Updating known distribution models for forecasting climate change impact on endangered species

To plan endangered species conservation and to design adequate management programmes, it is necessary to predict their distributional response to climate change, especially under the current situation of rapid change. However, these predictions are customarily done by relating de novo the distribution of the species with climatic conditions with no regard of previously available knowledge about the factors affecting the species distribution. We propose to take advantage of known species distribution models, but proceeding to update them with the variables yielded by climatic models before projecting them to the future. To exemplify our proposal, the availability of suitable habitat across Spain for the endangered Bonelli’s Eagle (Aquila fasciata) was modelled by updating a pre-existing model based on current climate and topography to a combination of different general circulation models and Special Report on Emissions Scenarios. Our results suggested that the main threat for this endangered species would not be climate change, since all forecasting models show that its distribution will be maintained and increased in mainland Spain for all the XXI century. We remark on the importance of linking conservation biology with distribution modelling by updating existing models, frequently available for endangered species, considering all the known factors conditioning the species’ distribution, instead of building new models that are based on climate change variables only.Ministerio de Ciencia e Innovación and FEDER (project CGL2009-11316/BOS

Molecular Analysis of Precursor Lesions in Familial Pancreatic Cancer

PMCID: PMC3553106This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The Diverse and Dynamic Nature of Leishmania Parasitophorous Vacuoles Studied by Multidimensional Imaging

An important area in the cell biology of intracellular parasitism is the customization of parasitophorous vacuoles (PVs) by prokaryotic or eukaryotic intracellular microorganisms. We were curious to compare PV biogenesis in primary mouse bone marrow-derived macrophages exposed to carefully prepared amastigotes of either Leishmania major or L. amazonensis. While tight-fitting PVs are housing one or two L. major amastigotes, giant PVs are housing many L. amazonensis amastigotes. In this study, using multidimensional imaging of live cells, we compare and characterize the PV biogenesis/remodeling of macrophages i) hosting amastigotes of either L. major or L. amazonensis and ii) loaded with Lysotracker, a lysosomotropic fluorescent probe. Three dynamic features of Leishmania amastigote-hosting PVs are documented: they range from i) entry of Lysotracker transients within tight-fitting, fission-prone L. major amastigote-housing PVs; ii) the decrease in the number of macrophage acidic vesicles during the L. major PV fission or L. amazonensis PV enlargement; to iii) the L. amazonensis PV remodeling after homotypic fusion. The high content information of multidimensional images allowed the updating of our understanding of the Leishmania species-specific differences in PV biogenesis/remodeling and could be useful for the study of other intracellular microorganisms

Neither loss of Bik alone, nor combined loss of Bik and Noxa, accelerate murine lymphoma development or render lymphoma cells resistant to DNA damaging drugs

The pro-apoptotic BH3-only protein, BIK, is widely expressed and although many critical functions in developmental or stress-induced death have been ascribed to this protein, mice lacking Bik display no overt abnormalities. It has been postulated that Bik can serve as a tumour suppressor, on the basis that its deficiency and loss of apoptotic function have been reported in many human cancers, including lymphoid malignancies. Evasion of apoptosis is a major factor contributing to c-Myc-induced tumour development, but despite this, we found that Bik deficiency did not accelerate Eμ-Myc-induced lymphomagenesis. Co-operation between BIK and NOXA, another BH3-only protein, has been previously described, and was attributed to their complementary binding specificities to distinct subsets of pro-survival BCL-2 family proteins. Nevertheless, combined deficiency of Bik and Noxa did not alter the onset of Eμ-Myc transgene induced lymphoma development. Moreover, although p53-mediated induction of Bik has been reported, neither Eμ-Myc/Bik−/− nor Eμ-Myc/Bik−/−Noxa−/− lymphomas were more resistant than control Eμ-Myc lymphomas to killing by DNA damaging drugs, either in vitro or in vivo. These results suggest that Bik, even in combination with Noxa, is not a potent suppressor of c-Myc-driven tumourigenesis or critical for chemotherapeutic drug-induced killing of Myc-driven tumours

Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis

Introduction: Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk. Material and Methods: We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998–2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously. Results: Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value#0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value$0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95%CI 1.05–1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation. Discussion: We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies.This work was supported by the Fondo de Investigacion Sanitaria, Spain (grant numbers 00/0745, PI051436, PI061614, G03/174); Red Tematica de Investigacion Cooperativa en Cancer (grant number RD06/0020-RTICC), Spain; Marato TV3 (grant number 050830); European Commission (grant numbers EU-FP7-HEALTH-F2-2008-201663-UROMOL; US National Institutes of Health (grant number USA-NIH-RO1-CA089715); and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute at the National Institutes of Health, USA; Consolider ONCOBIO (Ministerio de Economia y Competitividad, Madrid, Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Early peri-operative hyperglycaemia and renal allograft rejection in patients without diabetes

BACKGROUND: Patients with diabetes have an increased risk for allograft rejection, possibly related to peri-operative hyperglycaemia. Hyperglycaemia is also common following transplantation in patients without diabetes. We hypothesise that exposure of allograft tissue to hyperglycaemia could influence the risk for rejection in any patient with high sugars. To investigate the relationship of peri-operative glucose control to acute rejection in renal transplant patients without diabetes, all patients receiving their first cadaveric graft in a single center were surveyed and patients without diabetes receiving cyclosporin-based immunosuppression were reviewed (n = 230). Records of the plasma blood glucose concentration following surgery and transplant variables pertaining to allograft rejection were obtained. All variables suggestive of association were entered into multivariate logistic regression analysis, their significance analysed and modeled. RESULTS: Hyperglycaemia (>8.0 mmol/L) occurs in over 73% of non-diabetic patients following surgery. Glycaemic control immediately following renal transplantation independently predicted acute rejection (Odds ratio=1.08). 42% of patients with a glucose < 8.0 mmol/L following surgery developed rejection compared to 71% of patients who had a serum glucose above this level. Hyperglycaemia was not associated with any delay of graft function. CONCLUSION: Hyperglycaemia is associated with an increased risk for allograft rejection. This is consistent with similar findings in patients with diabetes. We hypothesise a causal link concordant with epidemiological and in vitro evidence and propose further clinical research

RNA Binding Protein CUGBP2/CELF2 Mediates Curcumin-Induced Mitotic Catastrophe of Pancreatic Cancer Cells

Curcumin inhibits the growth of pancreatic cancer tumor xenografts in nude mice; however, the mechanism of action is not well understood. It is becoming increasingly clear that RNA binding proteins regulate posttranscriptional gene expression and play a critical role in RNA stability and translation. Here, we have determined that curcumin modulates the expression of RNA binding protein CUGBP2 to inhibit pancreatic cancer growth.In this study, we show that curcumin treated tumor xenografts have a significant reduction in tumor volume and angiogenesis. Curcumin inhibited the proliferation, while inducing G2-M arrest and apoptosis resulting in mitotic catastrophe of various pancreatic cancer cells. This was further confirmed by increased phosphorylation of checkpoint kinase 2 (Chk2) protein coupled with higher levels of nuclear cyclin B1 and Cdc-2. Curcumin increased the expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) mRNA, but protein levels were lower. Furthermore, curcumin increased the expression of RNA binding proteins CUGBP2/CELF2 and TIA-1. CUGBP2 binding to COX-2 and VEGF mRNA was also enhanced, thereby increasing mRNA stability, the half-life changing from 30 min to 8 h. On the other hand, silencer-mediated knockdown of CUGBP2 partially restored the expression of COX-2 and VEGF even with curcumin treatment. COX-2 and VEGF mRNA levels were reduced to control levels, while proteins levels were higher.Curcumin inhibits pancreatic tumor growth through mitotic catastrophe by increasing the expression of RNA binding protein CUGBP2, thereby inhibiting the translation of COX-2 and VEGF mRNA. These data suggest that translation inhibition is a novel mechanism of action for curcumin during the therapeutic intervention of pancreatic cancers