Physiology

tTARGIT AAVs: A sensitive and flexible method to manipulate intersectional neuronal populations

1. Paul V. Sabatini
2. Jine Wang
3. Alan C. Rupp
4. Alison H. Affinati
5. Jonathan N. Flak
6. Chien Li
7. David P. Olson
8. Martin G. Myers

• Curated by eLife

  Evaluation Summary:

  The combination of Cre and Flp recombinase dependent system is powerful in manipulating specific intersectional neurons and has been successfully used in many systems. However, the system cannot express target genes sufficiently in some neurons, e.g., the LepRb VMH neurons. This paper solved this problem. It is therefore an important technical advance.

  (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

The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy

1. Yang Guo
2. Ze-Yan Yu
3. Jianxin Wu
4. Hutao Gong
5. Scott Kesteven
6. Siiri E Iismaa
7. Andrea Y Chan
8. Sara Holman
9. Silvia Pinto
10. Andy Pironet
11. Charles D Cox
12. Robert M Graham
13. Rudi Vennekens
14. Michael P Feneley
15. Boris Martinac

• Curated by eLife

  Evaluation Summary:

  In this work, the authors subjected mice with cardiomyocyte-specific deletion of ion channel TRPM4 to transverse aortic constriction-induced pressure overload, which is a well-validated model for heart failure. The study showed that cell-specific loss of TRPM4 in cardiomyocytes could protect against pathological left ventricular hypertrophy which is associated with an attenuation of pathological changes in the expression several genes that become dysregulated during the development pathological hypertrophy. These findings are likely to contribute to understanding of pressure overload-induced hypertrophy heart disease and the pathophysiology of heart failure.

  (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

Identifying Plasmodium falciparum transmission patterns through parasite prevalence and entomological inoculation rate

1. Benjamin Amoah
2. Robert S McCann
3. Alinune N Kabaghe
4. Monicah Mburu
5. Michael G Chipeta
6. Paula Moraga
7. Steven Gowelo
8. Tinashe Tizifa
9. Henk van den Berg
10. Themba Mzilahowa
11. Willem Takken
12. Michele van Vugt
13. Kamija S Phiri
14. Peter J Diggle
15. Dianne J Terlouw
16. Emanuele Giorgi

• Curated by eLife

  Evaluation Summary:

  The association between metrics of malaria transmission based on prevalence of existing infections and the incidence of new infections has epidemiologically important consequences for malaria control and elimination efforts. The association between P. falciparum entomological inoculation rate and parasite prevalence has been previously characterized, and this report evaluates the added-value of spatio-temporal models to such analyses.

  (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

OPA1 deletion in brown adipose tissue improves thermoregulation and systemic metabolism via FGF21

1. Renata O Pereira
2. Alex Marti
3. Angela Crystal Olvera
4. Satya Murthy Tadinada
5. Sarah Hartwick Bjorkman
6. Eric Thomas Weatherford
7. Donald A Morgan
8. Michael Westphal
9. Pooja H Patel
10. Ana Karina Kirby
11. Rana Hewezi
12. William Bùi Trân
13. Luis Miguel García-Peña
14. Rhonda A Souvenir
15. Monika Mittal
16. Christopher M Adams
17. Kamal Rahmouni
18. Matthew J Potthoff
19. E Dale Abel

• Curated by eLife

  Evaluation Summary:

  The new work utilizes several elegant genetic mouse models to evaluate the importance of the mitochondrial fusion protein OPA1 in thermogenic brown adipocytes. This well-written and rigorous study sheds insight into the importance of OPA1 in brown adipocytes and also uncovers an unexpected compensatory mechanism that ensures thermoregulation in 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

The mechanism underlying transient weakness in myotonia congenita

1. Jessica H Myers
2. Kirsten Denman
3. Chris DuPont
4. Ahmed A Hawash
5. Kevin R Novak
6. Andrew Koesters
7. Manfred Grabner
8. Anamika Dayal
9. Andrew A Voss
10. Mark M Rich

• Curated by eLife

  Evaluation Summary:

  Patients with myotonia congenita (or Becker disease) experience episodes of transient muscle weakness but the reasons underlying this phenomenon are unknown. This study provides the most definitive experimental evidence to date for the mechanistic basis of transient weakness in myotonia congenita and also suggests ranolazine may be beneficial for prophylactic management.

  (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. Reviewers #1, #2, and #3 agreed to share their names with the authors.)

Reviewed by eLife

Early maternal loss leads to short- but not long-term effects on diurnal cortisol slopes in wild chimpanzees

1. Cédric Girard-Buttoz
2. Patrick J Tkaczynski
3. Liran Samuni
4. Pawel Fedurek
5. Cristina Gomes
6. Therese Löhrich
7. Virgile Manin
8. Anna Preis
9. Prince F Valé
10. Tobias Deschner
11. Roman M Wittig
12. Catherine Crockford

• Curated by eLife

  Summary: This paper tests the biological embedding model by asking whether and how early maternal loss affects cortisol levels and diurnal cortisol slopes among wild chimpanzees at the Tai Forest, Côte d'Ivoire. The results suggest that maternal loss alters the HPA stress axis in wild chimpanzees, but these effects are not visible later in life. Authors suggest that the lack of a later life association between maternal loss and cortisol levels may be due to selective early mortality of individuals with high cortisol levels but did not provide any survival or behavioural data to show that orphans and non-orphans differ in any fitness-related traits other than cortisol. Furthermore, the association between cortisol and the HPA axis is in the opposite direction to that observed in humans and there seems to be no significant increase in cortisol in orphans compared to non-orphans. Overall, the study is the result of extensive fieldwork, the number of samples collected is impressive and the subject is very interesting.

  The analyses will benefit greatly if the authors use effect sizes and confidence intervals for inferences instead of p-values. This may solve the significance threshold issues. Moreover, the reliance on p-values seem to limit the value of the data. For example, authors suggest that results from model 1 should be treated with caution because the full model is not significantly different from the null model, but by relying on it as the key finding of the study without exploring effect sizes, it does not seem that they did exercise sufficient caution.

Reviewed by eLife

Asprosin Neutralizing Antibodies as a Treatment for Metabolic Syndrome

1. Ila Mishra
2. Clemens Duerrschmid
3. Zhiqiang Ku
4. Wei Xie
5. Elizabeth Sabath Silva
6. Jennifer Hoffmann
7. Wei Xin
8. Ningyan Zhang
9. Zhiqiang An
10. Atul R. Chopra

• Curated by eLife

  Summary: Mishra et al. present data characterizing the effect of asprosin neutralizing antibodies on the parameters of metabolic syndrome (weight, glucose, lipids, etc). This group were the initial discoverers and characterized asprosin as a hormone that increases blood sugar and stimulates appetite. In their Nature Medicine 2017 article they also present data on a neutralizing antibody. In this follow-up manuscript the group characterizes the impact of neutralizing monoclonal antibodies on metabolic parameters of three mouse models of obesity (DIO, NASH diet and Leptin receptor knockout). The translational focus of the manuscript is potential use of monoclonal antibodies against aprosin as a treatment of metabolic syndrome.

Reviewed by eLife

Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α

1. Shivani N Mann
2. Niran Hadad
3. Molly Nelson Holte
4. Alicia R Rothman
5. Roshini Sathiaseelan
6. Samim Ali Mondal
7. Martin-Paul Agbaga
8. Archana Unnikrishnan
9. Malayannan Subramaniam
10. John Hawse
11. Derek M Huffman
12. Willard M Freeman
13. Michael B Stout

Reviewed by eLife

Enhanced C/EBPβ function promotes hyperplastic versus hypertrophic fat tissue growth and prevents steatosis in response to high-fat diet feeding

1. Christine Müller
2. Laura M Zidek
3. Sabrina Eichwald
4. Gertrud Kortman
5. Mirjam H Koster
6. Cornelis F Calkhoven

Reviewed by eLife

Effects of Early Life Stress on Bone Homeostasis in Mice and Humans

1. Karin Wuertz-Kozak
2. Martin Roszkowski
3. Elena Cambria
4. Andrea Block
5. Gisela A. Kuhn
6. Thea Abele
7. Wolfgang Hitzl
8. David Drießlein
9. Ralph Müller
10. Michael A. Rapp
11. Isabelle M. Mansuy
12. Eva M. J. Peters
13. Pia M. Wippert

Reviewed by eLife