Fumarate drives EMT in renal cancer

Medical Research Counci

Isoflavones and other compounds from the roots of Iris marsica I. Ricci E Colas. Collected from Majella National Park, Italy

In this study, a phytochemical analysis was performed, for the first time, on Iris marsica I. Ricci e Colas. In particular, the attention was focused on the constituents of the roots. Twenty-one compounds were isolated by column chromatography and were analyzed/identified by NMR spectroscopy and mass spectrometry. They all own chemotaxonomic, ethno-pharmacological and nutraceutical relevance which allowed us to provide a phytochemical rationale, for the correct botanical classification of this species, for the employment of its roots in folk medicine like for all the other species belonging to the Iris genus and, lastly, for their further uses as food with important healthy benefits. All of these parts were broadly discussed about within the text

Essential oil composition and polar fraction analysis of Tanacetum macrophyllum (Waldst. et Kit.) Schultz Bip.

Tanacetum macrophyllum (Waldst. et Kit.) Schultz Bip, also known as Tansy, is a perennial herbaceous plant belonging to the Asteraceae family. This species is typical of the Balcan area but is punctually spread in other European countries as a rare species [1]. In Italy, it is found mainly within forests [1, 2]. This species is often erroneously confused with Achillea grandifolia Friv. [1, 2]. In this work, a comprehensive phytochemical analysis on the volatile components and polar fraction of T. macrophyllum growing in central Italy was carried out. Flowers and leaves were separately analyzed for the essential oil composition and were characterized by oxygenated monoterpenes (39.4%) and oxygenated sesquiterpenes (28.0%) and sesquiterpene hydrocarbons (39.3%) and oxygenated monoterpenes (25.4%), respectively. The phytochemical analysis conducted on the ethanolic extract of the total aerial parts evidenced the presence of twelve compounds: apigenin, cirsimaritin, apigenin-7-O-glucoside, apigenin-7-O-glucuronide, kaempferol-7-O-glucoside, kaempferol-7-O-glucuronide, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, chlorogenic acid, shikimic acid, quinic acid and 4-O-β-D-glucopyranosyl-vanillic acid. Most of these compounds were reported for the first time in the species while three of them are new phytochemicals for the Tanacetum genus. The presence of all these compounds provides a phytochemical rationale for the botanical classification of this species and encourages further ethno-pharmacological studies just like for T. parthenium [3]

Fumarate drives EMT in renal cancer

Medical Research Counci

Evolution of human IgH3 ' EC duplicated structures: both enhancers HS1,2 are polymorphic with variation of transcription factor's consensus sites

The enhancer complex regulatory region at the 3' of the immunoglobulin heavy cluster (IgH3'EC) is duplicated in apes along with four constant genes and the region is highly conserved throughout humans. Both human IgH3'ECs consist of three loci high sensitive (HS) to DNAse I with enhancer activity. It is thus possible that the presence of structural divergences between the two IgH3'ECs and of relative polymorphisms correspond to functional regulatory changes. To analyse the polymorphisms of these almost identical regions, it resulted mandatory to identify the presence of divergent sequences, in order to select distinctive primers for specific PCR genomic amplifications. To this aim, we first compared the two entire IgH3'ECs in silicio, utilising the updated GenBank (GB) contigs, then we analysed the two IgH3'ECs by cloning and sequencing amplicons from independent genomes. In silicio analysis showed that several inversions, deletions and short insertions had occurred after the duplication. We analysed in detail, by sequencing specific regions, the polymorphisms occurring in enhancer HS1,2-A (which lies in IgH3'EC-1, 3' to the C alpha-1 gene) and in enhancer HS1,2-B (which lies in IgH3'EC-2, 3' to C alpha-2). Polymorphisms are due to the repetition (occurring one to four times) of a 38-bp sequence present at the 3' of the core of enhancers HS1,2. The structure of both human HS1,2 enhancers has revealed not yet described polymorphic features due to the presence of variable spacer elements separating the 38-bp repetitions and to variable external elements bordering the repetition cluster. We found that one of the external elements gave rise to a divergent allele 3 in the two clusters. The frequency of the different alleles of the two loci varies in the Italian population and allele 3 of both loci are very rare. The analysis of the Callicebus moloch, Gorilla gorilla and Pan troglodytes HS1,2 enhancers showed the transformation from the ancestral structure with the 31- to the 17-by external element in hominids. The relevance of the polymorphisms in the HS1,2 enhancers is due to the variable number of binding sites for the transcription factors: NF-kappa B, CMYB, BSAP1/2, AP1/4, E47, MyoD and mu E5 and thus to the possible influence of these variations on switch, production of Ig and on maturation of B cells. (c) 2004 Elsevier B.V. All rights reserved

Spaceship Earth. Space-driven technologies and systems for sustainability on ground

As awareness towards the problem is growing, eco-friendliness is today a paramount requirement for all space activities and in particular for the ground segment, fully comparable to other industrial sectors. The present work focuses on the assessment and the sustainable development enhancement of a ground-based space facility, the European Astronaut Centre (EAC), located in Germany. The project is framed within the European Space Agency development of an environmental outlook, which aims not only at the full compliance with the legislation and at assessing the impact of its activities, but also at laying the foundation for future evolution through innovation. Indeed, ESA promotes the sustainable use of space as a necessity and duty for Europe. As history teaches us, technical knowledge emerged within the space sector serves as innovation driver in other industrial branches: the goal of the project is to transform the EAC building into a spaceship integrated with the territory through the conscious management of this spontaneous process, fostering the combination between the space sector and the architecture and civil engineering fields. The work explores the potential of space technologies, processes and systems applied on ground and presents a range of space-driven innovative concepts which may improve the sustainability of the EAC building, focusing on different aspects of its resource demand – energy, water and waste management – and defining the integration with the pre-existing compound, the limitation of the impact on the surrounding landscape and the participation of the local community as additional fundamental requirements. Indeed, the project embraces the full concept of sustainability, which considers not only eco-friendliness but also its balance with economic and social aspects. Two factors – a certain urgency for action, which leaves little space for research and experimentation, and a call for ground-breaking solutions – guided the design activity: taking advantage of these conflicting requirements, a comparison between standard technologies and innovative space-related concepts was performed. When dealing with complex and uncertain scenarios, decision among the possible solutions is not straightforward and needs to be supported by appropriate methodologies: a multi-criteria and quantitative decision-making tool, able to concentrate on the main goal while considering all other relevant aspects – environmental, economic, social sustainability – was therefore developed. Furthermore, the project promotes local community participation in the decisional process, as a way to enhance knowledge, generate understanding and promote towards the EAC redesign, space activities and their potential innovative impact on sustainability

OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation

The dynamin-related GTPase OPA1 is mutated in autosomal dominant optic atrophy (DOA) (Kjer type), an inherited neuropathy of the retinal ganglion cells. OPA1 is essential for the fusion of the inner mitochondrial membranes, but its mechanism of action remains poorly understood. Here we show that OPA1 has a low basal rate of GTP hydrolysis that is dramatically enhanced by association with liposomes containing negative phospholipids such as cardiolipin. Lipid association triggers assembly of OPA1 into higher order oligomers. In addition, we find that OPA1 can promote the protrusion of lipid tubules from the surface of cardiolipin-containing liposomes. In such lipid protrusions, OPA1 assemblies are observed on the outside of the lipid tubule surface, a protein-membrane topology similar to that of classical dynamins. The membrane tubulation activity of OPA1 is suppressed by GTPγS. OPA1 disease alleles associated with DOA display selective defects in several activities, including cardiolipin association, GTP hydrolysis and membrane tubulation. These findings indicate that interaction of OPA1 with membranes can stimulate higher order assembly, enhance GTP hydrolysis and lead to membrane deformation into tubules

Mitochondrial dynamics–fusion, fission, movement, and mitophagy–in neurodegenerative diseases

Neurons are metabolically active cells with high energy demands at locations distant from the cell body. As a result, these cells are particularly dependent on mitochondrial function, as reflected by the observation that diseases of mitochondrial dysfunction often have a neurodegenerative component. Recent discoveries have highlighted that neurons are reliant particularly on the dynamic properties of mitochondria. Mitochondria are dynamic organelles by several criteria. They engage in repeated cycles of fusion and fission, which serve to intermix the lipids and contents of a population of mitochondria. In addition, mitochondria are actively recruited to subcellular sites, such as the axonal and dendritic processes of neurons. Finally, the quality of a mitochondrial population is maintained through mitophagy, a form of autophagy in which defective mitochondria are selectively degraded. We review the general features of mitochondrial dynamics, incorporating recent findings on mitochondrial fusion, fission, transport and mitophagy. Defects in these key features are associated with neurodegenerative disease. Charcot-Marie-Tooth type 2A, a peripheral neuropathy, and dominant optic atrophy, an inherited optic neuropathy, result from a primary deficiency of mitochondrial fusion. Moreover, several major neurodegenerative diseases—including Parkinson's, Alzheimer's and Huntington's disease—involve disruption of mitochondrial dynamics. Remarkably, in several disease models, the manipulation of mitochondrial fusion or fission can partially rescue disease phenotypes. We review how mitochondrial dynamics is altered in these neurodegenerative diseases and discuss the reciprocal interactions between mitochondrial fusion, fission, transport and mitophagy