Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis: a multicentric 2004 national PHRC study

We used a 2D-electrophoresis (2-DE) proteomic approach to identify novel biomarkers in node-negative breast cancers. This retrospective study focused on a population of patients with ductal pN0M0 tumours. A subset of patients who developed metastases and in whose tumours were found high levels of uPA and PAI-1 (metastatic relapse, MR: n=20) were compared to another subset in whom no metastatic relapse occurred and whose tumours were found to have low levels of uPA and PAI-1 (no relapse, NR: n=21). We used a 2-DE coupled with MS approach to screen cytosol fractions using two pH-gradient scales, a broad scale (3.0-11.0) and a narrower scale focussing in on a protein rich region (5.0-8.0). This study was conducted on 41 cytosol specimens analyzed in duplicate on two platforms. The differential analysis of more than 2,000 spots in 2-DE gels, obtained on the two platforms, allowed the identification of 13 proteins which were confirmed by western blotting. Two proteins, GPDA and FABP4 were down-regulated in the MR subset whereas all the others were up-regulated. An in silico analysis revealed that GMPS (GUAA), GAPDH (G3P), CFL1 (COF1) and FTL (FRIL), the most informative genes, displayed a proliferation profile (high expression in basal-like, HER2+ and luminal B molecular subtypes). Inversely, similar to FABP4, GPD1 [GPDA] displayed a high expression in luminal A subtype, a profile characteristic of tumour suppressor genes. Despite the small size of our cohort, the 2-DE analysis gave interesting results which were confirmed by the in silico analysis showing that some of the corresponding genes had a strong prognostic impact in breast cancer, mostly because of their link with proliferation: GMPS, GAPDH, FTL and GPD1. A validation phase on a larger cohort is now needed before these biomarkers could be considered for use in clinical practice

Mid‐Holocene site formation, diagenesis and human activity at the foothills of Serra da Estrela (Portugal)

UIDB/00749/2020 UIDP/00749/2020The Neolithic occupation of Penedo dos Mouros in the foothills of Serra da Estrela, Portugalʼs highest mountain, dates to the 5th to 4th millennia cal B.C. The siteʼs faunal assemblage is extremely rare in the regional prehistoric archaeological record, due to the acidity of the granitic geology. This underlines Penedo dos Mouros importance as a reference site for understanding early pastoralism in the region. Due to the insufficient survival of bone collagen for radiocarbon dating and the homogeneity of the stratigraphy, where most visible contacts are due to postdepositional processes, we chose micromorphology to address the reasons behind the bone preservation and to assess the stratigraphic integrity of the prehistoric deposit. Reworking of eroding saprolitic soils was a major factor in the sediment accumulation, with remains of short human occupation events. Possible evidence for clearance fires linked to the first occurrences of pastoralism practised in the region, creating open spaces for grazing, was identified. Post‐depositional carbonate cementation derived from ashes, identifiable at the microscopic scale, enabled bone preservation. Carbonate and spodic‐like features document water saturation once the sedimentation ceased. This sedimentary dynamic has broader geomorphological implications, such as an inferred post‐Neolithic incision of the stream valley adjacent to the site.publishersversionpublishe

The Shift from Local to Global Visual Processing in 6-Year-Old Children Is Associated with Grey Matter Loss

International audienceBackground: A real-world visual scene consists of local elements (e.g. trees) that are arranged coherently into a global configuration (e.g. a forest). Children show psychological evolution from a preference for local visual information to an adult-like preference for global visual information, with the transition in visual preference occurring around 6 years of age. The brain regions involved in this shift in visual preference have not been described. Methods and Results: We used voxel-based morphometry (VBM) to study children during this developmental window to investigate changes in gray matter that underlie the shift from a bias for local to global visual information. Six-year-old children were assigned to groups according to their judgment on a global/local task. The first group included children who still presented with local visual processing biases, and the second group included children who showed global visual processing biases. VBM results indicated that compared to children with local visual processing biases, children with global visual processing biases had a loss of gray matter in the right occipital and parietal visuospatial areas. Conclusions: These anatomical findings are in agreement with previous findings in children with neurodevelopmental disorders and represent the first structural identification of brain regions that allow healthy children to develop a global perception of the visual world

Element redistribution along hydraulic and redox gradients of low-centered polygons, Lena Delta, northern Siberia

Wetland soils affected by permafrost are extensive in subarctic and arctic tundra. However, this fact does not imply these soils have been sufficiently investigated. In particular, studies of element translocation processes are scarce. This study was conducted (i) to determine the relationship between water and redox regimes in wetland soils in the Siberian tundra, and (ii) to investigate their influence on the distribution of redox sensitive and associate elements (Mn, Fe, P). Major geomorphic units were chosen (microhigh, polygon rim and slope; microlow, polygon center) from two low-centered polygons in the Lena Delta. Within polygons, redox potential, permafrost, and water level were measured during summer in 1999 and 2000 and (related) compared with element distribution. Manganese, Fe, and P accumulations were preferentially observed in aerobic microhighs. Anaerobic conditions in the microlows lead to a mobilization of Mn, Fe, and P. The elements migrate via water and are immobilized at the microhigh, which acts as an oxidative barrier. The element pattern, indicating an upward flux via water along redox gradients, is explained by higher evapotranspiration from soils and vegetation of the microhighs (Typic Aquiturbel) compared with soils and vegetation of the microlows (Typic Historthel). However, in further research this upward transport should be validated using labeled elements

Schmidt-hammer exposure ages from periglacial patterned ground (sorted circles) in Jotunheimen, Norway, and their interpretative problems

© 2016 Swedish Society for Anthropology and Geography Periglacial patterned ground (sorted circles and polygons) along an altitudinal profile at Juvflya in central Jotunheimen, southern Norway, is investigated using Schmidt-hammer exposure-age dating (SHD). The patterned ground surfaces exhibit R-value distributions with platycurtic modes, broad plateaus, narrow tails, and a negative skew. Sample sites located between 1500 and 1925 m a.s.l. indicate a distinct altitudinal gradient of increasing mean R-values towards higher altitudes interpreted as a chronological function. An established regional SHD calibration curve for Jotunheimen yielded mean boulder exposure ages in the range 6910 ± 510 to 8240 ± 495 years ago. These SHD ages are indicative of the timing of patterned ground formation, representing minimum ages for active boulder upfreezing and maximum ages for the stabilization of boulders in the encircling gutters. Despite uncertainties associated with the calibration curve and the age distribution of the boulders, the early-Holocene age of the patterned ground surfaces, the apparent cessation of major activity during the Holocene Thermal Maximum (HTM) and continuing lack of late-Holocene activity clarify existing understanding of the process dynamics and palaeoclimatic significance of large-scale sorted patterned ground as an indicator of a permafrost environment. The interpretation of SHD ages from patterned ground surfaces remains challenging, however, owing to their diachronous nature, the potential for a complex history of formation, and the influence of local, non-climatic factors

Reconciling Deep Calibration and Demographic History: Bayesian Inference of Post Glacial Colonization Patterns in Carcinus aestuarii (Nardo, 1847) and C. maenas (Linnaeus, 1758)

A precise inference of past demographic histories including dating of demographic events using Bayesian methods can only be achieved with the use of appropriate molecular rates and evolutionary models. Using a set of 596 mitochondrial cytochrome c oxidase I (COI) sequences of two sister species of European green crabs of the genus Carcinus (C. maenas and C. aestuarii), our study shows how chronologies of past evolutionary events change significantly with the application of revised molecular rates that incorporate biogeographic events for calibration and appropriate demographic priors. A clear signal of demographic expansion was found for both species, dated between 10,000 and 20,000 years ago, which places the expansions events in a time frame following the Last Glacial Maximum (LGM). In the case of C. aestuarii, a population expansion was only inferred for the Adriatic-Ionian, suggestive of a colonization event following the flooding of the Adriatic Sea (18,000 years ago). For C. maenas, the demographic expansion inferred for the continental populations of West and North Europe might result from a northward recolonization from a southern refugium when the ice sheet retreated after the LGM. Collectively, our results highlight the importance of using adequate calibrations and demographic priors in order to avoid considerable overestimates of evolutionary time scales

Task-Specific Sites and Paleoindian Landscape Use in the Shaw Creek Flats, Alaska

The Shaw Creek Flats and nearby middle Tanana river, in central Alaska, constitute one of the areas in the Americas with the densest known distribution of Late Glacial (about 14,500-11,700 cal. B.P.) archaeological sites. Local high rates of sediment deposition and low post-depositional disturbance allow for the interpretation of the function of archaeological occupations within larger economic and mobility strategies. Residential sites used over the long term seem to be located near critical but immovable resources such as clear water and vegetation. The spatial association of artifacts and faunal remains at other sites in the Flats suggest that they were specialized, short-lived locations dedicated to a single or few activities. For instance, the site of Swan Point Cultural Zone 4b is interpreted as a workshop related to the production of composite tools, particularly on mammoth ivory, and the site of Keystone Dune is interpreted as a camp related to wapiti (Cervus elaphus) hunting. These task-specific sites and others were probably used as part of a predominantly logistical mobility and economy strategy, which maximized efficiency in harvesting and processing resources that were distributed heterogeneously on the landscape.National Science Foundation [BCS-1504654]; Lewis and Clark Fellowship of the American Philosophical Society; Otto Geist Fund of the University of Alaska Museum of the North; Social and Behavioral Sciences Research Institute; School of Anthropology at the University of Arizona12 month embargo; published online: 08 December 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]