Overexpression of EphB4 in the mammary epithelium shifts the differentiation pathway of progenitor cells and promotes branching activity and vascularization

Postnatally, the mammary gland undergoes continuous morphogenesis and thereby is especially prone to malignant transformation. Thus, the maintenance of the epithelium depends on a tight control of stem cell recruitment. We have previously shown that epithelial overexpression of the EphB4 receptor results in defective mammary epithelial development and conferred a metastasizing tumor phenotype on experimental mouse mammary tumors accompanied by a preponderance of progenitor cells. To analyze the effect of EphB4 overexpression on mammary epithelial cell fate, we have used Fluorescence Activated Cell Sorting (FACS) analyses to quantify epithelial sub-populations and repopulation assays of cleared fat pads to investigate their regenerative potential. These experiments revealed that deregulated EphB4 expression leads to an augmentation of bi-potent progenitor cells and to a shift of the differentiation pathway towards the luminal lineage. The analyses of the ductal outgrowths indicated that EphB4 overexpression leads to enforced branching activity, impedes ductal differentiation and stimulates angiogenesis. To elucidate the mechanisms forwarding EphB4 signals, we have compared the expression profile of defined cell populations between EphB4 transgene and wild type mammary glands concentrating on the wnt signaling pathway and on genes implicated in cell migration. With respect to wnt signaling, the progenitor cell population was the most affected, whereas the stem cell-enriched population showed the most pronounced deregulation of migration-associated genes. Thus, the luminal epithelial EphB4 signaling contributes, most likely via wnt signaling, to the regulation of migration and cell fate of early progenitors and is involved in the determination of branching points along the ductal tree.

Challenges in the participatory assessment of sustainable management practices in dryland ecosystems under regime shifts

Regime shifts, defined as a radical and persistent reconfiguration of an ecosystem following a disturbance, have been acknowledged by scientists as a very important aspect of the dynamic of ecosystems. However, their consideration in land management planning remains marginal and limited to specific processes and systems. Current research focuses on mathematical modeling and statistical analysis of spatio-temporal data for specific environmental variables. These methods do not fulfill the needs of land managers, who are confronted with a multitude of processes and pressure types and require clear and simple strategies to prevent regime shift or to increase the resilience of their environment. The EU-FP7 CASCADE project is looking at regime shifts of dryland ecosystems in southern Europe and specifically focuses on rangeland and forest systems which are prone to various land degradation threats. One of the aims of the project is to evaluate the impact of different management practices on the dynamic of the environment in a participatory manner, including a multi-stakeholder evaluation of the state of the environment and of the management potential. To achieve this objective we have organized several stakeholder meetings and we have compiled a review of management practices using the WOCAT methodology, which enables merging scientific and land users knowledge. We highlight here the main challenges we have encountered in applying the notion of regime shift to real world socio-ecological systems and in translating related concepts such as tipping points, stable states, hysteresis and resilience to land managers, using concrete examples from CASCADE study sites. Secondly, we explore the advantages of including land users’ knowledge in the scientific understanding of regime shifts. Moreover, we discuss useful alternative concepts and lessons learnt that will allow us to build a participatory method for the assessment of resilient management practices in specific socio-ecological systems and to foster adaptive dryland management.

Shifts in microbial communities do not explain the response of grassland ecosystem function to plant functional composition and rainfall change

Ecosystem functioning in grasslands is regulated by a range of biotic and abiotic factors, and the role of microbial communities in regulating ecosystem function has been the subject of much recent scrutiny. However, there are still knowledge gaps regarding the impacts of rainfall and vegetation change upon microbial communities and the implications of these changes for ecosystem functioning. We investigated this issue using data from an experimental mesotrophic grassland study in south-east England, which had been subjected to four years of rainfall and plant functional composition manipulations. Soil respiration, nitrogen and phosphorus stocks were measured, and the abundance and community structure of soil microbes were characterised using quantitative PCR and multiplex-TRFLP analysis, respectively. Bacterial community structure was strongly related to the plant functional composition treatments, but not the rainfall treatment. However, there was a strong effect of both rainfall change and plant functional group upon bacterial abundance. There was also a weak interactive effect of the two treatments upon fungal community structure, although fungal abundance was not affected by either treatment. Next, we used a statistical approach to assess whether treatment effects on ecosystem function were regulated by the microbial community. Our results revealed that ecosystem function was influenced by the experimental treatments, but was not related to associated changes to the microbial community. Overall, these results indicate that changes in fungal and bacterial community structure and abundance play a relatively minor role in determining grassland ecosystem function responses to precipitation and plant functional composition change, and that direct effects on soil physical and chemical properties and upon plant and microbial physiology may play a more important role.

Structural Organization of the Corpus Callosum Predicts Attentional Shifts after Continuous Theta Burst Stimulation

Repetitive transcranial magnetic stimulation (rTMS) applied over the right posterior parietal cortex (PPC) in healthy participants has been shown to trigger a significant rightward shift in the spatial allocation of visual attention, temporarily mimicking spatial deficits observed in neglect. In contrast, rTMS applied over the left PPC triggers a weaker or null attentional shift. However, large interindividual differences in responses to rTMS have been reported. Studies measuring changes in brain activation suggest that the effects of rTMS may depend on both interhemispheric and intrahemispheric interactions between cortical loci controlling visual attention. Here, we investigated whether variability in the structural organization of human white matter pathways subserving visual attention, as assessed by diffusion magnetic resonance imaging and tractography, could explain interindividual differences in the effects of rTMS. Most participants showed a rightward shift in the allocation of spatial attention after rTMS over the right intraparietal sulcus (IPS), but the size of this effect varied largely across participants. Conversely, rTMS over the left IPS resulted in strikingly opposed individual responses, with some participants responding with rightward and some with leftward attentional shifts. We demonstrate that microstructural and macrostructural variability within the corpus callosum, consistent with differential effects on cross-hemispheric interactions, predicts both the extent and the direction of the response to rTMS. Together, our findings suggest that the corpus callosum may have a dual inhibitory and excitatory function in maintaining the interhemispheric dynamics that underlie the allocation of spatial attention. SIGNIFICANCE STATEMENT: The posterior parietal cortex (PPC) controls allocation of attention across left versus right visual fields. Damage to this area results in neglect, characterized by a lack of spatial awareness of the side of space contralateral to the brain injury. Transcranial magnetic stimulation over the PPC is used to study cognitive mechanisms of spatial attention and to examine the potential of this technique to treat neglect. However, large individual differences in behavioral responses to stimulation have been reported. We demonstrate that the variability in the structural organization of the corpus callosum accounts for these differences. Our findings suggest novel dual mechanism of the corpus callosum function in spatial attention and have broader implications for the use of stimulation in neglect rehabilitation.

Space-time clustering of childhood cancers in Switzerland: A nationwide study.

The aetiology of childhood cancers remains largely unknown. It has been hypothesized that infections may be involved and that mini-epidemics thereof could result in space-time clustering of incident cases. Most previous studies support spatio-temporal clustering for leukaemia, while results for other diagnostic groups remain mixed. Few studies have corrected for uneven regional population shifts which can lead to spurious detection of clustering. We examined whether there is space-time clustering of childhood cancers in Switzerland identifying cases diagnosed at age <16 years between 1985 and 2010 from the Swiss Childhood Cancer Registry. Knox tests were performed on geocoded residence at birth and diagnosis separately for leukaemia, acute lymphoid leukaemia (ALL), lymphomas, tumours of the central nervous system, neuroblastomas and soft tissue sarcomas. We used Baker's Max statistic to correct for multiple testing and randomly sampled time-, sex- and age-matched controls from the resident population to correct for uneven regional population shifts. We observed space-time clustering of childhood leukaemia at birth (Baker's Max p = 0.045) but not at diagnosis (p = 0.98). Clustering was strongest for a spatial lag of <1 km and a temporal lag of <2 years (Observed/expected close pairs: 124/98; p Knox test = 0.003). A similar clustering pattern was observed for ALL though overall evidence was weaker (Baker's Max p = 0.13). Little evidence of clustering was found for other diagnostic groups (p > 0.2). Our study suggests that childhood leukaemia tends to cluster in space-time due to an etiologic factor present in early life.

Abrupt shifts of the Sahara-Sahel boundary during Heinrich stadials demonstrated on a sediment core transect

Relict dune fields that are found as far south as 14° N in the modern-day African Sahel are testament to equatorward expansions of the Sahara desert during the Late Pleistocene. However, the discontinuous nature of dune records means that abrupt millennial-timescale climate events are not always resolved. High-resolution marine core studies have identified Heinrich stadials as the dustiest periods of the last glacial in West Africa although the spatial evolution of dust export on millennial timescales has so far not been investigated. We use the major-element composition of four high-resolution marine sediment cores to reconstruct the spatial extent of Saharan-dust versus river-sediment input to the continental margin from West Africa over the last 60 ka. This allows us to map the position of the sediment composition corresponding to the Sahara-Sahel boundary. Our records indicate that the Sahara-Sahel boundary reached its most southerly position (13° N) during Heinrich stadials and hence suggest that these were the periods when the sand dunes formed at 14° N on the continent. Heinrich stadials are associated with cold North Atlantic sea surface temperatures which appear to have triggered abrupt increases of aridity and wind strength in the Sahel. Our study illustrates the influence of the Atlantic meridional overturning circulation on the position of the Sahara-Sahel boundary and on global atmospheric dust loading.

Shifts in the microbial community structure in different temperatures during sample storage from IODP Hole 325-M0058A

The objective of this study was to determine shifts in the microbial community structure and potential function based on standard Integrated Ocean Drilling Program (IODP) storage procedures for sediment cores. Standard long-term storage protocols maintain sediment temperature at 4°C for mineralogy, geochemical, and/or geotechnical analysis whereas standard microbiological sampling immediately preserves sediments at -80°C. Storage at 4°C does not take into account populations may remain active over geologic time scales at temperatures similar to storage conditions. Identification of active populations within the stored core would suggest geochemical and geophysical conditions within the core change over time. To test this potential, the metabolically active fraction of the total microbial community was characterized from IODP Expedition 325 Great Barrier Reef sediment cores prior to and following a 3-month storage period. Total RNA was extracted from complementary 2, 20, and 40 m below sea floor sediment samples, reverse transcribed to complementary DNA and then sequenced using 454 FLX sequencing technology, yielding over 14,800 sequences from the six samples. Interestingly, 97.3% of the sequences detected were associated with lineages that changed in detection frequency during the storage period including key biogeochemically relevant lineages associated with nitrogen, iron, and sulfur cycling. These lineages have the potential to permanently alter the physical and chemical characteristics of the sediment promoting misleading conclusions about the in situ biogeochemical environment. In addition, the detection of new lineages after storage increases the potential for a wider range of viable lineages within the subsurface that may be underestimated during standard community characterizations.

Effect of increased pCO2 on bacterial assemblage shifts in response to glucose addition in Fram Strait seawater mesocosms

Ocean acidification may stimulate primary production through increased availability of inorganic carbon in the photic zone, which may in turn change the biogenic flux of dissolved organic carbon (DOC) and the growth potential of heterotrophic bacteria. To investigate the effects of ocean acidification on marine bacterial assemblages, a two-by-three factorial mescosom experiment was conducted using surface sea water from the East Greenland Current in Fram Strait. Pyrosequencing of the V1-V2 region of bacterial 16S ribosomal RNA genes was used to investigate differences in the endpoint (Day 9) composition of bacterial assemblages in mineral nutrient-replete mesocosms amended with glucose (0 µm, 5.3 µm and 15.9 µm) under ambient (250 µatm) or acidified (400 µatm) partial pressures of CO2 (pCO2). All mesocosms showed low richness and diversity by Chao1 estimator and Shannon index, respectively, with general dominance by Gammaproteobacteria and Flavobacteria. Nonmetric multidimensional scaling analysis and two-way analysis of variance of the Jaccard dissimilarity matrix (97% similarity cut-off) demonstrated that the significant community shift between 0 µm and 15.9 µm glucose addition at 250 µatm pCO2 was eliminated at 400 µatm pCO2. These results suggest that the response potential of marine bacteria to DOC input may be altered under acidified conditions.

Adaptation to enemy shifts: rapid resistance evolution to local Vibrio spp. in invasive Pacific oysters

One hypothesis for the success of invasive species is reduced pathogen burden, resulting from a release from infections or high immunological fitness (low immunopathology) of invaders. Despite of strong selection exerted on the host, the evolutionary response of invaders to newly acquired pathogens has rarely been considered. The two independent and genetically distinct invasions of the Pacific oyster Crassostrea gigas into the North Sea represent an ideal model system to study fast evolutionary responses of invasive populations. By exposing both invasion sources to ubiquitous and phylogenetically diverse pathogens (Vibrio spp.) we demonstrate that within a few generations hosts adapted to sympatric pathogen communities. However, this local adaptation only became apparent in selective environments, i.e. at elevated temperatures reflecting patterns of disease outbreaks in natural populations. Resistance against sympatric and allopatric Vibrio spp. strains was dominantly inherited in crosses between both invasion sources, resulting in an overall higher resistance of admixed individuals than pure lines. Therefore we suggest that a simple genetic resistance mechanism of the host is matched to a common virulence mechanism shared by local Vibrio strains. This combination might have facilitated a fast evolutionary response that can explain another dimension of why invasive species can be so successful in newly invaded ranges.

Shallow water marine sediment bacterial community shifts along a natural CO2 gradient in the Mediterranean Sea Off vulcano, Italy

The effects of increasing atmospheric CO(2) on ocean ecosystems are a major environmental concern, as rapid shoaling of the carbonate saturation horizon is exposing vast areas of marine sediments to corrosive waters worldwide. Natural CO(2) gradients off Vulcano, Italy, have revealed profound ecosystem changes along rocky shore habitats as carbonate saturation levels decrease, but no investigations have yet been made of the sedimentary habitat. Here, we sampled the upper 2 cm of volcanic sand in three zones, ambient (median pCO(2) 419 µatm, minimum Omega (arag) 3.77), moderately CO(2)-enriched (median pCO(2) 592 µatm, minimum Omega (arag) 2.96), and highly CO(2)-enriched (median pCO(2) 1611 µatm, minimum Omega (arag) 0.35). We tested the hypothesis that increasing levels of seawater pCO(2) would cause significant shifts in sediment bacterial community composition, as shown recently in epilithic biofilms at the study site. In this study, 454 pyrosequencing of the V1 to V3 region of the 16S rRNA gene revealed a shift in community composition with increasing pCO(2). The relative abundances of most of the dominant genera were unaffected by the pCO(2) gradient, although there were significant differences for some 5 % of the genera present (viz. Georgenia, Lutibacter, Photobacterium, Acinetobacter, and Paenibacillus), and Shannon Diversity was greatest in sediments subject to long-term acidification (>100 years). Overall, this supports the view that globally increased ocean pCO(2) will be associated with changes in sediment bacterial community composition but that most of these organisms are resilient. However, further work is required to assess whether these results apply to other types of coastal sediments and whether the changes in relative abundance of bacterial taxa that we observed can significantly alter the biogeochemical functions of marine sediments.

The contribution of supply and demand shifts to earnings inequality in urban China

This paper examines the degree to which supply and demand shift across skill groups contributed to the earnings inequality increase in urban China from 1988 to 2002. Product demand shift contributed to an equalizing of earnings distribution in urban China from 1988 to 1995 by increasing the relative product for the low educated. However, it contributed to enlarging inequality from 1995 to 2002 by increasing the relative demand for the highly educated. Relative demand was continuously higher for workers in the coastal region and contributed to a raising of interregional inequality. Supply shift contributed essentially nothing or contributed only slightly to a reduction in inequality. Remaining factors, the largest disequalizer, may contain skill-biased technological and institutional changes, and unobserved supply shift effects due to increasing numbers of migrant workers.

Urbanization, socio-economic changes and population growth in Brazil: dietary shifts and environmental implications.

Population growth, economic globalization, improving living standards and urbanization are causing important changes in the global food system and modifying the dietary habits in many parts of the world (Molden, 2007; Godfray et al., 2010). The nutritional transition (linked to the development of countries and the increasing wealth of its population) implies a shift away from traditional staple food such as roots and tuber vegetables and a rise in consumption of meat and milk products, refined and processed foods, as well as sugars, oils and fats (Ambler-Edwards et al., 2009). The contemporary food system puts significant pressure on natural resources, especially on land and water, because the growing food demand pushes the agricultural frontier beyond, causing large impacts on ecosystems (Ambler-Edwards et al. 2009: 11-18). Also, the trend towards richer diets in animal proteins and processed food adds further pressure on the environment, since it requires larger amount of water and land to be produced (Allan, 2011; Mekonnen and Hoekstra, 2012).

Analytic optical design of linear Fresnel collectors with variable widths and shifts of mirrors

Linear Fresnel collectors still present a large margin to improve efficiency. Solar fields of this kind installed until current time, both prototypes and commercial plants, are designed with widths and shifts of mirrors that are constant across the solar field. However, the physical processes that limit the width of the mirrors depend on their relative locations to the receiver; the same applies to shading and blocking effects, that oblige to have a minimum shift between mirrors. In this work such phenomena are studied analytically in order to obtain a coherent design, able to improve the efficiency with no increase in cost. A ray tracing simulation along one year has been carried out for a given design, obtaining a moderate increase in radiation collecting efficiency in comparison to conventional designs. Moreover, this analytic theory can guide future designs aiming at fully optimizing linear Fresnel collectors' performance.