Cloning of a protease gene family of Fasciola hepatica by the polymerase chain reaction

Degenerate oligonucleotide primers derived from conserved cysteine protease sequences were used in the reverse transcription polymerase chain reaction to amplify seven different cysteine protease cDNA clones, Fcp1-7, from RNA isolated from adult Fasciola hepatica. Five of the amplified F. hepatica sequences showed homology to the cathepsin L type and two were more related to the cathepsin B type. Southern blot analysis suggests that some members of this protease gene family are present in multiple copies. Northern blot analysis revealed differences in the levels of steady state mRNA expression for some of these proteases. The 5' and the 3' regions of Fcp1 were amplified using the rapid amplification of cDNA ends PCR protocol (RACE-PCR) and an additional clone was obtained by screening a lambda gt10 cDNA library using Fcp1 as a probe. The Fcp1 cDNA fragment was also subcloned in the expression vector pGEX and expressed as a glutathione-S-transferase (GST) fusion protein in Escherichia coli. Antibodies, raised in rabbits against the GST:Fcp1 fusion protein, were used in western blot analysis to examine expression in different life-cycle stages of F. hepatica. In extracts from adult and immature parasites, the immune serum recognised predominantly two proteins of 30 kDa and 38 kDa. In other parasite stages, proteins of different molecular weight were recognised by the anti-GST:Fcp1 antiserum, indicating stage-specific gene expression or processing of Fcp1. In gelatine substrate gel analysis, strong proteolytic activity could be detected at 30 kDa, but not at 38 kDa, suggesting that the 30 kDa protein represents the mature enzyme and the 38 kDa protein the proenzyme.

Acceleration of the PanIN Development in Mice Expressing Oncogenic K-Ras Due to a High Fat Diet

Obesity is postulated to be one of the major risk factors for pancreatic cancer, and recently it was indicated that an elevated body mass index (BMI correlates strongly with a decrease in patient survival. Despite the evident relationship, the molecular mechanisms involved are unclear. Oncogenic mutation of K-Ras is found early and is universal in pancreatic cancer. Extensive evidence indicates oncogenic K-Ras is not entirely active and it requires a triggering event to surpass the activity of Ras beyond the threshold necessary for a Ras-inflammation feed-forward loop. We hypothesize that high fat intake induces a persistent low level inflammatory response triggering increased K-Ras activity and that Cox-2 is essential for this inflammatory reaction. To determine this, LSL-K-Ras mice were crossed with Ela-CreER (Acinar-specific) or Pdx-1-Cre (Pancreas-specific) to “knock-in” oncogenic K-Ras. Additionally, these animals were crossed with Cox-2 conditional knockout mice to access the importance of Cox-2 in the inflammatory loop present. The mice were fed isocaloric diets containing 60% energy or 10% energy from fat. We found that a high fat diet increased K-Ras activity, PanIN formation, and fibrotic stroma significantly compared to a control diet. Genetic deletion of Cox-2 prevented high fat diet induced fibrosis and PanIN formation in oncogenic K-Ras expressing mice. Additionally, long term consumption of high fat diet, increased the progression of PanIN lesions leading to invasive cancer and decreased overall survival rate. These findings indicate that a high fat diet can stimulate the activation of oncogenic K-Ras and initiate an inflammatory feed forward loop requiring Cox-2 leading to inflammation, fibrosis, and PanINs. This mechanism could explain the relationship between a high fat diet and elevated risk for pancreatic cancer.

Planktonic foraminifera in the latest Maastrichtian of Walvis Ridge, South Atlantic

An abrupt global warming of 3-4°C occurred near the end of the Maastrichtian at 65.45-65.10 Ma. The environmental effects of this warm event are here documented based on stable isotopes and quantitative analysis of planktonic foraminifera at the South Atlantic DSDP Site 525A. Stable isotopes of individual species mark a rapid increase in temperature and a reduction in the vertical water mass stratification that is accompanied by a decrease in niche habitats, reduced species diversity and/or abundance, smaller species morphologies or dwarfing, and reduced photosymbiotic activity. During the warm event, the relative abundance of a large number of species decreased, including tropical-subtropical affiliated species, whereas typical mid-latitude species retained high abundances. This indicates that climate warming did not create favorable conditions for all tropical-subtropical species at mid-latitudes and did not cause a massive retreat in the local mid-latitude population. A noticeable exception is the ecological generalist Heterohelix dentata Stenestad that dominated during the cool intervals, but significantly decreased during the warm event. However, dwarfing is the most striking response to the abrupt warming and occurred in various species of different morphologies and lineages (e.g. biserial, trochospiral, keeled globotruncanids). Dwarfing is a typical reaction to environmental stress conditions and was likely the result of increased reproduction rates. Similarly, photosymbiotic activity appears to have been reduced significantly during the maximum warming, as indicated by decreased delta13C values. The foraminiferal response to climate change is thus multifaceted resulting in decreased species diversity, decreased species populations, increased competition due to reduced niche habitats, dwarfing and reduced photosymbiotic activity.

Family diversity in social exclusion situations. Results and reflections on research, teaching and knowledge transfer activities

The purpose of this paper is to characterize the configurations of the families that live in contexts of social exclusion; provide conceptualizations of their operation mode; highlight the formative effects that neighborhood interdisciplinary practices with such families produce in the just graduated psychologists, included on the Extension Program. We wish to contribute to produce systematic knowledge that can account for such family configurations as potential receiver of integration policies. We are also interested on transferring the approach to diversity in the training of young professionals, in order not to be regarded as a deviation from ideal models, but as an expression of different strategies built by members of a community, to resolve children breeding and to bear their existences. This work is the result about reflections on productions inside a research fellowship: The complexities that takes the breeding in families who lives in a social exclusion situation; researches about breeding, carried out from signature Developmental Psychology II, and from de interdisciplinary work with psychologically assisted families in twelve suburbs of the city of La Plata (University Extension Program "Free Legal Offices" (Convention between Law and Social Sciences and Psychology Faculties, U.N.L.P.). From a qualitative methodology and an interdisciplinary participation, the results have arrive at the characterization and proposed conceptualizations of the included families and at the same time determine the benefits that brings with the work that articulates research and extension activities for the training of advanced students and young graduates.

Family diversity in social exclusion situations. Results and reflections on research, teaching and knowledge transfer activities

The purpose of this paper is to characterize the configurations of the families that live in contexts of social exclusion; provide conceptualizations of their operation mode; highlight the formative effects that neighborhood interdisciplinary practices with such families produce in the just graduated psychologists, included on the Extension Program. We wish to contribute to produce systematic knowledge that can account for such family configurations as potential receiver of integration policies. We are also interested on transferring the approach to diversity in the training of young professionals, in order not to be regarded as a deviation from ideal models, but as an expression of different strategies built by members of a community, to resolve children breeding and to bear their existences. This work is the result about reflections on productions inside a research fellowship: The complexities that takes the breeding in families who lives in a social exclusion situation; researches about breeding, carried out from signature Developmental Psychology II, and from de interdisciplinary work with psychologically assisted families in twelve suburbs of the city of La Plata (University Extension Program "Free Legal Offices" (Convention between Law and Social Sciences and Psychology Faculties, U.N.L.P.). From a qualitative methodology and an interdisciplinary participation, the results have arrive at the characterization and proposed conceptualizations of the included families and at the same time determine the benefits that brings with the work that articulates research and extension activities for the training of advanced students and young graduates.

Family diversity in social exclusion situations. Results and reflections on research, teaching and knowledge transfer activities

The purpose of this paper is to characterize the configurations of the families that live in contexts of social exclusion; provide conceptualizations of their operation mode; highlight the formative effects that neighborhood interdisciplinary practices with such families produce in the just graduated psychologists, included on the Extension Program. We wish to contribute to produce systematic knowledge that can account for such family configurations as potential receiver of integration policies. We are also interested on transferring the approach to diversity in the training of young professionals, in order not to be regarded as a deviation from ideal models, but as an expression of different strategies built by members of a community, to resolve children breeding and to bear their existences. This work is the result about reflections on productions inside a research fellowship: The complexities that takes the breeding in families who lives in a social exclusion situation; researches about breeding, carried out from signature Developmental Psychology II, and from de interdisciplinary work with psychologically assisted families in twelve suburbs of the city of La Plata (University Extension Program "Free Legal Offices" (Convention between Law and Social Sciences and Psychology Faculties, U.N.L.P.). From a qualitative methodology and an interdisciplinary participation, the results have arrive at the characterization and proposed conceptualizations of the included families and at the same time determine the benefits that brings with the work that articulates research and extension activities for the training of advanced students and young graduates.

Primary structure and expression of a pathogen-induced protease (PR-P69) in tomato plants: Similarity of functional domains to subtilisin-like endoproteases.

A 69-kDa proteinase (P69), a member of the pathogenesis-related proteins, is induced and accumulates in tomato (Lycopersicon esculentum) plants as a consequence of pathogen attack. We have used the polymerase chain reaction to identify and clone a cDNA from tomato plants that represent the pathogenesis-related P69 proteinase. The nucleotide sequence analysis revealed that P69 is synthesized in a preproenzyme form, a 745-amino acid polypeptide with a 22-amino acid signal peptide, a 92-amino acid propolypeptide, and a 631-amino acid mature polypeptide. Within the mature region the most salient feature was the presence of domains homologous to the subtilisin serine protease family. The amino acid sequences surrounding Asp-146, His-203, and Ser-532 of P69 are closely related to the catalytic sites (catalytic triad) of the subtilisin-like proteases. Northern blot analysis revealed that the 2.4-kb P69 mRNA accumulates abundantly in leaves and stem tissues from viroid-infected plants, whereas the mRNA levels in tissues from healthy plants were undetectable. Our results indicate that P69, a secreted calcium-activated endopeptidase, is a plant pathogenesis-related subtilisin-like proteinase that may collaborate with other defensive proteins in a general mechanism of active defense against attacking pathogens.

Induction of cellular immunity in chimpanzees to human tumor-associated antigen mucin by vaccination with MUC-1 cDNA-transfected Epstein-Barr virus-immortalized autologous B cells.

Aberrant glycosylation of the mucin molecule (encoded by the gene MUC-1) on human epithelial cell tumors leads to the exposure of tumor-associated epitopes recognized by patients' antibodies and cytotoxic T cells. Consequently, these epitopes could be considered targets for immunotherapy. We designed a cellular vaccine, employing, instead of tumor cells, autologous Epstein-Barr virus (EBV)-immortalized B cells as carriers of tumor-associated mucin, to take advantage of their costimulatory molecules for T-cell activation. The vaccine was tested in chimpanzees because of the identity of the human and chimpanzee MUC-1 tandem repeat sequence. EBV-immortalized B cells derived from two chimpanzees were transfected with MUC-1 cDNA, treated with glycosylation inhibitor phenyl-N-acetyl-alpha-D-galactosaminide to expose tumor-associated epitopes, irradiated, and injected subcutaneously four times at 3-week intervals. One vaccine preparation also contained cells transduced with the interleukin 2 (IL-2) cDNA and producing low levels of IL-2. Already after the first injection we found in the peripheral blood measurable frequency of cytotoxic T-cell precursors specific for underglycosylated mucin. The highest frequency observed was after the last boost, in the lymph node draining the vaccination site. Delayed-type hypersensitivity reaction to the injected immunogens was also induced, whereas no appearance of mucin-specific antibodies was seen. Long-term observation of the animals yielded no signs of adverse effects of this immunization. Autologous antigen-presenting cells, like EBV-immortalized B cells, expressing tumor-associated antigens are potentially useful immunogens for induction of cellular anti-tumor responses in vivo.

Parametric & nonparametric approaches to event studies: an application to a hotel’s market value

The main objective of this paper is twofold: on the one hand, to analyse the impact that the announcement of the opening of a new hotel has on the performance of its chain by carrying out an event study, and on the other hand, to compare the results of two different approaches to this method: a parametric specification based on the autoregressive conditional heteroskedasticity models to estimate the market model, and a nonparametric approach, which implies employing Theil’s nonparametric regression technique, which in turn, leads to the so-called complete nonparametric approach to event studies. The results that the empirical application arrives at are noteworthy as, on average, the reaction to such news releases is highly positive, both approaches reaching the same level of significance. However, a word of caution must be said when one is not only interested in detecting whether the market reacts, but also in obtaining an exhaustive calculation of the abnormal returns to further examine its determining factors.

Participatory approaches in the management of Natura 2000: when EU biodiversity policy gets closer to its citizens. Bruges Political Research Paper No. 26/May 2012

The Habitats Directive has created a European network of protected areas combining environmental protection with social and economic activities. Although not clearly advocated in the Directive, participatory approaches have incrementally emerged in order to ensure an adequate management of the Natura 2000 network. This paper looks at the reasons why the European Commission on one side and the national/local authorities on the other side chose to engage in participatory approaches and assesses the structure, degree and scope of these approaches in the light of input and output legitimacy. Main findings are that participation was mostly implemented as a reaction to conflicts and out of a concern over policy implementation, two elements that continue to drive the philosophy of the Natura 2000 network‘s management. The limits of participation in Brussels are contrasted with the potential for more genuine and effective participation mechanisms on the field.

From the sublime to the subliminal: Fear, awe and wonder in international politics

Key events in international politics, such as terrorist attacks, can be characterised as sublime: our minds clash with phenomena that supersede our cognitive abilities, triggering a range of powerful emotions, such as pain, fear and awe. Encounters with the sublime allow us an important glimpse into the contingent and often manipulative nature of representation. For centuries, philosophers have sought to learn from these experiences, but in political practice the ensuing insights are all too quickly suppressed and forgotten. The prevailing tendency is to react to the elements of fear and awe by reimposing control and order. We emphasise an alternative reaction to the sublime, one that explores new moral and political opportunities in the face of disorientation. But we also stress that we do not need to be dislocated by dramatic events to begin to wonder about the world. Moving from the sublime to the subliminal, we explore how it is possible to acquire the same type of insight into questions of representation and contingency by engaging more everyday practices of politics.

Support for diversity initiatives in organisations: An intergroup perspective

Despite institutional commitment to diversity initiatives (e.g., affirmative action), employees often harbour negative attitudes towards such initiatives and their beneficiaries. Dispositional variables (e.g., neo-sexism), have often been implicated in these negative reactions. We reason that more immediate group-based beliefs (e.g., subjective beliefs about the intergroup context), also shape attitudinal and behavioural reactions and that individual and group-based beliefs are rationalised through appeals to justice and fairness concerns. In this study using early career academics we examined the role of individual differences and socio-structural beliefs (about the stability, legitimacy and permeability of the intergroup situation), to feelings of relative deprivation, perceived justice and attitudes towards gender equity initiatives. Results provided support for the role of group-based beliefs and for the mediating role of justice concerns.

Introduction

Werner Sombart (1863-1941) was a famous and controversial social scientist in Germany during the early 20th century. Highly influential, his work and reputation have been indelibly tainted by his embrace of National Socialism in the last decade of his life. Although Sombart left an enormous opus spanning disciplinary boundaries, the scholarly assessment of and intellectual reaction to his work inside and outside of Germany is divided, and ambivalent. Best known for his analyses of capitalism - his essay "Why is There No Socialism in the United States?" remains a classic - Sombart consistently responded to the social and political developments that have shaped the 20th century. This collection provides a representative sampling of those portions of Sombart's work that have stood the test of time. The volume opens with a substantial introduction by the editors reviewing Sombart's life and career, the evolution of his major intellectual concerns, his relation to Marx and Weber, and his political affiliation with the Nazis. Their selection of texts emphasizes areas of his economic and cultural thought that remain relevant to intellectual trends in the social sciences, particularly those trends that seek a more broadly based, cross-disciplinary approach to the relationship of culture and economics. Sombart's writings on capitalism are represented by essays on the nature and origin of the market system and the diversity of its actors and motives among the bourgeoisie and the proletariat. Also included is an excerpt from Sombart's controversial volume "The Jews and Modern Capitalism" exploring the widely perceived relation between economic life and Judaism as a religion. In essays on the economics of cultural processes, Sombart's comprehensive and expansive idea of cultural science yields remarkable and prophetic insights into the nature of urbanism, luxury consumption, fashion and the cultural secularization of love. The volume's final section consists of Sombart's reflections on the social influences of technology, the economic life of the future, and on socialism, including the influential essay "Why is There No Socialism in the United States?". Encapsulating the most valuable aspects of his work, this study provides clear demonstration of Sombart's sense for fine cultural distinctions and broad cultural developments and the predictive power of his analyses. It should be of interest to sociologists, economists, political scientists and specialists in cultural studies.

Stock price reaction following large one-day price changes: UK evidence

We examine the short-term price reaction of 424 UK stocks to large one-day price changes. Using the GJR-GARCH(1,1), we find no statistical difference amongst the cumulative abnormal returns (CARs) of the Single Index, the Fama–French and the Carhart–Fama–French models. Shocks bigger or equal to 5% are followed by a significant one-day CAR of 1% for all the models. Whilst shocks smaller or equal to -5% are followed by a significant one-day CAR of -0.43% for the Single Index, the CARs are around -0.34% for the other two models. Positive shocks of all sizes and negative shocks maller or equal to -5% are followed by return continuations, whilst the market is efficient following larger negative shocks. The price reaction to shocks is unaffected when we estimate the CARs using the conditional covariances of the pricing variables.

Economic life in the modern age

Werner Sombart (1863-1941) may well have been the most famous and controversial social scientist in Germany during the early twentieth century. Highly influential, his work and reputation have been indelibly tainted by his embrace of National Socialism in the last decade of his life. Although Sombart left an enormous opus spanning disciplinary boundaries, intellectual reaction to his work inside and outside of Germany is divided and ambivalent. Sombart consistently responded to the social and political developments that have shaped the twentieth century. Economic Life in the Modern Age provides a representative sampling of those portions of Sombart's work that have stood the test of time. The volume opens with a substantial introduction reviewing Sombart's life and career, the evolution of his major intellectual concerns, his relation to Marx and Weber, and his political affiliation with the Nazis. The editors' selection of texts emphasizes areas of Sombart's economic and cultural thought that remain relevant, particularly to those intellectual trends that seek a more broadly based, cross-disciplinary approach to culture and economics. Sombart's writings on capitalism are represented by essays on the nature and origin of the market system and the diversity of motives among the bourgeoisie and the proletariat. Also included is an excerpt from Sombart's controversial The Jews and Modern Capitalism, exploring the widely perceived relation between economic life and Judaism as a religion. In essays on the economics of cultural processes, Sombart's comprehensive and expansive idea of cultural science yields prophetic insights into the nature of urbanism, luxury consumption, fashion, and the cultural secularization of love. The volume's final section consists of Sombart's reflections on the social influences of technology, the economic life of the future, and on socialism, including the influential essay "Why is there no Socialism in the United States." Encapsulating the most valuable aspects of his work, Economic Life in the Modern Age provides clear demonstration of Sombart's sense for fine cultural distinctions and broad cultural developments and the predictive power of his analyses. It will be of interest to sociologists, economists, political scientists, and specialists in cultural studies.