engage in goal-directed control after limited training, and adopt more habitual responding after extended training. The authors conclude that the sequential choice model is specific to habitual choice.

      While the Reviewers appreciate the approach and conceptual framework described in this manuscript, they are all in agreement that additional data and analyses are needed to better support the claims surrounding goal-directed versus habitual control of reward-seeking behavior. For example, an independent evaluation of whether the target behavior is in fact goal-directed or habitual seems necessary to support such claims. Reviewers’ comments and suggestions for improvement are included below.

      Reviewer #1 and Reviewer #2 opted to reveal their name to the authors in the decision letter after review.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  9. Archaeal chromatin ‘slinkies’ are inherently dynamic complexes with deflected DNA wrapping pathways

    This article has 3 authors:
    1. Samuel Bowerman
    2. Jeff Wereszczynski
    3. Karolin Luger
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      In their manuscript titled "Archaeal chromatin 'slinkies' are inherently dynamic complexes with deflected DNA wrapping pathways", Bowerman et al. use an elegant combination of cryo-EM, analytical ultracentrifugation and molecular dynamics simulations to investigate the structure and dynamics of archaeal histone — DNA complexes, termed archaeasomes to distinguish them from eukaryotic nucleosomes. This study builds upon the crystal structure of an archaeasome and the functional analysis of its disruption recently published by the same group (Mattiroli et al, 2017) by analyzing the dynamics of this complex and discussing how these dynamics could relate to archaeal genome biology. How chromatin evolved is a fundamental question in biology, marking a striking departure from the bacterial nucleoid. This current manuscript describes a rigorous biophysical study that not only provides substantial new insights into archaeal genome biology but also raises intriguing questions for future study. This manuscript will therefore no doubt be of interest not only to the archaeal research community but also to the field of chromatin biology.

      (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.)

    Reviewed by eLife

    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  10. Rapid recycling of glutamate transporters on the astroglial surface

    This article has 3 authors:
    1. Piotr Michaluk
    2. Janosch Peter Heller
    3. Dmitri A Rusakov
    This article has been curated by 1 group:
    • Curated by eLife

      Summary: In this study, Michaluk et al. examined the membrane dynamics of the main glial glutamate transporter GLT1 in hippocampal astrocytes, which was previously shown to shape synaptic transmission through regulating extracellular levels of glutamate. Using GLT1 tagged on its surface with a pH-sensitive fluorescent marker, GLT1-SEP, the authors performed (1) fluorescence recovery after photobleaching (FRAP) experiments to assess the basal and activity-dependent dynamics of surface GLT1-SEP and (2) super-resolution dSTORM imaging to determine the relationship between GLT1 and PSD-95, an excitatory synapse marker. A large proportion of surface GLT1-SEP underwent turnover with a surface lifetime of 22 s, whereas a smaller fraction (~25%) remained largely immobile, which was decreased upon increased activity. Notably, the cytoplasmic domain of GLT1-SEP was shown to attenuate the basal turnover of surface GLT1 and to facilitate its proximal localization to synapses; moreover, GLT1 cytoplasmic domain was required for activity-dependent increase in the mobile fraction.

      While previous studies using single molecule tracking have demonstrated a role for the lateral diffusion of GLT1 in controlling the recruitment of GLT1 near active synapses, the present study uses powerful optical approaches and analysis tools to access both the surface lateral mobility and the exchange between surface and intracellular pools of GLT1. Furthermore, characterization of the nanoscale organization of GLT1 relative to synapses and its dependence on the C-terminal domain of GLT1 is presented. Altogether, the results are interesting and valuable, and underscore the importance of the GLT1 C-terminus in the membrane turnover and in the activity-dependent lateral diffusion of the surface GLT1. Nevertheless, some of the conclusions are not strongly supported by the data shown.

      Reviewer #2 opted to reveal their name to the authors in the decision letter after review.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  11. Inhibitory control of frontal metastability sets the temporal signature of cognition

    This article has 5 authors:
    1. Vincent Fontanier
    2. Matthieu Sarazin
    3. Frederic M Stoll
    4. Bruno Delord
    5. Emmanuel Procyk
    This article has been curated by 1 group:
    • Curated by eLife

      Summary: Both reviewers found this study's findings to be interesting and novel, and they appreciated the integration of intrinsic timescale analysis, coding of behavioral signals, and exploration of mechanisms in a biophysical circuit model. However, they both raised serious concerns about methodological and interpretational aspects of the analyses which would need to be satisfactorily addressed in subsequent review. In consultation, both reviewers were in agreement with all points raised in the other's review. I view the two reviewers' requests and suggestions as appropriate and complementary, and all of them needed response.

      I highlight here two of the major concerns raised by the reviewers (but all raised by the reviewers merit addressing). First is the need for intrinsic timescale analysis to not be confounded by slowly varying changes in firing rate coding task variables (Point 1.2 of Reviewer 2). This is important for interpretation on intrinsic timescale and its correlation with task variable coding as a major result. Second is the interpretation and implementation of Hidden Markov Models to non-simultaneously recorded neurons (Points 6 of Reviewer 1 and 3 of Reviewer 2). Here again the HMM states may be driven by task variable coding which is not corrected for, which could confound interpretation of results as in terms of meta-stable states and its link to the circuit model. Furthermore, HMM analysis of the circuit model does not match its methodology for experimental data, but could be through non-simultaneous model spike trains, which the manuscript does not justify. I will add my own suggestion that perhaps both of these methodological data analysis concerns could potentially be addressed through comparison to the null model of a non-homogeneous Poisson process with firing rate given by the variable-coding PSTH. I do not consider it necessary to study a network model that performs the task, as suggested for consideration by Reviewer 1.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 1 listLatest version Latest activity