32 research outputs found
Rare Monogenic Diseases: Molecular Pathophysiology and Novel Therapies
No full textA rare disease is defined by its low prevalence in the general population [...
El Pirineu i la construcció nacional: El fet literari gascó a l\u27inici del segle XX i la seua relació amb l\u27àmbit català (Camelat, Sarrieu, Condò)
No full textFrom the beginning of the 20th century to approximately the 1940s the strongest (and, in many ways, the definitive) tide of linguistic substitution in favour of the French language reaches the Occitan speech area at the same time as an Occitan cultural consciousness develops, which comes from the relationship between the Catalan Renaixença and the Occitan Félibrige movements, both going back to the middle of the previous century. In this context, the case of Mistral and his contacts to e.g. Verdaguer have attracted researcher’s interest. The Gascony extensions of this literary correlation are however less reputed. At that point Miquèu de Camelat writes his work. Born in Arrens, a small village in the Bigorre mountains, he is well known as author of Belina, a Pyrenean version of Mistral’s Mireia. With far more explicit ideologic aspects, Camelat publishes in 1920 Mort e viva, a piece that presents itself evidently as the big epic poem from the Gascony Pyrenees, obviously inspired by Verdaguer and concentrating on the important events that – according to the author – determined and still determine the existence or non-existence of the Gascon nation. The comparison of Camelat with his contemporaries, especially with Gascons like Bernat Sarrieu form Luchon and with the Aranese Jusèp Condò, shows us how the same cultural space (provided that we assume a cultural continuity in the whole of the Pyrenean area, at least concerning forms of interaction between man and mountain) was conceived in a total different manner by the Gascons and the Catalans and – depending on the various historic conditions – was transformed differently into literature
Cis-acting signals controlling translational initiation in the thermophilic archaeon Sulfolobus solfataricus
No full textIn this work, we have studied the in vitro translational features of a bicistronic mRNA of the extremely thermophilic Archaeon Sulfolobus solfataricus, with the aim of determining the nature of the cis-acting signals controlling the recognition of the translation initiation sites in the Archaea. We found that the most important feature for efficient initiation was the presence of a Shine-Dalgarno (SD)-like ribosome-binding motif, whose disruption entirely abolished the translation of the corresponding cistron. The influence of other features, such as the type of initiation codon, was variable and depended upon the gene and its position in the mRNA. However, the translational block caused by the disruption of the SD sequences could be removed by deleting the 5' untranslated region altogether, thereby creating a 'leaderless' mRNA. This suggests that 'leaderless' initiation operates by a default mechanism that does not require a specific mRNA-rRNA interaction and may be common to all three primary domains of life
A caspaselike activity is triggered by LPS and is required for survival of human dendritic cells
No full textBacterial endotoxin (lipopolysaccharide [LPS]) is a potent inducer of human dendritic cell (DC) maturation and survival. Here we show that immature DCs exposed to LPS trigger an early and sustained caspase-like activity, which can be blocked by zVAD (z-Val-Ala-Asp), in the absence of detectable caspase 8 and caspase 10 activation, or poly(ADP-ribose) polymerase (PARP)-cleaving activity. Preventing LPS-induced caspase-like activation in DC results in massive cell death. Importantly, triggering of the caspase-like activity is required for LPS-induced activation of extracellular signal-regulated kinases (ERKs) and for LPS-induced up-regulation of cFLIP (Fas-associating protein with death domain-like interleukin-1 beta-converting enzyme [FLICE]-like inhibitory protein). Therefore, a caspase-dependent pathway initiated by LPS controls survival of human DCs
Intracellular mediators of programmed cell death initiated at the cell surface receptor Fas
No full textApoptosis is a programmed cell death process, which plays a pivotal role in development, in tissue homeostasis and in several human diseases. Fas (CD95/Apo-1) is a member of the "death receptors" family, a group of cell surface proteins that trigger apoptosis upon binding with their natural ligands. In the immune system, intracellular signal transduction triggered from Fas splits into two different pathways. The proteolytic pathway is mediated by a family of cysteine proteases, the caspases, responsible for the morphological changes occurring in the apoptotic process. To complete this death program, another series of events, involving a lipid pathway, is necessary. Upon Fas stimulation, a sequential activation of specific enzymes results in the accumulation of ceramides and GD3 ganglioside. GD3 directly induces mitochondrial damage and triggers the release of apoptogenic factors, allowing efficient execution of Fas-mediated apoptosis
A pool of extramitochondrial frataxin that promotes cell survival
No full textFrataxin is a mitochondrial protein involved in iron metabolism. Defective expression of frataxin causes Friedreich ataxia (FA), an inherited degenerative syndrome characterized by ataxia, cardiomyopathy, and high incidence of diabetes. Here we report that frataxin-deficient cells are more prone to undergo stress-induced mitochondrial damage and apoptosis, while the overexpression of frataxin confers protection to a variety of cell types. Moreover, we reveal the existence of an extramitochondrial pool of frataxin, which can efficiently prevent mitochondrial damage and apoptosis in different cellular systems. Remarkably, extramitochondrial frataxin can fully replace mitochondrial frataxin in promoting survival of FA cells
Reduced expression of frataxin extends the lifespan of Caenorhabditis elegans
No full textDefects in the expression of the mitochondrial protein frataxin cause Friedreich's ataxia, an hereditary neurodegenerative syndrome characterized by progressive ataxia and associated with reduced life expectancy in humans. Homozygous inactivation of the frataxin gene results in embryonic lethality in mice, suggesting that frataxin is required for organismic survival. Intriguingly, the inactivation of many mitochondrial genes in the nematode Caenorhabditis elegans by RNAi extends lifespan. We therefore investigated whether inactivation of frataxin by RNAi-mediated suppression of the frataxin homolog gene (frh-1) would also prolong lifespan in the nematode. Frataxin-deficient animals have a small body size, reduced fertility and altered responses to oxidative stress. Importantly, frataxin suppression by RNAi significantly extends lifespan in C. elegans
Fluorinated Agents Effects on Orthodontic Alloys: A Descriptive In Vitro Study
No full textFluoride-based mouthwashes and gels are preventive measures in countering demineralization and caries but, modifying environmental acidity, can reduce the wet corrosion resistance of orthodontic alloys. To evaluate chemical stability, in vitro experiments were conducted on stainless steel and nickel–titanium wires, weighed before and after immersion in household fluorinated mouthwashes and gels, measuring weight variations and elution of metal ions from acid corrosion phenomena. Elution samples were analyzed by inductively coupled plasma mass spectrometry, detecting residual ion concentration, while surface changes were analyzed under scanning electron microscopy. Results showed stainless steel wires do not undergo significant erosion when exposed to most fluorinated mouthwashes but, at prolonged exposure, alloys elute gradually greater amounts of metals and Ni–Ti wires become more sensitive to some mouthwashes. Ions’ elution varies considerably, especially for Ni–Ti wires, if exposed to household fluorinated gels, for which significant negative values were obtained. Changes, affecting wires’ outer layer, negatively act on shiny appearance and luster, reducing corrosion resistance. Although examined orthodontic wires showed good chemical stability and low toxicity, surface corrosion from exposure to fluorinated agents was observed. Home use must be accompanied by clinician prescription and, for household dental gels, must follow manufacturers’ recommendations, ensuring prophylactic action without damaging alloys surfaces
Caspase-dependent cleavage of c-Abl contributes to apoptosis
No full textThe nonreceptor tyrosine kinase c-Abl may contribute to the regulation of apoptosis. c-Abl activity is induced in the nucleus upon DNA damage, and its activation is required for execution of the apoptotic program. Recently, activation of nuclear c-Abl during death receptor-induced apoptosis has been reported; however, the mechanism remains largely obscure. Here we show that c-Abl is cleaved by caspases during tumor necrosis factor- and Fas receptor-induced apoptosis. Cleavage at the very C-terminal region of c-Abl occurs mainly in the cytoplasmic compartment and generates a 120-kDa fragment that lacks the nuclear export signal and the actin-binding region but retains the intact kinase domain, the three nuclear localization signals, and the DNA-binding domain. Upon caspase cleavage, the 120-kDa fragment accumulates in the nucleus. Transient-transfection experiments show that cleavage of c-Abl may affect the efficiency of Fas-induced cell death. These data reveal a novel mechanism by which caspases can recruit c-Abl to the nuclear compartment and to the mammalian apoptotic program
