Gene deletion of P-Selectin and ICAM-1 does not inhibit neutrophil infiltration into peritoneal cavity following cecal ligation-puncture

BACKGROUND: Neutrophil infiltration is one of the critical cellular components of an inflammatory response during peritonitis. The adhesion molecules, P-selectin and intercellular adhesion molecule (ICAM)-1, mediate neutrophil-endothelial cell interactions and the subsequent neutrophil transendothelial migration during the inflammatory response. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy, suggesting that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the objective of this study was to determine the role of P-selectin and ICAM-1 in neutrophil infiltration into the peritoneal cavity during early and late phases of peritonitis. METHODS: Peritonitis was induced in both male wild-type and P-selectin/ICAM-1 double deficient (P/I null) mice by cecal ligation-puncture (CLP). Peripheral blood and peritoneal lavage were collected at 6 and 24 hours after CLP. The total leukocyte and neutrophil contents were determined, and neutrophils were identified with the aid of in situ immunohistochemical staining. Comparisons between groups were made by applying ANOVA and student t-test analysis. RESULTS: CLP induced a severe inflammatory response associated with a significant leukopenia in both wild-type and P/I null mice. Additionally, CLP caused a significant neutrophil infiltration into the peritoneal cavity that was detected in both groups of mice. However, neutrophil infiltration in the P/I null mice at 6 hours of CLP was significantly lower than the corresponding wild-type mice, which reached a similar magnitude at 24 hours of CLP. In contrast, in peritonitis induced by intraperitoneal inoculation of 2% glycogen, no significant difference in neutrophil infiltration was observed between the P/I null and wild-type mice at 6 hours of peritonitis. CONCLUSIONS: The data suggest that alternative adhesion pathway(s) independent of P-selectin and ICAM-1 can participate in neutrophil migration during peritonitis and that the mode of stimuli and duration of the injury modulate the neutrophil infiltration

Pre-agricultural plant management in the uplands of the central Zagros: the archaeobotanical evidence from Sheikh-e Abad

Prior to the emergence of agriculture in southwest Asia, sedentarising human communities were experimenting with a diverse range of wild plant species over a prolonged period. In some cases, this involved the cultivation of species that would go on to be domesticated and form the foundation of future agricultural economies. However, many forms of plant use did not follow this trajectory, and in multiple places farming was only taken up later as an established ‘package’. In this paper, we present new archaeobotanical evidence from the Early Neolithic site of Sheikh-e Abad in the central Zagros of western Iran. Sheikh-e Abad is unique in being the only settlement known to date within southwest Asia that lies at an altitude above 1000m and which has occupation spanning the agricultural transition. Thus, it provides a rare opportunity to examine pre-agricultural plant management strategies in an upland zone. Our analyses of the plant remains from Sheikh-e Abad suggest that from its earliest occupation inhabitants were unconsciously ‘auditioning’ a suite of locally available wild grasses which ultimately were never domesticated. We discuss the possible reasons for this from a socio-ecological perspective, considering both the biology and ecology of the plant species in question, as well as the ways in which they were potentially managed

Diet and body constitution in relation to subgroups of breast cancer defined by tumour grade, proliferation and key cell cycle regulators

BACKGROUND: The general lack of clear associations between diet and breast cancer in epidemiological studies may partly be explained by the fact that breast cancer is a heterogeneous disease that may have disparate genetic associations and different aetiological bases. METHOD: A total of 346 incident breast cancers in a prospective cohort of 17,035 women enrolled in the Malmö Diet and Cancer study (Sweden) were subcategorized according to conventional pathology parameters, proliferation and expression of key cell cycle regulators. Subcategories were compared with prediagnostic diet and body measurements using analysis of variance. RESULTS: A large hip circumference and high body mass index were associated with high grade tumours (P = 0.03 and 0.009, respectively), whereas low energy and unadjusted fat intakes were associated with high proliferation (P = 0.03 and 0.004, respectively). Low intakes of saturated, monounsaturated and polyunsaturated fatty acids were also associated with high proliferation (P = 0.02, 0.004 and 0.003, respectively). Low energy and unadjusted fat intakes were associated with cyclin D(1 )overexpression (P = 0.02 and 0.007, respectively), whereas cyclin E overexpression was positively correlated with fat intake. Oestrogen receptor status and expression of the tumour suppressor gene p27 were not associated with either diet or body constitution. CONCLUSION: Low energy and low total fat (polyunsaturated fatty acids in particular) intakes, and high body mass index were associated with relatively more malignant breast tumours. Dietary behaviours and body constitution may be associated with specific types of breast cancer defined by conventional pathology parameters and cyclin D(1 )and cyclin E expression. Further studies including healthy control individuals are needed to confirm our results

Domestic Water Demand During Droughts in Temperate Climates: Synthesising Evidence for an Integrated Framework

In the upcoming years, as the population is growing and ageing, as lifestyle changes create the need for more water and as fewer people live in each household, the UK water sector will have to deal with challenges in the provision of adequate water services. Unless critical action is taken, every area in the UK may face a supply-demand gap by the 2080s. Extreme weather events and variations that alter drought and flood frequency add to these pressures. However, little evidence is available about householders’ response to drought and there are few if any studies incorporating this evidence into models of demand forecasting. The present work lays the groundwork for modelling domestic water demand response under drought conditions in temperate climates. After discussing the current literature on estimating and forecasting domestic water consumption under both ‘normal’ and drought conditions, this paper identifies the limited ability of current domestic demand forecasting techniques to include the many different and evolving factors affecting domestic consumption and it stresses the need for the inclusion of inter and intra household factors as well as water use practices in future demand forecasting models

Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS

Coding SNPs analysis highlights genetic relationships and evolution pattern in eggplant complexes

[EN] Brinjal (Solanum melongena), scarlet (S. aethiopicum) and gboma (S. macrocarpon) eggplants are three Old World domesticates. The genomic DNA of a collection of accessions belonging to the three cultivated species, along with a representation of various wild relatives, was characterized for the presence of single nucleotide polymorphisms (SNPs) using a genotype-by-sequencing approach. A total of 210 million useful reads were produced and were successfully aligned to the reference eggplant genome sequence. Out of the 75,399 polymorphic sites identified among the 76 entries in study, 12,859 were associated with coding sequence. A genetic relationships analysis, supported by the output of the FastSTRUCTURE software, identified four major sub-groups as present in the germplasm panel. The first of these clustered S. aethiopicum with its wild ancestor S. anguivi; the second, S. melongena, its wild progenitor S. insanum, and its relatives S. incanum, S. lichtensteinii and S. linneanum; the third, S. macrocarpon and its wild ancestor S. dasyphyllum; and the fourth, the New World species S. sisymbriifolium, S. torvum and S. elaeagnifolium. By applying a hierarchical FastSTRUCTURE analysis on partitioned data, it was also possible to resolve the ambiguous membership of the accessions of S. campylacanthum, S. violaceum, S. lidii, S. vespertilio and S. tomentsum, as well as to genetically differentiate the three species of New World Origin. A principal coordinates analysis performed both on the entire germplasm panel and also separately on the entries belonging to sub-groups revealed a clear separation among species, although not between each of the domesticates and their respective wild ancestors. There was no clear differentiation between either distinct cultivar groups or different geographical provenance. Adopting various approaches to analyze SNP variation provided support for interpretation of results. The genotyping-by-sequencing approach showed to be highly efficient for both quantifying genetic diversity and establishing genetic relationships among and within cultivated eggplants and their wild relatives. The relevance of these results to the evolution of eggplants, as well as to their genetic improvement, is discussed.This work has been funded in part by European Unions Horizon 2020 Research and Innovation Programme under grant agreement No 677379 (G2P-SOL project: Linking genetic resources, genomes and phenotypes of Solanaceous crops) and by Spanish Ministerio de Economia, Industria y Competitividad and Fondo Europeo de Desarrollo Regional (grant AGL2015-64755-R from MINECO/FEDER). Funding has also been received from the initiative "Adapting Agriculture to Climate Change: Collecting, Protecting and Preparing Crop Wild Relatives", which is supported by the Government of Norway. This last project is managed by the Global Crop Diversity Trust with the Millennium Seed Bank of the Royal Botanic Gardens, Kew and implemented in partnership with national and international gene banks and plant breeding institutes around the world. For further information see the project website:http://www.cwrdiversity.org/. Pietro Gramazio is grateful to Universitat Politecnica de Valencia for a pre-doctoral (Programa FPI de la UPV-Subprograma 1/2013 call) contract. Mariola Plazas is grateful to Spanish Ministerio de Economia, Industria y Competitividad for a post-doctoral grant within the Santiago Grisolia Programme (FCJI-2015-24835). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Acquadro, A.; Barchi, L.; Gramazio, P.; Portis, E.; Vilanova Navarro, S.; Comino, C.; Plazas Ávila, MDLO.... (2017). Coding SNPs analysis highlights genetic relationships and evolution pattern in eggplant complexes. PLoS ONE. 12(7). https://doi.org/10.1371/journal.pone.0180774Se018077412