Stand-alone tsunami alarm equipment

One of the quickest means of tsunami evacuation is transfer to higher ground soon after strong and long ground shaking. Ground shaking itself is a good initiator of the evacuation from disastrous tsunami. Longer period seismic waves are considered to be more correlated with the earthquake magnitude. We investigated the possible application of this to tsunami hazard alarm using single-site ground motion observation. Information from the mass media is sometimes unavailable due to power failure soon after a large earthquake. Even when an official alarm is available, multiple information sources of tsunami alert would help people become aware of the coming risk of a tsunami. Thus, a device that indicates risk of a tsunami without requiring other data would be helpful to those who should evacuate. Since the sensitivity of a low-cost MEMS (microelectromechanical systems) accelerometer is sufficient for this purpose, tsunami alarm equipment for home use may be easily realized. Amplitude of long-period (20 s cutoff) displacement was proposed as the threshold for the alarm based on empirical relationships among magnitude, tsunami height, hypocentral distance, and peak ground displacement of seismic waves. Application of this method to recent major earthquakes indicated that such equipment could effectively alert people to the possibility of tsunami

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

Los desafíos de la escolaridad en el Perú : estudios sobre los procesos pedagógicos, los saberes previos y el rol de las familias

El Proyecto Educativo Nacional y el Plan Nacional de Educación para Todos señalan que las políticas de calidad y equidad deben ser prioritarias. El planteamiento de esas políticas es respaldado por diversos diagnósticos que muestran tanto los bajos rendimientos estudiantiles, como la permanencia de desigualdades en el sistema educativo. Estas desigualdades están relacionadas principalmente con la procedencia socioeconómica, cultural o geográfica de los estudiantes. A pesar que las propuestas para mejorar la calidad y equidad no son nuevas, es poco lo que se ha avanzado en esa línea. Si bien en parte esto se debe a decisiones políticas, la ausencia de información sobre los mecanismos para mejorar los rendimientos estudiantiles, y el poco conocimiento de las formas de producción de las desigualdades educativas, tampoco contribuyen al objetivo de mejorar la calidad y equidad. Esta publicación recoge tres artículos que precisamente tienen como denominador común el intento de identificar los mecanismos que pueden permitir mejorar la calidad y los procesos que deben generarse para avanzar hacia la equidad. Se espera que los tres estudios incluidos en este volumen puedan ser de utilidad para poder definir políticas que permitan que la experiencia escolar de los niños y niñas peruanas tenga el resultado positivo que todos queremosÍndice: Presentación 9. I. Oportunidades de aprendizaje y rendimiento en comunicación integral de estudiantes en tercer y cuarto grado de primaria en Lima y Ayacucho / Santiago Cueto, Cecilia Ramírez, Juan León y Sandra Azañedo 13. II. Educación y cultura: la importancia de los saberes previos en los procesos de enseñanza-aprendizaje / Patricia Ruíz Bravo, José Luis Rosales y Eloy Neira Riquelme 79. III. De papás y mamás a hijos e hijas: las aspiraciones sobre el futuro y rol de las familias en las actividades escolares en el Perú rural / Martín Benavides, Inés Olivera, Magrith Mena 157

Whole transcriptome analysis of the fasting and fed Burmese python heart: insights into extreme physiological cardiac adaptation

The infrequently feeding Burmese python (Python molurus) experiences significant and rapid postprandial cardiac hypertrophy followed by regression as digestion is completed. To begin to explore the molecular mechanisms of this response, we have sequenced and assembled the fasted and postfed Burmese python heart transcriptomes with Illumina technology using the chicken (Gallus gallus) genome as a reference. In addition, we have used RNA-seq analysis to identify differences in the expression of biological processes and signaling pathways between fasted, 1 day postfed (DPF), and 3 DPF hearts. Out of a combined transcriptome of ∼2,800 mRNAs, 464 genes were differentially expressed. Genes showing differential expression at 1 DPF compared with fasted were enriched for biological processes involved in metabolism and energetics, while genes showing differential expression at 3 DPF compared with fasted were enriched for processes involved in biogenesis, structural remodeling, and organization. Moreover, we present evidence for the activation of physiological and not pathological signaling pathways in this rapid, novel model of cardiac growth in pythons. Together, our data provide the first comprehensive gene expression profile for a reptile heart

Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy

Background: Fibrosis, an excessive collagen accumulation, results in scar formation, impairing function of vital organs and tissues. Fibrosis is a hallmark of muscular dystrophies, including the lethal Duchenne muscular dystrophy (DMD), which remains incurable. Substitution of muscle by fibrotic tissue also complicates gene/cell therapies for DMD. Yet, no optimal models to study muscle fibrosis are available. In the widely used mdx mouse model for DMD, extensive fibrosis develops in the diaphragm only at advanced adulthood, and at about two years of age in the ‘easy-to-access’ limb muscles, thus precluding fibrosis research and the testing of novel therapies.Methods: We developed distinct experimental strategies, ranging from chronic exercise to increasing muscle damage on limb muscles of young mdx mice, by myotoxin injection, surgically induced trauma (laceration or denervation) or intramuscular delivery of profibrotic growth factors (such as TGFβ). We also extended these approaches to muscle of normal non-dystrophic mice. Results: These strategies resulted in advanced and enhanced muscle fibrosis in young mdx mice, which persisted over time, and correlated with reduced muscle force, thus mimicking the severe DMD phenotype. Furthermore, increased fibrosis was also obtained by combining these procedures in muscles of normal mice, mirroring aberrant repair after severe trauma. Conclusions: We have developed new and improved experimental strategies to accelerate and enhance muscle fibrosis in vivo. These strategies will allow rapidly assessing fibrosis in the easily accessible limb muscles of young mdx mice, without necessarily having to use old animals. The extension of these fibrogenic regimes to the muscle of non-dystrophic wild-type mice will allow fibrosis assessment in a wide array of pre-existing transgenic mouse lines, which in turn will facilitate understanding the mechanisms of fibrogenesis. These strategies should improve our ability to combat fibrosis-driven dystrophy progression and aberrant regeneration.The authors acknowledge funding from MINECO-Spain (SAF2012-38547, FIS-PS09/01267, FIS-PI13/02512, PLE2009-0124), AFM, E-Rare, Fundació-MaratóTV3, Duchenne PP-NL, EU-FP7 (Myoage, Optistem and Endostem), MDA, CARE PFB12/2007 and FONDECYT 111042

ACE2 Is Augmented in Dystrophic Skeletal Muscle and Plays a Role in Decreasing Associated Fibrosis

<div><p>Duchenne muscular dystrophy (DMD) is the most common inherited neuromuscular disease and is characterized by absence of the cytoskeletal protein dystrophin, muscle wasting, and fibrosis. We previously demonstrated that systemic infusion or oral administration of angiotensin-(1-7) (Ang-(1-7)), a peptide with opposing effects to angiotensin II, normalized skeletal muscle architecture, decreased local fibrosis, and improved muscle function in <i>mdx</i> mice, a dystrophic model for DMD. In this study, we investigated the presence, activity, and localization of ACE2, the enzyme responsible for Ang-(1-7) production, in wild type (wt) and <i>mdx</i> skeletal muscle and in a model of induced chronic damage in wt mice. All dystrophic muscles studied showed higher ACE2 activity than wt muscle. Immunolocalization studies indicated that ACE2 was localized mainly at the sarcolemma and, to a lesser extent, associated with interstitial cells. Similar results were observed in the model of chronic damage in the tibialis anterior (TA) muscle. Furthermore, we evaluated the effect of ACE2 overexpression in <i>mdx</i> TA muscle using an adenovirus containing human ACE2 sequence and showed that expression of ACE2 reduced the fibrosis associated with TA dystrophic muscles. Moreover, we observed fewer inflammatory cells infiltrating the <i>mdx</i> muscle. Finally, <i>mdx</i> gastrocnemius muscles from mice infused with Ang-(1-7), which decreases fibrosis, contain less ACE2 associated with the muscle. This is the first evidence supporting ACE2 as an important therapeutic target to improve the dystrophic skeletal muscle phenotype.</p></div

Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy

Background: Fibrosis, an excessive collagen accumulation, results in scar formation, impairing function of vital organs and tissues. Fibrosis is a hallmark of muscular dystrophies, including the lethal Duchenne muscular dystrophy (DMD), which remains incurable. Substitution of muscle by fibrotic tissue also complicates gene/cell therapies for DMD. Yet, no optimal models to study muscle fibrosis are available. In the widely used mdx mouse model for DMD, extensive fibrosis develops in the diaphragm only at advanced adulthood, and at about two years of age in the ‘easy-to-access’ limb muscles, thus precluding fibrosis research and the testing of novel therapies.Methods: We developed distinct experimental strategies, ranging from chronic exercise to increasing muscle damage on limb muscles of young mdx mice, by myotoxin injection, surgically induced trauma (laceration or denervation) or intramuscular delivery of profibrotic growth factors (such as TGFβ). We also extended these approaches to muscle of normal non-dystrophic mice. Results: These strategies resulted in advanced and enhanced muscle fibrosis in young mdx mice, which persisted over time, and correlated with reduced muscle force, thus mimicking the severe DMD phenotype. Furthermore, increased fibrosis was also obtained by combining these procedures in muscles of normal mice, mirroring aberrant repair after severe trauma. Conclusions: We have developed new and improved experimental strategies to accelerate and enhance muscle fibrosis in vivo. These strategies will allow rapidly assessing fibrosis in the easily accessible limb muscles of young mdx mice, without necessarily having to use old animals. The extension of these fibrogenic regimes to the muscle of non-dystrophic wild-type mice will allow fibrosis assessment in a wide array of pre-existing transgenic mouse lines, which in turn will facilitate understanding the mechanisms of fibrogenesis. These strategies should improve our ability to combat fibrosis-driven dystrophy progression and aberrant regeneration.The authors acknowledge funding from MINECO-Spain (SAF2012-38547, FIS-PS09/01267, FIS-PI13/02512, PLE2009-0124), AFM, E-Rare, Fundació-MaratóTV3, Duchenne PP-NL, EU-FP7 (Myoage, Optistem and Endostem), MDA, CARE PFB12/2007 and FONDECYT 111042

ACE2 activity and protein levels are increased in dystrophic skeletal muscle.

<p>(A) ACE2 activity of wt and <i>mdx</i> muscle extracts from TA, GAST and DIA. Cleavage rate is expressed as percentage of relative fluorescence units per minute normalized to total protein (%RFU/min*μg protein). Activity of each wt muscle was set as 100%, ANOVA *p<0.05 vs. wt muscle. (B) ACE2 activity of wt TA muscle was set as 100% and compared among all muscles analyzed. Significance between wt GAST and DIA, ANOVA *p<0.05. Significance between <i>mdx</i> GAST and <i>mdx</i> TA, ANOVA **p<0.05. <i>mdx</i> DIA had the greatest activity of all analyzed muscles, ANOVA ***p<0.01. Data are presented as mean ± standard error. TA wt n = 8, <i>mdx</i> n = 15; GAST wt n = 7, <i>mdx</i> n = 10; DIA wt n = 9, <i>mdx</i> n = 13. (C) Wt (lanes 1–4) and <i>mdx</i> (lanes 5–8) muscle extracts were analyzed by western blotting to detect ACE2, fibronectin, and GAPDH (loading control). Molecular weight standards are shown on the right. (D) Levels of ACE2 and fibronectin were quantified using relative expression compared with wt; data are mean ± standard error. ANOVA * p<0.001 wt vs. <i>mdx</i>.</p