9,109,941 research outputs found
Bioavailability of flavonoids: in vitro methods for assessing bilitranslocase-mediated membrane transport
No full textB
ilitranslocase (TC 2.A.65.1.1) is a plasma membrane transporter
expressed in the gastro-intestinal epithelium (luminal side), the
liver and kidney (vascular side) (1) and in the vascular endothelium (2).
It transports bilirubin, flavonoids and other organic anions. By using
specific anti-sequence bilitranslocase antibodies targeting extracellular
epitopes critical for the carrier function, we can investigate both
the tissue and cellular localisation of the protein and its function
in absorption and tissue distribution of flavonoids, by a system of in
vitro methods featured by increasing structural complexity: i) plasma
membrane vesicles, ii) cell cultures, iii) tissue fragments, and iv)
isolated organs. The best example of implementation of this chain
of in vitro methods is the cardiovascular system, where consistent
observations were obtained throughout the chain. It can be concluded
that the first method, i.e. a bilitranslocase-specific functional assay
(3) in membrane vesicles where potential ligands (competitive and
non-competitive inhibitors) are identified, yields data predictive of
bilitranslocase function in organs. This approach can be helpful for
exploiting bilitranslocase as a membrane transporter in drug targeting
and development.
1 Passamonti S, Terdoslavich M, Franca R, Vanzo A, Tramer F, Braidot
E, et al. Curr Drug Metab. 2009 May;10(4):369-94.
2 Maestro A, Terdoslavich M, Vanzo A, Kuku A, Tramer F, Nicolin V, et
al.. Cardiovasc Res. 2009 Aug 25.
3 Passamonti S, Tramer F, Petrussa E, Braidot E, Vianello A. In: FettNeto AG, editor. Plant Secondary Metabolism Engineering Methods
and Applications. Totowa, NJ: Humana Press Inc.; 2010
Stem cell transplant in MF: It’s time to personalize
No full textIn this issue of Blood, Gagelmann et al1 describe an integrated clinical-molecular prognostic model (Myelofibrosis Transplant Scoring System [MTSS]) to predict outcome post stem cell transplant (SCT) in myelofibrosis (MF). MF is a clonal stem cell neoplasm with heterogeneous clinical phenotypes and well-defined driver mutations found in ∼90% of the cases.2 Despite the introduction of JAK inhibitors,3 MF still remains an incurable disease with a median survival of 4 to 5 years. SCT is an option for MF patients,4 but, because of the very high risk of mortality, the patient selection is very critical
The enigma of flavonoids and bilitranslocase activity in the cardiovascular system
No full textNumerous epidemiologic studies showed an inverse correlation
between dietary flavonoid consumption and cardiovascular risk, but the exact
mechanisms are still largely unknown. Flavonoids exhibit hormetic properties,
where low concentrations activate adaptive cellular stress response pathways
and thus lead towards cytoprotection, whereas high concentrations are
cytotoxic. However, the limited bioavailability of dietary flavonoids doubts the
relevance of effective flavonoid intracellular concentrations to induce bioactivity
in endothelial cells. Therefore, translocation of flavonoids through the cell plasma
membrane must occur via specific transporter proteins. Hereby, we describe the
involvement of the membrane transporter bilitranslocase (TC #2.A.65.1.1) as
the key underlying molecular mechanism for membrane transport, which might
help resolve the enigma of flavonoids bioactivity
Entry of the University of Trieste in the Cross-Border Cooperation Programme Italy-Slovenia 2007-2013
No full textThe CBC Programme Italy-Slovenia 2007-2013 and the University of Trieste:
correspondence between Programme’s objectives for the European territorial
cooperation and the institutional University missio
TRANS2CARE. Working plans: consciousness and perspectives
No full textThe project started on 1st April 2011 and will end on 30th September 2014.
The project received a budget of € 2,611,118 from the Italy-Slovenia 2007-2013
Cross-border Cooperation Programme.
Seven universities and research institutions, five hospitals and a center for technology
transfer distributed over the Programme area constitute the “Interregional network
for innovation and technology transfer for health improvement”, which will
continuously develop new protocols and biotechnological devices for the prevention,
early diagnosis and treatment of neurodegenerative, cardiovascular, orthopaedic and
oncological diseases
An unusual case of gender-associated mitochondrial DNA heteroplasmy: the mytilid Musculista senhousia (Mollusca Bivalvia)
No full textBackground
Doubly Uniparental Inheritance (DUI) represents the most outstanding exception to matrilinear inheritance of mitochondial DNA (mtDNA), typical of Metazoa. In a few bivalve mollusks, two sex-linked mtDNAs (the so-called M and F) are inherited in a peculiar way: both daughters and sons receive their F from the mother, whereas sons inherit M from the father (males do not transmit F to their progeny). This realizes a double mechanism of transmission, in which M and F mtDNAs are inherited uniparentally.
DUI systems represent a unique experimental model for testing the evolutionary mechanisms that apply to mitochondrial genomes and their transmission patterns as well as to mtDNA recombination.
Results
A new case of DUI is described in Musculista senhousia (Mollusca: Bivalvia: Mytilidae). Its heteroplasmy pattern is in line with standard DUI. Sequence variability analysis evidenced two main results: F haplotypes sequence variability is higher than that of M haplotypes, and F mitochondrial haplotypes experience a higher mutation rate in males’ somatic tissues than in females’ ones. Phylogenetic analysis revealed also that M. senhousia M and F haplotypes cluster separately from that of the other mytilids.
Conclusions
Sequence variability analysis evidenced some unexpected traits. The inverted variability pattern (the F being more variable than M) was new and it challenges most of the rationales proposed to account for sex-linked mtDNA evolution. We tentatively related this to the history of the Northern Adriatic populations analyzed. Moreover, F sequences evidenced a higher mutation level in male’s soma, this variability being produced de novo each generation. This suggests that mechanisms evolved to protect mtDNA in females (f.i. antioxidant gene complexes) might be under relaxed selection in males. Phylogenetic analysis of sex-linked haplotypes confirmed that they have switched their roles during the evolutionary history of mytilids, at variance to what has been observed in unionids. Consequently, reciprocal monophyly of M and F lineages got easily lost because of role-reversals and consequent losses of M lineages, as already observed in Mytilus
Doubly Uniparental Inheritance: two mitochondrial genomes, one precious model for organelle DNA inheritance and evolution.
No full textEukaryotes have exploited several mechanisms for organelle uniparental inheritance, so that this feature arose and evolved independently many times in their history. Metazoans’ mitochondria commonly experience Strict Maternal Inheritance (SMI), i.e. they are only transmitted by females. However, the most noteworthy exception comes from some bivalve mollusks, in which two mitochondrial lineages (together with their genomes) are inherited, one through females (F), the other through males (M). M and F genomes show up to 30% sequence divergence. This inheritance mechanism is known as Doubly Uniparental Inheritance (DUI), since both sexes inherit uniparentally their mitochondria. Here we review what we know about this unusual system and we propose a model for evolution of DUI that might account for its origin as sex determination mechanism. Moreover, we propose DUI as a choice model to address many aspects that should be of interest to a wide range of biological sub-fields, such as mitochondria inheritance, mtDNA evolution and recombination, genomic conflicts, evolution of sex, developmental biology, etc. Actually, as researches proceed, mitochondria appear to have acquired a central role in many fundamental processes of life, which are not only in their metabolic activity as cellular power plants, such as cell signaling, fertilization, development, differentiation, ageing, apoptosis and sex determination. A function of mitochondria in the origin and maintenance of sex has been also proposed
Myelofibrosis
No full textThe clinical phenotype of primary and post–polycythemia vera and postessential thrombocythemia myelofibrosis (MF) is dominated by splenomegaly, symptomatology, a variety of blood cell alterations, and a tendency to develop vascular complications and blast phase. Diagnosis requires assessing complete cell blood counts, bone marrow morphology, deep genetic evaluations, and disease history. Driver molecular events consist of JAK2V617F, CALR, and MPL mutations, whereas about 8% to 10% of MF are “triple-negative.” Additional myeloid-gene variants are described in roughly 80% of patients. Currently available clinical-based and integrated clinical/molecular-based scoring systems predict the survival of patients with MF and are applied for conventional treatment decision-making, indication to stem cell transplant (SCT) and allocation in clinical trials. Standard treatment consists of anemia-oriented therapies, hydroxyurea, and JAK inhibitors such as ruxolitinib, fedratinib, and pacritinib. Overall, spleen volume reduction of 35% or greater at week 24 can be achieved by 42% of ruxolitinib-, 47% of fedratinib-, 19% of pacritinib-, and 27% of momelotinib-treated patients. Now, it is time to move towards new paradigms for evaluating efficacy like disease modification, that we intend as a robust and unequivocal effect on disease biology and/or on patient survival. The growing number of clinical trials potentially pave the way for new strategies in patients with MF. Translational studies of some molecules showed an early effect on bone marrow fibrosis and on variant allele frequencies of myeloid genes. SCT is still the only curative option, however, it is associated with relevant challenges. This review focuses on the diagnosis, prognostication, and treatment of MF
Tra le isole di Darwin
No full textL'interesse naturalistico dell'arcipelago delle Galápagos e della sua fauna è determinato dalla coincidenza di alcune circostanze, tra le quali la posizione geografica e l'origine geologica. Tutte le isole dell'arcipelago hanno, infatti, origine vulcanica, ossia derivano da eruzioni avvenute sul fondo marino (in una zona molto attiva da questo punto di vista), che hanno provocato l'emersione di una parte più o meno estesa del relativo cono vulcanico.
Questa nascita, comune anche ad altri arcipelaghi oceanici, ha fatto sì che al momento della loro emersione le isole fossero ambienti virtualmente sterili, completamente privi di vita, e che il loro popolamento faunistico e floristico sia potuto avvenire soltanto attraverso la colonizzazione di specie provenienti dai continenti vicini. Qui entra in gioco la posizione geografica: le isole si trovano a circa 1000 chilometri dalle coste del Sud America, e ciò ha reso la loro colonizzazione un'impresa assai ardua per molte specie poco adatte a percorrere grandi distanze, o a sopportare, se trasportate passivamente, un viaggio così lungo
Footprints of unconventional mitochondrial inheritance in bivalve phylogeny: Signatures of positive selection on clades with doubly uniparental inheritance.
No full textThe doubly uniparental inheritance (DUI) of some bivalve mollusks is the major exception to the common maternal inheritance of mitochondria in animals. DUI involves two mitochondrial lineages with paternal and maternal transmission routes, and it appears as a complex phenomenon requiring both nuclear and mitochondrial adaptations. DUI distribution seems to be scattered among the Bivalvia, and there are several clues for its multiple origins. In this paper, we investigate whether the incipient DUI systems had left possible selective signatures on mitochondrial gen- omes. Alongside the outstanding divergence of amino acid sequences, we confirmed strong purifying selection to act on mitochondrial genes. However, we found evi- dence that distinct episodes of intense directional pressure are associated with the origins of different DUI systems: We interpret these signals as footprints of the coevolution with the nuclear genome that ought to take place at the base of a DUI clade. Six genes (atp6, cox1, cox2, cox3, nad4L, and nad6) seem to be more com- monly linked to the appearance of DUI. We also identified few putative DUI‐specific mutations, thus extending support to the hypothesis of multiple independent origins of this complex phenomenon
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