Steps towards decolonising biogeography

This is the final version. Available on open access from the International Biogeography Society via the DOI in this recordBiogeography has its origins in European colonialism. The legacies of colonial relations are evident in the distribution of practicing biogeographers, the direction of flow of biogeographical data, and the language used when describing and interpreting our studies. Biogeographers can address these legacies through increasing access to research data and publication outlets, improved recognition of collaborative relationships, and critically reflecting upon how our assumptions and perspectives might perpetuate colonial attitudes. Achieving these goals will improve not only inclusivity and equity within our field but also increase the diversity of insights and validity of our findings. If biogeography is to be a truly global science then decolonisation is a collective responsibility

Smash the windows

This is the final version. Available on open access from the International Biogeography Society via the DOI in this recor

Gauges and functional measures in quantum gravity I: Einstein theory

We perform a general computation of the off-shell one-loop divergences in Einstein gravity, in a two-parameter family of path integral measures, corresponding to different ways of parametrizing the graviton field, and a two-parameter family of gauges. Trying to reduce the gauge- and measure-dependence selects certain classes of measures and gauges respectively. There is a choice of two parameters (corresponding to the exponential parametrization and the partial gauge condition that the quantum field be traceless) that automatically eliminates the dependence on the remaining two parameters and on the cosmological constant. We observe that the divergences are invariant under a Z2 \u201cduality\u201d transformation that (in a particularly important special case) involves the replacement of the densitized metric by a densitized inverse metric as the fundamental quantum variable. This singles out a formulation of unimodular gravity as the unique \u201cself-dual\u201d theory in this class. \ua9 2016, The Author(s)

Expansion and Harvesting of hMSC-TERT

The expansion of human mesenchymal stem cells as suspension culture by means of spinner flasks and microcarriers, compared to the cultivation in tissue culture flasks, offers the advantage of reducing the requirements of large incubator capacities as well as reducing the handling effort during cultivation and harvesting. Nonporous microcarriers are preferable when the cells need to be kept in viable condition for further applications like tissue engineering or cell therapy. In this study, the qualification of Biosilon, Cytodex 1, Cytodex 3, RapidCell and P102-L for expansion of hMSC-TERT with an associated harvesting process using either trypsin, accutase, collagenase or a trypsin-accutase mixture was investigated. A subsequent adipogenic differentiation of harvested hMSC-TERT was performed in order to observe possible negative effects on their (adipogenic) differentiation potential as a result of the cultivation and harvesting method. The cultivated cells showed an average growth rate of 0.52 d-1. The cells cultivated on Biosilon, RapidCell and P102-L were harvested succesfully achieving high cell yield and vitalities near 100%. This was not the case for cells on Cytodex 1 and Cytodex 3. The trypsin-accutase mix was most effective. After spinner expansion and harvesting the cells were successfully differentiated to adipocytes

Too close for comfort: spatial patterns in acorn barnacle populations

Spatial patterns in aggregations form as a result of the interplay between costs and benefits experienced by individuals. Such self-organisation of aggregations can be explained using a zonal model in which a short-range zone of repulsion and longer-range zone of attraction surrounding individuals leads to emergent pattern properties. The signal of these processes can be detected using spatial pattern analyses. Furthermore, in sessile organisms, post-settlement mortality reveals the relative costs and benefits of positions within the aggregation. Acorn barnacles are known to require contact with conspecifics for reproduction and are therefore believed to aggregate for this purpose; isolated individuals may also be more susceptible to abiotic stress and predation. At short distances, however, competition for space and resources is likely to occur. In this study spatial patterns of barnacles (Semibalanus balanoides L.) were analysed using pair-correlation functions. Individuals were dispersed at distances below 0.30 cm, but peak relative density occurred at a distance of 0.36 cm from conspecifics. This is much closer than required for reproductive access, implying a strong aggregative drive, up to the point of physical contact with neighbours. Nevertheless, analysis of dead barnacles illustrated that such proximity carries a cost as barnacles with many neighbours were more likely to have died. The inferences obtained from these patterns are that barnacles aggregate as closely as they can, and that local neighbourhood competition is a powerful determinant of mortality. These processes give rise to the observed pattern properties

Targeting the hedgehog transcription factors GLI1 and GLI2 restores sensitivity to vemurafenib-resistant human melanoma cells

BRAF inhibitor (BRAFi) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms underpinning BRAFi-based therapy is therefore an important issue. Here we identified a previously unsuspected mechanism of BRAFi resistance driven by elevated Hedgehog (Hh) pathway activation that is observed in a cohort of melanoma patients after vemurafenib treatment. Specifically, we demonstrate that melanoma cell lines, with acquired in vitro-induced vemurafenib resistance, show increased levels of glioma-associated oncogene homolog 1 and 2 (GLI1/GLI2) compared with naive cells. We also observed these findings in clinical melanoma specimens. Moreover, the increased expression of the transcription factors GLI1/GLI2 was independent of canonical Hh signaling and was instead correlated with the noncanonical Hh pathway, involving TGF beta/SMAD (transforming growth factor-beta/Sma- and Mad-related family) signaling. Knockdown of GLI1 and GLI2 restored sensitivity to vemurafenib-resistant cells, an effect associated with both growth arrest and senescence. Treatment of vemurafenib-resistant cells with the GLI1/GLI2 inhibitor Gant61 led to decreased invasion of the melanoma cells in a three-dimensional skin reconstruct model and was associated with a decrease in metalloproteinase (MMP2/MMP9) expression and microphthalmia transcription factor upregulation. Gant61 monotherapy did not alter the drug sensitivity of naive cells, but could reverse the resistance of melanoma cells chronically treated with vemurafenib. We further noted that alternating dosing schedules of Gant61 and vemurafenib prevented the onset of BRAFi resistance, suggesting that this could be a potential therapeutic strategy for the prevention of therapeutic escape. Our results suggest that targeting the Hh pathway in BRAFi-resistant melanoma may represent a viable therapeutic strategy to restore vemurafenib sensitivity, reducing or even inhibiting the acquired chemoresistance in melanoma patients.Fapesp-grant number 2012/04194-1, 2013/05172-4, 2014/24400-0 and 2015/10821-7, CNPq-grant number 150447/2013-2 and 471512/2013-3 and PRODOC-grant no 3193-32/2010. Work in the lab of KS Smalley was supported by the National Institutes of Health grants R01 CA161107, R21 CA198550, and Skin SPORE grant P50 CA168536info:eu-repo/semantics/publishedVersio

Conservation of Mediterranean oak woodlands: understorey dynamics under different shrub management

The effect of experimental disturbances on the dynamics of a shrub community was studied on a ‘Montado’ ecosystem, in southern Portugal. The evolution of the community physiognomy, composition and diversity were monitored after shrub clearing followed by biomass removal, deposition on soil surface and incorporation with the soil, over a 9-year period. Maximum shrub density was recorded in the first year after the disturbances, excepting in mulched plots which showed the greatest number of individuals 1 year later. The increment of shrub leaf biomass was very fast in the first 3 years, whereas wood production was slower but occurred along the whole study period. At the end of the study, leaf and wood biomass was still significantly lower than in the predisturbance situation. The variation pattern of leaf area index was similar to that of leaf biomass. The evolution of total plant cover and diversity was similar across treatments. The highest species richness and diversity were recorded 2 years after cutting, decreasing afterwards with the increasing dominance of shrubs. Thus it seems likely that, although a 9 year period is too short for these communities to reach steady equilibrium, they are very resistant and resilient to disturbances, as regeneration was fast and vegetation dynamics was not influenced by differences among treatments. We can conclude that shrub clearing promotes biodiversity and the time of permanence of shrub patches depends on the particular goal we want to achieve

Conservation of Mediterranean oak woodlands: understorey dynamics under different shrub management

The effect of experimental disturbances on the dynamics of a shrub community was studied on a ‘Montado’ ecosystem, in southern Portugal. The evolution of the community physiognomy, composition and diversity were monitored after shrub clearing followed by biomass removal, deposition on soil surface and incorporation with the soil, over a 9-year period. Maximum shrub density was recorded in the first year after the disturbances, excepting in mulched plots which showed the greatest number of individuals 1 year later. The increment of shrub leaf biomass was very fast in the first 3 years, whereas wood production was slower but occurred along the whole study period. At the end of the study, leaf and wood biomass was still significantly lower than in the predisturbance situation. The variation pattern of leaf area index was similar to that of leaf biomass. The evolution of total plant cover and diversity was similar across treatments. The highest species richness and diversity were recorded 2 years after cutting, decreasing afterwards with the increasing dominance of shrubs. Thus it seems likely that, although a 9 year period is too short for these communities to reach steady equilibrium, they are very resistant and resilient to disturbances, as regeneration was fast and vegetation dynamics was not influenced by differences among treatments. We can conclude that shrub clearing promotes biodiversity and the time of permanence of shrub patches depends on the particular goal we want to achieve

High-throughput profiling of caenorhabditis elegans starvation-responsive microRNAs

MicroRNAs (miRNAs) are non-coding RNAs of ~22 nucleotides in length that regulate gene expression by interfering with the stability and translation of mRNAs. Their expression is regulated during development, under a wide variety of stress conditions and in several pathological processes. In nature, animals often face feast or famine conditions. We observed that subjecting early L4 larvae from Caenorhabditis elegans to a 12-hr starvation period produced worms that are thinner and shorter than well-fed animals, with a decreased lipid accumulation, diminished progeny, reduced gonad size, and an increased lifespan. Our objective was to identify which of the 302 known miRNAs of C. elegans changed their expression under starvation conditions as compared to well-fed worms by means of deep sequencing in early L4 larvae. Our results indicate that 13 miRNAs (miR-34-3p, the family of miR-35-3p to miR-41-3p, miR-39-5p, miR-41-5p, miR-240-5p, miR-246-3p and miR-4813-5p) were upregulated, while 2 miRNAs (let-7-3p and miR-85-5p) were downregulated in 12-hr starved vs. well-fed early L4 larvae. Some of the predicted targets of the miRNAs that changed their expression in starvation conditions are involved in metabolic or developmental process. In particular, miRNAs of the miR-35 family were upregulated 6-20 fold upon starvation. Additionally, we showed that the expression of gld-1, important in oogenesis, a validated target of miR-35-3p, was downregulated when the expression of miR-35-3p was upregulated. The expression of another reported target, the cell cycle regulator lin-23, was unchanged during starvation. This study represents a starting point for a more comprehensive understanding of the role of miRNAs during starvation in C. elegans

Smad phosphoisoform signals in acute and chronic liver injury: similarities and differences between epithelial and mesenchymal cells

Hepatocellular carcinoma (HCC) usually arises from hepatic fibrosis caused by chronic inflammation. In chronic liver damage, hepatic stellate cells undergo progressive activation to myofibroblasts (MFB), which are important extracellular-matrix-producing mesenchymal cells. Concomitantly, perturbation of transforming growth factor (TGF)-β signaling by pro-inflammatory cytokines in the epithelial cells of the liver (hepatocytes) promotes both fibrogenesis and carcinogenesis (fibro-carcinogenesis). Insights into fibro-carcinogenic effects on chronically damaged hepatocytes have come from recent detailed analyses of the TGF-β signaling process. Smad proteins, which convey signals from TGF-β receptors to the nucleus, have intermediate linker regions between conserved Mad homology (MH) 1 and MH2 domains. TGF-β type I receptor and pro-inflammatory cytokine-activated kinases differentially phosphorylate Smad2 and Smad3 to create phosphoisoforms phosphorylated at the COOH-terminal, linker, or both (L/C) regions. After acute liver injury, TGF-β-mediated pSmad3C signaling terminates hepatocytic proliferation induced by the pro-inflammatory cytokine-mediated mitogenic pSmad3L pathway; TGF-β and pro-inflammatory cytokines synergistically enhance collagen synthesis by activated hepatic stellate cells via pSmad2L/C and pSmad3L/C pathways. During chronic liver disease progression, pre-neoplastic hepatocytes persistently affected by TGF-β together with pro-inflammatory cytokines come to exhibit the same carcinogenic (mitogenic) pSmad3L and fibrogenic pSmad2L/C signaling as do MFB, thereby accelerating liver fibrosis while increasing risk of HCC. This review of Smad phosphoisoform-mediated signals examines similarities and differences between epithelial and mesenchymal cells in acute and chronic liver injuries and considers Smad linker phosphorylation as a potential target for the chemoprevention of fibro-carcinogenesis