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Digital archives change more quickly than traditional ones: they are adaptable and transient. This has advantages and disadvantages; digital archives can disappear from sight almost instantly but they can also be easily safeguarded and restored. Borrowing the critical vocabulary of performance studies, digital archives could thus be understood as "repertoires" rather than traditional archives. By treating digital archives as repertoires, this article explores different threats and opportunities presented by their volatile nature and makes policy and technical recommendations on how to ensure their relevance and sustainability. [ABSTRACT FROM AUTHOR]

The article describes the semantic web and its applications in other domains. Topics discussed include how performance studies can benefit from implementing said technologies, the pitfalls and limitation of introducing a semantic web structure to performance studies research, and the advantages of having an open knowledge about semantic web.

The essay/ontology workflow aims to combine formal and interpretive methods. Writing essays and developing ontologies can be considered as complementary approaches that feed into an iterative process. The article uses examples from a research project on Javanese theatre, but aims to offer reflections of general interest to researchers working in the Digital Humanities (DH). The conclusion argues that DH projects which combine formal and interpretive methods should not aim to minimize the differences between these approaches. Rather, research outputs should allow users to examine the contrasts and interactions between different modes of knowledge production. [ABSTRACT FROM AUTHOR]

Wayang Hip Hop is a group led by dalang Ki Catur "Benyek" Kuncoro that combines Javanese wayang kulit conventions and hip hop music. This article traces the history of the group in relation to key developments in wayang kontemporer, while exploring controversies in its reception. Wayang Hip Hop is analyzed as an important new version of wayang that has garnered substantial attention from young spectators. Five reasons for the appeal of the performance are identified: (1) its complex musical intersections, (2) the radical adaptation of classical wayang stories to address contemporary problems, (3) the extension of the conventions of the gara-gara comic interlude into a full performance, (4) the adaption of Javanese wisdom to new settings, and (5) the adaptability of the production, which can has been presented in very diverse contexts. [ABSTRACT FROM AUTHOR]

The most fundamental roles of non-coding RNAs (ncRNAs) and epigenetic mechanisms are the guidance of cellular differentiation in development and the regulation of gene expression in adult tissues. In brain, both ncRNAs and the various epigenetic gene regulatory mechanisms play a fundamental role in neurogenesis and normal neuronal function. Thus, epigenetic chromatin remodelling can render coding sites transcriptionally inactive by DNA methylation, histone modifications or antisense RNA interactions. On the other hand, microRNAs (miRNAs) are ncRNA molecules that can regulate the expression of hundreds of genes post-transcriptionally, typically recognising binding sites in the 3′ untranslated region (UTR) of mRNA transcripts. Furthermore, there are a myriad of interactions in the interface of miRNAs and epigenetics. For example, epigenetic mechanisms can silence miRNA coding sites, and miRNAs can be the effectors of transcriptional gene silencing, targeting complementary promoters or silencing the expression of epigenetic modifier genes like MECP2 and EZH2 leading to global changes in the epigenome. Alterations in this regulatory machinery play a key role in the pathology of complex disorders including cancer and neurological diseases. For example, miRNA genes are frequently inactivated by epimutations in gliomas. Here we describe the interactions between epigenetic and ncRNA regulatory systems and discuss therapeutic potential, with an emphasis on tumors, cognitive disorders and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the genetic diversity and population structure in the razor clam Ensis siliqua along the European Atlantic coast taking into account their recent history of exploitation and the ‘Prestige' oil spill. To this end we examined the genetic variability of microsatellite markers in 211 razor clams from five populations in Ireland, Portugal and Spain. Microsatellite data revealed a low genetic differentiation between the Spanish and Portuguese populations (FST = 0–0.032) and a moderate differentiation of these populations and the Irish samples (FST = 0.071–0.100). Although we observed changes in genetic diversity in accordance with the level of exploitation and the distribution of the oil spill, these changes were mild and not significant after Bonferroni correction. This could be the result of a genuine low impact, lack of statistical power and/or the capacity of this species to recolonize quickly after the impact of anthropogenic stressors. Supporting the latter argument we found a significant temporal heterogeneity of allelic frequencies in samples coming from the same sampling locality that could be attributed to the movement of adults or larvae from unaffected source populations. [ABSTRACT FROM PUBLISHER]

Microsatellites are short tandem repeats that evolve predominantly through a stepwise mutation model. Despite intensive study, many aspects of their evolution remain unresolved, particularly the question of how compound microsatellites containing two different motifs evolve. Previous work described profound asymmetries in the probability that any given second motif lies either 3′ or 5′ of an AC repeat tract. Here we confirm and extend this analysis to examine the length dependence of these asymmetries. We then use the differences in length between homologous human and chimpanzee microsatellites as a surrogate measure of the slippage-based mutation rate to explore factors that influence this process. We find that the dominant predictor of mutation rate is the length of the tract being considered, which is a stronger predictor than the length of the two tracts combined, but other factors also have a significant impact, including the length of the second tract and which of the two tracts lies upstream. We conclude that compound microsatellites rarely arise through random point mutations generating a second motif within a previously pure tract. Instead, our analyses point toward a model in which poorly understood mutation biases, probably affecting both slippage and point mutations and often showing 3′-5′ polarity, promote the formation of compound microsatellites. The result is convergent evolution. We suggest that, although their exact nature remains unclear, these biases are likely attributable to structural features, such as the propensity of AC tracts to form Z-DNA. [ABSTRACT FROM AUTHOR]

Some aspects of microsatellite evolution, such as the role of base substitutions, are far from being fully understood. To examine the significance of base substitutions underlying the evolution of microsatellites we explored the nature and the distribution of interruptions in dinucleotide repeats from the human genome. The frequencies that we inferred in the repetitive sequences were statistically different from the frequencies observed in other noncoding sequences. Additionally, we detected that the interruptions tended to be towards the ends of the microsatellites and 5′-3′ asymmetry. In all the estimates nucleotides forming the same repetitive motif seem to be affected by different base substitution rates in AC and AG. This tendency itself could generate patterning and similarity in flanking sequences and reconcile these phenomena with the high mutation rate found in flanking sequences without invoking convergent evolution. Nevertheless, our data suggest that there is a regional bias in the substitution pattern of microsatellites. The accumulation of random substitutions alone cannot explain the heterogeneity and the asymmetry of interruptions found in this study or the relative frequency of different compound microsatellites in the human genome. Therefore, we cannot rule out the possibility of a mutational bias leading to convergent or parallel evolution in flanking sequences. [ABSTRACT FROM AUTHOR]

Purpose: Although gait velocity (GV) measurement could predict poor outcomes, few studies regarding its usefulness as a single test in well functioning elderly persons have been pursued. The aim of this study was to asses whether GV could be sufficient to predict adverse events such as hospitalization for any cause, requirement for a caregiver, nursing home placement, falls, fractures, or death in healthy elderly persons.Methods: Ours was a cohort study comprising 102 well functioning participants aged 75 and older. Demographic features, health status, and functional capacity were assessed at baseline and followed for adverse outcomes. Measurements included evaluation of cognition, activities of daily living, and mobility. The time required to walk the middle 8 meters of 10 meters was defined as GV. Three GV groups were distinguished: high GV (>1.1 m/s), median GV (1-0.7 m/s), and low GV (<0.7 m/s).Results: At baseline, the three groups were comparable in their health status with an average age of 79.6 +/- 4 years. At 24 months, the low GV group had a significantly higher incidence of adverse events than did the other groups. Low GV was a predictor of hospitalization (relative risk [RR] = 5.9, 95% confidence interval [CI], 1.9-8.5), requirement of a caregiver (RR = 9.5, 95% CI, 1.3-2.5), and new falls (RR = 5.4, 95% CI, 2.0-4.3). These associations remained significant after a multiple logistic regression analysis.Conclusions: GV measurement in the ambulatory setting may allow the detection of healthy elderly people at risk for adverse events. These data may suggest that simple assessment of GV is enough to predict adverse events in well functioning older persons. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease with a mean survival time of three years. The 97% of the cases have TDP-43 nuclear depletion and cytoplasmic aggregation in motor neurons. TDP-43 prevents non-conserved cryptic exon splicing in certain genes, maintaining transcript stability, including ATG4B, which is crucial for autophagosome maturation and Microtubule-associated proteins 1A/1B light chain 3B (LC3B) homeostasis. In ALS mice (G93A), Atg4b depletion worsens survival rates and autophagy function. For the first time, we observed an elevation of LC3ylation in the CNS of both ALS patients and atg4b−/− mouse spinal cords. Furthermore, LC3ylation modulates the distribution of ATG3 across membrane compartments. Antisense oligonucleotides (ASOs) targeting cryptic exon restore ATG4B mRNA in TARDBP knockdown cells. We further developed multi-target ASOs targeting TDP-43 binding sequences for a broader effect. Importantly, our ASO based in peptide-PMO conjugates show brain distribution post-IV administration, offering a non-invasive ASO-based treatment avenue for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Spinal Muscular Atrophy (SMA) is a neuromuscular disease caused by decreased levels of the survival of motoneuron (SMN) protein. Post-translational mechanisms for regulation of its stability are still elusive. Thus, we aimed to identify regulatory phosphorylation sites that modulate function and stability. Our results show that SMN residues S290 and S292 are phosphorylated, of which SMN pS290 has a detrimental effect on protein stability and nuclear localization. Furthermore, we propose that phosphatase and tensin homolog (PTEN), a novel phosphatase for SMN, counteracts this effect. In light of recent advancements in SMA therapies, a significant need for additional approaches has become apparent. Our study demonstrates S290 as a novel molecular target site to increase the stability of SMN. Characterization of relevant kinases and phosphatases provides not only a new understanding of SMN function, but also constitutes a novel strategy for combinatorial therapeutic approaches to increase the level of SMN in SMA. [ABSTRACT FROM AUTHOR]

The hepatitis E virus (HEV) affects almost 20 million individuals annually, causing approximately 3.3 million acute liver injuries, 56,600 deaths, and huge healthcare-associated economic losses. Shellfish produced close to urban and livestock areas can bioaccumulate this virus and transmit it to the human population. The aim of this study was to evaluate the presence of HEV in molluscan shellfish, in order to deepen the knowledge about HEV prevalence in Galicia (northwestern Spain), and to investigate this as a possible route of HEV transmission to humans. A total of 168 shellfish samples was obtained from two different Galician rías (Ría de Ares-Betanzos and Ría de Vigo). The samples were analyzed by reverse transcription-quantitative PCR (RT-qPCR). RT-nested PCR and sequencing were used for further genotyping and phylogenetic analysis of positive samples. HEV was detected in 41 (24.4%) samples, at quantification levels ranging from non-quantifiable (<102 copies of the RNA genome (RNAc)/g tissue) to 1.1 × 105 RNAc/g tissue. Phylogenetic analysis based on the open reading frame (ORF)2 region showed that all sequenced isolates belonged to genotype 3, and were closely related to strains of sub-genotype e, which is of swine origin. The obtained results demonstrate a significant prevalence of HEV in bivalve molluscs from Galician rías, reinforcing the hypothesis that shellfish may be a potential route for HEV transmission to humans. [ABSTRACT FROM AUTHOR]

Viral agents of human gastroenteritis affect people of all ages across the globe. As a mainly self-limiting disease, it is difficult to evaluate the real prevalence of etiological agents circulating in each region. Many of the analyzed outbreaks are caused by viruses of the family Caliciviridae, especially the genus Norovirus (NoV). Most studies have focused on other enteric viruses, leaving sapovirus (SaV) underestimated as an important emerging human threat. This one-year study analyzed clinical samples from hospital outpatients with acute gastroenteritis in Spain, with the aim of revealing the importance of human SaV as an emerging viral pathogen. A total of 2667 stools were tested using reverse transcription (RT)-qPCR to detect and quantify SaV. Sapovirus was detected in all age groups, especially in infants, children, and the elderly. The prevalence was 15.64% (417/2667), and was slightly higher in 0–2- and 3–5-year-olds (19.53% and 17.95%, respectively) and much lower in 13–18-year-olds (9.86%). Positive samples were detected throughout the year, with peaks of detection during autumn and the late winter to early spring months. The mean value for the quantified samples was 6.5 × 105 genome copies per gram of stool (GC/g) (range 2.4 × 103–6.6 × 1011 GC/g). RT-nested PCR and sequencing were used for further genotyping. Genetic characterization showed a predominance of genogroup I (GI), followed by GII and GIV. The detection of multiple genotypes suggests the circulation of different strains without any clear tendency. The results obtained suggest SaV as the second major gastroenteritis agent after NoV in the region. [ABSTRACT FROM AUTHOR]