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Showing papers by "National University of Cuyo published in 2016"


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
TL;DR: In this article, the authors present an overview in order to up-to-date knowledge regarding NADES with special emphasis on their analytical applications and further perspectives as truly green solvents.
Abstract: Developing new green solvents is one of the key subjects in Green Chemistry. Ionic liquids and deep eutectic solvents were discovered as an option to replace organic solvents. However, ionic liquids and deep eutectic solvents (DES) have still some limitations to be applied to real chemical industry. In this sense, a new generation of designer solvents have emerged in the last decade as promising green media. When the compounds that constitute DES are primary metabolites, namely, aminoacids, organic acids, sugars, or choline derivatives, DES are called Natural Deep Eutectic Solvents (NADES). NADES fully represent green chemistry principles. These solvents offer many striking advantages including biodegradability, low toxicity, solute stabilization, sustainability, low costs and simple preparation. Thus, interesting applications in health-related areas can be proposed. This review presents an overview in order to up-to-date knowledge regarding NADES with special emphasis on their analytical applications and further perspectives as truly green solvents.

257 citations


Proceedings ArticleDOI
15 Jun 2016
TL;DR: This work provides an analysis of the viability of Recurrent Neural Networks to detect the behavior of network traffic by modeling it as a sequence of states that change over time, which makes it a potential candidate for implementation and deployment on real-world scenarios.
Abstract: A Botnet can be conceived as a group of compromised computers which can be controlled remotely to execute coordinated attacks or commit fraudulent acts. The fact that Botnets keep continuously evolving means that traditional detection approaches are always one step behind. Recently, the behavior analysis of network traffic has arisen as a way to tackle the Botnet detection problem. The behavioral analysis approach aims to look at the common patterns that Botnets follow across their life cycle, trying to generalize in order to become capable of detecting unseen Botnet traffic. This work provides an analysis of the viability of Recurrent Neural Networks (RNN) to detect the behavior of network traffic by modeling it as a sequence of states that change over time. The recent success applying RNN to sequential data problems makes them a viable candidate on the task of sequence behavior analysis. The performance of a RNN is evaluated considering two main issues, the imbalance of network traffic and the optimal length of sequences. Both issues have a great impact in potentially real-life implementation. Evaluation is performed using a stratified k-fold cross validation and an independent test is conducted on not previously seen traffic belonging to a different Botnet. Preliminary results reveal that the RNN is capable of classifying the traffic with a high attack detection rate and an very small false alarm rate, which makes it a potential candidate for implementation and deployment on real-world scenarios. However, experiments exposed the fact that RNN detection models have problems for dealing with traffic behaviors not easily differentiable as well as some particular cases of imbalanced network traffic.

138 citations


Journal ArticleDOI
TL;DR: This is the first study in which a multiple lesion model reveals fine-grained alterations of body sensing, offering new theoretical insights into neuroanatomical foundations of interoceptive dimensions.
Abstract: Interoception is a complex process encompassing multiple dimensions, such as accuracy, learning and awareness. Here, we examined whether each of those dimensions relies on specialized neural region...

131 citations


Journal ArticleDOI
01 Nov 2016-Brain
TL;DR: Analysis of social bargaining behaviour in relation to its structural neural correlates, ongoing brain dynamics, and functional connectivity signatures in healthy subjects and patients offering contrastive lesion models of neurodegeneration and focal stroke offers new insights into the critical roles of prefrontal hubs and associated temporo-parietal networks for strategic social negotiation.
Abstract: Recursive social decision-making requires the use of flexible, context-sensitive long-term strategies for negotiation. To succeed in social bargaining, participants' own perspectives must be dynamically integrated with those of interactors to maximize self-benefits and adapt to the other's preferences, respectively. This is a prerequisite to develop a successful long-term self-other integration strategy. While such form of strategic interaction is critical to social decision-making, little is known about its neurocognitive correlates. To bridge this gap, we analysed social bargaining behaviour in relation to its structural neural correlates, ongoing brain dynamics (oscillations and related source space), and functional connectivity signatures in healthy subjects and patients offering contrastive lesion models of neurodegeneration and focal stroke: behavioural variant frontotemporal dementia, Alzheimer's disease, and frontal lesions. All groups showed preserved basic bargaining indexes. However, impaired self-other integration strategy was found in patients with behavioural variant frontotemporal dementia and frontal lesions, suggesting that social bargaining critically depends on the integrity of prefrontal regions. Also, associations between behavioural performance and data from voxel-based morphometry and voxel-based lesion-symptom mapping revealed a critical role of prefrontal regions in value integration and strategic decisions for self-other integration strategy. Furthermore, as shown by measures of brain dynamics and related sources during the task, the self-other integration strategy was predicted by brain anticipatory activity (alpha/beta oscillations with sources in frontotemporal regions) associated with expectations about others' decisions. This pattern was reduced in all clinical groups, with greater impairments in behavioural variant frontotemporal dementia and frontal lesions than Alzheimer's disease. Finally, connectivity analysis from functional magnetic resonance imaging evidenced a fronto-temporo-parietal network involved in successful self-other integration strategy, with selective compromise of long-distance connections in frontal disorders. In sum, this work provides unprecedented evidence of convergent behavioural and neurocognitive signatures of strategic social bargaining in different lesion models. Our findings offer new insights into the critical roles of prefrontal hubs and associated temporo-parietal networks for strategic social negotiation.

101 citations


Journal ArticleDOI
TL;DR: Elucidating the IR signaling pathways and the roles of NO and HSPs is relevant to the application of new treatments, such as heat shock and thermal therapy, nitrosylated drugs, chemical chaperones or exercise training.
Abstract: Insulin resistance (IR) is present in pathologies such as diabetes, obesity, metabolic syndrome, impaired glucose tolerance, hypertension, inflammation, cardiac disease, and dyslipidemias. Population studies show that IR is multifactorial and has genetic components, such as defects in the insulin-signaling pathway (as serine phosphorylation on insulin substrate or decreased activation of signaling molecules) and RAS/MAPK-dependent pathways. IR is connected to mitochondrial dysfunction, overproduction of oxidants, accumulation of fat, and an over-activation of the renin-angiotensin system linked to the NADPH oxidase activity. In addition, nitric oxide (NO), synthesized by nitric oxide synthases (endothelial and inducible), is also associated with IR when both impaired release and reduced bioavailability of all which lead to inflammation and hypertension. However, increased NO may promote vasculoprotection. Moreover, reduced NO release induces heat shock protein 70 kDa (HSP70) expression in IR and diabetes, mediating beneficial effects against oxidative stress injury, inflammation and apoptosis. HSP70 may be used as biomarker of the chronicity of diabetes. Hsp72 (inducible protein) is linked to vascular complications with a high-fat diet by blocking inflammation signaling (cytoprotective and anti-cytotoxicity intracellular role). Elucidating the IR signaling pathways and the roles of NO and HSPs is relevant to the application of new treatments, such as heat shock and thermal therapy, nitrosylated drugs, chemical chaperones or exercise training.

82 citations


Journal ArticleDOI
TL;DR: There is strong evidence that the causal link between abundance and generalisation is uni-directional, and null model analyses suggest that abundant species interact with many other species simply because they are more likely to encounter potential interaction partners.
Abstract: A frequent observation in plant-animal mutualistic networks is that abundant species tend to be more generalised, interacting with a broader range of interaction partners than rare species. Uncovering the causal relationship between abundance and generalisation has been hindered by a chicken-and-egg dilemma: is generalisation a by-product of being abundant, or does high abundance result from generalisation ? Here, we analyse a database of plant-pollinator and plant-seed disperser networks, and provide strong evidence that the causal link between abundance and generalisation is uni-directional. Specifically, species appear to be generalists because they are more abundant, but the converse, that is that species become more abundant because they are generalists, is not supported by our analysis. Furthermore, null model analyses suggest that abundant species interact with many other species simply because they are more likely to encounter potential interaction partners.

81 citations


Journal ArticleDOI
TL;DR: The results highlight the relevance of studying naturalistic discourse features to tap the integrity of neural (and, particularly, motor) networks, beyond the possibilities of standard token-level instruments.

71 citations


Journal ArticleDOI
05 Dec 2016
TL;DR: A mouse model of DIO that will allow us to study the effect of MS in different organs and systems has been developed and characterized and showed steatohepatitis and systemic oxidative stress/inflammation.
Abstract: Increased chicken-derived fat and fructose consumption in the human diet is paralleled by an increasing prevalence of obesity and metabolic syndrome (MS). Herein, we aimed at developing and characterizing a mouse model of diet-induced obesity (DIO) resembling most of the key features of the human MS. To accomplish this, we fed male C57BL/6J mice for 4, 8, 12, and 16 weeks with either a low-fat diet (LFD) or a high-chicken-fat diet (HFD) and tap water with or without 10% fructose (F). This experimental design resulted in the following four experimental groups: LFD, LFD + F, HFD, and HFD + F. Over the feeding period, and on a weekly basis, the HFD + F group had more caloric intake and gained more weight than the other experimental groups. Compared to the other groups, and at the end of the feeding period, the HFD + F group had a higher adipogenic index, total cholesterol, low-density lipoprotein cholesterol, fasting basal glycemia, insulin resistance, hypertension, and atherogenic index and showed steatohepatitis and systemic oxidative stress/inflammation. A mouse model of DIO that will allow us to study the effect of MS in different organs and systems has been developed and characterized.

71 citations


Journal ArticleDOI
TL;DR: The results suggest that (-)-epicatechin ingestion would benefit when renal alterations occur associated with inflammation or metabolic diseases, as well as preventing or ameliorating the adverse effects of high fructose consumption.

69 citations


Journal ArticleDOI
TL;DR: This study represents one of the most comprehensive analyses of whole genome sequence data for Group I and II BoNT-producing strains and illustrates the diversity of botulinum-neurotoxin- producing strains and the plasticity of the genomic backgrounds in which bont genes are found.
Abstract: Clostridium botulinum is a diverse group of bacteria characterized by the production of botulinum neurotoxin. Botulinum neurotoxins are classified into serotypes (BoNT/A–G), which are produced by six species/Groups of Clostridia, but the genetic background of the bacteria remains poorly understood. The purpose of this study was to use comparative genomics to provide insights into the genetic diversity and evolutionary history of bacteria that produce the potent botulinum neurotoxin. Comparative genomic analyses of over 170 Clostridia genomes, including our draft genome assemblies for 59 newly sequenced Clostridia strains from six continents and publicly available genomic data, provided in-depth insights into the diversity and distribution of BoNT-producing bacteria. These newly sequenced strains included Group I and II strains that express BoNT/A,/B,/E, or/F as well as bivalent strains. BoNT-producing Clostridia and closely related Clostridia species were delineated with a variety of methods including 16S rRNA gene, concatenated marker genes, core genome and concatenated multi-locus sequencing typing (MLST) gene phylogenies that related whole genome sequenced strains to publicly available strains and sequence types. These analyses illustrated the phylogenetic diversity in each Group and the diversity of genomic backgrounds that express the same toxin type or subtype. Comparisons of the botulinum neurotoxin genes did not identify novel toxin types or variants. This study represents one of the most comprehensive analyses of whole genome sequence data for Group I and II BoNT-producing strains. Read data and draft genome assemblies generated for 59 isolates will be a resource to the research community. Core genome phylogenies proved to be a powerful tool for differentiating BoNT-producing strains and can provide a framework for the study of these bacteria. Comparative genomic analyses of Clostridia species illustrate the diversity of botulinum-neurotoxin-producing strains and the plasticity of the genomic backgrounds in which bont genes are found.

Journal ArticleDOI
TL;DR: Describing 2 HCMV proteins, TRS1 and IRS1, and finding the BECN1-binding domain (BBD) of IRS1 and T RS1 to be essential for autophagy inhibition demonstrate a new proviral role of autophagic for a DNA virus.
Abstract: Autophagy is activated early after human cytomegalovirus (HCMV) infection but, later on, the virus blocks autophagy. Here we characterized 2 HCMV proteins, TRS1 and IRS1, which inhibit autophagy during infection. Expression of either TRS1 or IRS1 was able to block autophagy in different cell lines, independently of the EIF2S1 kinase, EIF2AK2/PKR. Instead, TRS1 and IRS1 interacted with the autophagy protein BECN1/Beclin 1. We mapped the BECN1-binding domain (BBD) of IRS1 and TRS1 and found it to be essential for autophagy inhibition. Mutant viruses that express only IRS1 or TRS1 partially controlled autophagy, whereas a double mutant virus expressing neither protein stimulated autophagy. A mutant virus that did not express IRS1 and expressed a truncated form of TRS1 in which the BBD was deleted, failed to control autophagy. However, this mutant virus had similar replication kinetics as wild-type virus, suggesting that autophagy inhibition is not critical for viral replication. In fact, using pharmacological modulators of autophagy and inhibition of autophagy by shRNA knockdown, we discovered that stimulating autophagy enhanced viral replication. Conversely, inhibiting autophagy decreased HCMV infection. Thus, our results demonstrate a new proviral role of autophagy for a DNA virus.

Journal ArticleDOI
TL;DR: In this article, a study of the magnetic structure vs temperature showed the occurrence of a progressive spin reorientation from the perovskite family to the transition metal sublattice, and in the Tm-based sample, a long-range magnetic order was found.
Abstract: Three members of the perovskite family $R\mathrm{F}{\mathrm{e}}_{0.5}\mathrm{C}{\mathrm{r}}_{0.5}{\mathrm{O}}_{3}$ ($R=\mathrm{Lu},\mathrm{Yb}$, and Tm) have been synthesized and characterized. A systematic study of the crystal and magnetic structures was performed by neutron powder diffraction combined with magnetization measurements. All these compounds crystallize in a Pbnm orthorhombic unit cell and they are already antiferromagnetic at room temperature. The study of the magnetic structure vs temperature showed the occurrence of a progressive spin reorientation from ${\mathrm{\ensuremath{\Gamma}}}_{4}^{\text{TM}}$ to ${\mathrm{\ensuremath{\Gamma}}}_{2}^{\text{TM}}$ for the transition metal sublattice, and in the Tm-based sample, a long-range magnetic order of the $\mathrm{T}{\mathrm{m}}^{3+}$ sublattice was found $({\mathrm{\ensuremath{\Gamma}}}_{8}^{R})$. These results are in excellent agreement with the magnetic susceptibility measurements. No spin reorientation is observed in the Lu-based sample for which a magnetization reversal at a compensation temperature ${T}_{\mathrm{comp}}=225\phantom{\rule{0.16em}{0ex}}\mathrm{K}$ was detected. A clear magnetostrictive effect was observed in the samples with $R=\mathrm{Yb}$ and Tm associated with a negative thermal expansion and was assigned to a magnetoelastic effect produced by repulsion between the magnetic moments of neighboring transition metal ions.

Proceedings ArticleDOI
07 Mar 2016
TL;DR: This work introduces uRank and investigates interactive methods for understanding, refining and reorganizing documents on-the-fly as information needs evolve, and shows that gathering items relevant to a particular topic of interest with uRank incurs in lower cognitive load compared to a traditional ranked list.
Abstract: Whenever users engage in gathering and organizing new information, searching and browsing activities emerge at the core of the exploration process. As the process unfolds and new knowledge is acquired, interest drifts occur inevitably and need to be accounted for. Despite the advances in retrieval and recommender algorithms, real-world interfaces have remained largely unchanged: results are delivered in a relevance-ranked list. However, it quickly becomes cumbersome to reorganize resources along new interests, as any new search brings new results. We introduce uRank and investigate interactive methods for understanding, refining and reorganizing documents on-the-fly as information needs evolve. uRank includes views summarizing the contents of a recommendation set and interactive methods conveying the role of users' interests through a recommendation ranking. A formal evaluation showed that gathering items relevant to a particular topic of interest with uRank incurs in lower cognitive load compared to a traditional ranked list. A second study consisting in an ecological validation reports on usage patterns and usability of the various interaction techniques within a free, more natural setting.

Journal ArticleDOI
TL;DR: The results support the validity of the VSTM binding test and their neural correlates in the early detection of AD and highlight the importance of studies comparing samples at different risk for AD conversion.
Abstract: Deficits in visual short-term memory (VSTM) binding have been proposed as an early and specific marker for Alzheimer's disease (AD). However, no studies have explored the neural correlates of this domain in clinical categories involving prodromal stages with different risk levels of conversion to AD. We assessed underlying electrophysiological modulations in patients with mild cognitive impairment (MCI), patients in the MCI stages of familial AD carrying the mutation E280A of the presenilin-1 gene (MCI-FAD), and healthy controls. Moreover, we compared the behavioral performance and neural correlates of both patient groups. Participants completed a change-detection VSTM task assessing recognition of changes between shapes or shape-color bindings, presented in two consecutive arrays (i.e., study and test) while event related potentials (ERPs) were recorded. Changes always occurred in the test array and consisted of new features replacing studied features (shape-only) or features swapping across items (shape-color binding). Both MCI and MCI-FAD patients performed worse than controls in the shape-color binding condition. Early electrophysiological activity (100-250 ms) was significantly reduced in both clinical groups, particularly over fronto-central and parieto-occipital regions. However, shape-color binding performance and their reduced neural correlates were similar between MCI and MCI-FAD. Our results support the validity of the VSTM binding test and their neural correlates in the early detection of AD and highlight the importance of studies comparing samples at different risk for AD conversion. The combined analysis of behavioral and ERP data gleaned with the VSTM binding task can offer a valuable memory biomarker for AD.

Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (697)
TL;DR: Author(s): Klionsky, DJ; Abdelmohsen, K; Abe, A; Abedin, MJ; Abeliovich, H; A Frozena, AA; Adachi, H, Adeli, K, Adhihetty, PJ; Adler, SG; Agam, G; Agarwal, R; Aghi, MK; Agnello, M; Agostinis, P; Aguilar, PV; Aguirre-Ghis
Abstract: Author(s): Klionsky, DJ; Abdelmohsen, K; Abe, A; Abedin, MJ; Abeliovich, H; Arozena, AA; Adachi, H; Adams, CM; Adams, PD; Adeli, K; Adhihetty, PJ; Adler, SG; Agam, G; Agarwal, R; Aghi, MK; Agnello, M; Agostinis, P; Aguilar, PV; Aguirre-Ghiso, J; Airoldi, EM; Ait-Si-Ali, S; Akematsu, T; Akporiaye, ET; Al-Rubeai, M; Albaiceta, GM; Albanese, C; Albani, D; Albert, ML; Aldudo, J; Algul, H; Alirezaei, M; Alloza, I; Almasan, A; Almonte-Beceril, M; Alnemri, ES; Alonso, C; Altan-Bonnet, N; Altieri, DC; Alvarez, S; Alvarez-Erviti, L; Alves, S; Amadoro, G; Amano, A; Amantini, C; Ambrosio, S; Amelio, I; Amer, AO; Amessou, M; Amon, A; An, Z; Anania, FA; Andersen, SU; Andley, UP; Andreadi, CK; Andrieu-Abadie, N; Anel, A; Ann, DK; Anoopkumar-Dukie, S; Antonioli, M; Aoki, H; Apostolova, N; Aquila, S; Aquilano, K; Araki, K; Arama, E; Aranda, A; Araya, J; Arcaro, A; Arias, E; Arimoto, H; Ariosa, AR; Armstrong, JL; Arnould, T; Arsov, I; Asanuma, K; Askanas, V; Asselin, E; Atarashi, R; Atherton, SS; Atkin, JD; Attardi, LD; Auberger, P; Auburger, G; Aurelian, L; Autelli, R

Journal ArticleDOI
TL;DR: The obtained results demonstrated that the proposed method is able for the determination of QR in complex food samples, and has proved to be faster, greener and cheaper than other sensors and chromatographic methods available with the additional advantage of being completely portable.

Journal ArticleDOI
TL;DR: Results suggest that, in addition to repressing direct defense, phyB inactivation has consequences for VOC-mediated tritrophic interactions in canopies, presumably attracting predators to less defended plants, where they are likely to find more abundant prey.
Abstract: Under conditions of competition for light, which lead to the inactivation of the photoreceptor phytochrome B (phyB), the growth of shade-intolerant plants is promoted and the accumulation of direct anti-herbivore defenses is down-regulated. Little is known about the effects of phyB on emissions of volatile organic compounds (VOCs), which play a major role as informational cues in indirect defense. We investigated the effects of phyB on direct and indirect defenses in tomato (Solanum lycopersicum) using two complementary approaches to inactivate phyB: illumination with a low red to far-red ratio, simulating competition, and mutation of the two PHYB genes present in the tomato genome. Inactivation of phyB resulted in low levels of constitutive defenses and down-regulation of direct defenses induced by methyl jasmonate (MeJA). Interestingly, phyB inactivation also had large effects on the blends of VOCs induced by MeJA. Moreover, in two-choice bioassays using MeJA-induced plants, the predatory mirid bug Macrolophus pygmaeus preferred VOCs from plants in which phyB was inactivated over VOCs from control plants. These results suggest that, in addition to repressing direct defense, phyB inactivation has consequences for VOC-mediated tritrophic interactions in canopies, presumably attracting predators to less defended plants, where they are likely to find more abundant prey.

Journal ArticleDOI
TL;DR: It is demonstrated that Rab22a is recruited to DC endosomes and phagosomes, as well as to the vacuole containing T. gondii parasites, and plays a central role in the MHC‐I endocytic trafficking, which is crucial for efficient cross‐presentation by DCs.
Abstract: Cross-presentation by MHC class I molecules allows the detection of exogenous antigens by CD8+ T lymphocytes. This process is crucial to initiate cytotoxic immune responses against many pathogens (i.e., Toxoplasma gondii) and tumors. To achieve efficient cross-presentation, dendritic cells (DCs) have specialized endocytic pathways; however, the molecular effectors involved are poorly understood. In this work, we identify the small GTPase Rab22a as a key regulator of MHC-I trafficking and antigen cross-presentation by DCs. Our results demonstrate that Rab22a is recruited to DC endosomes and phagosomes, as well as to the vacuole containing T. gondii parasites. The silencing of Rab22a expression did not affect the uptake of exogenous antigens or parasite invasion, but it drastically reduced the intracellular pool and the recycling of MHC-I molecules. The knockdown of Rab22a also hampered the cross-presentation of soluble, particulate and T. gondii-associated antigens, but not the endogenous MHC-I antigen presentation through the classical secretory pathway. Our findings provide compelling evidence that Rab22a plays a central role in the MHC-I endocytic trafficking, which is crucial for efficient cross-presentation by DCs.

Journal ArticleDOI
TL;DR: The hypothesis that action-verb processing in PD may rely on alternative disembodied semantic circuits subserving amodal semantics is tested and new insights into differential neurofunctional mechanisms recruited to process action semantics in PD are offered.
Abstract: Action verbs are critically embodied in motor brain networks. In Parkinson's disease (PD), damage to the latter compromises access to such words. However, patients are not fully incapable of processing them, as their performance is far from floor level. Here we tested the hypothesis that action-verb processing in PD may rely on alternative disembodied semantic circuits. Seventeen PD patients and 15 healthy controls listened to action verbs and nouns during functional MRI scanning. Using cluster-mass analysis with a permutation test, we assessed task-related functional connectivity considering seeds differentially engaged by action and non-action words (namely, putamen and M1 versus posterior superior temporal lobe, respectively). The putamen seed showed reduced connectivity within the basal ganglia in patients for both lexical categories. However, only action verbs recruited different cortical networks in each group. Specifically, the M1 seed exhibited more anterior connectivity for controls and more posterior connectivity for patients, with no differences in the temporal seed. Moreover, the patients' level of basal ganglia atrophy positively correlated with their reliance on M1-posterior connectivity during action-verb processing. PD patients seem to have processed action verbs via non-motor cortical networks subserving amodal semantics. Such circuits may afford alternative pathways to process words when default embodied mechanisms are disturbed. Moreover, the greater the level of basal ganglia atrophy, the greater the patients' reliance on this alternative route. Our findings offer new insights into differential neurofunctional mechanisms recruited to process action semantics in PD.

Journal ArticleDOI
07 Nov 2016
TL;DR: This article investigates strategies to recommend visualizations considering different aspects of user preferences, including a multi-dimensional scale used to estimate aspects of quality for visualizations for collaborative filtering and tag vectors describing visualizations used to recommend potentially interesting visualizations based on content.
Abstract: Visualizations have a distinctive advantage when dealing with the information overload problem: Because they are grounded in basic visual cognition, many people understand them. However, creating proper visualizations requires specific expertise of the domain and underlying data. Our quest in this article is to study methods to suggest appropriate visualizations autonomously. To be appropriate, a visualization has to follow known guidelines to find and distinguish patterns visually and encode data therein. A visualization tells a story of the underlying data; yet, to be appropriate, it has to clearly represent those aspects of the data the viewer is interested in. Which aspects of a visualization are important to the viewer? Can we capture and use those aspects to recommend visualizations? This article investigates strategies to recommend visualizations considering different aspects of user preferences. A multi-dimensional scale is used to estimate aspects of quality for visualizations for collaborative filtering. Alternatively, tag vectors describing visualizations are used to recommend potentially interesting visualizations based on content. Finally, a hybrid approach combines information on what a visualization is about (tags) and how good it is (ratings). We present the design principles behind VizRec, our visual recommender. We describe its architecture, the data acquisition approach with a crowd sourced study, and the analysis of strategies for visualization recommendation.

Journal ArticleDOI
TL;DR: In this paper, the Lloyd's Register Foundation (LRF) and the U.S. National Oceanic and Atmospheric Administration (NOAA) proposed a water security network for water security.

Journal ArticleDOI
TL;DR: Evaluated effects of high-altitude solar UV-B, moderate water deficit and ABA applications on Vitis vinifera cv.

Proceedings ArticleDOI
12 Sep 2016
TL;DR: An overlapping spatiotemporal stimulation method, that distributes stimuli spatially and temporally with a minima gap is devised, and an empirical study shows that, compared with spatial stimulation, OST is preferred in terms of recall.
Abstract: This paper investigates the communication of natural language messages using a wearable haptic display. Our research spans both the design of the haptic display, as well as the methods for communication that use it. First, three wearable configurations are proposed basing on haptic perception fundamentals. To encode symbols, we devise an overlapping spatiotemporal stimulation (OST) method, that distributes stimuli spatially and temporally with a minima gap. An empirical study shows that, compared with spatial stimulation, OST is preferred in terms of recall. Second, we propose an encoding for the entire English alphabet and a training method for letters, words and phrases. A second study investigates communication accuracy. It puts four participants through five sessions, for an overall training time of approximately 5 hours per participant. Results reveal that after one hour of training, participants were able to discern 16 letters, and identify two- and three-letter words. They could discern the full English alphabet (26 letters, 92% accuracy) after approximately three hours of training, and after five hours participants were able to interpret words transmitted at an average duration of 0.6s per word.

Journal ArticleDOI
TL;DR: The results suggest that garlic exhibits genetic and epigenetic polymorphism under field growing conditions, however, during in vitro culture system both kinds of polymorphisms intensify indicating that this system induces somaclonal variation.
Abstract: This is the first report assessing epigenetic variation in garlic. High genetic and epigenetic polymorphism during in vitro culture was detected. Sequencing of MSAP fragments revealed homology with ESTs. Garlic (Allium sativum) is a worldwide crop of economic importance susceptible to viral infections that can cause significant yield losses. Meristem tissue culture is the most employed method to sanitize elite cultivars. Often the virus-free garlic plants obtained are multiplied in vitro (micro propagation). However, it was reported that micro-propagation frequently produces somaclonal variation at the phenotypic level, which is an undesirable trait when breeders are seeking to maintain varietal stability. We employed amplification fragment length polymorphism and methylation sensitive amplified polymorphism (MSAP) methodologies to assess genetic and epigenetic modifications in two culture systems: virus-free plants obtained by meristem culture followed by in vitro multiplication and field culture. Our results suggest that garlic exhibits genetic and epigenetic polymorphism under field growing conditions. However, during in vitro culture system both kinds of polymorphisms intensify indicating that this system induces somaclonal variation. Furthermore, while genetic changes accumulated along the time of in vitro culture, epigenetic polymorphism reached the major variation at 6 months and then stabilize, being demethylation and CG methylation the principal conversions. Cloning and sequencing differentially methylated MSAP fragments allowed us to identify coding and unknown sequences of A. sativum, including sequences belonging to LTR Gypsy retrotransposons. Together, our results highlight that main changes occur in the initial 6 months of micro propagation. For the best of our knowledge, this is the first report on epigenetic assessment in garlic.

Journal ArticleDOI
TL;DR: The results suggest that M. imperiale, K. erythromyxa and mainly T. saccharophilus are able to induce a systemic response that trigger increases on monoterpene, sesquiterpenes, tocopherols and membrane sterols that enhance the antioxidant capacity in leaf tissues that may help grapevine to cope with stresses.

Journal ArticleDOI
12 Jul 2016-Anaerobe
TL;DR: Three different culture-independent methods used in this study show that high proportion of concentrate in goat diet does not induce any serious disturbance of their rumen ecosystem and indicate the good adaptive response of caprine ruminal bacteria to incorporation of corn into the diet.

Journal ArticleDOI
TL;DR: It is shown that supplementation with GP and GPE to a greater extent can counteract adiposity, inflammation, liver damage and impaired insulin signaling associated to MetS, supporting the utilization of winemaking residues in food industry/human health due to their high amount of bioactive compounds.
Abstract: In this study the effect of diet supplementation with grape pomace (GP) and grape pomace extract (GPE) on insulin sensitive tissues (adipose, liver and muscle) was evaluated in an experimental model of metabolic syndrome (MetS). MetS was developed by giving a high-fat-fructose (HFF) diet to Wistar rats. Six weeks of HFF diet induced weight gain, which was partially attenuated by GP (1 g per kg per day) and GPE (300 mg per kg per day) supplementation. HFF diet increased systolic blood pressure, triglycerides, insulin resistance (HOMA:IR) and inflammation (c-reactive protein (CRP)). Supplementation with GP prevented SBP, triglycerides and CRP increased and partially attenuated insulin resistance. On the other hand, GPE partially reduced SBP and triglycerides and significantly prevented insulin resistance and inflammation. Also, HFF diet induced higher triglycerides content and enhanced NADPH oxidase activity in the liver. Also, HFF diet increased the epididymal adipose tissue weight, enlarged adipocyte size, and c-jun N-terminal kinase (JNK) activation, probably contributing to a pro-inflammatory cytokine pattern (higher resistin) and lower adiponectin protein expression. These alterations may result in an impairment of insulin signaling cascade observed in adipose, liver and muscle tissue (IRS1, Akt, and extracellular signal-regulated kinases (ERK1/2)) from HFF rats. Supplementation with GP and to a greater extent GPE attenuated liver triglyceride content and adiposity and restored adipose, liver and muscle response to insulin. These findings show that supplementation with GP and GPE to a greater extent can counteract adiposity, inflammation, liver damage and impaired insulin signaling associated to MetS, supporting the utilization of winemaking residues in food industry/human health due to their high amount of bioactive compounds.

Journal ArticleDOI
TL;DR: Besides the methodological development for a high throughput routine quality control of GPEs, this is the first report of PPs content for Bonarda and Aspirant Bouchet GPE, so the results add knowledge for these grape varieties cultivated in Argentina.

Journal ArticleDOI
TL;DR: A pathway that connects cAMP to calcium mobilization from the acrosome during sperm exocytosis is described, and direct evidence that cAMP, Epac, Rap1, and PLCε are necessary for calcium mobilize from sperm's secretory granule is presented.