6) The authors claim that daf-7 and tph-1 define a new class of DR modulators (Results and Discussion) because they mediate a bidirectional lifespan response to DR. However, the other genes they highlight have not been studies in the same manner across multiple food concentrations, so it seems premature to make such a claim.
We have revised the text to indicate that this is a new phenotypic class and emphasize this comment made by the reviewers: In the Results: "Thus, tph-1 and daf-7 mutants reveal a previously unobserved DR phenotype, and our results suggest that these genes mediate a bidirectional lifespan response to DR".
Thus, tph-1 and daf-7 mutants reveal a previously unobserved DR phenotype, and our results suggest that these genes mediate a bidirectional lifespan response to DR. tph-1 is expressed in the ADF sensory neurons, the NSM neurons within the foregut, and the hermaphrodite-specific HSN motor neurons (Sze et al., 2000).
This is a bidirectional communication mediated through the transport of various growth factors, such as GDF9 and BMP15, from oocytes to their surrounding cumulus cells [ 44- 46], and cyclic adenosine monophosphate (cAMP) from somatic cells to the oocyte [ 47] via gap junctions.
PICK1, a key candidate as a bidirectional regulator of synaptic AMPARs trafficking, mediates the trafficking of GluR2/3 and participate in many physiological and pathological processes.
Motivation: Phospholipid scramblases (PLSCRs) constitute a family of cytoplasmic membrane-associated proteins that were identified based upon their capacity to mediate a Ca2+-dependent bidirectional movement of phospholipids across membrane bilayers, thereby collapsing the normally asymmetric distribution of such lipids in cell membranes.
Since PEG3 and MIMT1 share a bidirectional promoter, one possibility is that MIMT1 expression mediates transcriptional silencing of PEG3 and/or USP29 throughout bidirectional transcription.
Although the inverse association of testosterone with diabetes is partially mediated by SHBG, low testosterone is linked to diabetes via a bidirectional relationship with visceral fat, muscle, and possibly bone (12).
Fisher and colleagues [ 27] have stated that there is a bidirectional relationship between periodontal disease and CKD, an association mediated by diabetic status and hypertension.
Cell adhesion to the extracellular matrix is mediated by integrins through regulation of the formation of different FA complexes, being a bidirectional cross-talk between integrins and FA proteins [ 43].
