Glutamine-Fructose-6-Phosphate Transaminase 2 (GFPT2) Is Upregulated in Breast Epithelial–Mesenchymal Transition and Responds to Oxidative Stress

Breast cancer cells that have undergone partial epithelial–mesenchymal transition (EMT) are believed to be more invasive than cells that have completed EMT. To study metabolic reprogramming in different mesenchymal states, we analyzed protein expression following EMT in the breast epithelial cell model D492 with single-shot LFQ supported by a SILAC proteomics approach. The D492 EMT cell model contains three cell lines: the epithelial D492 cells, the mesenchymal D492M cells, and a partial mesenchymal, tumorigenic variant of D492 that overexpresses the oncogene HER2. The analysis classified the D492 and D492M cells as basal-like and D492HER2 as claudin-low. Comparative analysis of D492 and D492M to tumorigenic D492HER2 differentiated metabolic markers of migration from those of invasion. Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) was one of the top dysregulated enzymes in D492HER2. Gene expression analysis of the cancer genome atlas showed that GFPT2 expression was a characteristic of claudin-low breast cancer. siRNA-mediated knockdown of GFPT2 influenced the EMT marker vimentin and both cell growth and invasion in vitro and was accompanied by lowered metabolic flux through the hexosamine biosynthesis pathway (HBP). Knockdown of GFPT2 decreased cystathionine and sulfide:quinone oxidoreductase (SQOR) in the transsulfuration pathway that regulates H₂S production and mitochondrial homeostasis. Moreover, GFPT2 was within the regulation network of insulin and EGF, and its expression was regulated by reduced glutathione (GSH) and suppressed by the oxidative stress regulator GSK3-β. Our results demonstrate that GFPT2 controls growth and invasion in the D492 EMT model, is a marker for oxidative stress, and associated with poor prognosis in claudin-low breast cancer.     

Hidden patterns of phylogenetic non‐stationarity overwhelm comparative analyses of niche conservatism and divergence

Aim Despite the importance of the niche concept in ecological and evolutionary theory, there are still many discussions about its definition and operational evaluation, especially when dealing with niche divergence and conservatism in an explicit phylogenetic context. Here we evaluate patterns of niche evolution in 67 New World Carnivora species, measured using Hellinger distances based on MAXENT models of species distribution. We show how inferences on niche conservatism or divergence depend on the way phylogenetic patterns are analysed using matrix comparison techniques. Innovation Initially we used the simplest approach of Mantel tests to compare Hellinger distances ( N ) derived from MAXENT and phylogenetic distances ( P ) among species. Then we extended the Mantel test to generate a multivariate correlogram, in which phylogenetic patterns are analysed at multiple levels in the phylogeny and can reveal nonlinearity in the relationship between divergence and time. Finally, we proposed a new approach to generate ‘local’ (or ‘specific’) leverages of components for Mantel correlation, evaluating the non‐stationarity in the relationship between N and P for each species. This new approach was used to show if some lineages are more prone to niche shift or conservatism than others. Main conclusions Standard Mantel tests indicated a poor correspondence between N and P matrices, discarding the idea of niche conservatism for Carnivora, but the correlogram supports that closely related species tend to be more similar than expected by chance. Moreover, the variance among Hellinger distances between pairs of closely phylogenetically related species is much larger than for the entire clade. Phylogenetic non‐stationarity analysis shows that in some Carnivora families the niche tends to divergence (Mustelidae and Canidae), whereas in others it tends to conservatism (Procyonidae and Mustelidae) at short phylogenetic distances. Our analyses clearly show that misleading results may appear if niche divergence is analysed only by simple matrix correlations not taking into account complex patterns of phylogenetic nonlinearity and non‐stationarity.     

Variation in the magnitude of morphological and dietary differences between individuals among populations of small benthic Arctic charr in relation to ecological factors

The early stages of intraspecific diversity are important for the evolution of diversification and speciation. Early stages of diversification can be seen in individual specialization, where individuals consume only a portion of the diet of the population as a whole, and how such specialization is related to phenotypic diversity within populations. Here, we study the strength of the relationship between morphological and dietary distances among individuals in eighteen populations of Icelandic small benthic charr. We furthermore studied if the strength of the relationship could be related to variation in local ecological factors these populations inhabit. In all the populations studied, there was a clear relationship between morphological and dietary distances, indicating that fish that had similar morphology were at the same time‐consuming similar food items. Our findings show a systematic variation in the relationship between morphology and diet at early stages of diversification in a highly specialized small benthic charr morph. The results show the importance of fine scale comparisons within populations and furthermore the value that systematic comparisons among populations under parallel evolution can contribute toward our increased understanding of evolutionary and ecological processes.     

Comparison of three different ways of measuring distances between residences and high voltage power lines

The aim of this study was to evaluate whether distance data based on calculations by use of digitalized geographical information systems (GIS) and distance data based on measurements on 1:5000 maps agree sufficiently with on site distance measurements to be used as input to magnetic field calculations in epidemiological studies. The analysis were performed by use of weighted kappa (kappa(w)) statistical method described by Bland and Altman for comparison of measures of agreement. Map measurements showed better agreement with on site measurements than GIS calculations did. However, we consider both methods appropriate for use in larger epidemiological studies if the results are interpreted with caution. GIS calculations have the advantage of being both time and cost saving.     

Evolution of the RNA-dependent RNA polymerase (RdRP) genes: Duplications and possible losses before and after the divergence of major eukaryotic groups

Eukaryotic RNA-dependent RNA polymerases (RdRPs, encoded by RDR genes) play critical roles in developmental regulation, maintenance of genome integrity, and defense against foreign nucleic acids. However, the phylogenetic relationship of RDRs remains unclear. From available genome sequences, we identified 161 putative RDR genes from 56 eukaryotes, ranging from protists to multicellular organisms, including plants, fungi and invertebrate animals, such as nematodes, lancelet and sea anemone. On the other hand, we did not detect RDR homologs in vertebrates and insects, even though RNA interference functions in these organisms. Our phylogenetic analysis of the RDR genes suggests that the eukaryotic ancestor might have had three copies, i.e. RDRα, RDRβ and RDRγ. These three ancient copies were also supported by the patterns of protein sequence motifs. Further duplication events after the divergence of major eukaryotic groups were supported by the phylogenetic analyses, including some that likely occurred before the separation of subgroups within each kingdom. We present a model for a possible evolutionary history of RDR genes in eukaryotes.     

Quantifying the effects of nutrient addition on the taxonomic distinctness of serpentine vegetation

Traditional diversity indices summarize the information about the relative abundances of species within a community without regard to differences between species. However, intuitively, a community composed of dissimilar taxa is more diverse than a community composed of more similar taxa. Therefore, useful indices of diversity should account for taxonomic relations among species. In this paper, a new parametric diversity index that combines species relative abundances and their taxonomic distinctiveness is used to quantify the way in which soil fertilization affects the diversity of a garigue community on ultramafic soils of Tuscany (central Italy). Results show that, while ultramafic soils generally host plant communities of limited taxonomic diversity with respect to similar communities on other substrates, fertilization significantly enhances the biomass production of species that are not exclusive to ultramafic soils. As a consequence, if diversity is measured combining species relative abundances with their taxonomic distinctiveness, nutrient addition tends to increase the diversity of ultramafic communities.     

Evidence for the presence of two sympatric species of mice (genus Mus L.) in southern France based on biochemical genetics

Populations of mice established outdoors as well as indoors have been investigated at 24 loci using starch gel electrophoresis. Two reproductively isolated groups are recognized, one of which is referable to a house mouse subspecies, Mus musculus brevirostris, and the other to a different species, Mus spretus, contrary to the view of Schwarz and Schwarz that only one species of Mus is present in the Mediterranean Basin. The genetic distance between these two groups is larger than between any pair of investigated subspecies of M. musculus. M. m. brevirostris is biochemically almost indistinguishable from M. m. domesticus. On the other hand, M. spretus exhibits several allelic variants unknown or at most very infrequent in M. musculus, as for instance at the lactate dehydrogenase B-chain locus.This work was supported by research grants from the Centre National de la Recherche Scientifique (E.R.A. No. 261) and the Ecole Pratique des Hautes Etudes.     

Early Holocene human skeletal remains from Santana do Riacho,Brazil: implications for the settlement of the New World

In this study we compare the cranial morphology of several late Paleoindian skeletons uncovered at Santana do Riacho, Central Brazil, with worldwide human cranial variation. Mahalanobis Distance and Principal Component Analysis are used to explore the extra-continental morphological affinities of the Brazilian Paleoindian sample. Santana do Riacho is a late Paleoindian burial site where approximately 40 individuals were recovered in varying states of preservation. The site is located at Lagoa Santa/Serra do Cipó, State of Minas Gerais. The first human activities in this rockshelter date back to the terminal Pleistocene, but the burials are bracketed between circa 8200 and 9500BP. The collection contains only six skulls well-enough preserved to be measured. The Santana do Riacho late Paleoindians present a cranial morphology characterized by long and narrow neurocrania, low and narrow faces, with low nasal apertures and orbits. The multivariate analyses show that they exhibit strong morphological affinities with present day Australians and Africans, showing no resemblance to recent Northern Asians and Native Americans. These findings confirm our long held opinion that the settlement of the Americas was more complicated in terms of biological input than has been widely assumed. The working hypothesis is that two very distinct populations entered the New World by the end of the Pleistocene, and that the transition between the cranial morphology of the Paleoindians and the morphology of later Native Americans, which occurred around 8-9ka, was abrupt. This, in our opinion, is a more parsimonious explanation for the diversity detected than a long, local microevolutionary process mediated by selection and drift. The similarities of the first South Americans with sub-Saharan Africans may result from the fact that the non-Mongoloid Southeast Asian ancestral population came, ultimately, from Africa, with no major modification in the original cranial bau plan of the first modern humans.     

Description of the cytochrome c oxidase subunit II gene in some genera of New World monkeys (primates,Platyrrhini)

Nucleotide sequence variation at the mitochondrial cytochrome c oxidase subunit II gene (COII) was analyzed in 27 New World monkey specimens, nine newly reported herein. The study involved comparisons among platyrrhines and also between platyrrhines and catarrhines. The analysis of the frequencies of transitions and transversions at each codon position showed transitional saturation at third codon position. Neighbor-Joining trees obtained from genetic distances estimated by means of Kimura's (1980) two-parameter model showed poor resolution of phylogenetic relationships among platyrrhine genera. Rates of nucleotide substitutions were largely homogeneous except in the genus Saimiri that showed low numbers of unique substitutions suggesting the maintenance of ancestral or plesiomorphic states of platyrrhine mt DNA nucleotide characters probably due to its large population sizes as compared to other platyrrhines.     

A new species of Sturisoma Swainson, 1838 (Loricariidae: Loricariinae), from the Madeira River basin,with a discussion of historical biogeography of western Amazonas and Paraguay River basins

A new loricariin species of Sturisoma is described from the Cautário, Guaporé, Mamoré, Machado and Soteiro rivers, Madeira River basin, in Bolivia and Brazil. The new species is distinguished from its congeners by the presence of a middorsal longitudinal, thin dark brown stripe on the caudal peduncle, extending from two or three plates posterior to the dorsal-fin base, reaching the origin of the caudal fin, or one or two plates anterior to the origin of the caudal fin; small squarish anteriormost abdominal plates; and a middorsal longitudinal dark-brown stripe from first predorsal plate to near the dorsal-fin origin. Furthermore, the new species is diagnosed from congeners by plate morphology, counts on the median series, coalescent plates and ventrolateral thoracic plates, in addition to measurements related to body and head structures. An analysis of genetic distances using cytochrome C oxidase subunit 1 gene marker of the mitochondrial genome between the new species and several congeners is presented, in addition to a likelihood analysis to illustrate the position of the new taxon within Sturisoma. An identification key for species of the genus currently recorded at the upper Amazonas River basin is provided.