Je trouve que quelque soit le type de postures, ces corps renvoient, pour moi, l'image de la mort. En aucun cas, ils ne ressemblent à des allures effrontées et, cette maigreur, cette pâleur, me fait surtout très peur et me choque.

Good picture (and article) on parts of pi 4

Reviewer #4:

General assessment of the work

Gene drives can be used for sustainable control of disease vectors, and there is a need for a different gene drive strategies that can be tailored to the particular species, timescale, and desired spatial spread. Kandul and colleagues present a welcome new addition to the growing number of strategies for gene drive, called HomeR, that combines elements of killer-rescue and homing-based drive to exert spatiotemporal control over its spread, whilst counteracting the rise of resistant mutations. Whilst it is extremely promising, some major claims of this manuscript are inaccurate or unsupported by the evidence. The authors could easily address the most important concerns by expanding their sequencing analysis to better detect and quantify resistant mutations, paying careful attention not to overstress the potential of this drive to mitigate resistance, and by comparing the relative strengths of different drive strategies instead of focussing only on features that are most flattering to the HomeR strategy.

Numbered summary of any substantive concerns

1) The drive release strategy of Fig 4A + 4C is primed to underestimate and potentially mask resistance. In Fig 4A, where the authors search for signs of resistance, the population was seeded with males that were all homozygous for the drive, meaning that 100% of their G0 progeny will inherit it. As the rate of homing is close to 99%, only a small fraction of their G1 could have inherited a non-drive (potentially resistant allele) allele. In a realistic release scenario, resistant alleles will have ample opportunity to be generated and subsequently selected. Though still far from adequate, resistance testing would have been better performed on samples collected from the lower frequency releases in panel C. This experiment should not be used to draw strong conclusions about resistance to pHomeR, but should be used to make broader observations regarding the spread and stability of the construct.

2) The strategy for sampling resistance will obscure almost all resistance in the population, and would fail to detect even a strong selection for it. Flies were only selected for resistance genotyping if they lacked GFP, meaning they carry two non-HomeR alleles (i.e. homozygous for the R1 allele or transheterozygous with another R1/R2/WT). One would expect most resistant alleles to be heterozygous in a population that was seeded with almost complete drive homozygosity. The authors could, and should, have done more to identify and quantify these. Amplicon sequencing was used to sample the full diversity of alleles in a larger pool of individuals (including GFP+ flies) collected at G10, why was this approach not used throughout? By adopting the approach earlier they would have been able to track the changing frequencies of R1 and R2 alleles over time.

3) The impression given in the figure and main text is that R1 alleles were rare (or entirely absent), when they were not. In spite of the incredible advantage given to the drive, and a bias in sampling method that would mask the presence of resistant alleles, resistance was observed in every generation tested (G2, G3 and G10). The authors claim that because GFP-individuals were not observed in later generations, the resistant alleles had not come under positive selection. This logic is flawed, and indeed their own amplicon sequencing analysis performed on G10 flies revealed several resistant alleles, including an R1 present in 80% of non-drive alleles. The two most frequent mutant alleles detected were in frame, and I do not agree that these are likely to be deleterious recessive (as the authors speculated). These could be functionally resistant mutations. I believe there were many more R1 alleles in heterozygosity with the HomeR allele, these alleles could have been spreading, but were excluded from the genotyping analysis. Could these putative R1 individuals not have been specifically tested to see if they do, or do not confer resistance?

4) The modelling takes a very limited approach to comparing different drive strategies, and by comparing proof-of-principle designs, important differences are obscured. For example, simple modifications that would mitigate resistance are likely to be included in many designs - such as multiplexing gRNAs. The nuances of each design are lost in a discussion focused on the rate of spread, which is largely irrelevant now because all of the drives are predicted to spread well.

5) The authors did not discuss the relevance of having performed releases in a population that was already homozygous for Cas9. Do the release experiments and model really suggest the drive could spread if released into an otherwise WT population? I'm not sure the data presented in this manuscript can support that claim.

Reviewer #4:

PREreview of "Structural characterization of an RNA bound antiterminator protein reveal a successive binding mode" Authored by James L. Walshe et al. and posted on bioRxiv DOI: 10.1101/2020.09.27.315978

Review authors in alphabetical order: Monica Granados, Katrina Murphy

This review is the result of a virtual, live-streamed journal club organized and hosted by PREreview and eLife. The discussion was joined by ten people in total, including researchers and publishers from several regions of the world and the event organizing team.

Overview and take-home message

In this preprint, Walshe et al. use a structural approach to examine a bacteria's RNA-binding ANTAR protein, EutV, including how EutV's antitermination mechanism works to prevent transcription termination and thus regulate gene expression. In addition, the team examined how a single hexaloop with the conserved G4 is recognized in succession by conserved residues in the ANTAR domains, how conserved A1 helps with proper RNA folding, and how these interactions support RNA binding. Although this research is of interest in the field, there are some concerns that could be addressed in the next version. These are outlined below.

Positive Feedback:

-I appreciate the comment on how crucial it is to understand the system and structure of these proteins for therapeutic purposes. It helps exemplify the relevancy for people outside of this field.

-I think it's interesting that there is potential for a new current model for ANTAR-mediated antitermination.

-I found it interesting that the two domains of the dimer cannot bind to the P1 and P2 helices of the same RNA.

-New data is used in this preprint and displayed openly in Supplementary Table 1.

-This research is novel because it's the start of looking at specifics of the mechanisms ANTAR domain proteins use to prevent termination.

-It will be interesting to look at bioinformatic analyses for the ANTAR domain across diverse bacterial strains. Especially in diverse ecological niches such as host-pathogen.

-It would be interesting to look at the structure in the context of an RNA construct that includes the P1, P2, and all of the T-loop.

-I am outside of this field of study, however, there are definitely a lot of details in this paper that it seems to be enough to reproduce. Though others possibly in the field have said, reproducibility is less likely in this type of work.

-I'm outside of the field, but it is nice that they deposited the atomic sequences on a public repository. I wonder whether this is mandatory for acceptance?

-Yes [the results are likely to lead to future research], now that there is more interest in mechanisms that ANTAR domain proteins use for antitermination.

-Are these findings applicable for similar ANTAR proteins (homologues/orthologues) in other bacteria? What about more complex organisms?

-Interesting topic!

-First RNA bound!

-Yes [I would recommend this manuscript to others and peer review], I think this is a promising manuscript.

Major Concerns:

-Lot of the details are included [in the preprint], lacking, however, is information in the method section about the modeling of the RNA using RNAComposer. It is mentioned in the results section, but not in the methods section.

-It's not clear where the EMSA assay is used in the paper. It's mentioned in the methods section, but not anywhere else.

-I think it would be helpful to see whether ANTAR mutants have anti-termination defects in a transcription reaction. Authors might consider being cautious talking about anti-termination without functional studies.

Acknowledgments:

We thank all participants for attending the live-streamed preprint journal club. We especially thank those that engaged in the discussion.

Below are the names of participants who wanted to be recognized publicly for their contribution to the discussion:

Aaron Frank | University of Michigan | Assistant Professor, Biophysics and Chemistry | Ann Arbor, MI Monica Granados | PREreview | Leadership Team | Ottawa, ON Katrina Murphy | PREreview | Project Manager | Portland, OR

No obstante, aunque desconocemos qué partícula constituye la materia oscura, ésto no significa que no entendamos cómo se comporta.

El comprender el comportamiento de la materia oscura es un gran aporte a la ciencia

A finales de la década de los 70 y comienzos de la década de los 80 del siglo XX, la necesidad de materia oscura no bariónica para explicar la formación de estructuras cosmológicas, junto con una muestra cada vez mayor de curvas de rotación de galaxias que mostraban un comportamiento plano, consolidaban la hipótesis de la existencia de materia oscura en el Universo.

Casi 100 años después de que se empezara a hablar de materia oscura, la realidad es que no sabemos lo que es, pero afortunadamente sabemos qué no es.

A pesar de todas las investigaciones, nos falta mucho por aprender y descubrir.

Context of production

This is why the text exists

DOI: 10.1016/j.celrep.2020.108404

Resource: (ZFIN Cat# ZDB-ALT-081212-4,RRID:ZFIN_ZDB-ALT-081212-4)

Curator: @Naa003

SciCrunch record: RRID:ZFIN_ZDB-ALT-081212-4

Curator comments: allele name: s896Tg Danio rerio ZFIN Cat# ZDB-ALT-081212-4

What is this?

This is basically the entire definition of what we are focusing on this week.

This is very important and easy to understand

Difference between reaction and response

This is really interesting. I definitely think there's no way to know what someone else's experience is like and we should all constantly be learning and educating ourselves to be more empathetic.

DOI: 10.7554/eLife.59469

Resource: (ZFIN Cat# ZDB-ALT-160119-4,RRID:ZFIN_ZDB-ALT-160119-4)

Curator: @evieth

SciCrunch record: RRID:ZFIN_ZDB-ALT-160119-4

What is this?

DOI: 10.7554/eLife.59469

Resource: (ZFIN Cat# ZDB-ALT-181113-4,RRID:ZFIN_ZDB-ALT-181113-4)

Curator: @evieth

SciCrunch record: RRID:ZFIN_ZDB-ALT-181113-4

What is this?

Her body was changing, but her father taught her out from home, far from her sister in school she learned how to fight and when her father fight with her, he felt her muscles were soft.

This is a mystery from past that Krishna thought to his friend. the question is does anyone else able to be discipline or not?

Was könnte das für eine Content strategy 4 degrowth bedeuten?

1. Sie findet in einer heterogenen/hybriden Umgebung statt.
2. Sie bezieht immer auch nichtmenschliche Stakeholder ein.
3. Sie hängt von einer genauen Analyse der Situation ab, die diese nicht nur abbildet, sondern verändert.
4. Sie ist auf Kollaboration angelegt.

DOI: 10.1016/j.molcel.2020.02.020

Resource: (ZFIN Cat# ZDB-ALT-030922-4,RRID:ZFIN_ZDB-ALT-030922-4)

Curator: @ethanbadger

SciCrunch record: RRID:ZFIN_ZDB-ALT-030922-4

What is this?

It shows the the Sumerians culture, that they believed to the dreams.

DOI: 10.7554/eLife.47699

Resource: (ZFIN Cat# ZDB-ALT-181113-4,RRID:ZFIN_ZDB-ALT-181113-4)

Curator: @evieth

SciCrunch record: RRID:ZFIN_ZDB-ALT-181113-4

What is this?

DOI: 10.1016/j.devcel.2020.03.017

Resource: (ZFIN Cat# ZDB-ALT-180511-4,RRID:ZFIN_ZDB-ALT-180511-4)

Curator: @ethanbadger

SciCrunch record: RRID:ZFIN_ZDB-ALT-180511-4

What is this?

DOI: 10.1016/j.cub.2019.12.046

Resource: (ZFIN Cat# ZDB-ALT-060623-4,RRID:ZFIN_ZDB-ALT-060623-4)

Curator: @ethanbadger

SciCrunch record: RRID:ZFIN_ZDB-ALT-060623-4

What is this?

DOI: 10.1016/j.cub.2019.12.071

Resource: (ZFIN Cat# ZDB-ALT-181113-4,RRID:ZFIN_ZDB-ALT-181113-4)

Curator: @ethanbadger

SciCrunch record: RRID:ZFIN_ZDB-ALT-181113-4

What is this?

DOI: 10.1016/j.cub.2019.12.071

Resource: (ZFIN Cat# ZDB-ALT-160119-4,RRID:ZFIN_ZDB-ALT-160119-4)

Curator: @ethanbadger

SciCrunch record: RRID:ZFIN_ZDB-ALT-160119-4

What is this?

DOI: 10.1016/j.celrep.2020.107755

Resource: (IMSR Cat# OBS_4,RRID:IMSR_OBS:4)

Curator: @ethanbadger

SciCrunch record: RRID:IMSR_OBS:4

What is this?

DOI: 10.1111/bph.15156

Resource: ZFIN_ZDB-ALT-110209-4

Curator: @Naa003

SciCrunch record: RRID:ZFIN_ZDB-ALT-110209-4

What is this?

Julis Steinberger's thread about the numbers of potential victims of global warming, Important remarks and important links.

DOI: 10.1016/j.cub.2020.05.016

Resource: (ZFIN Cat# ZDB-ALT-150701-4,RRID:ZFIN_ZDB-ALT-150701-4)

Curator: @ethanbadger

SciCrunch record: RRID:ZFIN_ZDB-ALT-150701-4

What is this?

DOI: 10.1016/j.cub.2020.05.016

Resource: (ZFIN Cat# ZDB-ALT-151028-4,RRID:ZFIN_ZDB-ALT-151028-4)

Curator: @ethanbadger

SciCrunch record: RRID:ZFIN_ZDB-ALT-151028-4

What is this?

argument de l'auteure en faveur de l'outil numérique pour aider les personnes âgées. Argument épistémique déductif

fait référence à l'article L 111-4 du code de l'éducation

Là aussi ce texte nous place dans l'école, c'est au-delà d'un simple partenariat

good quote

L'auteur parle d'une pratique très précise, la prise de notes, le nombre de mots qu'on peut écrire. Il s'appuie sur des expériences ( mais dont on en connait pas les sources) qui conclurait que l'utilisation du clavier pour juste enregistrer des mots serait plus performant.

Joue sur la pénibilité du travail accompli et la notion d'usinage dans les tâches pour accentuer le coté harassant ("sélectionnent, éditent, publient.... rythme soutenu...quand ils ont le temps" )

hypothèse plus que louable sur le fait que le journalisme n'est surement pas représentatif d'un plagiat constant. Mais qu'il est sûrement "l'arbre qui cache la forêt" et qu'il faut le voir dans son ensemble et sa globalité .

Met en évidence le côté répréhensible et sans honte du journalisme plagiat.

"de l'information journalistique" généralisation sur un certain journalisme, sans toutefois représenter une majorité .

L’enchaînement des idées a un effet persuasif au service de l'auteure. Fluide, "non, vous n'êtes pas seul. Oui, il existe d'autres manière de vivre." encourage le lecteur tout en défendant le point de vue de l'auteure.

L'auteure accroche le lecteur par des questions fermées où le lecteur peut s'identifier. Il en découle une phrase "vous êtes peut-être accro au digital" incitant à continuer la lecture.

L'auteure cite des études scientifiques avec les liens de celle-ci pour argumenter sa première partie. Elle enchaîne et présente les différents études sans réellement les mettre en lien entre elles. On peut considérer qu'il s'agit d'un raisonnement épistémique de type inductif où les faits vérifiés (de l'étude) permettent d'élaborer une conclusion générale émise juste après. On peut néanmoins mettre en avant le raccourci que fait l'auteure en citant ces différentes études une par une pour finir par poser sa conclusion, regroupant les conclusions des différentes études sans lien apparent entre elles.

Dans un premier temps, l'auteure utilise un raisonnement rhétorique de type pathos pour susciter des émotions chez le lecteur afin d'argumenter sa première partie. Original, cette partie permet de faire adhérer le lecteur à son premier argument: "passer du temps en ligne affecte notre productivité".

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001166

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001388

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001533

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0002650

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0000098

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0002616

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001653

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001634

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0000400

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0011800

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0000194

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0000322

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0000276

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001290

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0000718

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001249

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001263

allele id lookup result: https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA414193300

DOI: 10.7554/eLife.47061

Resource: (ZFIN Cat# ZDB-GENO-190322-4,RRID:ZFIN_ZDB-GENO-190322-4)

Curator: @evieth

SciCrunch record: RRID:ZFIN_ZDB-GENO-190322-4

What is this?

DOI: 10.1016/j.celrep.2019.07.078

Resource: (IMSR Cat# OBS_4,RRID:IMSR_OBS:4)

Curator: @ethanbadger

SciCrunch record: RRID:IMSR_OBS:4

What is this?

DOI: 10.7554/eLife.42455

Resource: (ZFIN Cat# ZDB-ALT-150424-4,RRID:ZFIN_ZDB-ALT-150424-4)

Curator: @evieth

SciCrunch record: RRID:ZFIN_ZDB-ALT-150424-4

What is this?

DOI: 10.7554/eLife.42881

Resource: (ZFIN Cat# ZDB-ALT-060821-4,RRID:ZFIN_ZDB-ALT-060821-4)

Curator: @evieth

SciCrunch record: RRID:ZFIN_ZDB-ALT-060821-4

What is this?

allele id lookup result: http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA399193709

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0002415

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001250

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001249

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001263

variant id lookup result: https://www.ncbi.nlm.nih.gov/clinvar/variation/692269/

variant id lookup result: https://www.ncbi.nlm.nih.gov/clinvar/variation/692269/

Monarch lookup result: https://monarchinitiative.org/phenotype/HP:0001508

PC magazine is a online compuer magazine, based on popular topics ranging form hackers to smartphones.

Rating: 9/10

Are you looking for portable sink manufacturer to get portable 4 compartment sink? At MONSAM Portable Sinks, they offer four-compartment portable self-contained sinks which are perfect for use as a commercial portable sink.

Monarch lookup result: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294674/#annotations:NNq7xL0dEemwJUvA1NrCBA

Monarch lookup result: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294674/#annotations:NNq7xL0dEemwJUvA1NrCBA

Monarch lookup result: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294674/#annotations:NNq7xL0dEemwJUvA1NrCBA

Is this the same Communism as the Soviet Union Communism?

The emperor basically saying that diplomat sent to his country cannot return home

throughout the entire passage the emperor had a condescending tone

The selling of opium is punishable by death