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The N6-methyladenosine (m6A) modification is the most prevalent post-transcriptional mRNA modification, regulating mRNA decay and splicing. It plays a major role during normal development, differentiation, and disease progression. The modification is regulated by a set of writer, eraser, and reader proteins. The YTH domain family of proteins consists of three homologous m6A-binding proteins, Ythdf1, Ythdf2, and Ythdf3, which were suggested to have different cellular functions. However, their sequence similarity and their tendency to bind the same targets suggest that they may have overlapping roles. We systematically knocked out (KO) the Mettl3 writer, each of the Ythdf readers, and the three readers together (triple-KO). We then estimated the effect in vivo in mouse gametogenesis, postnatal viability, and in vitro in mouse embryonic stem cells (mESCs). In gametogenesis, Mettl3-KO severity is increased as the deletion occurs earlier in the process, and Ythdf2 has a dominant role that cannot be compensated by Ythdf1 or Ythdf3, due to differences in readers' expression pattern across different cell types, both in quantity and in spatial location. Knocking out the three readers together and systematically testing viable offspring genotypes revealed a redundancy in the readers' role during early development that is Ythdf1/2/3 gene dosage-dependent. Finally, in mESCs there is compensation between the three Ythdf reader proteins, since the resistance to differentiate and the significant effect on mRNA decay occur only in the triple-KO cells and not in the single KOs. Thus, we suggest a new model for the Ythdf readers function, in which there is profound dosage-dependent redundancy when all three readers are equivalently coexpressed in the same cell types.

Given the powerful implications of relationship quality for health and well-being, a central mission of relationship science is explaining why some romantic relationships thrive more than others. This large-scale project used machine learning (i.e., Random Forests) to 1) quantify the extent to which relationship quality is predictable and 2) identify which constructs reliably predict relationship quality. Across 43 dyadic longitudinal datasets from 29 laboratories, the top relationship-specific predictors of relationship quality were perceived-partner commitment, appreciation, sexual satisfaction, perceived-partner satisfaction, and conflict. The top individual-difference predictors were life satisfaction, negative affect, depression, attachment avoidance, and attachment anxiety. Overall, relationship-specific variables predicted up to 45% of variance at baseline, and up to 18% of variance at the end of each study. Individual differences also performed well (21% and 12%, respectively). Actor-reported variables (i.e., own relationship-specific and individual-difference variables) predicted two to four times more variance than partner-reported variables (i.e., the partner's ratings on those variables). Importantly, individual differences and partner reports had no predictive effects beyond actor-reported relationship-specific variables alone. These findings imply that the sum of all individual differences and partner experiences exert their influence on relationship quality via a person's own relationship-specific experiences, and effects due to moderation by individual differences and moderation by partner-reports may be quite small. Finally, relationship-quality change (i.e., increases or decreases in relationship quality over the course of a study) was largely unpredictable from any combination of self-report variables. This collective effort should guide future models of relationships.

This paper presents the results of an empirical study following up on Mizrahi (2021 (See CR19)). Using the same methods of text mining and corpus analysis used by Mizrahi (2021 (See CR19)), we test empirically a philosophical account of scientific progress that Mizrahi (2021 (See CR19)) left out of his empirical study, namely, the so-called functional-internalist account of scientific progress according to which the aim or goal or scientific research is to solve problems. In general, our results do not lend much empirical evidence in support of the problem-solving model of scientific progress over the other philosophical accounts of scientific progress (namely, the epistemic, noetic, and semantic accounts of scientific progress) tested in Mizrahi (2021 (See CR19)) and in this follow-up study. Of all the subjects in the JSTOR database we have tested in this study, however, Mathematics is an interesting exception as far as the problem-solving model of scientific progress is concerned. For, in Mathematics alone, we have found that there is significantly more talk of the aims and/or goals of research in terms of solutions than in terms of truth, knowledge, or understanding., Author(s): Moti Mizrahi [sup.1] Author Affiliations: (1) grid.255966.b, 0000 0001 2229 7296, School of Arts and Communication, Florida Institute of Technology, , 150 W. University Blvd, 32901, Melbourne, FL, USA [...]