Evidence of strong stabilizing effects on the evolution of boreoeutherian (Mammalia) dental proportions.

The dentition is an extremely important organ in mammals with variation in timing and sequence of eruption, crown morphology, and tooth size enabling a range of behavioral, dietary, and functional adaptations across the class. Within this suite of variable mammalian dental phenotypes, relative sizes of teeth reflect variation in the underlying genetic and developmental mechanisms. Two ratios of postcanine tooth lengths capture the relative size of premolars to molars (premolar-molar module, PMM), and among the three molars (molar module component, MMC), and are known to be heritable, independent of body size, and to vary significantly across primates. Here, we explore how these dental traits vary across mammals more broadly, focusing on terrestrial taxa in the clade of Boreoeutheria (Euarchontoglires and Laurasiatheria). We measured the postcanine teeth of N = 1,523 boreoeutherian mammals spanning six orders, 14 families, 36 genera, and 49 species to test hypotheses about associations between dental proportions and phylogenetic relatedness, diet, and life history in mammals. Boreoeutherian postcanine dental proportions sampled in this study carry conserved phylogenetic signal and are not associated with variation in diet. The incorporation of paleontological data provides further evidence that dental proportions may be slower to change than is dietary specialization. These results have implications for our understanding of dental variation and dietary adaptation in mammals

A metodologia de Lamarck

Neste artigo, o método científico de Jean-Baptiste Lamarck é estudado sob o ponto de vista de seu discurso metodológico, bem como sob o ponto de vista de sua prática científica. Essa metodologia é comparada à preconizada por Condillac, assim como à dos "ideólogos" (idéologues) grupo no qual se costuma incluir o próprio Lamarck. Mostra-se que o discurso metodológico de Lamarck assemelha-se ao dos ideólogos; no entanto, sua prática científica não se coaduna com esse enfoque. Em vez de seguir uma abordagem empirista, a obra de Lamarck se fundamenta em princípios metafísicos gerais sobre a natureza. Sob o ponto de vista dos ideólogos, seu trabalho deveria ser rejeitado - o que de fato ocorreu - como um mero sistema (système) metafísico - no sentido pejorativo utilizado pelos seguidores de Condillac. No entanto, o presente artigo argumenta que esse é justamente um importante e inovador aspecto da obra de Lamarck, que permitiu a eclosão do evolucionismo moderno

Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer

Conceptual models of carcinogenesis typically consist of an evolutionary sequence of heritable changes in genes controlling proliferation, apoptosis, and senescence. We propose that these steps are necessary but not sufficient to produce invasive breast cancer because intraductal tumour growth is also constrained by hypoxia and acidosis that develop as cells proliferate into the lumen and away from the underlying vessels. This requires evolution of glycolytic and acid-resistant phenotypes that, we hypothesise, is critical for emergence of invasive cancer. Mathematical models demonstrate severe hypoxia and acidosis in regions of intraductal tumours more than 100 m from the basement membrane. Subsequent evolution of glycolytic and acid-resistant phenotypes leads to invasive proliferation. Multicellular spheroids recapitulating ductal carcinoma in situ (DCIS) microenvironmental conditions demonstrate upregulated glucose transporter 1 (GLUT1) as adaptation to hypoxia followed by growth into normoxic regions in qualitative agreement with model predictions. Clinical specimens of DCIS exhibit periluminal distribution of GLUT-1 and Na+/H+ exchanger (NHE) indicating transcriptional activation by hypoxia and clusters of the same phenotype in the peripheral, presumably normoxic regions similar to the pattern predicted by the models and observed in spheroids. Upregulated GLUT-1 and NHE-1 were observed in microinvasive foci and adjacent intraductal cells. Adaptation to hypoxia and acidosis may represent key events in transition from in situ to invasive cancer

Cohomology of Filippov algebras and an analogue of Whitehead's lemma

We show that two cohomological properties of semisimple Lie algebras also hold for Filippov (n-Lie) algebras, namely, that semisimple n-Lie algebras do not admit non-trivial central extensions and that they are rigid i.e., cannot be deformed in Gerstenhaber sense. This result is the analogue of Whitehead's Lemma for Filippov algebras. A few comments about the n-Leibniz algebras case are made at the end.Comment: plain latex, no figures, 29 page

A critical appraisal of appendage disparity and homology in fishes

Fishes are both extremely diverse and morphologically disparate. Part of this disparity can be observed in the numerous possible fin configurations that may differ in terms of the number of fins as well as fin shapes, sizes and relative positions on the body. Here, we thoroughly review the major patterns of disparity in fin configurations for each major group of fishes and discuss how median and paired fin homologies have been interpreted over time. When taking into account the entire span of fish diversity, including both extant and fossil taxa, the disparity in fin morphologies greatly complicates inferring homologies for individual fins. Given the phylogenetic scope of this review, structural and topological criteria appear to be the most useful indicators of fin identity. We further suggest that it may be advantageous to consider some of these fin homologies as nested within the larger framework of homologous fin‐forming morphogenetic fields. We also discuss scenarios of appendage evolution and suggest that modularity may have played a key role in appendage disparification. Fin modules re‐expressed within the boundaries of fin‐forming fields could explain how some fins may have evolved numerous times independently in separate lineages (e.g., adipose fin), or how new fins may have evolved over time (e.g., anterior and posterior dorsal fins, pectoral and pelvic fins). We favour an evolutionary scenario whereby median appendages appeared from a unique field of competence first positioned throughout the dorsal and ventral midlines, which was then redeployed laterally leading to paired appendages.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151971/1/faf12402_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151971/2/faf12402.pd

CUL-2^LRR-1 and UBXN-3 drive replisome disassembly during DNA replication termination and mitosis

Replisome disassembly is the final step of DNA replication in eukaryotes, involving the ubiquitylation and CDC48-dependent dissolution of the CMG helicase (CDC45-MCM-GINS). Using Caenorhabditis elegans early embryos and Xenopus laevis egg extracts, we show that the E3 ligase CUL-2(LRR-1) associates with the replisome and drives ubiquitylation and disassembly of CMG, together with the CDC-48 cofactors UFD-1 and NPL-4. Removal of CMG from chromatin in frog egg extracts requires CUL2 neddylation, and our data identify chromatin recruitment of CUL2(LRR1) as a key regulated step during DNA replication termination. Interestingly, however, CMG persists on chromatin until prophase in worms that lack CUL-2(LRR-1), but is then removed by a mitotic pathway that requires the CDC-48 cofactor UBXN-3, orthologous to the human tumour suppressor FAF1. Partial inactivation of lrr-1 and ubxn-3 leads to synthetic lethality, suggesting future approaches by which a deeper understanding of CMG disassembly in metazoa could be exploited therapeutically