eLife

Latest preprint reviews

1. Transcriptome-wide association study and eQTL colocalization identify potentially causal genes responsible for human bone mineral density GWAS associations

   This article has 16 authors:

   1. Basel Maher Al-Barghouthi
   2. Will T Rosenow
   3. Kang-Ping Du
   4. Jinho Heo
   5. Robert Maynard
   6. Larry Mesner
   7. Gina Calabrese
   8. Aaron Nakasone
   9. Bhavya Senwar
   10. Louis Gerstenfeld
   11. James Larner
   12. Virginia Ferguson
   13. Cheryl Ackert-Bicknell
   14. Elise Morgan
   15. David Brautigan
   16. Charles R Farber

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript is of broad interest to geneticists and bone biologists because it describes a method to filter candidate genes, identified from GWAS, and pinpoint the gene that affects bone biology. This method identified a gene with a previously unknown role in bone biology and the authors showed that its loss reduces bone mineral density, supporting the key claims in the paper.

     (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

2. Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape

   This article has 14 authors:

   1. James Boot
   2. Gabriel Rosser
   3. Dailya Kancheva
   4. Claire Vinel
   5. Yau Mun Lim
   6. Nicola Pomella
   7. Xinyu Zhang
   8. Loredana Guglielmi
   9. Denise Sheer
   10. Michael Barnes
   11. Sebastian Brandner
   12. Sven Nelander
   13. Kiavash Movahedi
   14. Silvia Marino

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Glioblastoma is a challenging disease with a high level of heterogeneity. Here the authors use global methylation profiling of tumor-initiating cells and matched iNSCs and identify a subgroup of hypomethylated tumors with an astrocytic phenotype. Understanding heterogeneity in glioblastoma is a major challenge, and the identification of alterations of functional and clinical impact is of importance to the field.

     (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

3. Multiple ciliary localization signals control INPP5E ciliary targeting

   This article has 13 authors:

   1. Dario Cilleros-Rodriguez
   2. Raquel Martin-Morales
   3. Pablo Barbeito
   4. Abhijit Deb Roy
   5. Abdelhalim Loukil
   6. Belen Sierra-Rodero
   7. Gonzalo Herranz
   8. Olatz Pampliega
   9. Modesto Redrejo-Rodriguez
   10. Sarah C Goetz
   11. Manuel Izquierdo
   12. Takanari Inoue
   13. Francesc R Garcia-Gonzalo

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript is of interest to developmental and cell biologists exploring cilia dynamics and ciliopathies. The authors address the molecular mechanisms by which INPP5E, a phosphoinositide phosphatase essential for regulating cilia function, is targeted to the primary cilium of cultured mammalian cells. Using immunoprecipitation, ciliary localization, phosphatase activity assays in combination with structural modelling, the authors identify four motifs important for ciliary localization of INPP5E, and uncover several novel and important interactions with other ciliary proteins providing a likely mechanism for ciliary targeting. The claims are generally well supported by the data, but some additional data acquisition and analysis are required to fully support the authors' conclusions and provide a conceptual advance in the field.

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

   Reviewed by eLife

4. Chronic neurotransmission increases the susceptibility of lateral-line hair cells to ototoxic insults

   This article has 3 authors:

   1. Daria Lukasz
   2. Alisha Beirl
   3. Katie Kindt

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Hair cell activity has been postulated to underlie their vulnerability to environmental insult including toxin exposure. Previous work has been confounded by the fact that reducing mechanotransduction also reduces entry of toxic chemicals. Here Lukasz and colleagues test these ideas by examining the vulnerability of zebrafish mutants with impaired synaptic activity, thought to be a major driver of neuronal metabolic load.

     (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

5. Protein phosphatase 1 regulatory inhibitor subunit 14C promotes triple‐negative breast cancer progression via sustaining inactive glycogen synthase kinase 3 beta

   This article has 19 authors:

   1. Yunting Jian
   2. Lingzhi Kong
   3. Hongyi Xu
   4. Yawei Shi
   5. Xinjian Huang
   6. Wenjing Zhong
   7. Shumei Huang
   8. Yue Li
   9. Dongni Shi
   10. Yunyun Xiao
   11. Muwen Yang
   12. Siqi Li
   13. Xiangfu Chen
   14. Ying Ouyang
   15. Yameng Hu
   16. Xin Chen
   17. Libing Song
   18. Runyi Ye
   19. Weidong Wei

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     The manuscript presents data that high expression of Protein Phosphatase 1 (PP1) inhibitor in triple-negative breast cancer contributes to poor outcomes by downregulation of an important kinase, GSK3β. The study clearly demonstrates that changes in PPP1R14C expression alter the behaviour of the studied cancer cells and mouse models and proposes a mechanism linking PP1 inhibitor to GSK3β. If this mechanism were substantiated, this would enhance our understanding of the pathophysiology of this important disease and might suggest new treatment options.

     (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

6. Mir155 regulates osteogenesis and bone mass phenotype via targeting S1pr1 gene

   This article has 15 authors:

   1. Zhichao Zheng
   2. Lihong Wu
   3. Zhicong Li
   4. Ruoshu Tang
   5. Hongtao Li
   6. Yinyin Huang
   7. Tianqi Wang
   8. Shaofen Xu
   9. Haoyu Cheng
   10. Zhitong Ye
   11. Dong Xiao
   12. Xiaolin Lin
   13. Gang Wu
   14. Richard T Jaspers
   15. Janak L Pathak

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Caner/cancer metastasis-induced bone loss-mediated fracture is a serious clinical problem. In this regard the authors have done an interesting study to show how miR155 exhibits a catabolic effect on osteogenesis and bone mass phenotype via interaction with the Sphingosine 1-phosphate receptor-1 (S1PR1) gene. The study suggests that inhibition of miR155 could be a potential strategy for bone regeneration and bone defect healing.

     (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

7. The spatiotemporal patterns of major human admixture events during the European Holocene

   This article has 3 authors:

   1. Manjusha Chintalapati
   2. Nick Patterson
   3. Priya Moorjani

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript presents DATES, a method to infer the timing of admixture events using genetic data from present-day or ancient individuals. This is a robust method that is useful in the field of paleogenomics and outperforms existing methods. In this manuscript, DATES is applied to >1000 ancient human genomes to characterize major admixture events during the European Holocene. This work will be of interest to scholars in the fields of population genetics, paleogenomics, archeology, biological anthropology, and history.

     (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

8. Elevated brain-derived cell-free DNA among patients with first psychotic episode – a proof-of-concept study

   This article has 13 authors:

   1. Asael Lubotzky
   2. Ilana Pelov
   3. Ronen Teplitz
   4. Daniel Neiman
   5. Adama Smadja
   6. Hai Zemmour
   7. Sheina Piyanzin
   8. Bracha-Lea Ochana
   9. Kirsty L Spalding
   10. Benjamin Glaser
   11. Ruth Shemer
   12. Yuval Dor
   13. Yoav Kohn

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This study explores the utility of cell free DNA analysis in non-malignant disease using epigenomic methods. By using brain specific methylation loci the authors identify higher levels of brain-related DNA in the plasma of patients with acute psychotic illness compared with non-disease controls. This paper will be of interest to readers in the field of liquid biopsy.

     (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

9. Quantifying concordant genetic effects of de novo mutations on multiple disorders

   This article has 10 authors:

   1. Hanmin Guo
   2. Lin Hou
   3. Yu Shi
   4. Sheng Chih Jin
   5. Xue Zeng
   6. Boyang Li
   7. Richard P Lifton
   8. Martina Brueckner
   9. Hongyu Zhao
   10. Qiongshi Lu

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Lu et al. provide a new method that looks at whether disorders tend to share excess de novo mutations in genes across the genome. The authors apply the method to nine disorders including a developmental disorder, autism spectrum disorder, congenital heart disease, schizophrenia, and intellectual disability, finding statistically significant overlap between 12 pairs of disorders in de novo mutations that cause a loss of gene function. This method will be of interest to researchers working on disorders caused by de novo mutations, but further clarification of its strengths and weaknesses compared to alternative approaches (mTADA in particular) would strengthen the paper.

     (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

10. Mitotically heritable, RNA polymerase II-independent H3K4 dimethylation stimulates INO1 transcriptional memory

    This article has 5 authors:

    1. Bethany Sump
    2. Donna G Brickner
    3. Agustina D'Urso
    4. Seo Hyun Kim
    5. Jason H Brickner

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      Transcriptional memory is a phenomenon via which certain genes are activated more robustly in response to repeated stimulation and in this manner, are able to "remember" previous experiences. This report dissects the molecular mechanism of inositol-driven transcriptional memory and highlights the key role of the histone mark H3K4 di-methylation, which is deposited independently from RNA Polymerase II activity. This memory-specific H3K4 di-methylation is found to be inherited over multiple cell divisions and to require specific transcription factors and chromatin machinery components to be established and maintained. The work will be of interest to those studying transcriptional regulation and epigenetics.

      (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