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Cuny, G.

Publications and source records attributed to Cuny, G..

2 recordsLinked to original sources

Fossil-based analyses of clades' diversification patterns require taxonomic expertise and appropriate methodology

SummaryEstimating deep-time diversification patterns and the establishment of extant biodiversity represent major challenges in macroevolution. Fossil record data provide essential information to address these topics, but their heterogeneous temporal and geographical distributions require using analytical approaches to process these data. Gardiner et al.1 (hereafter GEA) used a deep-learning model2 and a fossil-occurrences dataset3 to estimate neoselachian richness over the last 145 myr. Results and DiscussionGEA1 found that neoselachian diversity increased throughout the Cretaceous, was little impacted by the Cretaceous-Paleogene (K/Pg) mass extinction ([~]10% species loss), and peaked in the mid-Eocene but declined until the Present. While the Cretaceous increase in neoselachian richness is well known4, the other findings of GEA1 are at odds with current knowledge. With the exception of lamniform sharks, the perceived decrease in species richness in the recent past is most likely due to a drop in available fossil record data combined with difficulties in identifying extant species in the fossil record5. Similarly, all previous analyses of the impact of the K/Pg mass extinction on elasmobranch diversification have reported high extinction rates, a marked diversity drop, and delayed recovery6-7, despite heterogeneity across clades, ecology, and geographical distribution7. Taking the K/Pg as an example, we demonstrate that the discrepancies between GEA1s results and current consensus is most likely due to a combination of incomplete, unverified, and incorrect fossil-occurrence data with inappropriate methodology.

paleontology↗

Targeted degradation of the oncogenic phosphatase SHP2

SHP2 is a protein tyrosine phosphatase that plays a critical role in the full activation of the Ras/MAPK pathway upon stimulation of receptor tyrosine kinases (RTKs), which are frequently amplified or mutationally activated in human cancer. In addition, activating mutations in SHP2 result in developmental disorders and hematologic malignancies. Several allosteric inhibitors have been developed for SHP2 and are currently in clinical trials. Here, we report the development and evaluation of a SHP2 PROTAC created by conjugating RMC-4550 with pomalidomide using a PEG linker. This molecule is highly selective for SHP2, induces degradation of SHP2 in leukemic cells at sub-micromolar concentration, inhibits MAPK signaling, and suppresses cancer cell growth. SHP2 PROTACs serve as an alternative strategy for targeting ERK-dependent cancers and are useful tools alongside allosteric inhibitors for dissecting the mechanisms by which SHP2 exerts its oncogenic activity.

biochemistry↗