New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes

Probably not a substantial claim: may not pass S3 (load-bearing).

CYFIP1 and CYFIP2 are members of a protein family that interacts with FMRP in mammals and in the fly.

“CYFIP1 and CYFIP2 are members of a family of proteins interacting with the Fragile X mental retardation protein (FMRP, encoded by FMR1) in mammals, as well as in the fly (Abekhoukh and Bardoni, 2014; Schenck et al., 2001, 2003).”

• cites Abekhoukh and Bardoni, 2014 sourceSupported
• cites Schenck et al., 2001, 2003Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The co-repressor activity of CYFIP1-FMRP does not affect G-quadruplex-containing mRNAs, which represent a subset of FMRP targets.

“We can thus conclude that the co-repressor activity of CYFIP1-FMRP does not affect G-quadruplex-containing mRNAs, which represent a subset of FMRP targets (Brown et al., 2001; Maurin et al., 2014; Suhl et al., 2015).”

• cites Brown et al., 2001 sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites Maurin et al., 2014 sourceNot checked — no full text of the source
• cites Suhl et al., 2015 sourceSupported

May combine two claims.

The mTor pathway alteration in Fmr1-knockout neurons is not due to altered expression of mTor but rather to overactivation of PI3K because of overexpression of the catalytic PI3K subunit p110β.

“This alteration is not due to an altered expression of mTor (Sharma et al., 2010), but rather to the overactivation of PI3K, because of the overexpression of the catalytic PI3K subunit p110β (Gross et al., 2010; Gross and Bassell, 2012).”

• cites Sharma et al., 2010 sourceSupported
• cites Gross et al., 2010 sourcePartly supported

  The Results report increased PI3K activity and increased synaptic p110β protein in Fmr1-knockout neurons. They say excess p110β could contribute to the abnormal PI3K activity, but do not establish it as the definitive cause implied by “because of.” The mTOR-expression clause is cited to Sharma et al., not to this paper. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites Gross and Bassell, 2012 sourceSupported

May combine two claims.

G-quadruplex mRNA is a structure bound by FMRP and is harbored by some of its critical targets, including MAP1B, PP2AC, FMR1, SHANKL and SEMA3F.

“G-quadruplex mRNA is a structure bound by FMRP harbored by some of its critical targets (MAP1B, PP2AC, FMR1, SHANKL, SEMA3F) (Brown et al., 2001; Castets et al., 2005; Schaeffer et al., 2001; Zhang et al., 2014; Menon and Mihailescu, 2007).”

• cites Brown et al., 2001 sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites Castets et al., 2005 sourcePartly supported

  The Results and Figure 5 report that FMRP binds the G-quartet-containing PP2ACβ mRNA and use a G-quartet-containing FMR1 mRNA fragment as a binding reference. Our copy does not establish the same claim for MAP1B, SHANKL, or SEMA3F, which are also included in the cited sentence. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Schaeffer et al., 2001 sourcePartly supported

  The Introduction and ‘A specific RNA motif for FMRP binding’ (page not provided) report that FMRP binds a purine-quartet motif in its own FMR1 mRNA, supporting the FMR1 example and the general structural claim. The paper does not establish the listed motifs or FMRP binding for MAP1B, PP2AC, SHANKL, or SEMA3F. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Reduction of Cyfip1 or fly Hspc300 affects the level of the other components of the WRC.

“Indeed, it is reported that reduction of Cyfip1 or fly Hspc300 affects the level of the other components of the WRC (Kunda et al., 2003; Schenck et al., 2004; Abekhoukh and Bardoni, 2014; Gautier et al., 2011; Qurashi et al., 2007; De Rubeis et al., 2013).”

• cites Kunda et al., 2003 sourcePartly supported

  The Results report that silencing fly Sra1 or HSPC300 reduced the level of SCAR, another WRC component. This supports the claim for SCAR, but the paper does not establish that levels of the other WRC components generally are affected, or test reduction of mammalian CYFIP1. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Schenck et al., 2004 sourcePartly supported

  The section “The WAVE/SCAR complex regulates axon pathfinding and motor nerve branching” reports that loss of fly CYFIP reduces the protein levels of its complex partners; Fig. 3 likewise shows loss of the remaining components in CYFIP mutants. The paper does not report that reducing fly HSPC300 has this effect, and its experiment concerns fly CYFIP rather than specifically CYFIP1. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Abekhoukh and Bardoni, 2014 sourcePartly supported

  The DROSOPHILA section reports that inactivating fly CYFIP reduces expression of the other WAVE-complex members, supporting the CYFIP portion of the claim. The paper identifies HSPC300 as a complex member, but the passages found do not report that reducing fly HSPC300 affects the levels of other members. No page numbers were available in our copy. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

CYFIP1 has a positive role in pS6-mediated translational regulation, opposite to FMRP.

“This finding shows a positive role for CYFIP1 in pS6-mediated translational regulation, which is an opposite function with respect to FMRP (Sharma et al., 2010; Maurin et al., 2014).”

• cites Sharma et al., 2010 sourceSupported
• cites Maurin et al., 2014 sourceNot checked — no full text of the source

May combine two claims.

CYFIP1 interacts with FMRP and with the translation initiation factor eIF4E.

“CYFIP1 interacts with the Fragile X mental retardation protein (FMRP, encoded by the FMR1 gene), whose absence causes Fragile X syndrome, and with the translation initiation factor eIF4E.”

• cites Schenck et al., 2001 sourcePartly supported

  The Interaction Between FMRP and CYFIP1 section (page not provided) reports experimental evidence that CYFIP1 interacts with FMRP. The cited paper does not report an interaction between CYFIP1 and eIF4E; its Discussion addresses translational regulation only as a proposed role. (LLM, conf=0.89)

  Experimental — accuracy not yet measured
• cites Napoli et al., 2008 sourceSupported
• cites Beggs et al., 2015 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

CYFIP1 is a candidate gene for intellectual disability, autism, schizophrenia and epilepsy.

“Cytoplasmic FMRP interacting protein 1 (CYFIP1) is a candidate gene for intellectual disability (ID), autism, schizophrenia and epilepsy.”

• cites Schenck et al., 2001, 2003Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Madrigal et al., 2012 sourceNot checked — no full text of the source
• cites Wang et al., 2015 sourcePartly supported

  The Introduction identifies CYFIP1 as a possible contributor to autism and schizophrenia, and the Discussion reports an association between CYFIP1 regulatory variants and ASD or classical autism. The passages do not identify CYFIP1 as a candidate gene for intellectual disability or epilepsy; the gene’s expanded name is not evidence for those conditions. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The G-quadruplex/FMRP complex mediates the repression activity of FMRP in translational regulation.

“Moreover, the G-quadruplex/FMRP complex mediates the repression activity of FMRP in translational regulation (Schaeffer et al., 2001; Brown et al., 2001; Castets et al., 2005; Melko and Bardoni, 2010; Suhl et al., 2015).”

• cites Schaeffer et al., 2001 sourcePartly supported

  In “FMRP-FBS interaction occurring in chimeric mRNAs is capable of inhibiting translation in vitro” (page unavailable), the paper reports that FMRP binding to the purine-quartet-containing site represses translation of a reporter with that site in its 5′ UTR. The claim generalizes this experimental result to FMRP’s translational repression activity; “Implications for FMRP functions” says the mechanism for regulation of FMRP’s own mRNA remains to be demonstrated. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Brown et al., 2001 sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites Castets et al., 2005 sourcePartly supported

  The Discussion reports FMRP binding to G-quartet structures in the pp2acb mRNA 5′-UTR, but says this binding *could* cause translational repression. The cited paper supports the proposed mechanism for this specific mRNA, not the unqualified claim that the complex mediates FMRP’s translational repression generally. Page numbers were not available in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

The mTor pathway is enhanced in Fmr1-knockout neurons.

“Conversely, it was reported that the mTor pathway is enhanced in Fmr1-knockout neurons (Sharma et al., 2010; Sawicka et al., 2016).”

• cites Sharma et al., 2010 sourcePartly supported

  The Results report increased basal mTOR signaling in the hippocampus of Fmr1-knockout mice, supported by kinase activity and mTOR–raptor association. The claim is broader than that finding: the Results also report no difference in cortical mTOR phosphorylation between knockout and wild-type mice, so the source does not establish enhancement in knockout neurons generally. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Sawicka et al., 2016 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The CYFIP1-FMRP interaction was confirmed by GST pull-down and immunoprecipitation both in mouse and fly cell lines and tissues.

“The CYFIP1-FMRP interaction, initially identified by two-hybrid screening in yeast (Bardoni et al., 1999; Schenck et al., 2001), was confirmed by GST pull-down and immunoprecipitation both in mouse and fly cell lines and tissues (Schenck et al., 2001, 2003; De Rubeis et al., 2013).”

• cites Schenck et al., 2001, 2003Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites De Rubeis et al., 2013 sourcePartly supported

  In Results, “CYFIP1 Is Part of Two Complexes,” the paper reports that CYFIP1 coimmunoprecipitates with FMRP in mouse cortical synaptoneurosomes. The “CYFIP1 Interactome Is Linked to Human Disease” section also reports validation by reverse immunoprecipitation in mouse cortical material. Our copy does not establish the attributed GST pull-down confirmation or confirmation in fly cell lines and tissues; no page numbers are provided. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Knockdown of CYFIP2 induces a dramatic reduction of proliferation while knockdown of FMR1 does not have an impact on these cells.

“Conversely, knockdown of CYFIP2 induces a dramatic reduction of proliferation while knockdown of FMR1 does not have an impact on these cells (Silva et al., 2009).”

• cites Silva et al., 2009 sourcePartly supported

  In Results, under “Cyfip1 regulates epithelial morphogenesis as part of the WAVE complex” (page unavailable), the paper reports a dramatic reduction in MCF-10A cell proliferation after Cyfip2 RNAi. It also reports no evident difference in 2D colonies or 3D acinar structures after FMR1 suppression, but does not establish that FMR1 knockdown had no impact on proliferation or on the cells generally. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

While both CYFIP1 and CYFIP2 interact with FMRP, only CYFIP2 interacts with FXR1P and FXR2P.

“(i) while both CYFIP1 and CYFIP2 interact with FMRP, only CYFIP2 interacts with FXR1P and FXR2P, the two paralogs and interactors of FMRP (Schenck et al., 2001);”

• cites Schenck et al., 2001 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

CYFIP1 and CYFIP2 have been often considered as having the same function.

“Owing to their high level of homology, CYFIP1 and CYFIP2 have been often considered as having the same function (Abekhoukh and Bardoni, 2014).”

• cites Abekhoukh and Bardoni, 2014 sourceSupported

May combine two claims.

In mouse, CYFIP2 has been described both as a co-effector and a downstream target of FMRP.

“It is interesting to notice that in mouse, while we are describing CYFIP1 as an antagonist of FMRP, CYFIP2 has been described both as a co-effector (e.g. depletion of CYFIP2 worsens some phenotypes of Fmr1-knockout mouse) (Han et al., 2015) and a downstream target of FMRP.”

• cites Han et al., 2015 sourceSupported
• cites Darnell et al., 2011 sourceCould not verify

  The Introduction and Results describe FMRP regulation of mouse-brain mRNA targets, but the passages found for “CYFIP2” and a targeted search for its transcript do not identify CYFIP2 as one of them. The co-effector example is separately attributed to Han et al. (2015) in the citing sentence. Our copy therefore does not verify the CYFIP2-specific claim attributed to this paper. (LLM, conf=0.73)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

CYFIP1 interacts with many proteins (Rac, WRC members and membrane components) that are not known partners of FMRP.

“while it is known that CYFIP1 interacts with many proteins (Rac, WRC members and membrane components) that are not known partners of FMRP (Abekhoukh and Bardoni, 2014).”

• cites Abekhoukh and Bardoni, 2014 sourcePartly supported

  The section “CYFIP PROTEINS: THE WAVE COMPLEX AND BEYOND” (page not provided) describes CYFIP1’s interaction with Rac1, its membership in the WAVE regulatory complex, and a membrane-protein motif that binds a surface formed by CYFIP and Abi2. It distinguishes CYFIP’s WRC role from its interaction with FMRP, but does not state that Rac, WRC members, or those membrane proteins are not known partners of FMRP. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

May combine two claims.

FMRP is not only involved in translation regulation and CYFIP1 is a component of complexes that do not contain FMRP.

“These conclusions are consistent with the fact that FMRP is, indeed, not only involved in translation regulation (Maurin et al., 2014) and CYFIP1 is a component of complexes that do not contain FMRP (Abekhoukh and Bardoni, 2014; Chen et al., 2014).”

• cites Maurin et al., 2014 sourceNot checked — no full text of the source
• cites Abekhoukh and Bardoni, 2014 sourceSupported
• cites Chen et al., 2014 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

FMRP is not only involved in translational repression, it is also a translational enhancer.

“Indeed, FMRP is not only involved in translational repression, it is also a translational enhancer (Bechara et al., 2009; Gross et al., 2011; Kwan et al., 2012; Tabet et al., 2016)”

• cites Bechara et al., 2009 sourceSupported
• cites Gross et al., 2011 sourceSupported
• cites Kwan et al., 2012 sourceSupported

Classified as probably not a substantial claim.

BDNF regulates translation by causing release of CYFIP1 from eIF4E via the action of MNK1.

“It was reported that BDNF regulates translation by causing release of CYFIP1 from eIF4E via the action of MAP kinase interacting serine/threonine kinase 1 (MNK1) (Napoli et al., 2008; Panja et al., 2014).”

• cites Napoli et al., 2008 sourcePartly supported

  The Summary (p. 1) and the synaptic-stimulation discussion (p. 8) say that BDNF causes CYFIP1 and eIF4E to dissociate, relieving translational repression. Neither passage identifies MNK1 as the mediator, and searches for MNK1 and its full name found no support for that mechanism in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Panja et al., 2014 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Depletion of Cyfip1 has a different impact in different brain regions.

“or, alternatively, depletion of Cyfip1 has a different impact in different brain regions as also shown for Cyfip2 (Han et al., 2014).”

• cites Han et al., 2014 sourceSupported

Classified as probably not a substantial claim.

In Mnk1-null neurons, altered expression of a subset of proteins was observed, including 26 proteins whose encoding mRNAs are bound by FMRP in translating ribosomes.

“In particular, in Mnk1-null neurons, altered expression of a subset of proteins was observed, including 26 proteins whose encoding mRNAs are bound by FMRP in translating ribosomes (Genheden et al., 2016; Darnell et al., 2011).”

• cites Genheden et al., 2016 sourceSupported
• cites Darnell et al., 2011 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

The CYFIP1-FMRP interaction was initially identified by two-hybrid screening in yeast.

“The CYFIP1-FMRP interaction, initially identified by two-hybrid screening in yeast (Bardoni et al., 1999; Schenck et al., 2001), was confirmed by GST pull-down and immunoprecipitation both in mouse and fly cell lines and tissues (Schenck et al., 2001, 2003; De Rubeis et al., 2013).”

• cites Bardoni et al., 1999 sourcePartly supported

  The Results and Discussion describe a yeast two-hybrid screen for FMRP interactors, so the screening method is supported. But the paper identifies NUFIP—not CYFIP1—as the novel interactor found by that screen. The cited paper therefore does not establish the claimed CYFIP1–FMRP identification. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Schenck et al., 2001 sourceSupported

May combine two claims.

Depletion of CYFIP1 in epithelial cancer cells interferes with the morphology of the cells and induces invasion.

“(iii) depletion of CYFIP1 in epithelial cancer cells interferes with the morphology of the cells and induces invasion (Silva et al., 2009).”

• cites Silva et al., 2009 sourceSupported

May combine two claims.

In 14 DIV primary cultured cortical neurons, FMRP repressor activity in the presence of a G-quadruplex structure was confirmed, but no impact of CYFIP1 on luciferase activity was observed in either the presence or absence of FMRP.

“We repeated the same experiment in 14 DIV primary cultured cortical neurons and we also confirmed the repressor activity of FMRP in the presence of a G-quadruplex structure, but we did not observe any impact of CYFIP1 on luciferase activity in either the presence or absence of FMRP (Fig. 4B).”

May combine two claims.

Recombinant double homozygous mutant animals have NMJs significantly different from dFMR1 and dCYFIP single mutants and very close to wild type.

“In contrast, recombinant double homozygous mutant animals (dCYFIP85.1; dFMR1Δ113 rec) (Fig. 1A,D) have NMJs significantly different from dFMR1 and dCYFIP single mutants (Fig. 1D) (P<0.01 in both cases) and very close to the wild type (W1118) [dCYFIP85.1, dFMR1Δ113=107.8 µm; dCYFIP85.1=69.8 µm (P=2.99×10−9) dFMR1Δ113=134.6 µm (P=2.39×10−5); n>30 for each case].”

May combine two claims.

In blood of five patients carrying the BP1-BP2 deletion, CYFIP1 mRNA level is significantly reduced, accompanied by decreased levels of CYFIP2, NAP1, ABI1, WAVE2 and HSPC300 mRNAs compared with four controls.

“In all patients analyzed, a significant reduction of the CYFIP1 mRNA level was detectable, accompanied by a decreased level of CYFIP2, NAP1, ABI1, WAVE2 (the only WAVE member expressed in blood cells) and HSPC300 mRNAs compared with the four controls (Fig. S7B).”

May combine two claims.

In Cyfip1-knockdown neurons, mRNA levels of WRC members (Cyfip2, Nap1, Abi1, Wave1, Hspc300) are all reduced, while Fmr1 mRNA level is unchanged.

“We were surprised to find that the levels of these mRNAs were all reduced, while the level of Fmr1 mRNA was unchanged (Fig. 5).”

• Also stated in: § Expression level of mRNA of WRC members · plain

  “We confirmed the reduced mRNA expression level of all the WRC members in Cyfip1 mutants (Fig. S6).”

May combine two claims.

Reduced expression of CYFIP1 results in reduced mRNA levels of other WRC members in mouse neurons and in blood and lymphoblastoid cell lines of patients carrying the BP1-BP2 deletion of chromosome 15q11.2.

“We show that reduced expression of CYFIP1 results in reduced mRNA levels of the other members of the WAVE complex in mouse neurons, as well as in blood and lymphoblastoid cell lines of patients carrying the BP1-BP2 deletion of chromosome 15q11.2.”

• Also stated in: § Abstract · hedged

  “Here, we present data showing a correlation between mRNA levels of CYFIP1 and other members of the WRC.”

May combine two claims.

The number of dendritic spines of KO sh89-injected mice is intermediate between WT shScr and KO shScr, but not statistically different from either.

“The number of dendritic spines of the knockout sh89-injected mice (KO sh89; Fig. 2G) is intermediate between that of WT mice injected with shScr (WT shScr; Fig. 2D) and that of KO shScr (Fig. 2F), but not statistically different from either (Fig. 2C)”

May combine two claims.

The numbers of dendritic spines of WT sh89 and KO shScr were significantly different from WT shScr.

“whereas the numbers of dendritic spines of WT sh89 and KO shScr (Fig. 2E,F) were significantly different from WT shScr (Fig. 2C,D).”

May combine two claims.

The mRNA level of Cyfip1 was reduced 70-80% by Sh89 and 45-50% by Sh18.

“The mRNA level of Cyfip1 was reduced 70-80% by Sh89 and 45-50% by Sh18 (Fig. S2A).”

May combine two claims.

The absence of FMRP does not modify the wild-type 'size of spine heads' phenotype, and the depletion of Cyfip1 does not impact this phenotype.

“On the other hand, the absence of FMRP does not modify the wild-type ‘size of spine heads’ phenotype, and the depletion of Cyfip1 does not impact this phenotype”

May combine two claims.

The number of dendritic spines in the double knockout is intermediate between wild-type and Fmr1-knockout mice, not appearing significantly different from both values.

“The fact that the number of dendritic spines in the double knockout is intermediate between wild-type and Fmr1-knockout mice, not appearing significantly different from both values”

Classified as probably not a substantial claim. May combine two claims.

The residual expression of CYFIP1 does not allow observation of its effect in the absence of FMRP, or alternatively, a more complex interaction between these two proteins exists.

“suggesting that the residual expression of CYFIP1 does not allow to observe its effect in the absence of FMRP or, alternatively, a more complex interaction between these two proteins exists (see Discussion).”

May combine two claims.

FMRP and CYFIP1 antagonize each other's function during neuromuscular junction growth in the fly and during new neuronal differentiation in the olfactory bulb of adult mice.

“We show that these two proteins antagonize each other's function not only during neuromuscular junction growth in the fly but also during new neuronal differentiation in the olfactory bulb of adult mice.”

May combine two claims.

CYFIP1 is a member of the WAVE regulatory complex (WRC), representing a link between translational regulation and the actin cytoskeleton.

“It is a member of the WAVE regulatory complex (WRC), thus representing a link between translational regulation and the actin cytoskeleton.”

• cites Cory and Ridley, 2002 sourceNot checked — no full text of the source

May combine two claims.

dFMR1 and dCYFIP interact genetically at the fly larval NMJ, where they have an opposite and dosage-dependent role on NMJ length.

“In summary, dFMR1 and dCYFIP interact genetically at the fly larval NMJ, where they have an opposite and dosage-dependent role on NMJ length.”

May combine two claims.

FMRP and CYFIP1 modulate mTor signaling in an antagonistic manner, likely via independent pathways.

“Mechanistically, FMRP and CYFIP1 modulate mTor signaling in an antagonistic manner, likely via independent pathways, supporting the results obtained in mouse as well as in fly at the morphological level.”

May combine two claims.

dCYFIP promotes synapse growth, behaving in an opposing way to dFMR1.

“We confirmed that dCYFIP promotes synapse growth, behaving in an opposing way to dFMR1.”

May combine two claims.

Cyfip1 plays a role in upregulating spine production, consistent with its role in actin remodeling.

“This suggests that Cyfip1 plays a role in upregulating spine production, consistent with its role in actin remodeling.”

May combine two claims.

CYFIP and dFMR1 control a common pathway and/or two antagonizing pathways.

“suggests that they control a common pathway and/or two antagonizing pathways”

Probably not a substantial claim: may not pass S2 (checkable).

These pathways appear to be modulated in different ways by this protein complex, probably depending on the presence of other partners or specific inputs.

“These pathways appear to be modulated in different ways by this protein complex, probably depending on the presence of other partners or specific inputs.”

Classified as probably not a substantial claim.

RNA G-quadruplex-forming structures are involved in several steps of mRNA metabolism.

“RNA G-quadruplex-forming structures are involved in several steps of mRNA metabolism (Melko and Bardoni, 2010; Subramanian et al., 2011).”

• cites Melko and Bardoni, 2010 sourceNot checked — no full text of the source
• cites Subramanian et al., 2011 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Only a strong reduction of Cyfip1 expression level would allow phenotypes or their severity to be uncovered.

“It is thus possible that only a strong reduction of the Cyfip1 expression level (not reached in those studies) would allow the phenotypes or their severity to be uncovered”

Probably not a substantial claim: may not pass S1 (asserted). The quote only partly states this claim.

Co-regulation of WRC members takes place at the transcriptional level.

“Possibly, this co-regulation takes place at the transcriptional level since no difference in the half-life of the mRNAs coding for the WRC components is observed in Cyfip1-depleted neurons.”

• AssumptionRests on an assumption: Common transcriptional regulatory elements are present in the promoters of all WRC members.

May combine two claims.

The expression of CYFIP1 and CYFIP2 appears differently modulated in different brain regions during post-natal brain development, while the three FXR proteins have the same expression pattern during development.

“(ii) the expression of the two proteins appears differently modulated in different brain regions during post-natal brain development, while the three FXR proteins have the same expression pattern during development (Bonaccorso et al., 2015);”

• cites Bonaccorso et al., 2015 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

FMRP is involved in RNA transport along neurites and between nucleus and cytoplasm.

“In addition, this protein is involved in RNA transport along neurites and between nucleus and cytoplasm (Maurin et al., 2014).”

• cites Maurin et al., 2014 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

WRC mRNAs are common targets of a subset of microRNAs.

“Since the WRC mRNAs are common targets of a subset of microRNAs (www.microrna.org/microrna/home.do), we can hypothesize that these genes are part of a network of regulation”

• cites www.microrna.org/microrna/home.doNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The FMRP phenotype dominates the CYFIP1 phenotype in this context and, at the molecular level, the function of CYFIP1 depends on the presence of FMRP.

“the FMRP phenotype dominates the CYFIP1 phenotype in this context and, at the molecular level, the function of CYFIP1 depends on the presence of FMRP.”

May combine two claims.

CYFIP1/dCYFIP and FMRP/dFMR1 can act antagonistically and independently.

“Moreover, our data leading to the conclusion that CYFIP1/dCYFIP and FMRP/dFMR1 can also act antagonistically and independently, are supported at the molecular level by results showing an antagonistic regulation of the mTor signaling via different pathways involving FMRP and CYFIP1.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

All human patient samples were obtained according to the guidelines of the ethic rules of medical centers involved and written informed consent was obtained from all participants.

“All human patient samples were obtained according to the guidelines of the ethic rules of medical centers involved in the study (CIBER of Rare Diseases, Barcelona, Spain; Instituto de Pesquisa Pelé Pequeno Principe, Curitiba, Brazil; Institute of Rare Diseases; Institute of Medical Genetics; The Chaim Sheba Medical Center, Tel Hashomer, Israel; Hospital for Sick Children, Toronto, Ontario, Canada)”

• Also stated in: § Mouse and human samples · plain

  “and written informed consent was obtained from all participants.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The virus concentration was chosen so that infection of neurons was maximal for biochemical studies (ideally 100%) and lowest for studies of neuronal morphology (about 5%).

“The virus concentration is chosen so that the infection of neurons is maximal for biochemical studies (ideally 100%) and lowest for studies of neuronal morphology (about 5%).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Correct insertion of the shRNA-encoding oligonucleotides into the pLL3.7 vector was verified by sequencing.

“The oligonucleotides coding the different shRNAs were cloned in the pLL3.7 vector (Addgene) in the HpaI and XhoI sites and correct insertion were verified by sequencing using the following primers: F: 5′-CCGGCAGCAGGCCGCGGGAAG-3′; R: 5′-ACTATTAATAACTAATGCATG-3′.”

May combine two claims.

Altering the level/activity of CYFIP1 results in an altered antagonistic action on FMRP downstream pathways, possibly contributing to neuronal pathologies.

“This can link WRC and FMRP-containing complexes since altering the level/activity of CYFIP1 results in an altered antagonistic action on FMRP downstream pathways, possibly contributing to neuronal pathologies.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Animal care was conducted in accordance with standard ethical guidelines and experiments were approved by the local ethics committee.

“Animal care was conducted in accordance with standard ethical guidelines (National Institutes of Health publication no. 85-23, revised 1985 and European Committee Guidelines on the Care and Use of Laboratory Animals 86/609/EEC). The experiments were approved by the local ethics committee (Comité d'Ethique en Expérimentation Animale Charles Darwin C2EA-05).”

Classified as probably not a substantial claim. May combine two claims.

At least two rounds of independent assays were carried out per genotype; for each round, at least 10 late L3 larvae of normal body size were dissected and 30 NMJs were analyzed.

“At least two rounds of independent assays were carried out per genotype; for each round, at least 10 late L3 larvae of normal body size were dissected and 30 NMJs were analyzed.”