The aim of this work was to determine the mass transfer properties of pumpkin (Cucurbita moschata) exposed to air drying. The drying temperatures tested ranged between 30°C and 70°C, and the kinetic ...behavior was studied in this temperature band. The samples were analyzed in terms of moisture content, acidity, proteins, lipids, and crude fiber, both in the fresh state and after drying. From the chemical analyses made, it was possible to conclude that drying induces some reductions in acidity, lipids, fibers, and proteins. As to the influence of the drying temperature on the process, it was observed that a temperature rise from 30°C to 70°C led to a 70% saving in drying time. The results obtained by fitting the experimental data to the kinetic models tested allowed concluding that the best model for the present case is Henderson–Pabis, and the worst is Vega–Lemus. Furthermore, in this work, it was possible to determine the values of the diffusion coefficient at an infinite temperature, D e 0 , and activation energy for moisture diffusion, E d, which were, respectively, 0.0039 m2/s and 32.26 kJ/mol. Similarly, the values of the Arrhenius constant and the activation energy for convective mass transfer, respectively, h m 0 and E c, were also calculated, the first being 3.798 × 108 m/s and the latter 86.25 kJ/mol. These results indicate that the activation energy for convective mass transfer is higher than that for mass diffusion.
This paper explores the nationalist conflict in Catalonia and how it is lived and experienced by actors within it. It focuses on the people mobilised against independence who see themselves primarily ...as defenders of the Spanish Constitution and not of Spanish nationalism. Critics of civic nationalism in political theory and Nationalism Studies argue that anti‐nationalist rhetoric tends to be the expression of structural or hegemonic nationalism. Drawing on fieldwork carried out in Barcelona, I look at how the conflict has influenced discourse and language used in everyday life, how participants negotiate their identity, why people do (and do not) get involved in organisations that defend their political ideas, how they see themselves within the conflict and their perceptions of public space and its significance in relation to the constitution. An ethnographic approach explores these issues and discovers that although anti‐independence actors base their mobilisation in nationalism, civic nationalism cannot be reduced to just another form of nationalism. I aim to go beyond critics of civic nationalism to explore how my interlocutors act within and against nationalism, reproducing nationalist discourse in some aspect (boundaries of the nation) in order to challenge it in others (content and relevance of nationalism in everyday life).
Abstract
Alpha-synuclein (aSyn) is a central player in Parkinson's disease (PD) but the precise molecular mechanisms underlying its pathogenicity remain unclear. It has recently been suggested that ...nuclear aSyn may modulate gene expression, possibly via interactions with DNA. However, the biological behavior of aSyn in the nucleus and the factors affecting its transcriptional role are not known. Here, we investigated the mechanisms underlying aSyn-mediated transcription deregulation by assessing its effects in the nucleus and the impact of phosphorylation in these dynamics. We found that aSyn induced severe transcriptional deregulation, including the downregulation of important cell cycle-related genes. Importantly, transcriptional deregulation was concomitant with reduced binding of aSyn to DNA. By forcing the nuclear presence of aSyn in the nucleus (aSyn-NLS), we found the accumulation of high molecular weight aSyn species altered gene expression and reduced toxicity when compared with the wild-type or exclusively cytosolic protein. Interestingly, nuclear localization of aSyn, and the effect on gene expression and cytotoxicity, was also modulated by phosphorylation on serine 129. Thus, we hypothesize that the role of aSyn on gene expression and, ultimately, toxicity, may be modulated by the phosphorylation status and nuclear presence of different aSyn species. Our findings shed new light onto the subcellular dynamics of aSyn and unveil an intricate interplay between subcellular location, phosphorylation and toxicity, opening novel avenues for the design of future strategies for therapeutic intervention in PD and other synucleinopathies.
Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. Sirtuin 2 was previously shown to modulate proteotoxicity associated with age-associated ...neurodegenerative disorders such as Alzheimer and Parkinson disease (PD). However, the precise molecular mechanisms involved remain unclear. Here, we provide mechanistic insight into the interplay between sirtuin 2 and α-synuclein, the major component of the pathognomonic protein inclusions in PD and other synucleinopathies. We found that α-synuclein is acetylated on lysines 6 and 10 and that these residues are deacetylated by sirtuin 2. Genetic manipulation of sirtuin 2 levels in vitro and in vivo modulates the levels of α-synuclein acetylation, its aggregation, and autophagy. Strikingly, mutants blocking acetylation exacerbate α-synuclein toxicity in vivo, in the substantia nigra of rats. Our study identifies α-synuclein acetylation as a key regulatory mechanism governing α-synuclein aggregation and toxicity, demonstrating the potential therapeutic value of sirtuin 2 inhibition in synucleinopathies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is compelling evidence that fruit, vegetables, whole cereals, and legumes make about 80 % of the total food fibre intake and have a potential to help in the prevention of a number of diseases. ...The aim of our study was to estimate total fibre intake from consumption of this fibre-rich food, partly reported in our earlier study in Croatian adult population. Current data analysis involved a non-probabilistic sample of 1,034 adult participants from Dalmatia, Croatia who responded to a validated food frequency questionnaire between October 2014 and March 2015. We also analysed the sales data obtained from three shopping centres in the Zadar area (Croatian coast) to establish a list of most frequently bought fruit, vegetables, whole cereals, and legumes and to calculate dietary fibre (DF) intake for each of the top-selling items and conversion factors for each food group. We then used these conversion factors to calculate individual total fibre intake (TFI) in our population. It was 11.4 g per person per day, which is less than half the recommended dietary requirements. On average, respondents reported to consume one piece of fruit and one meal of vegetables a day, which is less than half the daily recommendation for either. 25.8 % of respondents reported no consumption of whole cereals at all, and only 0.2 % of the population consumed the recommended 3–5 servings of whole grains or legumes a day. We also observed significantly higher consumption of fruit and whole grains/legumes in women than men. Our findings alert to poor dietary fibre intake in Croatian adult population, which is similar to other western countries and points to issues deeply rooted in these economies. However, our findings may be either an over- or under-estimation and need to be verified through longitudinal research on a wider sample using more precise tools.
Parkinson´s disease (PD) is characterized by the presence of proteinaceous inclusions called Lewy bodies that are mainly composed of α-synuclein (αSyn). Elevated levels of oxidative or nitrative ...stresses have been implicated in αSyn related toxicity. Phosphorylation of αSyn on serine 129 (S129) modulates autophagic clearance of inclusions and is prominently found in Lewy bodies. The neighboring tyrosine residues Y125, Y133 and Y136 are phosphorylation and nitration sites. Using a yeast model of PD, we found that Y133 is required for protective S129 phosphorylation and for S129-independent proteasome clearance. αSyn can be nitrated and form stable covalent dimers originating from covalent crosslinking of two tyrosine residues. Nitrated tyrosine residues, but not di-tyrosine-crosslinked dimers, contributed to αSyn cytotoxicity and aggregation. Analysis of tyrosine residues involved in nitration and crosslinking revealed that the C-terminus, rather than the N-terminus of αSyn, is modified by nitration and di-tyrosine formation. The nitration level of wild-type αSyn was higher compared to that of A30P mutant that is non-toxic in yeast. A30P formed more dimers than wild-type αSyn, suggesting that dimer formation represents a cellular detoxification pathway in yeast. Deletion of the yeast flavohemoglobin gene YHB1 resulted in an increase of cellular nitrative stress and cytotoxicity leading to enhanced aggregation of A30P αSyn. Yhb1 protected yeast from A30P-induced mitochondrial fragmentation and peroxynitrite-induced nitrative stress. Strikingly, overexpression of neuroglobin, the human homolog of YHB1, protected against αSyn inclusion formation in mammalian cells. In total, our data suggest that C-terminal Y133 plays a major role in αSyn aggregate clearance by supporting the protective S129 phosphorylation for autophagy and by promoting proteasome clearance. C-terminal tyrosine nitration increases pathogenicity and can only be partially detoxified by αSyn di-tyrosine dimers. Our findings uncover a complex interplay between S129 phosphorylation and C-terminal tyrosine modifications of αSyn that likely participates in PD pathology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Alpha-synuclein (aSyn) accumulates in intracellular inclusions in synucleinopathies, but the molecular mechanisms leading to disease are unclear. We identify the 10 kDa heat shock protein (HSP10) as ...a mediator of aSyn-induced mitochondrial impairments in striatal synaptosomes. We find an age-associated increase in the cytosolic levels of HSP10, and a concomitant decrease in the mitochondrial levels, in aSyn transgenic mice. The levels of superoxide dismutase 2, a client of the HSP10/HSP60 folding complex, and synaptosomal spare respiratory capacity are also reduced. Overexpression of HSP10 ameliorates aSyn-associated mitochondrial dysfunction and delays aSyn pathology in vitro and in vivo. Altogether, our data indicate that increased levels of aSyn induce mitochondrial deficits, at least partially, by sequestering HSP10 in the cytosol and preventing it from acting in mitochondria. Importantly, these alterations manifest first at presynaptic terminals. Our study not only provides mechanistic insight into synucleinopathies but opens new avenues for targeting underlying cellular pathologies.
Display omitted
•aSyn sequesters HSP10 in the cytosol and prevents it from acting in the mitochondria•Overexpression of HSP10 delays aSyn pathology in vitro and in vivo•HSP10 modulates aSyn pathology in synaptic terminals
Szegő et al. identify HSP10 as a modulator of alpha-synuclein-induced mitochondrial impairment in striatal synaptosomes. Age-associated increase in the cytosolic and decrease in mitochondrial levels of HSP10 results in a reduction in the levels of SOD2 and of synaptosomal ATP production on demand. HSP10 overexpression delays alpha-synuclein pathology both in vitro and in vivo.
The innovative technologies developed in the different fields of science (nanotechnology, artificial intelligence, genetic modification, etc.) opened new and infinite possibilities for the several ...stakeholders that carry out their activities in the different economic sectors. For agriculture, these new approaches are particularly relevant and may bring interesting contributions, considering the specificities of the sector, often dealing with contexts of land abandonment and narrow profit margins. Nonetheless, the question in these unstopped evolutions is about the interlinkages with sustainability. In this context, the objectives of this study are to highlight the main insights from the available scientific literature about the interrelationships between the new trends in the agriculture and the sustainability. To achieve these aims, a search on the Web of Science Core Collection (WoS) and Scopus databases was carried out, on 15 May 2021, for the topics ‘smart agriculture’ and ‘sustainability’. A total of 231 documents (102 from WoS and 129 from Scopus) were obtained, remaining 155 documents after removing the duplicated, which were surveyed through systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach. As main insights, the concerns of the researchers with the impacts on the sustainability from the transformations in the farming organization are highlighted. On the other hand, it was shown the relevance and the new opportunities, including in terms of food supply, arising from the precision agriculture, agricultural intelligence, vertical/urban farming, circular economy, internet of things, and crowdfarming. We suggest the new and wider concept of ‘integrated-smart agriculture’, better than ‘climate-smart agriculture’.
Alpha-synuclein (aSyn) is the major protein component of Lewy bodies and Lewy neurites, the typical pathological hallmarks in Parkinson's disease (PD) and Dementia with Lewy bodies. aSyn is capable ...of inducing transcriptional deregulation, but the precise effect of specific aSyn mutants associated with familial forms of PD, remains unclear. Here, we used transgenic mice overexpressing human wild-type (WT) or A30P aSyn to compare the transcriptional profiles of the two animal models. We found that A30P aSyn promotes strong transcriptional deregulation and increases DNA binding. Interestingly, COL4A2, a major component of basement membranes, was found to be upregulated in both A30P aSyn transgenic mice and in dopaminergic neurons expressing A30P aSyn, suggesting a crucial role for collagen related genes in aSyn-induced toxicity. Finally, we observed that A30P aSyn alters Golgi morphology and increases the susceptibility to endoplasmic reticulum (ER) stress in dopaminergic cells. In total, our findings provide novel insight into the putative role of aSyn on transcription and on the molecular mechanisms involved, thereby opening novel avenues for future therapeutic interventions in PD and other synucleinopathies.
•A30P aSyn exhibits robust transcriptional deregulation in transgenic mice.•ER-related pathways are found deregulated in A30P aSyn transgenic mice.•A30P aSyn binds to several regions of DNA and affects exon usage.•A30P aSyn upregulates COL4A2, a major component of basement membranes.•A30P aSyn alters Golgi morphology and increases the susceptibility to ER stress.
Aberrant protein-protein interactions are a common pathological hallmark among neurodegenerative diseases, including Parkinson's disease (PD). Thus far, mutations in more than 20 genes have been ...associated with PD. These genes encode for proteins involved in distinct intracellular pathways, complicating our understanding of the precise molecular mechanisms underlying the disease. Recent reports suggested that the endolysosomal protein ATP13A2 can determine the fate of alpha-synuclein (α-Syn), although no consensus has yet been reached on the mechanisms underlying this effect. Here, we describe, for the first time, the deleterious effect arising from the interaction between the ATP13A2 familial mutant Dup22 with α-Syn. We show that this ATP13A2 mutant can enhance α-Syn oligomerization and aggregation in cell culture. Additionally, we report the accumulation of both proteins in abnormal endoplasmic reticulum membranous structures and the activation of the protein kinase RNA-like endoplasmic reticulum kinase pathway. Ultimately, our data bring new insight into the molecular mechanisms underlying the interplay of these two proteins, opening novel perspectives for therapeutic intervention.
PDF
