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See detailProteggere o controllare? Il sistema europeo comune di asilo nello spazio Schengen
Vianelli, Lorenzo UL

in Zapruder (2020), 51(Jan-Apr 2020), 34-53

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See detailProtein allostery, signal transmission and dynamics: a classification scheme of allosteric mechanisms
Tsai, C. J.; del Sol Mesa, Antonio UL; Nussinov, R.

in Molecular Biosystems (2009), 5(3), 207-16

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See detailProtein dynamics governed by interfaces of high polarity and low packing density.
Espinosa Angarica, Vladimir UL; Sancho, Javier

in PloS one (2012), 7(10), 48212

The folding pathway, three-dimensional structure and intrinsic dynamics of proteins are governed by their amino acid sequences. Internal protein surfaces with physicochemical properties appropriate to ... [more ▼]

The folding pathway, three-dimensional structure and intrinsic dynamics of proteins are governed by their amino acid sequences. Internal protein surfaces with physicochemical properties appropriate to modulate conformational fluctuations could play important roles in folding and dynamics. We show here that proteins contain buried interfaces of high polarity and low packing density, coined as LIPs: Light Interfaces of high Polarity, whose physicochemical properties make them unstable. The structures of well-characterized equilibrium and kinetic folding intermediates indicate that the LIPs of the corresponding native proteins fold late and are involved in local unfolding events. Importantly, LIPs can be identified using very fast and uncomplicated computational analysis of protein three-dimensional structures, which provides an easy way to delineate the protein segments involved in dynamics. Since LIPs can be retained while the sequences of the interacting segments diverge significantly, proteins could in principle evolve new functional features reusing pre-existing encoded dynamics. Large-scale identification of LIPS may contribute to understanding evolutionary constraints of proteins and the way protein intrinsic dynamics are encoded. [less ▲]

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See detailProtein fold recognition by prediction-based threading
Rost, B.; Schneider, Reinhard UL; Sander, C.

in Journal of Molecular Biology (1997), 270(3), 471-480

In fold recognition by threading one takes the amino acid sequence of a protein and evaluates how well it fits into one of the known three-dimensional (3D) protein structures. The quality of sequence ... [more ▼]

In fold recognition by threading one takes the amino acid sequence of a protein and evaluates how well it fits into one of the known three-dimensional (3D) protein structures. The quality of sequence-structure fit is typically evaluated using inter-residue potentials of mean force or other statistical parameters. Here, we present an alternative approach to evaluating sequence-structure fitness. Starting from the amino acid sequence we first predict secondary structure and solvent accessibility for each residue. We then thread the resulting one-dimensional (1D) profile of predicted structure assignments into each of the known 3D structures. The optimal threading for each sequence-structure pair is obtained using dynamic programming. The overall best sequence-structure pair constitutes the predicted 3D structure for the input sequence. The method is fine-tuned by adding information from direct sequence-sequence comparison and applying a series of empirical filters. Although the method relies on reduction of 3D information into 1D structure profiles, its accuracy is, surprisingly, not clearly inferior to methods based on evaluation of residue interactions in 3D. We therefore hypothesise that existing 1D-3D threading methods essentially do not capture more than the fitness of an amino acid sequence for a particular 1D succession of secondary structure segments and residue solvent accessibility. The prediction-based threading method on average finds any structurally homologous region at first rank in 29% of the cases (including sequence information). For the 22% first hits detected at highest scores, the expected accuracy rose to 75%. However, the task of detecting entire folds rather than homologous fragments was managed much better; 45 to 75% of the first hits correctly recognised the fold. [less ▲]

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See detailProtein Kinase A Activation Promotes Cancer Cell Resistance to Glucose Starvation and Anoikis.
Palorini, Roberta; Votta, Giuseppina; Pirola, Yuri et al

in PLoS genetics (2016), 12(3), 1005931

Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. Several studies showed that glycolytic cells are susceptible to cell death when subjected to low glucose availability or ... [more ▼]

Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. Several studies showed that glycolytic cells are susceptible to cell death when subjected to low glucose availability or to lack of glucose. However, some cancer cells, including glycolytic ones, can efficiently acquire higher tolerance to glucose depletion, leading to their survival and aggressiveness. Although increased resistance to glucose starvation has been shown to be a consequence of signaling pathways and compensatory metabolic routes activation, the full repertoire of the underlying molecular alterations remain elusive. Using omics and computational analyses, we found that cyclic adenosine monophosphate-Protein Kinase A (cAMP-PKA) axis activation is fundamental for cancer cell resistance to glucose starvation and anoikis. Notably, here we show that such a PKA-dependent survival is mediated by parallel activation of autophagy and glutamine utilization that in concert concur to attenuate the endoplasmic reticulum (ER) stress and to sustain cell anabolism. Indeed, the inhibition of PKA-mediated autophagy or glutamine metabolism increased the level of cell death, suggesting that the induction of autophagy and metabolic rewiring by PKA is important for cancer cellular survival under glucose starvation. Importantly, both processes actively participate to cancer cell survival mediated by suspension-activated PKA as well. In addition we identify also a PKA/Src mechanism capable to protect cancer cells from anoikis. Our results reveal for the first time the role of the versatile PKA in cancer cells survival under chronic glucose starvation and anoikis and may be a novel potential target for cancer treatment. [less ▲]

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See detailA Protein Prioritization Approach Tailored for the FA/BRCA Pathway
Haitjema, Anneke; Brandt, Bernd W.; Ameziane, Najim et al

in PLoS ONE (2013), 8(4), 62017

<sec><title/><p>Fanconi anemia (FA) is a heterogeneous recessive disorder associated with a markedly elevated risk to develop cancer. To date sixteen FA genes have been identified, three of which ... [more ▼]

<sec><title/><p>Fanconi anemia (FA) is a heterogeneous recessive disorder associated with a markedly elevated risk to develop cancer. To date sixteen FA genes have been identified, three of which predispose heterozygous mutation carriers to breast cancer. The FA proteins work together in a genome maintenance pathway, the so-called FA/BRCA pathway which is important during the <italic>S</italic> phase of the cell cycle. Since not all FA patients can be linked to (one of) the sixteen known complementation groups, new FA genes remain to be identified. In addition the complex FA network remains to be further unravelled. One of the FA genes, <italic>FANCI</italic>, has been identified via a combination of bioinformatic techniques exploiting FA protein properties and genetic linkage. The aim of this study was to develop a prioritization approach for proteins of the entire human proteome that potentially interact with the FA/BRCA pathway or are novel candidate FA genes. To this end, we combined the original bioinformatics approach based on the properties of the first thirteen FA proteins identified with publicly available tools for protein-protein interactions, literature mining (Nermal) and a protein function prediction tool (FuncNet). Importantly, the three newest FA proteins FANCO/RAD51C, FANCP/SLX4, and XRCC2 displayed scores in the range of the already known FA proteins. Likewise, a prime candidate FA gene based on next generation sequencing and having a very low score was subsequently disproven by functional studies for the FA phenotype. Furthermore, the approach strongly enriches for GO terms such as DNA repair, response to DNA damage stimulus, and cell cycle-regulated genes. Additionally, overlaying the top 150 with a haploinsufficiency probability score, renders the approach more tailored for identifying breast cancer related genes. This approach may be useful for prioritization of putative novel FA or breast cancer genes from next generation sequencing efforts.</p></sec> [less ▲]

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See detailProteogenomic basis for ecological divergence of closely related bacteria in natural acidophilic microbial communities
Denef, Vincent J.; Kalnejais, Linda H.; Mueller, Ryan S. et al

in Proceedings of the National Academy of Sciences of the United States of America (2010), 107(6), 2383-2390

Bacterial species concepts are controversial. More widely accepted is the need to understand how differences in gene content and sequence lead to ecological divergence. To address this relationship in ... [more ▼]

Bacterial species concepts are controversial. More widely accepted is the need to understand how differences in gene content and sequence lead to ecological divergence. To address this relationship in ecosystem context, we investigated links between genotype and ecology of two genotypic groups of Leptospirillum group II bacteria in comprehensively characterized, natural acidophilic biofilm communities. These groups share 99.7% 16S rRNA gene sequence identity and 95% average amino acid identity between their orthologs. One genotypic group predominates during early colonization, and the other group typically proliferates in later successional stages, forming distinct patches tens to hundreds of micrometers in diameter. Among early colonizing populations, we observed dominance of five genotypes that differed from each other by the extent of recombination with the late colonizing type. Our analyses suggest that the specific recombinant variant within the early colonizing group is selected for by environmental parameters such as temperature, consistent with recombination as a mechanism for ecological fine tuning. Evolutionary signatures, and strain-resolved expression patterns measured via mass spectrometry-based proteomics, indicate increased cobalamin biosynthesis, (de) methylation, and glycine cleavage in the late colonizer. This may suggest environmental changes within the biofilm during development, accompanied by redirection of compatible solutes from osmoprotectants toward metabolism. Across 27 communities, comparative proteo-genomic analyses show that differential regulation of shared genes and expression of a small subset of the similar to 15% of genes unique to each genotype are involved in niche partitioning. In summary, the results show how subtle genetic variations can lead to distinct ecological strategies. [less ▲]

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See detailProteomic analysis of a pleistocene mammoth femur reveals more than one hundred ancient bone proteins.
Cappellini, Enrico; Jensen, Lars J.; Szklarczyk, Damian et al

in Journal of proteome research (2012), 11(2), 917-26

We used high-sensitivity, high-resolution tandem mass spectrometry to shotgun sequence ancient protein remains extracted from a 43 000 year old woolly mammoth ( Mammuthus primigenius ) bone preserved in ... [more ▼]

We used high-sensitivity, high-resolution tandem mass spectrometry to shotgun sequence ancient protein remains extracted from a 43 000 year old woolly mammoth ( Mammuthus primigenius ) bone preserved in the Siberian permafrost. For the first time, 126 unique protein accessions, mostly low-abundance extracellular matrix and plasma proteins, were confidently identified by solid molecular evidence. Among the best characterized was the carrier protein serum albumin, presenting two single amino acid substitutions compared to extant African ( Loxodonta africana ) and Indian ( Elephas maximus ) elephants. Strong evidence was observed of amino acid modifications due to post-mortem hydrolytic and oxidative damage. A consistent subset of this permafrost bone proteome was also identified in more recent Columbian mammoth ( Mammuthus columbi ) samples from temperate latitudes, extending the potential of the approach described beyond subpolar environments. Mass spectrometry-based ancient protein sequencing offers new perspectives for future molecular phylogenetic inference and physiological studies on samples not amenable to ancient DNA investigation. This approach therefore represents a further step into the ongoing integration of different high-throughput technologies for identification of ancient biomolecules, unleashing the field of paleoproteomics. [less ▲]

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See detailProteomic analysis of Dhh1 complexes reveals a role for Hsp40 chaperone Ydj1 in yeast P-body assembly
Cary, Greg A.; Vinh, Dani B.H.; May, Patrick UL et al

in G3 (2015)

P-bodies (PB) are ribonucleoprotein (RNP) complexes that aggregate into cytoplasmic foci when cells are exposed to stress. While the conserved mRNA decay and translational repression machineries are known ... [more ▼]

P-bodies (PB) are ribonucleoprotein (RNP) complexes that aggregate into cytoplasmic foci when cells are exposed to stress. While the conserved mRNA decay and translational repression machineries are known components of PB, how and why cells assemble RNP complexes into large foci remain unclear. Using mass spectrometry to analyze proteins immunoisolated with the core PB protein Dhh1, we show that a considerable number of proteins contain low-complexity (LC) sequences, similar to proteins highly represented in mammalian RNP granules. We also show that the Hsp40 chaperone Ydj1, which contains an LC domain and controls prion protein aggregation, is required for the formation of Dhh1-GFP foci upon glucose depletion. New classes of proteins that reproducibly coenrich with Dhh1-GFP during PB induction include proteins involved in nucleotide or amino acid metabolism, glycolysis, tRNA aminoacylation, and protein folding. Many of these proteins have been shown to form foci in response to other stresses. Finally, analysis of RNA associated with Dhh1-GFP shows enrichment of mRNA encoding the PB protein Pat1 and catalytic RNAs along with their associated mitochondrial RNA-binding proteins. Thus, global characterization of PB composition has uncovered proteins important for PB assembly and evidence suggesting an active role for RNA in PB function. [less ▲]

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See detailProteomic Characterization of Primary Mouse Hepatocytes in Collagen Monolayer and Sandwich Culture.
Orsini, Malina; Sperber, Saskia; Noor, Fozia UL et al

in Journal of cellular biochemistry (2017)

Dedifferentiation of primary hepatocytes in vitro makes their application in long-term studies difficult. Embedding hepatocytes in a sandwich of extracellular matrix is reported to delay the ... [more ▼]

Dedifferentiation of primary hepatocytes in vitro makes their application in long-term studies difficult. Embedding hepatocytes in a sandwich of extracellular matrix is reported to delay the dedifferentiation process to some extent. In this study, we compared the intracellular proteome of primary mouse hepatocytes (PMH) in conventional monolayer cultures (ML) to collagen sandwich culture (SW) after 1 day and 5 days of cultivation. Quantitative proteome analysis of PMH showed no differences between collagen SW and ML cultures after 1 day. Glycolysis and gluconeogenesis were strongly affected by long-term cultivation in both ML and SW cultures. Interestingly, culture conditions had no effect on cellular lipid metabolism. After 5 days, PMH in collagen SW and ML cultures exhibit characteristic indications of oxidative stress. However, in the SW culture the defense system against oxidative stress is significantly up-regulated to deal with this, whereas in the ML culture a down-regulation of these important enzymes takes place. Regarding the multiple effects of ROS and oxidative stress in cells, we conclude that the down-regulation of these enzymes seem to play a role in the loss of hepatic function observed in the ML cultivation. In addition, enzymes of the urea cycle were clearly down-regulated in ML culture. Proteomics confirms lack in oxidative stress defense mechanisms as the major characteristic of hepatocytes in monolayer cultures compared to sandwich cultures. J. Cell. Biochem. 9999: 1-8, 2017. (c) 2017 Wiley Periodicals, Inc. [less ▲]

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See detailProtestantismus, Kapitalismus und Konsum
Lenz, Thomas UL

Presentation (2012)

Detailed reference viewed: 17 (1 UL)
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See detailProtesting Ethnic Minorities in Europe: A Fuzzy-Set Analysis
Cebotari, Victor UL

E-print/Working paper (2010)

Detailed reference viewed: 69 (0 UL)
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See detailProteum/FL: A tool for localizing faults using mutation analysis.
Papadakis, Mike UL; Delamaro, Eduardo Márcio; Le Traon, Yves UL

in International Working Conference on Source Code Analysis and Manipulation (2013)

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See detailLe protezioni sociali ravvicinate. Sogni e incubi
Bricocoli, Massimo UL; de Leonardis, Ota

in Bianchetti, Cristina (Ed.) Territori della condivisione. Una nuova città (2014)

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See detailLes prothèses cognitives du corps humain
Derian, Maxime UL

Book published by ISTE (2018)

Les machines informatisées se retrouvent, sous diverses formes, autour de nous, dans nos poches et parfois dans notre organisme. Elles sont aujourd'hui des éléments incontournables du quotidien pour la ... [more ▼]

Les machines informatisées se retrouvent, sous diverses formes, autour de nous, dans nos poches et parfois dans notre organisme. Elles sont aujourd'hui des éléments incontournables du quotidien pour la plupart d'entre nous. Qu'il s'agisse des smartphones, d'objets connectés ou de dispositifs numériques médicaux et d'e-santé, ces outils numériques prolifèrent littéralement dans notre environnement. Ils font office de prothèses qui « augmentent » nos capacités cognitives mais également d'orthèses qui influencent bon nombre de nos comportements. La généralisation de ces machines semble même en mesure de transformer nos modes d'organisation sociale de manière conséquente. Les outils numériques qui emmaillotent sans cesse davantage le corps et l'esprit sont-ils en mesure de bouleverser notre ordre social ? Pourraient-ils littéralement entraîner demain la disparition de la société telle que nous la connaissons aujourd'hui ? Les prothèses cognitives du corps humain explore cette réflexion qui est au centre des usages des outils numériques. [less ▲]

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See detailProto-industrialisation et immigration au Luxembourg
Pauly, Michel UL

in Allegrezza, Serge e.a. (Ed.) L’immigration au Luxembourg, et après? (2007)

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See detailA protocol for generating a high-quality genome-scale metabolic reconstruction.
Thiele, Ines UL; Palsson, Bernhard O.

in Nature Protocols (2010), 5(1), 93-121

Network reconstructions are a common denominator in systems biology. Bottom-up metabolic network reconstructions have been developed over the last 10 years. These reconstructions represent structured ... [more ▼]

Network reconstructions are a common denominator in systems biology. Bottom-up metabolic network reconstructions have been developed over the last 10 years. These reconstructions represent structured knowledge bases that abstract pertinent information on the biochemical transformations taking place within specific target organisms. The conversion of a reconstruction into a mathematical format facilitates a myriad of computational biological studies, including evaluation of network content, hypothesis testing and generation, analysis of phenotypic characteristics and metabolic engineering. To date, genome-scale metabolic reconstructions for more than 30 organisms have been published and this number is expected to increase rapidly. However, these reconstructions differ in quality and coverage that may minimize their predictive potential and use as knowledge bases. Here we present a comprehensive protocol describing each step necessary to build a high-quality genome-scale metabolic reconstruction, as well as the common trials and tribulations. Therefore, this protocol provides a helpful manual for all stages of the reconstruction process. [less ▲]

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See detailA Protocol to Strengthen Password-Based Authentication
Vazquez Sandoval, Itzel UL; Lenzini, Gabriele UL; Stojkovski, Borce UL

in Emerging Technologies for Authorization and Authentication (2018, November)

We discuss a password-based authentication protocol that we argue to be robust against password-guessing and o -line dictionary attacks. The core idea is to hash the passwords with a seed that comes from ... [more ▼]

We discuss a password-based authentication protocol that we argue to be robust against password-guessing and o -line dictionary attacks. The core idea is to hash the passwords with a seed that comes from an OTP device, making the resulting identity token unpredictable for an adversary. We believe that the usability of this new protocol is the same as that of password-based methods with OTP, but has the advan- tage of not burdening users with having to choose strong passwords. [less ▲]

Detailed reference viewed: 184 (64 UL)