Expression of Human Neutrophil Elastase in K. Lactis.

Human neutrophils are the most abundant type of white blood cell and provide the body with a line of defense against foreign, infectious microorganisms. Contained within the azurophilic granules in the cytoplasm of neutrophils are three serine proteases, Human Neutrophil Elastase, Cathepsin G, and Protease 3. Once a foreign bacterium is engulfed by white blood cells, these enzymes attack and degrade the invading body, thus killing it (Reeves et al., 2002). The focus of this research is centered on the production of one of the serine proteases, human neutrophil elastase (HNE), and while the importance of HNE can be seen, genetic mutations or improper regulation can compromise a person’s immunity. Neutropenia (a low neutrophil count) is one such disease caused by a genetic mutation of HNE that results in susceptibility to infection (Li and Horwitz, 2001). Additionally, HNE is a powerful enzyme that can attack the elastin of the lung if not properly controlled. Consequently, genetic deficiencies of alpha-1 proteinase inhibitor protein in the blood can result in emphysema because active HNE released from neutrophils is free to degrade lung tissue (Laurell and Eriksson, 1965). Recombinant HNE is not currently available, and the enzyme must be isolated from human blood cells, which has inherent hazards. Additionally, the lack of recombinant HNE has prevented studies involving site–directed mutagenesis to study the intracellular processing of HNE near its C-terminal end where mutations have been found to result in neutropenia. Kinetic studies of the full-length HNE might shed some light on why its C-terminal region is removed before storage in cytoplasmic granules. The HNE DNA sequence was first codon optimized for yeast and commercially synthesized. It was then fused with DNA for eGFP (enhanced green fluorescent protein) via an enterokinase cleavage site (D4K). This DNA construct (eGFP-D4K-HNE) was then inserted into the Kluyveromyces lactis (K. lactis) pKLAC1 vector, downstream of the alpha mating factor which directs proteins for secretion. Then, chemically competent GG799 cells (a strain of K. lactis) were transformed with the linearized pKLAC1-eGFP-D4K-HNE insert through a protocol from New England Biolabs. Theoretically, the gene integrates into the yeast genome upon transformation via sequences within the pKLAC1 vector that are homologous with the LAC4 gene promoter that allows for galactose utilization (Colussi 2005). Acetamide was used as a selectable marker because wild type K. lactis cells are not able to use acetamide as a nitrogen source. The pKLAC1 vector, however, contains the Aspergillus nidulans gene acetamidase (amdS) that allows only transformants to grow on plates with acetamide as the sole nitrogen source (Read 2007). Selected colonies were transferred to both liquid and agar-based synthetic media with galactose to induce transcription and translation of the HNE gene to produce the eGFP-D4K-HNE fusion, and screened via fluorescence microscopy for production of eGFP. None of the screened colonies tested positive for the presence of the fusion protein

From high finance to the debacle: a tale of two wannabe banks

Este artículo tiene como objetivo examinar la influencia de la desregulación neoliberal en el brote de desmutualizaciones que tuvieron lugar en los años noventa. Explora hasta qué punto la desmutualización de dos sociedades de crédito o cajas de ahorros - Northern Rock y Bradford & Bingley- y su consiguiente desaparición, en la estela de la contracción del crédito, ejemplifican características clave del experimento neoliberal, con un énfasis particular en sus modelos de negocio posteriores a dicha desmutualización. En el artículo se argumenta que la desmutualización de Northern Rock y Bradford & Bingley formó parte de un movimiento neoliberal más amplio que tenía como centro a los procesos de financiarización. Al convertirlos en bancos, las antiguas cajas de ahorros consiguieron un acceso mayor a préstamos en los mercados financieros, a nuevos tipos de inversores y a un uso sin restricciones de instrumentos financieros como las titulizaciones. El colapso de Northern Rock y Bradford & Bingley será interpretado a la luz de su acceso a estas nuevas fuentes de financiación y su uso de unos instrumentos financieros que o bien no habían estado disponibles, o eran antitéticos para las operaciones de las cajas de ahorros.This paper aims to examine the influence of neoliberalist deregulation on the rash of demutualisations of the 1990s. It explores the extent to which the demutualisation of two building societies – Northern Rock and Bradford & Bingley – and their subsequent demise in the wake of the credit crunch exemplify key features of the neoliberalist experiment, with a particular focus on their post-mutualisation business models. The paper argues that the demutualisation of Northern Rock and Bradford & Bingley was part of a broader neoliberal movement which had processes of financialisation at its centre. By converting into banks, former building societies gained greater access to wholesale borrowing, to new types of investors and to the unrestricted use of financial instruments such as securitisation. The collapse of Northern Rock and Bradford & Bingley is interpreted in the light of their access to these new sources of funding and their use of financial instruments which were either unavailable for, or antithetical to, the operation of mutual societies

Spreading positive change: Societal benefits of meditation

Research over the past decades has revealed a variety of beneficial effects of meditation training. These beneficial effects span the levels of health and well-being, cognition, emotion, and social behavior. Around the same time, sociologists have shown that traits and outcomes on the individual level have the potential to spread in communities over three or more degrees. This means, for example, that changes can spread from one person to the next, and on to yet another person. Here, we propose that meditation-induced changes may likewise spread through the social networks of meditation practitioners. Such spreading may happen by positively influencing others through prosocial actions, improved cognitive functioning, and increased positive affect. Positive affective states and their underlying physiological correlates may also be shared in the literal sense. We argue that the spreading of positive meditation effects could provide the basis for collective responses to some of the urgent challenges we face in our current time and society and call for future meditation research to examine the phenomenon

Functional Neural Plasticity and Associated Changes in Positive Affect After Compassion Training

The development of social emotions such as compassion is crucial for successful social interactions as well as for the maintenance of mental and physical health, especially when confronted with distressing life events. Yet, the neural mechanisms supporting the training of these emotions are poorly understood. To study affective plasticity in healthy adults, we measured functional neural and subjective responses to witnessing the distress of others in a newly developed task (Socio-affective Video Task). Participants' initial empathic responses to the task were accompanied by negative affect and activations in the anterior insula and anterior medial cingulate cortex—a core neural network underlying empathy for pain. Whereas participants reacted with negative affect before training, compassion training increased positive affective experiences, even in response to witnessing others in distress. On the neural level, we observed that, compared with a memory control group, compassion training elicited activity in a neural network including the medial orbitofrontal cortex, putamen, pallidum, and ventral tegmental area—brain regions previously associated with positive affect and affiliation. Taken together, these findings suggest that the deliberate cultivation of compassion offers a new coping strategy that fosters positive affect even when confronted with the distress of other

Polsko-ukrainska wojna o wschodnia Galicje 1918–1919 r. Polskie spojrzenie

Проаналізовано геополітику польсько-української війни (листопад 1918 – липень 1919 рр.), подано образ цієї війни в польській науковій і суспільній думці.The article analyzes the geopolitical aspects of the Polish-Ukrainian War (November 1918 – July 1919). It explores the image of this war in Polish historiography and public opinion

Structural Covariance Networks of the Dorsal Anterior Insula Predict Females' Individual Differences in Empathic Responding

Previous functional imaging studies have shown key roles of the dorsal anterior insula (dAI) and anterior midcingulate cortex (aMCC) in empathy for the suffering of others. The current study mapped structural covariance networks of these regions and assessed the relationship between networks and individual differences in empathic responding in 94 females. Individual differences in empathy were assessed through average state measures in response to a video task showing others' suffering, and through questionnaire-based trait measures of empathic concern. Overall, covariance patterns indicated that dAI and aMCC are principal hubs within prefrontal, temporolimbic, and midline structural covariance networks. Importantly, participants with high empathy state ratings showed increased covariance of dAI, but not aMCC, to prefrontal and limbic brain regions. This relationship was specific for empathy and could not be explained by individual differences in negative affect ratings. Regarding questionnaire-based empathic trait measures, we observed a similar, albeit weaker modulation of dAI covariance, confirming the robustness of our findings. Our analysis, thus, provides novel evidence for a specific contribution of frontolimbic structural covariance networks to individual differences in social emotions beyond negative affec

The psychometric properties of the compassionate love scale and the validation of the English and German 7-item compassion for others scale (COS-7)

An increasing body of scientific research on the nature, correlates, and effects of compassion has accrued over recent years. Expert agreement has not yet been reached on the conceptualisation of compassion for others, and existing self-report measures of compassion for others have often lacked psychometric quality and content validity. Recent publications of longer compassion measures represent significant strides towards ameliorating these issues. However, there is a need for psychometrically sound short scales for measuring compassion in time-constrained research settings. To meet this need, one can assess the psychometric qualities of existing scales in order to develop robust short adaptations of such scales. Study 1 (N = 501) empirically assessed the psychometric properties of the widely cited Compassionate Love Scale (CLS) to validate a new short scale of compassion for others (strangers) comprised of items from the CLS – the 7-item Compassion for Others Scale (COS-7). Study 2 (N = 332) addressed the absence of a German measure of compassion for others by validating a German version of the COS-7. The CLS did not display adequate model fit. Both the English and German versions of the COS-7 demonstrated adequate model fit, factor loadings, internal consistency, interpretability, convergent/divergent validity, and no floor/ceiling effects. Findings provide support for the English and German versions of the COS-7 as adequate short scales for measuring compassion for others. The German COS-7 is the first German measure of compassion for others published to date

Freedom – what’s in a name? An analysis of the construction of the UK mortgage market in the light of the global financial crisis

This thesis offers a detailed analysis of the politics of neoliberalism and financialization in the context of the UK mortgage market. The analysis addresses an often implied but conceptually and empirically neglected feature in the otherwise booming social sciences literature on financial markets and the global financial crisis: how political struggles shape economic space. It does this against the background of the construction of the UK mortgage market which, as opposed to its American counterpart, is still underresearched. The thesis addresses these shortcomings by engaging the theory of Ernesto Laclau and the associated logics approach of the Essex School of Political Discourse Theory. It provides a detailed genealogical analysis of the transformations in the mortgage market during the three decades leading up to the financial crisis emphasising the significance of hegemonic struggles and ideology in its constitution. Empirically, the thesis investigates the transformation of the mortgage market from a ‘sheltered circuit’ dominated by a building society price cartel in the 1970s to a sphere that is increasingly driven by global financial markets. It is argued that at the heart of these transformations was the neo-liberalist deregulation in the name of the signifier ‘freedom’ which, in the neoliberalist age, became almost exclusively equated with ‘free markets’. The demutualisations of the 1990s are presented as an outcome of neoliberalist deregulation leading to a fundamental shift of power in the market. In return for improved access to capital markets and powered by ideological discourses, the demutualisation of 10 societies resulted in a massive transfer of mortgage assets to the stock market and contributed significantly to the financialization of mortgages. The struggles and resistance surrounding these events illustrate their contingent nature. However, the proposed re-mutualisation of Northern Rock had been squandered amidst a re-affirmation of neoliberalist ideology centring on the market as the best provider of mortgages

Empathy and correct mental state inferences both promote prosociality

In a world with rapidly increasing population that competes for the earth's limited resources, cooperation is crucial. While research showed that empathizing with another individual in need enhances prosociality, it remains unclear whether correctly inferring the other's inner, mental states on a more cognitive level (i.e., mentalizing) elicits helping behavior as well. We applied a video-based laboratory task probing empathy and a performance measure of mentalizing in adult volunteers (N = 94) and assessed to which extent they were willing to help the narrators in the videos. We replicate findings that an empathy induction leads to more prosocial decisions. Crucially, we also found that correct mentalizing increases the willingness to help. This evidence helps clarify an inconsistent picture of the relation between mentalizing and prosociality

De las altas finanzas a la debacle: un relato sobre dos aspirantes a bancos

Este artículo tiene como objetivo examinar la influencia de la desregulación neoliberal en el brote de desmutualizaciones que tuvieron lugar en los años noventa. Explora hasta qué punto la desmutualización de dos sociedades de crédito o cajas de ahorros - Northern Rock y Bradford & Bingley- y su consiguiente desaparición, en la estela de la contracción del crédito, ejemplifican características clave del experimento neoliberal, con un énfasis particular en sus modelos de negocio posteriores a dicha desmutualización. En el artículo se argumenta que la desmutualización de Northern Rock y Bradford & Bingley formó parte de un movimiento neoliberal más amplio que tenía como centro a los procesos de financiarización. Al convertirlos en bancos, las antiguas cajas de ahorros consiguieron un acceso mayor a préstamos en los mercados financieros, a nuevos tipos de inversores y a un uso sin restricciones de instrumentos financieros como las titulizaciones. El colapso de Northern Rock y Bradford & Bingley será interpretado a la luz de su acceso a estas nuevas fuentes de financiación y su uso de unos instrumentos financieros que o bien no habían estado disponibles, o eran antitéticos para las operaciones de las cajas de ahorros