How does conformational flexibility influence key structural features involved in activation of anaplastic lymphoma kinase?

Anaplastic Lymphoma Kinase (ALK) plays a major role in developing tumor processes and therefore has emerged as a validated therapeutic target. Applying atomistic molecular dynamics simulations on the wild type enzyme and the nine most frequently occurring and clinically important activation mutants we revealed important conformational effects on key interactions responsible for the activation of the enzyme

Use of Vesicular - Arbuscular Mycorrhiza (VAM) as Biofertilizer for Horticultural Plants in Developing Countries

Mycorrhiza is the product of an association between a fungus and plant root. Vesicular-arbuscular mycorrhiza (VAM) is formed by the symbiotic association between certain phycomycetous fungi and angiosperm roots. The fungus colonizes the root cortex forming a mycelial network and characteristic vesicles (bladder-like structures) and arbuscules (branched finger-like hyphae). The mycelia are aseptate or septate ramifying intercellularly thus causing little damage to tissues. The arbuscules are the most characteristic structures, formed intracellularly and probably having an absorptive function. The vesicles are terminal swellings of hyphae formed inter and intracellularly having a storage function. There are six genera of fungi belonging to Endogonaceae which have been shown to form mycorrhizal associations: Glomus, Gigaspora, Acaulospora, Entrophospora Sclerocystis and Scutellospora. These are mainly identified by their characteristic spores and sporocarps which are formed mostly in the soil surrounding the roots and rarely inside the roots. The identification of VAM fungi directly from roots has been difficult. One of the striking features of VAM fungi is their very wide host range which includes angiosperm species belonging to almost all the families. Even the roots of some aquatic plants are colonized by VAM fungi

Low aerobic mitochondrial energy metabolism in poorly- or undifferentiated neuroblastoma

<p>Abstract</p> <p>Background</p> <p>Succinate dehydrogenase (SDH) has been associated with carcinogenesis in pheochromocytoma and paraganglioma. In the present study we investigated components of the oxidative phosphorylation system in human neuroblastoma tissue samples.</p> <p>Methods</p> <p>Spectrophotometric measurements, immunohistochemical analysis and Western blot analysis were used to characterize the aerobic mitochondrial energy metabolism in neuroblastomas (NB).</p> <p>Results</p> <p>Compared to mitochondrial citrate synthase, SDH activity was severely reduced in NB (n = 14) versus kidney tissue. However no pathogenic mutations could be identified in any of the four subunits of SDH. Furthermore, no genetic alterations could be identified in the two novel SDH assembly factors SDHAF1 and SDH5. Alterations in genes encoding nfs-1, frataxin and isd-11 that could lead to a diminished SDH activity have not been detected in NB.</p> <p>Conclusion</p> <p>Because downregulation of other complexes of the oxidative phosphorylation system was also observed, a more generalized reduction of mitochondrial respiration seems to be present in neuroblastoma in contrast to the single enzyme defect found in hereditary pheochromocytomas.</p

The nation and the family: the impact of national identification and perceived importance of family values on homophobic attitudes in Lithuania and Scotland

The meanings attached to the nation can be consequential for group members’ attitudes and beliefs. We examined how national identity definition can influence the extent of individuals’ homophobia with 159 Lithuanian and 176 Scottish university students who completed a questionnaire which measured their national identification, homophobia, and the extent to which they felt traditional family values were central to their nation’s identity. Consistent with nation-wide differences in the significance given to the family, Lithuanian participants perceived family values to be more important for their national identity and expressed higher levels of homophobia than did Scottish participants. Moreover, the relationship between level of national identification and homophobia was stronger in Lithuania than in Scotland. Analyses revealed that the perceived importance of family values helped explain the difference between homophobia levels in Lithuania and Scotland. In both sites we found an indirect effect of national identification on homophobia via the perceived importance of family values, but this effect was significantly stronger for Lithuanian participants. These findings illustrate the ways in which identification with the nation is relevant to attitudes concerning sexuality, and how this varies according to national context. Our work indicates that LGBT rights campaigns should be informed by the knowledge that homophobia may be perpetuated by national valorisation of the family

Religions, Poverty Reduction and Global Development Institutions

Religious traditions have always played a central role in supporting those experiencing poverty, through service delivery as well as the provision of spiritual resources that provide mechanisms for resilience at both the individual and community level. However, the fact that religions can be seen to support social structures and practices that contribute towards inequality and conflict, also underscores a role for religious traditions in creating conditions of poverty. While the Western-led modern global development institutions that have emerged since the Second World War have tended to be secular in nature, over the past decade or so there has been an apparent ‘turn to religion’ by these global development institutions, as well as in academic development studies. This reflects the realization that modernization and secularization do not necessarily go together, and that religious values and faith actors are important determinants in the drive to reduce poverty, as well as in structures and practices that underpin it. This paper traces three phases of engagement between religions and global development institutions. In phase one, the ‘pre-secular’ or the ‘integrated phase’ seen during the colonial era, religion and poverty reduction were intimately entwined, with the contemporary global development project being a legacy of this. The second phase is the ‘secular’ or the ‘fragmented’ phase, and relates to the era of the global development industry, which is founded on the normative secularist position that modernization will and indeed should lead to secularization. The third phase is characterized by the ‘turn to religion’ from the early 2000s. Drawing the three phases together and reflecting on the nature of the dynamics within the third phase, the ‘turn to religion’, this paper is underpinned by two main questions. First, what does this mean for the apparent processes of secularization? Is this evidence that they are being reversed and that we are witnessing the emergence of the ‘desecularization of development’ or of a ‘post-secular development praxis’? Second, to what extent are FBOs working in development to be defined as neo-liberalism’s ‘little platoons’—shaped by and instrumentalized to the service of secular neo-liberal social, political and economic systems, or do we need to develop a more sophisticated account that can contribute towards better policy and practice around poverty reduction

Receptor Tyrosine Kinases in Osteosarcoma: 2019 Update

The primary conclusions of our 2014 contribution to this series were as follows: Multiple receptor tyrosine kinases (RTKs) likely contribute to aggressive phenotypes in osteosarcoma and, therefore, inhibition of multiple RTKs is likely necessary for successful clinical outcomes. Inhibition of multiple RTKs may also be useful to overcome resistance to inhibitors of individual RTKs as well as resistance to conventional chemotherapies. Different combinations of RTKs are likely important in individual patients. AXL, EPHB2, FGFR2, IGF1R, and RET were identified as promising therapeutic targets by our in vitro phosphoproteomic/siRNA screen of 42 RTKs in the highly metastatic LM7 and 143B human osteosarcoma cell lines. This chapter is intended to provide an update on these topics as well as the large number of osteosarcoma clinical studies of inhibitors of multiple tyrosine kinases (multi-TKIs) that were recently published