Bioengineering

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

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

Directing Cholangiocyte Morphogenesis in Natural Biomaterial Scaffolds

1. Quinton Smith
2. Jennifer Bays
3. Linqing Li
4. Haniyah Shareef
5. Christopher S. Chen
6. Sangeeta N. Bhatia

• Curated by eLife

  Evaluation Summary:

  This paper is of interest for cell biologists, developmental biologists and tissue engineers. The authors identify a combination of natural extracellular matrix and growth factors that enables to grow cholangiocytes as branched three-dimensional ducts in culture. The work is physiologically relevant and represents an interesting step forward in the study of bile duct formation and disease, although the cultured ducts could be characterized more in depth.

  (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

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

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

Metrics of high cofluctuation and entropy to describe control of cardiac function in the stellate ganglion

1. Nil Z Gurel
2. Koustubh B Sudarshan
3. Joseph Hadaya
4. Alex Karavos
5. Taro Temma
6. Yuichi Hori
7. J Andrew Armour
8. Guy Kember
9. Olujimi A Ajijola

• Curated by eLife

  Evaluation Summary:

  This study will interest basic and clinical scientists and, potentially, device manufacturers interested in the regulation of heart rate in health and disease. A major control of the heart is from the nervous system originating in a neuronal cluster sitting outside the heart called the stellate ganglia. This study has identified the neural code associated with a healthy heart and describes how it changes in disease. Whether the change in code is cause or effect remains equivocal although normalising the code may have valued therapeutic benefit. The study opens the way for sophisticated mimicking of healthy neural code applied to a diseased heart as a potential electroceutical approach.

  (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

Non-invasive classification of macrophage polarisation by 2P-FLIM and machine learning

1. Nuno GB Neto
2. Sinead A O'Rourke
3. Mimi Zhang
4. Hannah K Fitzgerald
5. Aisling Dunne
6. Michael G Monaghan

• Curated by eLife

  Evaluation Summary:

  Neto et al set out to use Two-Photon FLIM and machine learning to classify macrophages that are polarised along the M1/M2 axis and then subjected to different metabolic stresses classically used to distinguish metabolic strategies of different cell states. Additional information is sought regarding the photophysics of the measurements and if there are an adequate number of photons to fairly compare the three conditions. The work will be of interest to immunologists, physiologists interested in metabolism and engineers looking to translate the findings.

  (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

Genetically engineered insects with sex-selection and genetic incompatibility enable population suppression

1. Ambuj Upadhyay
2. Nathan R Feltman
3. Adam Sychla
4. Anna Janzen
5. Siba R Das
6. Maciej Maselko
7. Michael Smanski

• Curated by eLife

  Evaluation Summary:

  This paper is of interest to entomologists caring for genetic pest control or molecular biologists following synthetic biology. The authors describe a fruit fly strain that combines constructs that establish both repressible female-lethality and genetic incompatibility based on CRISPR transactivation. They show that this strain has high penetrance for these two traits and that it can suppress wild-type flies when released into cycling cage populations. The paper is thus a neat technology demonstration for a genetic control strategy possibly applicable to other insects including pests or disease vectors.

  (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

Therapeutic downregulation of neuronal PAS domain 2 (Npas2) promotes surgical skin wound healing

1. Yoichiro Shibuya
2. Akishige Hokugo
3. Hiroko Okawa
4. Takeru Kondo
5. Daniel Khalil
6. Lixin Wang
7. Yvonne Roca
8. Adam Clements
9. Hodaka Sasaki
10. Ella Berry
11. Ichiro Nishimura
12. Reza Jarrahy

• Curated by eLife

  Evaluation Summary:

  The authors identify a novel compound called Dwn1 that suppresses the expression of Npas2, a key gene that delays wound healing. In doing so, they identify a novel treatment strategy for incisional surgical wounds that may have broader application to the treatment of scars in general.

  (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

Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain

1. Mitul Desai
2. Jitendra Sharma
3. Adrian L Slusarczyk
4. Ashley A Chapin
5. Robert Ohlendorf
6. Agata Wisniowska
7. Mriganka Sur
8. Alan Jasanoff

• Curated by eLife

  Evaluation Summary:

  This manuscript will be of interest to readers in the field of magnetic resonance imaging and responsive imaging probes. In this work, a new imaging probe is designed and applied in proof-of-principle animal models, with future promise for relevance in models that have higher relevance to human 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Temperature evolution following joint loading promotes chondrogenesis by synergistic cues via calcium signaling

1. Naser Nasrollahzadeh
2. Peyman Karami
3. Jian Wang
4. Lida Bagheri
5. Yanheng Guo
6. Philippe Abdel-Sayed
7. Lee Laurent-Applegate
8. Dominique P Pioletti

• Curated by eLife

  Evaluation Summary:

  This is the study to determine the effects of mechanical loading on temperature changes in the joint and how the mechano-thermal transduction may influence chondrocyte behavior. This manuscript will be of interest to the clinicians and researchers who are working on tissue engineering and cartilage regeneration. The study has high clinical relevance. It provides new evidence that the mechanical stimuli plus with the temperature increase could influence the cell chondrogenic response. The data support the conclusions of the manuscript within the current context, although several issues need to be addressed.

  (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

Humans optimally anticipate and compensate for an uneven step during walking

1. Osman Darici
2. Arthur D Kuo

• Curated by eLife

  Evaluation Summary:

  This study provides experimental evidence supporting an energy optimality principle for walking over uneven terrain. Using a simple rimless wheel model of human walking, the authors previously predicted speed fluctuations to emerge when a step up or down when energy is minimized over the entire walking path. New experimental evidence provides evidence that both anticipatory and reactive adjustments used by the nervous system follow the predictions of an energy minimization principle. The predictive power of an energy-minimization principle during transient, non-steady state behavior is notable. Certain issues regarding the generalizability of the results to variable step lengths and timing, alternative optimality criteria, and limitations of the modeling assumptions should be clarified.

  (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.)

Reviewed by eLife, preLights

Virtual mouse brain histology from multi-contrast MRI via deep learning

1. Zifei Liang
2. Choong H Lee
3. Tanzil M Arefin
4. Zijun Dong
5. Piotr Walczak
6. Song-Hai Shi
7. Florian Knoll
8. Yulin Ge
9. Leslie Ying
10. Jiangyang Zhang

• Curated by eLife

  Evaluation Summary:

  This paper demonstrates how MRI can be used to mimic histological measures. This is something that the field of MRI has dubbed virtual histology (or MR-histology) for a while, but to my knowledge this paper is the first convincing demonstration that it can be achieved. The paper combines open access mouse histology data from the Allen Institute with their own multimodal post-mortem MRI, and using deep convolutional networks, are able to build models that map MRI data onto multiple histological contrasts. Some of the results are impressive, such as predicting the outcome of histology on mutant shiverer mice.

  (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.)

Reviewed by eLife

Environmental fluctuations reshape an unexpected diversity-disturbance relationship in a microbial community

1. Christopher P Mancuso
2. Hyunseok Lee
3. Clare I Abreu
4. Jeff Gore
5. Ahmad S Khalil

• Curated by eLife

  Evaluation Summary:

  How species diversity responds to external perturbations (such as resource influxes and dilutions) is an important ecological question. Using soil microbial communities in devices where perturbations can be introduced in various forms and mathematical modelling, this study nicely illustrates how diversity is influenced by perturbations.

  (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.)

Reviewed by eLife

An engineered transcriptional reporter of protein localization identifies regulators of mitochondrial and ER membrane protein trafficking in high-throughput CRISPRi screens

1. Robert Coukos
2. David Yao
3. Mateo I Sanchez
4. Eric T Strand
5. Meagan E Olive
6. Namrata D Udeshi
7. Jonathan S Weissman
8. Steven A Carr
9. Michael C Bassik
10. Alice Y Ting

• Curated by eLife

  Evaluation Summary:

  Here authors present a robust, high-throughput and genome-wide strategy to identify genes that influence protein localization in individual subcellular compartments. The results profile subsets of genes that are involved in localization of tail-anchored proteins to mitochondrial and endoplasmic reticulum membranes and identify several unexpected regulators. This new tool is adaptable to studying various types of protein trafficking processes to shed light on their molecular mechanisms.

  (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, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife, preLights

An implant for long-term cervical vagus nerve stimulation in mice

1. Ibrahim T. Mughrabi
2. Jordan Hickman
3. Naveen Jayaprakash
4. Eleni S. Papadoyannis
5. Adam Abbas
6. Yao-Chuan Chang
7. Sunhee Lee
8. Timir Datta-Chaudhuri
9. Eric H. Chang
10. Theodoros P. Zanos
11. Robert C. Froemke
12. Cristin Welle
13. Yousef Al-Abed
14. Stavros Zanos

Reviewed by eLife

Host-associated microbe PCR (hamPCR): accessing new biology through convenient measurement of both microbial load and community composition

1. Derek S. Lundberg
2. Pratchaya Pramoj Na Ayutthaya
3. Annett Strauß
4. Gautam Shirsekar
5. Wen-Sui Lo
6. Thomas Lahaye
7. Detlef Weigel

• Curated by eLife

  Evaluation Summary:

  Overall, we agree that this new method is potentially impactful although the full versatility of the approach is currently unclear for several reasons. We appreciated the application of the approach to distinct systems and also the relatively low cost of this technique. The diagrams presented (particularly in Figure 3) nicely convey the steps in the protocol with expected sample outcomes to further facilitate the ability of other researchers to employ hamPCR. Overall, we are very positive about this work, but given that the impact of this paper rests on whether or not the technique is widely adopted, some revisions will lower the barrier to entry for future researchers to adopt this approach.

  (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

Innervated adrenomedullary microphysiological system to model prenatal nicotine and opioid exposure

1. Jonathan R. Soucy
2. Gabriel Burchett
3. Ryan Brady
4. David T. Breault
5. Abigail N. Koppes
6. Ryan A. Koppes

• Curated by eLife

  Summary: All three reviewers were not convinced that this screening platform has been properly validated vis-à-vis the neurobiology of the adrenal gland, nor that it has a physiologic relevance for the understanding of living processes and organs.

Reviewed by eLife