Molecular effect of an OPTN common variant associated to Paget's disease of bone

Paget's disease of bone (PDB) is a chronic bone disorder and although genetic factors appear to play an important role in its pathogenesis, to date PDB causing mutations were identified only in the Sequestosome 1 (SQSTM1) gene at the PDB3 locus. PDB6 locus, also previously linked to PDB, contains several candidate genes for metabolic bone diseases. We focused our analysis in the most significantly associated variant with PDB, within the Optineurin (OPTN) gene, i.e. the common variant rs1561570. Although it was previously shown to be strongly associated with PDB in several populations, its contribution to PDB pathogenesis remains unclear. In this study we have shown that rs1561570 may contribute to PDB since its Tallele results in the loss of a methylation site in patients' DNA, leading to higher levels of OPTN gene expression and a corresponding increase in protein levels in patients' osteoclasts. This increase in OPTN expression leads to higher levels of NF-KB translocation into the nucleus and increasing expression of its target genes, which may contribute to the overactivity of osteoclasts observed in PDB. We also reported a tendency for a more severe clinical phenotype in the presence of a haplotype containing the rs1561570 T allele, which appear to be re-enforced with the presence of the SQSTM1/P392L mutation. In conclusion, our work provides novel insight towards understanding the functional effects of this variant, located in OPTN intron 7, and its implication in the contribution to PDB pathogenesis.national funds from Foundation for Science and Technology (FCT) [UID/Multi/04326/2013]; Canadian Institutes for Health Research, Canada [MOP130457]; CHU de Quebec Foundation; Canadian Foundation for Innovation; Fonds de recherche du Quebec-sante; Laval University; CHU de Quebec-Universite Laval Research Centre; FCT [SFRH/BD/77227/2011, SFRH/BPD/111898/2015]; Fonds de recherche Quebec-Sante (FRQ-S), Quebec, Canad

Beta cells preferentially exchange cationic molecules via connexin 36 gap junction channels

Aims/hypothesis: Pancreatic beta cells are connected by gap junction channels made of connexin 36 (Cx36), which permit intercellular exchanges of current-carrying ions (ionic coupling) and other molecules (metabolic coupling). Previous studies have suggested that ionic coupling may extend to larger regions of pancreatic islets than metabolic coupling. The aim of the present study was to investigate whether this apparent discrepancy reflects a difference in the sensitivity of the techniques used to evaluate beta cell communication or a specific characteristic of the Cx36 channels themselves. Methods: We microinjected several gap junction tracers, differing in size and charge, into individual insulin-producing cells and evaluated their intercellular exchange either within intact islets of control, knockout and transgenic mice featuring beta cells with various levels of Cx36, or in cultures of wild-type and Cx36-transfected MIN6 cells. Results: We found that (1) Cx36 channels favour the exchange of cations and larger positively charged molecules between beta cells at the expense of anionic molecules; (2) this exchange occurs across sizable portions of pancreatic islets; and (3) during glibenclamide (known as glyburide in the USA and Canada) stimulation beta cell coupling increases to an extent that varies for different gap junction-permeant molecules. Conclusions/interpretation: The data show that beta cells are extensively coupled within pancreatic islets via exchanges of mostly positively charged molecules across Cx36 channels. These exchanges selectively increase during stimulation of insulin secretion. The identification of this permselectivity is expected to facilitate the identification of endogenous permeant molecules and of the mechanism whereby Cx36 signalling significantly contributes to the modulation of insulin secretio

Impact of traffic load and spectral occupancy on Gaussian noise models performance for multiband networks

In a network scenario, wavelength division multiplexing channels are added and dropped leading to fluctuations on the network traffic loads along the optical path. In this work, a comparison between the optical signal-to-noise ratio (OSNR) predictions of the recently proposed closed-form generalized Gaussian noise (GGN) model and a closed-form Gaussian noise (GN) model that does not take into account the stimulated Raman scattering (SRS) is performed, for different network traffic loads and spectral occupancy over the entire C+L band. In all results obtained, the maximum difference between the OSNR predictions of GN (without SRS) and GGN models closed forms is below 0.7 dB at optimum OSNR and maximum C+L band occupancy, indicating that the GN-model can also be used in C+L band transmission. For channel launch powers higher than the optimum, the OSNR differences increase up to 3 dB, being the GN-model (without SRS) unsuitable to assess the network performance in such situations.info:eu-repo/semantics/acceptedVersio

Assessing the quality of transmission of lightpaths in multiband C+L networks through Gaussian noise models

In an optical network scenario, wavelength division-multiplexing (WDM) channels are constantly being added and dropped, leading to dynamic traffic variations in the lightpaths. In this work, the impact of the network traffic load and spectral occupancy on the quality of transmission, namely on the normalized nonlinear interference (NLI) power, power transfer due to stimulated Raman scattering (SRS) and optical signal-to-noise ratio (OSNR) of the lightpaths in a C+L multiband optical network is assessed using the recently proposed closed-form interchannel SRS Gaussian noise model (ISRS GN-model). We show that, due to the dynamic traffic behavior, the normalized NLI power can oscillate up to 2 dB in the highest frequency channels due to NLI variations when the tested channels have unequal spacing along the spectrum. For the optimum channel launch power and by increasing the network traffic load, the power transfer between the outer channels can increase up to 5.1 dB due to the SRS effect. With 201 WDM channels, high traffic load and for the optimum channel power, we obtained a maximum OSNR variation along the channel frequencies of only about 0.7 dB. A comparison between the OSNR predictions of the closed-form ISRS GN-model and a closed-form Gaussian noise (GN) model that does not take into account the SRS effect is also performed. In all results obtained, the maximum difference between the OSNR predictions of GN (without SRS) and ISRS GN models is below 0.7 dB at optimum OSNR and maximum C+L band occupancy. For channel launch powers higher than the optimum, the OSNR differences increase up to 3 dB.info:eu-repo/semantics/publishedVersio

A framework for analyzing in-band crosstalk accumulation in ROADM-based optical networks

Reconfigurable optical add-drop multiplexers (ROADMs) are central pieces in building transparent optical transport networks. However, due to physical limitations, these devices can be a source of in-band crosstalk, which affects the quality of the lightpaths routed and the network performance. Hence, to efficiently design optical networks it is important to study how this impairment is generated and to understand its dependency on relevant network parameters, such as the number of wavelengths used and the node degree. In this paper, we propose a framework to analyze the in-band crosstalk accumulation inside of ROADM-based networks. The framework computes the number of accumulated crosstalk terms in each link of a lightpath considering different physical topologies, as well as different routing and wavelength assignment strategies. An empirical formula is also derived for computing the maximum number of accumulated crosstalk terms as a function of the network parameters. We observe that in the majority of the studied cases, there is a complete agreement between the results of the proposed framework and the empirical formula.info:eu-repo/semantics/acceptedVersio

Performance analysis of a graph coloring algorithm for wavelength assignment in dynamic optical networks

In the near future (5 to 10 years), dynamic optical networks will be crucial in global optical communications in order to respond to the fast growing of on-demand services. Routing and wavelength assignment (RWA) planning tools must be developed to effectively deal with the dynamic scenarios requirements. In this work, a simulation tool for RWA in dynamic optical networks was developed and wavelength assignment (WA) was implemented, through a recently proposed graph coloring algorithm, named Small-Buckets algorithm, that allows recolorings to occur. Several fiber based networks have been studied and it has been concluded that the Small-Buckets algorithm originates lower blocking probabilities than the ones obtained with the First fit algorithm. However, to reach this improved performance, the Small-Bucket algorithm requires a larger number of wavelengths and recolorings.info:eu-repo/semantics/acceptedVersio

Matrix gla protein in xenopus laevis: molecular cloning, tissue distribution, and evolutionary considerations

Matrix Gla protein (MGP) belongs to the family of vitamin K-dependent, Gla-containing proteins and in higher vertebrates, is found in the extracellular matrix of mineralized tissues and soft tissues. MGP synthesis is highly regulated at the transcription and posttranscription levels and is now known to be involved in the regulation of extracellular matrix calcification and maintenance of cartilage and soft tissue integrity during growth and development. However, its mode of action at the molecular level remains unknown. Because there is a large degree of conservation between amino,acid sequences of shark and human MGP, the function of MGP probably has been conserved throughout evolution. Given the complexity of the mammalian system, the study of MGP in a lower vertebrate might be advantageous to relate the onset of MGP expression with specific events during development. Toward this goal, MGP was purified from Xenopus long bones and its N-terminal amino acid sequence was determined and used to clone the Xenopus MGP complementary DNA (cDNA) by a mixture of reverse-transcription (RT)- and 5'- rapid amplification of cDNA ends (RACE)-polymerase chain reaction (PCR). MGP messenger RNA (mRNA) was present in all tissues analyzed although predominantly expressed in Xenopus bone and heart and its presence was detected early in development at the onset of chondrocranium development and long before the appearance of the first calcified structures and metamorphosis. These results show that in this system, as in mammals, MGP may be required to delay or prevent mineralization of cartilage and soft tissues during the early stages of development and indicate that Xenopus is an adequate model organism to further study MGP function during growth and development.NATO/CRG940751/SA5.2.05, Praxis XXI/BIA 469/94, (NIH; grant AR 25921) (Praxis XXI/BPD/18816) (Praxis XXI/BICJ-2985

Predators and dispersers: context-dependent outcomes of the interactions between rodents and a megafaunal fruit plant

Many plant species bear fruits that suggest adaptation to seed dispersal by extinct megafauna. Present-day seed dispersal of these megafaunal plants is carried out by rodents, which can act as predators or dispersers; whether this interaction is primarily positive or negative can depend on the context. Here, we parameterized a stochastic model using data from the field and experimental arenas to estimate the effect of rodents on the recruitment of Myrcianthes coquimbensis -an Atacama Desert shrub with megafaunal fruits- and examine whether environmental conditions can alter the sign and strength of these rodent-plant interactions. We show that the outcome of these interactions is context-dependent: in wet conditions seed removal by rodents negatively impacts the recruitment probability of M. coquimbensis; in contrast, in dry conditions, the interaction with rodents increases recruitment success. In all cases, the strength of the effect of rodents on the recruitment success was determined mainly by their role as dispersers, which could be positive or negative. This study demonstrates that by caching seeds, rodents can be effective dispersers of a megafaunal fruit plant, but that the sign and magnitude of their effect on recruitment changes as a function of the environmental context in which the interaction occursInstituto de Ecología y Biodiversidad, Chile | Ref. P05-002Universidad de La Serena, Chile | Ref. PT14122Ministerio de Ciencia e Innovación, España | Ref. PGC2018-096656-B-I00FONDECYT, Chile | Ref. 11140400Conicyt, Chile | Ref. AFB17000

Effects of Brain Gym® Exercises in Institutionalized Older Adults with Cognitive Impairment

Este estudio tuvo como objetivo comparar los efectos de un programa de ejercicios de Brain Gym® con un programa de gimnasia de mantenimiento en pacientes mayores institucionalizados con deterioro cognitivo. Veintinueve personas institucionalizadas con deterioro cognitivo participaron en dos programas, uno basado en ejercicios de Brain Gym® y otro de gimnasia de mantenimiento, durante 18 semanas. Se emplearon los test Mini-examen cognoscitivo, Fototest, Trail Making Test, Índice de Barthel y el Timed up and Go. No se encontraron mejoras significativas en las variables analizadas. Se observó una tendencia positiva, especialmente en el grupo de gimnasia de mantenimiento, en la función cognitiva global y salud física. En conclusión, los efectos de un programa de ejercicios de Brain Gym® en una muestra de personas mayores institucionalizadas con deterioro cognitivo fueron similares a los de un programa de gimnasia de mantenimiento, sin mejoras significativas de la función cognitiva o independencia funcionalThis study aimed at comparing the effects of a program based on Brain Gym® exercises against a fitness exercise program on the cognitive function and functional independence in institutionalized older adults with cognitive impairment. Twenty-nine institutionalized older adults with cognitive impairment took part either on a Brain Gym® based exercise program or on a fitness exercise program during eighteen weeks. The assessment measures used were the Mini-Examen Cognoscitivo, Fototest, Trail making test, Barthel Index and the Timed up and Go Test. None of the variables analysed improved significantly. A trend towards improvement, particularly in the fitness exercise group, in both cognitive status and functional independence was observed. In conclusion, the performance of a Brain Gym® exercise-based program had the same effects than taking part in a fitness exercise program, with no significant improvements on the cognitive function or functional independence, in a sample of institutionalized older adults with cognitive impairmen

Interplay between Cryptocurrency Transactions and Online Financial Forums

Cryptocurrencies are a type of digital money meant to provide security and anonymity while using cryptography techniques. Although cryptocurrencies represent a breakthrough and provide some important benefits, their usage poses some risks that are a result of the lack of supervising institutions and transparency. Because disinformation and volatility is discouraging for personal investors, cryptocurrencies emerged hand-in-hand with the proliferation of online users' communities and forums as places to share information that can alleviate users' mistrust. This research focuses on the study of the interplay between these cryptocurrency forums and fluctuations in cryptocurrency values. In particular, the most popular cryptocurrency Bitcoin (BTC) and a related active discussion community, Bitcointalk, are analyzed. This study shows that the activity of Bitcointalk forum keeps a direct relationship with the trend in the values of BTC, therefore analysis of this interaction would be a perfect base to support personal investments in a non-regulated market and, to confirm whether cryptocurrency forums show evidences to detect abnormal behaviors in BTC values as well as to predict or estimate these values. The experiment highlights that forum data can explain specific events in the financial field. It also underlines the relevance of quotes (regular mechanism to response a post) at periods: (1) when there is a high concentration of posts around certain topics; (2) when peaks in the BTC price are observed; and, (3) when the BTC price gradually shifts downwards and users intend to sell