Bioengineering

Improved isolation of extracellular vesicles by removal of both free proteins and lipoproteins

1. Dmitry Ter-Ovanesyan
2. Tal Gilboa
3. Bogdan Budnik
4. Adele Nikitina
5. Sara Whiteman
6. Roey Lazarovits
7. Wendy Trieu
8. David Kalish
9. George M Church
10. David R Walt

• Curated by eLife

  eLife assessment

  This study will be of interest and valuable to scientists of many different subareas in the study of eukaryotic extracellular vesicles. The authors' efforts to improve the way we analyze EVs are highly appreciated and their results are convincing: they not only used appropriate and validated methodologies in line with current state-of-the-art but also presented alternatives to improve these approaches.

Reviewed by eLife

Aggregating in vitro-grown adipocytes to produce macroscale cell-cultured fat tissue with tunable lipid compositions for food applications

1. John Se Kit Yuen Jr
2. Michael K Saad
3. Ning Xiang
4. Brigid M Barrick
5. Hailey DiCindio
6. Chunmei Li
7. Sabrina W Zhang
8. Miriam Rittenberg
9. Emily T Lew
10. Kevin Lin Zhang
11. Glenn Leung
12. Jaymie A Pietropinto
13. David L Kaplan

• Curated by eLife

  eLife assessment

  This manuscript describes an approach to creating fat tissue in culture for food applications. Specifically, the efforts of growing cultivated meat focus mostly on growing skeletal muscle. However, the taste component of such artificial meat would be determined by fat content. There is a significant desire and motivation to cultivate fat tissues in vitro for the purpose of the replacement of animal products. This paper provides new technological approaches to expand adipocytes and aggregate them into structures that resemble fat.

Reviewed by eLife

PhysiCOOL: A generalized framework for model Calibration and Optimization Of modeLing projects

1. Inês G. Gonçalves
2. David A. Hormuth
3. Sandhya Prabhakaran
4. Caleb M. Phillips
5. José Manuel García-Aznar

Reviewed by GigaByte

Cryo-EM reveals an unprecedented binding site for NaV1.7 inhibitors enabling rational design of potent hybrid inhibitors

1. Marc Kschonsak
2. Christine C Jao
3. Christopher P Arthur
4. Alexis L Rohou
5. Philippe Bergeron
6. Daniel F Ortwine
7. Steven J McKerrall
8. David H Hackos
9. Lunbin Deng
10. Jun Chen
11. Tianbo Li
12. Peter S Dragovich
13. Matthew Volgraf
14. Matthew R Wright
15. Jian Payandeh
16. Claudio Ciferri
17. John C Tellis

• Curated by eLife

  eLife assessment

  This fundamental study describes the structure-based design of novel hybrid inhibitors targeting a human sodium channel which is a pain target. Exceptionally strong evidence for key claims was produced with a structural biological pipeline for iterative structural determination of drugs complexed with an engineered sodium channel. This work is expected to be of interest to biophysicists, drug developers, neurobiologist, and pain researchers.

Reviewed by eLife

Optimization of energy and time predicts dynamic speeds for human walking

1. Rebecca Elizabeth Carlisle
2. Arthur D Kuo

• Curated by eLife

  eLife assessment

  This valuable study presents a new optimal control cost framework to predict features of walking bouts, adding a cost function term proportional to the duration of the walking bout in addition to the conventional energetic term. While predicted optimal trajectories from simulations qualitatively matched walking data from human subjects, the evidence supporting these claims is incomplete, as some methodological choices raise questions about the strength of the authors' claims.

Reviewed by eLife

A general approach for stabilizing nanobodies for intracellular expression

1. John G Dingus
2. Jonathan CY Tang
3. Ryoji Amamoto
4. Grace K Wallick
5. Constance L Cepko

• Curated by eLife

  eLife assessment

  Dingus et al. have developed an innovative approach for improving the intracellular stability of nanobodies. Working with a set of 75 nanobodies, the authors have identified key amino acid changes that can improve the stability of nanobodies expressed within the cell that might be generalized to other nanobodies.

Reviewed by eLife

High-resolution imaging of the osteogenic and angiogenic interface at the site of murine cranial bone defect repair via multiphoton microscopy

1. Kevin Schilling
2. Yuankun Zhai
3. Zhuang Zhou
4. Bin Zhou
5. Edward Brown
6. Xinping Zhang

• Curated by eLife

  eLife assessment

  The authors present very exciting findings on the cranial bone defect repair using cutting-edge multiphoton imaging to study the role of different vessel subtypes and related oxygen and metabolic microenvironments. The study used microscopy to visualize the oxygen distribution and energy metabolism within the defects at different time points during the process of bone healing. This allows one to understand the pathophysiological progressions of bone diseases and regeneration. It will also provide critical information to optimize the therapeutic bone healing and regeneration approach for different clinical situations.

Reviewed by eLife

Translational rapid ultraviolet-excited sectioning tomography for whole-organ multicolor imaging with real-time molecular staining

1. Wentao Yu
2. Lei Kang
3. Victor TC Tsang
4. Yan Zhang
5. Ivy HM Wong
6. Terence TW Wong

• Curated by eLife

  eLife Assessment:

  This paper demonstrates an integrated labeling and block face fluorescence imaging method that enables the rapid evaluation of biological specimens as large as an E18 mouse embryo with single cell resolution. Such capabilities will likely be of great interest to developmental biologists and pathologists. While the approach can be considered a major step forward, additional experimental support is necessary to gauge how quantitative the method is.

  (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.)

Reviewed by eLife

High spatial resolution analysis using automated indentation mapping differentiates biomechanical properties of normal vs. degenerated articular cartilage in mice

1. Anand O Masson
2. Bryce Besler
3. W Brent Edwards
4. Roman J Krawetz

• Curated by eLife

  Evaluation Summary:

  The work presented by Masson et al. highlights experimental approaches using spatial indentation and contrast-enhanced 3-D x-ray imaging to topographically map cartilage thickness in mouse knee joints. This methods described have the potential to impact the field of musculoskeletal biomechanics, especially for researchers using mouse models to study cartilage wear and disease, given the high resolution and sensitivity of the described approaches.

  (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.)

Reviewed by eLife

The mini-IDLE 3D biomimetic culture assay enables interrogation of mechanisms governing muscle stem cell quiescence and niche repopulation

1. Erik Jacques
2. Yinni Kuang
3. Allison P Kann
4. Fabien Le Grand
5. Robert S Krauss
6. Penney M Gilbert

• Curated by eLife

  Evaluation Summary:

  This Methods paper seeks procedures evaluating the balance between muscle cell quiescence and activation. These could well permit investigations of long-standing questions in key areas of muscle function. The latter include the regulation of adult stem cell pool size and functional heterogeneities in this, as well as regulators of muscle quiescence.

  (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