Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic Exercise Improves Endothelial Calcium Signaling and Vasodilatation in Hypercholesterolemic Rabbit Femoral Artery

Objective—This study was to investigate the effects of chronic exercise on vasodilatation and endothelial intracellular calcium (EC [Ca2+]i) signaling in atherosclerotic animals. Methods and Results—For 8 weeks, male New Zealand White rabbits were fed rabbit chow with or without the addition of 2% cholesterol. They were further divided into control and exercise groups. Animals in the exercise groups ran on a leveled treadmill at 0.88 km/h for 10 to 60 minutes gradually for 5 days per week for a total of 8 weeks. At the end of experiments, femoral arteries were dissected, loaded with fura 2-AM, and mounted in a tissue flow chamber. PE-precontracted vessel specimens were exposed to acetylcholine (ACh). The EC [Ca2+]i elevation and vasorelaxation were determined simultaneously under an epifluorescence microscope equipped with a ratio-imaging capability. Our results showed the following: (1) high cholesterol diet feeding caused lipid deposition on vascular surface, reduced the ACh-evoked EC [Ca2+]i elevation, and impaired endothelium-dependent and endothelium-independent vascular responses, but chronic exercise had the opposite effects; (2) ACh-induced vasorelaxation was associated with EC [Ca2+]i elevation in all groups; and (3) vasorelaxation at high levels of EC [Ca2+]i elevation decreased in hypercholesterolemia. Conclusions—Our data suggest that hypercholesterolemia induces vascular structural changes and impairs EC [Ca2+]i signaling and vasodilatation, whereas chronic exercise partially reverses these adverse effects.
Materiali per un catalogo dei terremoti italiani: eventi sconosciuti, rivalutati o riscoperti

The large-scale studies of historical seismology carried out in Italy and Europe in the last decades were mostly aimed at improving knowledge about earthquakes that were already listed in the extant parametric catalogues, rather than at identifying earthquakes that were not listed in them. From 1992 onwards, some of the authors of this study started to look for such “forgotten” earthquakes in different ways (by systematic surveys of serial historical sources, or by extensive investigation of local records in selected areas). More than 2000 pieces of evidence related to as many earthquakes not listed by any seismological compilations/catalogues were thus identified. In 2003 all resources were pooled in a common effort, meant to complete the revision of minor “known” earthquakes carried out by Molin et al. [2008] with a study of the most relevant “unknown” earthquakes identified so far. We present here the results of the analysis of 227 damaging earthquakes, 155 of which are “unknown” to the seismological tradition. Other 72 events were listed in the Postpischl [1985] catalogue, but not in newer parametric catalogues, no evidence of damage being availablefor them at thetime: such evidence has now been found and, in 21 cases at least, it allows for a significant re-evaluation of macroseismic intensity.
[Temperament and Character Inventory Revised (TCI-R). Standardization and normative data in a general population sample].

INTRODUCTION The revised version of the Temperament and Character Inventory (TCI-R), a tool designed by C. R. Cloninger for the evaluation of the seven dimensions defined in his psychobiological model of personality, was translated and adapted to Spanish. The aim of the study was to obtain normative data and scales with T-scores in a incidental sample of the general Spanish population. METHODS After adaptation to Spanish, the tool was administered to 400 subjects from several areas of Spain. The sample is stratified according to age and gender according to the year 2001 Spanish population census. We have studied the differences between men and women and the association between age and dimensions. We have checked the normal distribution of the traits, and proceeded with the standardization and normalization of the scores. RESULTS We present the mean and standard deviation according to sex for each of the main dimensions and subscales. The scores of the main dimensions obtained for general population according to gender show a normal distribution that has allowed us to standardize them into T-scores. The reliability of the dimensions is high. There are differences in the means depending on gender: women scored higher in Harm Avoidance, Reward Dependence and Cooperativeness. Men scored higher in Persistence. There were no high correlations between age and the dimensions. CONCLUSIONS The Spanish version of the new TCI-R is an adequate tool for the study of personality dimensions of normal population.
Reference genes selection for transcriptional profiling in blood of HD patients and R6/2 mice.

BACKGROUND Huntington's disease is a neurodegenerative disorder characterized by transcriptional alterations both in central and peripheral tissues. Therefore, the identification of a transcriptional signature in an accessible tissue can meaningfully complement current efforts in clinical biomarker development. Gene expression normalization represents an essential step in transcriptional signatures identification, and since many reference genes show altered expressions in several pathologies, the definition of stable genes in the desired tissue is required to allow correct result interpretations. OBJECTIVE The present work aimed at identifying a set of suitable reference genes for expression normalization in blood of HD patients and R6/2 mice. METHODS By crossing literature investigation and analysis of microarrays performed on blood of HD patients and healthy subjects, a set of genes was selected and tested by RT-qPCR. Employment of statistical algorithms allowed the identification of the most stable genes in human samples that were than confirmed in R6/2. RESULTS PPIB, PGK1, ACTB and YWHAZ represent the best possible genes combination, useful to normalize blood transcriptional analysis. To link clinical and preclinical studies, the identified genes were investigated also in blood of R6/2 and wild type mice, confirming that Ppib, Actb and Ywhaz were appropriate for expression normalization. Selected references were subsequently applied to evaluate expression of genes known to be involved in Huntington's pathological progression. CONCLUSIONS This work highlights the importance for correct data normalization to avoid misinterpretation of results, while providing a suitable method to support quantitative gene expression analysis in preclinical and clinical investigations.
Large Membrane Domains in Hair Bundles Specify Spatially Constricted Radixin Activation

The plasma membrane of vertebrate hair bundles interacts intimately with the bundle cytoskeleton to support mechanotransduction and homeostasis. To determine the membrane composition of bundles, we used lipid mass spectrometry with purified chick vestibular bundles. While the bundle glycerophospholipids and acyl chains resemble those of other endomembranes, bundle ceramide and sphingomyelin nearly exclusively contain short-chain, saturated acyl chains. Confocal imaging of isolated bullfrog vestibular hair cells shows that the bundle membrane segregates spatially into at least three large structural and functional domains. One membrane domain, including the stereocilia basal tapers and ∼1 μm of the shaft, the location of the ankle links, is enriched in the lipid phosphatase PTPRQ (protein tyrosine phosphatase Q) and polysialylated gangliosides. The taper domain forms a sharp boundary with the shaft domain, which contains the plasma membrane Ca2+-ATPase isoform 2 (PMCA2) and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]; moreover, a tip domain has elevated levels of cholesterol, PMCA2, and PI(4,5)P2. Protein mass spectrometry shows that bundles from chick vestibular hair cells contain a complete set of proteins that transport, synthesize, and degrade PI(4,5)P2. The membrane domains have functional significance; radixin, essential for hair-bundle stability, is activated at the taper–shaft boundary in a PI(4,5)P2-dependent manner, allowing assembly of protein complexes at that site. Membrane domains within stereocilia thus define regions within hair bundles that allow compartmentalization of Ca2+ extrusion and assembly of protein complexes at discrete locations.
Excessive Volatility in Capital Flows: A Pigouvian Taxation Approach

This paper analyzes prudential controls on capital flows to emerging markets from the perspective of a Pigouvian tax that addresses externalities associated with the deleveraging cycle. It presents a model in which restricting capital inflows during boom times reduces the potential outflows during busts. This mitigates the feedback effects of deleveraging episodes, when tightening financial constraints on borrowers and collapsing prices for collateral assets have mutually reinforcing effects. In our model, capital controls reduce macroeconomic volatility and increase standard measures of consumer welfare.
The Rank of Random Binary Matrices and Distributed Storage Applications

Random binary matrices appear in a variety of signal processing and encoding problems. They play an important role in rateless codes and in distributed storage applications. This paper focuses on block angular matrices, a class of random rectangular binary matrices that are particularly suited to distributed storage applications. We address one of the key issues regarding binary random matrices in general, and block angular matrices in particular: the probability of obtaining a full rank matrix, when drawing uniformly at random from the set of binary matrices with compatible structure. This paper gives a closed-form expression for this probability, as well as some bounds and approximations.
Creep and slip: Seismic precursors to the Nuugaatsiaq landslide (Greenland)

Precursory signals to material's failure are predicted by numerical models and observed in laboratory experiments or using field data. These precursory signals are a marker of slip acceleration on weak regions, such as crustal faults. Observation of these precursory signals of catastrophic natural events, such as earthquakes and landslides, is necessary for improving our knowledge about the physics of the nucleation process. Furthermore, observing such precursory signals may help to forecast these catastrophic events or reduce their hazard. I report here the observation of seismic precursors to the Nuugaatsiaq landslide in Greenland. Time evolution of the detected precursors implies that an aseismic slip event is taking place for hours before the landslide, with an exponential increase of slip velocity. Furthermore, time evolution of the precursory signals' amplitude sheds light on the evolution of the fault physics during the nucleation process.
Inactivation of the LOX‐1 Pathway Promotes the Golgi Apparatus during Cell Differentiation of Mural Granulosa Cells

In female mammals, granulosa cells of the ovarian follicle differentiate into the corpus luteum after ovulation of the pregnable oocyte into the fallopian tube. During these differentiation processes several morphological alterations have to occur and the molecular basis is not fully understood. As an endpoint estradiol production from granulosa cells has to switch off in favor for progesterone production from the proceeding corpus luteum to sustain the developing embryo. Previously, we demonstrated that the multiligand receptor LOX‐1 plays a critical role in steroid hormone synthesis of granulosa cells via intracellular calcium release from endoplasmic (ER)‐dependent and ER‐independent calcium pools. In the present study, we show that inhibition of LOX‐1 leads to a rearrangement of ceramide from the basal membrane toward the Golgi apparatus. This activity is accomplished by a calcium‐dependent phosphorylation of aromatase, the key step in estradiol production. Phosphorylated aromatase increased estradiol production in a dose‐dependent manner. Our data indicate that the ceramide cascade is essential for proper granulosa cell function and ceramide redistribution serves as a first step in order to proceed with the prosperous differentiation into a corpus luteum. J. Cell. Physiol. 229: 1946–1951, 2014. © 2014 Wiley Periodicals, Inc.
Transgenerational Exposure to Environmental Tobacco Smoke

Traditionally, nicotine from second hand smoke (SHS), active or passive, has been considered the most prevalent substance of abuse used during pregnancy in industrialized countries. Exposure to environmental tobacco smoke (ETS) is associated with a variety of health effects, including lung cancer and cardiovascular diseases. Tobacco is also a major burden to people who do not smoke. As developing individuals, newborns and children are particularly vulnerable to the negative effects of SHS. In particular, prenatal ETS has adverse consequences during the entire childhood causing an increased risk of abortion, low birth weight, prematurity and/or nicotine withdrawal syndrome. Over the last years, a decreasing trend in smoking habits during pregnancy has occurred, along with the implementation of laws requiring smoke free public and working places. The decrease in the incidence of prenatal tobacco exposure has usually been assessed using maternal questionnaires. In order to diminish bias in self-reporting, objective biomarkers have been developed to evaluate this exposure. The measurement of nicotine and its main metabolite, cotinine, in non-conventional matrices such as cord blood, breast milk, hair or meconium can be used as a non-invasive measurement of prenatal SMS in newborns. The aim of this review is to highlight the prevalence of ETS (prenatal and postnatal) using biomarkers in non-conventional matrices before and after the implementation of smoke free policies and health effects related to this exposure during foetal and/or postnatal life.
Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer.

Gene replacement therapy is an attractive approach for treatment of genetic disease, but may be complicated by the risk of a neutralizing immune response to the therapeutic gene product. There are examples of humoral and cellular immune responses against the transgene product as well as absence of such responses, depending on vector design and the underlying mutation in the dysfunctional gene. It has been unclear, however, whether transgene expression can induce tolerance to the therapeutic antigen. Here, we demonstrate induction of immune tolerance to a secreted human coagulation factor IX (hF.IX) antigen by adeno-associated viral gene transfer to the liver. Tolerized mice showed absence of anti-hF.IX and substantially reduced in vitro T cell responses after immunization with hF.IX in adjuvant. Tolerance induction was antigen specific, affected a broad range of Th cell subsets, and was favored by higher levels of transgene expression as determined by promoter strength, vector dose, and mouse strain. Hepatocyte-derived hF.IX expression induced regulatory CD4(+) T cells that can suppress anti-hF.IX formation after adoptive transfer. With a strain-dependent rate of success, tolerance to murine F.IX was induced in mice with a large F.IX gene deletion, supporting the relevance of these data for treatment of hemophilia B and other genetic diseases.
Experiments in Program Compilation by Interpreter Specialization

Interpretation and run-time compilation techniques are becoming increasingly important due to the need to support heterogeneous architectures, evolving programming languages, and dynamically downloaded code. Although interpreters are easy to write and maintain, they are inefficient. On the other hand, run-time compilation provides efficient execution, but is costly to implement. One way to get the best of both approaches is to apply program specialization to an interpreter in order to generate an efficient implementation automatical- ly. Recent advances in program specialization technology have resulted in important improvements in the performance of specialized interpreters. This paper presents and assesses experimental results for the application of program specialization to both bytecode and structured-language interpreter- s. The results show that for general-purpose bytecode, program specialization can yield speedups of up to a factor of four, while specializing certain structured-language interpreters can yield performance equivalent to code compiled by a general-purpose compiler.
Super-resolution Scanning Patch Clamp Reveals Clustering of Functional Ion Channels in Adult Ventricular Myocyte

Rationale: Compartmentation of ion channels on the cardiomyocyte surface is important for electric propagation and electromechanical coupling. The specialized T-tubule and costameric structures facilitate spatial coupling of various ion channels and receptors. Existing methods such as immunofluorescence and patch clamp techniques are limited in their ability to localize functional ion channels. As such, a correlation between channel protein location and channel function remains incomplete. Objective: To validate a method that permits routine imaging of the topography of a live cardiomyocyte and study clustering of functional ion channels from a specific microdomain. Methods and Results: We used scanning ion conductance microscopy and conventional cell-attached patch clamp with a software modification that allows controlled increase of pipette tip diameter. The sharp nanopipette used for topography scan was modified into a larger patch pipette that could be positioned with nanoscale precision to a specific site of interest (crest, groove, or T-tubules of cardiomyocytes) and sealed to the membrane for cell-attached recording of ion channels. Using this method, we significantly increased the probability of detecting activity of L-type calcium channels in the T-tubules of ventricular cardiomyocytes. We also demonstrated that active sodium channels do not distribute homogenously on the sarcolemma instead, they segregate into clusters of various densities, most crowded in the crest region, that are surrounded by areas virtually free of functional sodium channels. Conclusions: Our new method substantially increases the throughput of recording location-specific functional ion channels on the cardiomyocyte sarcolemma, thereby allowing characterization of ion channels in relation to the microdomain where they reside.
Small RNA Deep Sequencing Reveals Role for Arabidopsis thaliana RNA-Dependent RNA Polymerases in Viral siRNA Biogenesis

RNA silencing functions as an important antiviral defense mechanism in a broad range of eukaryotes. In plants, biogenesis of several classes of endogenous small interfering RNAs (siRNAs) requires RNA-dependent RNA Polymerase (RDR) activities. Members of the RDR family proteins, including RDR1and RDR6, have also been implicated in antiviral defense, although a direct role for RDRs in viral siRNA biogenesis has yet to be demonstrated. Using a crucifer-infecting strain of Tobacco Mosaic Virus (TMV-Cg) and Arabidopsis thaliana as a model system, we analyzed the viral small RNA profile in wild-type plants as well as rdr mutants by applying small RNA deep sequencing technology. Over 100,000 TMV-Cg-specific small RNA reads, mostly of 21- (78.4%) and 22-nucleotide (12.9%) in size and originating predominately (79.9%) from the genomic sense RNA strand, were captured at an early infection stage, yielding the first high-resolution small RNA map for a plant virus. The TMV-Cg genome harbored multiple, highly reproducible small RNA-generating hot spots that corresponded to regions with no apparent local hairpin-forming capacity. Significantly, both the rdr1 and rdr6 mutants exhibited globally reduced levels of viral small RNA production as well as reduced strand bias in viral small RNA population, revealing an important role for these host RDRs in viral siRNA biogenesis. In addition, an informatics analysis showed that a large set of host genes could be potentially targeted by TMV-Cg-derived siRNAs for posttranscriptional silencing. Two of such predicted host targets, which encode a cleavage and polyadenylation specificity factor (CPSF30) and an unknown protein similar to translocon-associated protein alpha (TRAP α), respectively, yielded a positive result in cleavage validation by 5′RACE assays. Our data raised the interesting possibility for viral siRNA-mediated virus-host interactions that may contribute to viral pathogenicity and host specificity.
Overexpression of plastidial thioredoxins f and m differentially alters photosynthetic activity and response to oxidative stress in tobacco plants

Plants display a remarkable diversity of thioredoxins (Trxs), reductases controlling the thiol redox status of proteins. The physiological function of many of them remains elusive, particularly for plastidial Trxs f and m, which are presumed based on biochemical data to regulate photosynthetic reactions and carbon metabolism. Recent reports revealed that Trxs f and m participate in vivo in the control of starch metabolism and cyclic photosynthetic electron transfer around photosystem I, respectively. To further delineate their in planta function, we compared the photosynthetic characteristics, the level and/or activity of various Trx targets and the responses to oxidative stress in transplastomic tobacco plants overexpressing either Trx f or Trx m. We found that plants overexpressing Trx m specifically exhibit altered growth, reduced chlorophyll content, impaired photosynthetic linear electron transfer and decreased pools of glutathione and ascorbate. In both transplastomic lines, activities of two enzymes involved in carbon metabolism, NADP-malate dehydrogenase and NADP-glyceraldehyde-3-phosphate dehydrogenase are markedly and similarly altered. In contrast, plants overexpressing Trx m specifically display increased capacity for methionine sulfoxide reductases, enzymes repairing damaged proteins by regenerating methionine from oxidized methionine. Finally, we also observed that transplastomic plants exhibit distinct responses when exposed to oxidative stress conditions generated by methyl viologen or exposure to high light combined with low temperature, the plants overexpressing Trx m being notably more tolerant than Wt and those overexpressing Trx f. Altogether, these data indicate that Trxs f and m fulfill distinct physiological functions. They prompt us to propose that the m type is involved in key processes linking photosynthetic activity, redox homeostasis and antioxidant mechanisms in the chloroplast.
Evolution of homing navigation in a real mobile robot

In this paper we describe the evolution of a discrete-time recurrent neural network to control a real mobile robot. In all our experiments the evolutionary procedure is carried out entirely on the physical robot without human intervention. We show that the autonomous development of a set of behaviors for locating a battery charger and periodically returning to it can be achieved by lifting constraints in the design of the robot/environment interactions that were employed in a preliminary experiment. The emergent homing behavior is based on the autonomous development of an internal neural topographic map (which is not pre-designed) that allows the robot to choose the appropriate trajectory as function of location and remaining energy.