eLife

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1. The Plasmodium falciparum apicoplast cysteine desulfurase provides sulfur for both iron-sulfur cluster assembly and tRNA modification

   This article has 5 authors:

   1. Russell P Swift
   2. Rubayet Elahi
   3. Krithika Rajaram
   4. Hans B Liu
   5. Sean T Prigge

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This study provides important new insights into iron sulfur biosynthesis in the human malaria parasite Plasmodium falciparum. The work is based on elegant and robust genetic approaches, and not only confirms the essentiality of the plastid-hosted Suf iron-sulfur cluster synthesis pathway, but also highlights an important additional role for the cysteine desulfurase SufS in apicoplast maintenance via tRNA modification. The work provides compelling evidence for a dual function of parasite SufS, although impact on tRNA has not been established directly. These findings reveal a potential new target for metabolic intervention, and will be of interest to researchers studying apicomplexan parasites, and more broadly, in the field of plastid biology.

   Reviewed by eLife

2. Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins

   This article has 13 authors:

   1. Kexin Li
   2. Qingji Huo
   3. Nathan H Dimmitt
   4. Guofan Qu
   5. Junjie Bao
   6. Pankita H Pandya
   7. M Reza Saadatzadeh
   8. Khadijeh Bijangi-Vishehsaraei
   9. Melissa A Kacena
   10. Karen E Pollok
   11. Chien-Chi Lin
   12. Bai-Yan Li
   13. Hiroki Yokota

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     There are no known effective treatments available to date for the treatment of osteosarcomas, the earliest identified bone cancer that can spread to other tissues. In this study, the authors have used novel approaches to identify calreticulin and procollagen C-endopeptidase enhancer (PCOLCE) as osteosarcoma tumor suppressor proteins that inhibit osteosarcoma growth both in animal and in vitro cell culture models. These important findings may provide a basis for the future development of more efficient targeted therapies for the treatment of osteosarcomas.

   Reviewed by eLife

3. Directed differentiation of human iPSCs to functional ovarian granulosa-like cells via transcription factor overexpression

   This article has 14 authors:

   1. Merrick D Pierson Smela
   2. Christian C Kramme
   3. Patrick RJ Fortuna
   4. Jessica L Adams
   5. Rui Su
   6. Edward Dong
   7. Mutsumi Kobayashi
   8. Garyk Brixi
   9. Venkata Srikar Kavirayuni
   10. Emma Tysinger
   11. Richie E Kohman
   12. Toshi Shioda
   13. Pranam Chatterjee
   14. George M Church

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This is an important and significant study that focuses on deriving ovarian granulosa-like cells from hiPSC lines. The strengths of the study include bioinformatics analysis to identify relevant candidate transcription factors that drive the iPSCs into the ovarian granulosa pathway, an attempt to derive ovaroid model by combining human PGC-like cells with the iPSC-derived granulosa-like cells, and a variety of endpoint analysis including hormone measurements. Some limitations of the study include poor quality of images, lack of convincing demonstration that follicle-like structures are indeed derived in vitro, lack of clear rationale for using different cell lines with different endpoints chosen for analysis, and lack of clear methods indicating stepwise which transcription factors were used.

   Reviewed by eLife

4. The rostral intralaminar nuclear complex of the thalamus supports striatally mediated action reinforcement

   This article has 4 authors:

   1. Kara K Cover
   2. Abby G Lieberman
   3. Morgan M Heckman
   4. Brian N Mathur

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     Cover et al., examine the pathway from the intralaminar nucleus of the thalamus (rILN) to the dorsal striatum (DS) in the reinforcement of behavior/actions. The rILN sends a large glutamatergic projection to the DS, but its role in action selection was unknown. The authors found that the rILN neurons that project to the DS were activated at both action initiation and with the reward. Activation and inhibition of this pathway increased the success or decreased the success of reward acquisition, respectively. The findings are an important advance our understanding of the function of rILN to DS projection in reward-based behavior. The manuscript has provided convincing evidence with the appropriate methodologies to support these claims.

   Reviewed by eLife

5. Pericytes control vascular stability and auditory spiral ganglion neuron survival

   This article has 8 authors:

   1. Yunpei Zhang
   2. Lingling Neng
   3. Kushal Sharma
   4. Zhiqiang Hou
   5. Anatasiya Johnson
   6. Junha Song
   7. Alain Dabdoub
   8. Xiaorui Shi

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This study presents a valuable finding in identifying the roles of the pericytes in maintaining vascular volume and integrity of spiral ganglion neurons (SGNs) in the cochlea, the main hearing organ. The evidence supporting the authors' claims is solid using an inducible and conditional pericyte depletion mouse model and the co-culture models. While the study provides a modest translational contribution, understanding the roles of organ-specific pericytes is paramount, making this study timely and significant. The work will be interesting for biomedical biologists working on hearing, blood vessels, signaling, and cell-to-cell interactions.

   Reviewed by eLife

6. Within-host virus evolution during the extended treatment of RSV infection with mutagenic drugs

   This article has 10 authors:

   1. Christopher J. R. Illingworth
   2. Alexandra Y. Kreins
   3. Adriana Margarit-Soler
   4. Tim Best
   5. Patricia Dyal
   6. Giovanna Lucchini
   7. Kanchan Rao
   8. Rachel Williams
   9. Austen Worth
   10. Judith Breuer

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     Illingworth et al. investigate the effectiveness of ribavirin and favipiravir on the treatment of a paediatric patient with chronic RSV and identify an increase in mutations caused by ribavirin while favipiravir had no apparent mutagenic effect. Strength of evidence is incomplete for the mathematical model and solid for the mutational load analysis with potential for improvement in both cases with clarification of the methods. Major strengths are an interesting hypothesis and appropriate modeling methodology that will be of interest to virologists, clinicians and evolutionary biologists. Weaknesses in methodology pertain to mutational load measures possibly also capturing clonal expansion of new mutants and lack of clarity about how viral fitness is related to viral load in the mathematical model.

   Reviewed by eLife

7. A mechanism of uncompetitive inhibition of the serotonin transporter

   This article has 10 authors:

   1. Shreyas Bhat
   2. Ali El-Kasaby
   3. Ameya Kasture
   4. Danila Boytsov
   5. Julian B Reichelt
   6. Thomas Hummel
   7. Sonja Sucic
   8. Christian Pifl
   9. Michael Freissmuth
   10. Walter Sandtner

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This study presents the important finding of an unusual uncompetitive inhibitor (ECSI#6) of the serotonin transporter that removes the neurotransmitter serotonin from the synaptic cleft. Through careful and comprehensive analysis, the authors convincingly show that the molecule most likely binds to the inward-facing and K+-bound state and that it assists in folding and targeting the transporter. The work will be of interest to those engaged in biophysical analyses of the serotonin transporter, and colleagues developing pharmacological chaperoning strategies for transporters in general.

   Reviewed by eLife

8. Conformational and oligomeric states of SPOP from small-angle X-ray scattering and molecular dynamics simulations

   This article has 4 authors:

   1. F Emil Thomasen
   2. Matthew J Cuneo
   3. Tanja Mittag
   4. Kresten Lindorff-Larsen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     In this important paper, the authors have developed an approach for simultaneously optimizing the conformational ensemble and degrees of oligomerization, and this has been tested by applying it to a specific protein (SPOP). Comparison of the quality of fits with different models also provides valuable insights into structural features important to the assembly of oligomers. The approach, presented with compelling experimental support, is potentially applicable to other systems as well.

   Reviewed by eLife

9. Synchronization of oscillatory growth prepares fungal hyphae for fusion

   This article has 6 authors:

   1. Valentin Wernet
   2. Marius Kriegler
   3. Vojtech Kumpost
   4. Ralf Mikut
   5. Lennart Hilbert
   6. Reinhard Fischer

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This valuable study combines live cell imaging and mathematical modeling to show how an emerging model fungus engages in an oscillatory chemical dialogue to prepare for cell-cell fusion. Cell data and modeling are in compelling agreement but leave many open questions as to the nature of coordination between cells and the significance of oscillations, rendering the strength of evidence in support of the authors' inferences incomplete.

   Reviewed by eLife

10. National Institutes of Health research project grant inflation 1998 to 2021

    This article has 3 authors:

    1. Michael S Lauer
    2. Joy Wang
    3. Deepshikha Roychowdhury

    This article has been curated by 1 group:

    • Curated by eLife

      eLife assessment

      This is an important manuscript that provides support for the hypothesis that the relative increase in NIH funding matches the rate of overall inflation. The level of evidence is solid, and a clearer description of the analysis will further strengthen the manuscript. This paper should be of relevance to funders, investigators who are currently funded, and those who are seeking federal support.

    Reviewed by eLife