Coactivación Muscular. Una Propuesta para Calcular su Índice utilizando Python / Muscle coactivation. A proposal to calculate its index utilising Python

Introducción. Fenómenos neurofisiológicos, como la coactivación muscular, se han utilizado para identificar tareas motoras que requieren una mayor estabilidad articular en personas sanas o con trastornos del movimiento. Sin embargo, existen varias formas de calcular el índice de coactivación (IC) muscular. Objetivo. El objetivo de este artículo fue crear una propuesta de procesamiento para calcular el IC muscular mediante el diseño de dos funciones utilizando el lenguaje Python. La primera función calcula el IC utilizando la fórmula planteada por Falconer y Winter, definida como "coactivation index". Se requiere introducir dos señales de músculos antagonistas con una misma longitud de datos y frecuencia de muestreo. Estas señales son previamente normalizadas a la contracción voluntaria máxima utilizando valores promedios rectificados. La segunda función definida como "plot_coactivacion" despliega una figura con los cambios de amplitud de ambos músculos y su área común. Estas funciones fueron creadas con un lenguaje de libre acceso (Python), destacando su clara sintaxis y la amplia gama de librerías en el procesamiento de señales biomédicas.

Introduction. Neurophysiological phenomena, such as muscle coactivation, have been used to identify motor tasks requiring greater joint stability in healthy people or with movement disorders. Nonetheless, there are many ways to calculate the coactivation index (CI). This article aimed to create a processing pipeline to calculate the muscular CI by designing two functions with the Python language. The first function calculates the CI utilising the formula proposed by Falconer and Winter, defined as "coactivation_index". It is required to introduce two signals of antagonist muscles with the same data long and sample frequency. These signals were previously normalised to the maximum voluntary contraction using the averaged rectified values. The second function was defined as "plot_coactivacion", which unfolds a figure that describes the amplitude changes for both muscles and their common area. These functions were designed with a freely accessible language (Python), highlighting its clear syntax and the number of libraries associated with biomedical signal processing.

Production of asphalt mixes with copper industry wastes: Use of copper slag as raw material replacement.

Copper slag is a waste obtained from copper production and it has a limited use, being mainly accumulated in landfills on a massive scale. This material presents a high hardness and it has hydrophobic properties, so it can be used as aggregate replacement in the production of asphalt mixtures. However, each size of copper slag behaves differently when used in asphalt mixes, especially under changing conditions of moisture or temperature. Precisely these climatic factors directly affect the service life of asphalt pavements. In this research, semi-dense graded asphalt mixtures were produced with copper slag as replacement of aggregates, varying the particle sizes used in the range from 2.5 to 0.08 mm to determine the size of copper slag with the best performance. Indirect tensile strength tests were used to analyze samples subjected to different moisture and temperature conditions and ageing degrees. The results show that copper slag can be used as aggregate replacement in asphalt mixes when the proper size is selected. The strength of the asphalt mixture increased as the size of the copper slag increased, especially under variable moisture and ageing conditions. Superior behaviour compared to a reference mixture was obtained when replacing the size of aggregate No. 8 with copper slag, increasing its indirect tensile strength and retained strength, reducing its stiffness under all the ageing periods, and being equally effective at the different temperatures, which results in mixtures with improved durability and delayed cracking. Furthermore, it would help to reduce between 15 and 20% of the virgin aggregate needed to produce asphalt mixes and it would also allow reducing the accumulated volume of this waste, decreasing the environmental impact of both industries.

Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors.

We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.

Rocky intertidal zonation pattern in Antofagasta, chile: invasive species and shellfish gathering.

BACKGROUND: Biological invasions affecting rocky intertidal zonation patterns, yield information on species interactions. In the Bay of Antofagasta, northern Chile, the non-indigenous tunicate Pyura praeputialis, originally from Australia, has invaded (in the past century or so) and monopolized a major portion of the mid-intertidal rocky shore, displacing upshore the native mussel Perumytilus purpuratus. In Antofagasta the tunicate is subjected to intensive exploitation. Monitoring protocols show that in the past 10 years Antofagasta's tunicate population has experienced a drastic decline, affecting the intertidal zonation pattern. METHODOLOGY/PRINCIPAL FINDINGS: A 12.5 km of coastline, on the southern eastern shore of the Bay of Antofagasta, was studied. Eight sites were systematically (1993-1994) or sporadically (2003-2014) monitored for the seaward-shoreward expansion or reduction of the tunicate Pyura praeputialis, and native mussel and barnacle bands. A notable reduction in the mid-intertidal band of P. praeputialis and a seaward expansion of the mussel, Perumytilus purpuratus, and barnacle bands was observed. We suggest that the major cause for the decline in the tunicate is due to its intensive exploitation by rocky shore Pyura-gathers. The rate of extraction of tunicates by professional Pyura-gathers ranged between 256-740 tunicates hour-(1). Between 2009-2014 the density of professional Pyura-gather ranged between 0.5-4.5 km(-1) per low tide. Hence, 10 professional Pyura-gathers working 1 h for 10 low tides per month, during 6 months, will remove between 307-888 m(2) of tunicates. A drastic decline in tunicate recruitment was observed and several P. praeputialis ecosystems services have been lost. CONCLUSION AND SIGNIFICANCE: In Antofagasta, the continuous and intensive intertidal gathering of the invasive tunicate Pyura praeputialis, has caused a drastic reduction of its population modifying the zonation pattern. Thereby, native mussel Perumytilus purpuratus has regained its ecological center in the intertidal zone. We recorded a Pyura recruitment failure and loss of ecosystem services.

Expression of mitochondrial non-coding RNAs (ncRNAs) is modulated by high risk human papillomavirus (HPV) oncogenes.

The study of RNA and DNA oncogenic viruses has proved invaluable in the discovery of key cellular pathways that are rendered dysfunctional during cancer progression. An example is high risk human papillomavirus (HPV), the etiological agent of cervical cancer. The role of HPV oncogenes in cellular immortalization and transformation has been extensively investigated. We reported the differential expression of a family of human mitochondrial non-coding RNAs (ncRNAs) between normal and cancer cells. Normal cells express a sense mitochondrial ncRNA (SncmtRNA) that seems to be required for cell proliferation and two antisense transcripts (ASncmtRNAs). In contrast, the ASncmtRNAs are down-regulated in cancer cells. To shed some light on the mechanisms that trigger down-regulation of the ASncmtRNAs, we studied human keratinocytes (HFK) immortalized with HPV. Here we show that immortalization of HFK with HPV-16 or 18 causes down-regulation of the ASncmtRNAs and induces the expression of a new sense transcript named SncmtRNA-2. Transduction of HFK with both E6 and E7 is sufficient to induce expression of SncmtRNA-2. Moreover, E2 oncogene is involved in down-regulation of the ASncmtRNAs. Knockdown of E2 in immortalized cells reestablishes in a reversible manner the expression of the ASncmtRNAs, suggesting that endogenous cellular factors(s) could play functions analogous to E2 during non-HPV-induced oncogenesis.

Angiotensin-(1-9) regulates cardiac hypertrophy in vivo and in vitro.

BACKGROUND: Angiotensin-(1-9) is present in human and rat plasma and its circulating levels increased early after myocardial infarction or in animals treated with angiotensin-converting enzyme inhibitor. However, the cardiovascular effects of this peptide are unknown. OBJECTIVE: To determine whether angiotensin-(1-9) is a novel anti-cardiac hypertrophy factor in vitro and in vivo and whether this peptide is involved in the pharmacological effects of cardiovascular drugs acting on the renin-angiotensin system. METHODS AND RESULTS: The administration of angiotensin-(1-9) to myocardial infarcted rats by osmotic minipumps (450 ng/kg per min, n = 6) vs. vehicle (n = 8) for 2 weeks decreased plasma angiotensin II levels, inhibited angiotensin-converting enzyme activity and also prevented cardiac myocyte hypertrophy. However, cardiac myocyte hypertrophy attenuation triggered by angiotensin-(1-9) was not modified with the simultaneous administration of the angiotensin-(1-7) receptor antagonist A779 (100 ng/kg per min, n = 6). In experiments in vitro with cultured cardiac myocytes incubated with norepinephrine (10 micromol/l) or with insulin-like growth factor-1 (10 nmol/l), angiotensin-(1-9) also prevented hypertrophy. In other experimental setting, myocardial infarcted rats (n = 37) were randomized to receive either vehicle (n = 12), enalapril (10 mg/kg per day, n = 12) or angiotensin II receptor blocker candesartan (10 mg/kg per day, n = 13) for 8 weeks. Both drugs prevented left ventricle hypertrophy and increased plasma angiotensin-(1-9) levels by several folds. Angiotensin-(1-9) levels correlated negatively with different left ventricular hypertrophy markers even after adjustment for blood pressure reduction. CONCLUSION: Angiotensin-(1-9) is an effective and a novel anti-cardiac hypertrophy agent not acting via the Mas receptor.

Menores niveles tisulares de la enzima convertidora de angiotensina I homologa (ECA-2) y angiotensina-(1-9) están asociados a mayor remodelamiento de la pared aórtica de ratas hipertensas / Lower tissue levels of homologous angiotensin I converting enzyme (ACE-2) and angiotensin 1-9 are associated to increased remodeling of the aortic wall of hypertensive rats

Antecedentes: Recientemente hemos propuesto en un modelo experimental de infarto al miocardio una significativa interregulación entre los niveles de la enzima convertidora de angiotensina I (ECA) y su homóloga (ECA-2), junto con que angiotensina (Ang)-(1-9) más que Ang-(1-7) actuaría como uncontrarregulador de Ang II. Sin embargo tal relación no se ha investigado en el remodelado aórtico hipertensivo. Objetivo: Determinar la expresión de ECA y ECA-2, los niveles de Angs I, II, (1-7) y (1-9) y los parámetros de remodelado de la pared aórtica de ratas hipertensas. Métodos: Ratas normotensas Lewis (n=18) fueron randomizadas a hipertensión (HTA) por sobrecarga de presión (modelo Goldblatt, GB, 2 riñones-1 pinzado, n=9). Ratas pseudo-operadas se usaron como controles (S, n=9). A las 6 semanas post cirugía, se determinó la masa cardíaca relativa (MCR) y la presión arterial sistólica (PAS). En la aorta torácica se determinó el grosor de la túnica media (GTM), área de la TM (ATM), niveles de mRNA de ECA y ECA-2, factor de crecimiento transformante tipo beta (TGF-beta), inhibidor del activador de plasminógeno (PAI-1) y de la proteína quimioatractante de monocitos (MCP-1) por RT-PCR. La actividad y niveles proteicos de ECA y ECA-2 por fluorimetría y Western blot y los niveles de Angs I, II, (1-7) y (1-9) por HPLC y radioinmunoensayo. Resultados: La MCR y la PAS aumentaron significativamente (p<0,05) en el grupo GB respecto a su control S. Las ratas hipertensas mostraron un aumento significativo (p<0.05) del GTM (18 por ciento), ATM (31 por ciento), niveles de mRNA de ECA (164 por ciento), TGF-beta (105 por ciento), PAI-1(51 por ciento), MCP-1 (53 por ciento) junto con mayor actividad (89 por ciento), niveles proteicos de ECA (130 por ciento) y Ang II (48 por ciento). Esos efectos se asociaron a una significativa disminución del mRNA, los niveles proteicos y actividad...

Background: In experimental models of myocardial infarction we have recently proposed a significantinter-regulation between levels of Angiotensin I converting enzyme (ACE) and its homologous, ACE-2; in addition, we have proposed that Angiotensin 1-9 (Ang-(1-9)) rather than Ang-(1-7) counter regulates Ang II. These relations have not been investigated in hypertensive aortic wall remodeling. Aim: To measure de expression of ACE and ACE-2, the aortic wall levels of Ang I, Ang II, Ang-(1-7) and Ang-(1-9), along with parameters of aortic wall remodeling in hypertensive rats. Methods: 18 Lewis rats were randomized to Goldblatt (2 kidneys, 1 clamped) induced hypertension (n=9) or sham operation (controls, n=9). Six weeks after surgery, relative cardiac mass (RCM), systolic blood pressure (SBP), medial layer aortic wall thickness (MLT) and ML area (MLA) were measured. The aortic wall levels of ACE and ACE-2, tissue growth factor beta (TGF- beta), plasminogen activator inhibitor (PAI-1) and monocyte chemoattractant protein (MCP-1) were determined by RT-PCR. Activity and protein levels of ACE and ACE-2 were measured by fluorometry and Western Blot and ANG I, Ang II, Ang-(1-7) and Ang-(1-9) levels were determined using HPLC and radioimmunoassay. Results: RCM and SBP increased significantly in hypertensive as opossed to sham operated rats...

Menor expresión de la enzima convertidora de angiotensinaI omóloga (ECA2) se asocia a mayor remodelamiento de la pared aórtica de ratas con niveles geneticamente elevados de angiotensina II / Decreased expression of homologous angiotensin I converting enzyme (ACE2) is associated to increased remodeling of the aortic arterial wall in rats with genetically elevated levels of angiotensin II

Introducción: El polimorfismo de la enzima convertidora de angiotensina I (ECA) determina mayor actividadde ECA y niveles de angiotensina (Ang) II en ratas Brown Norway (BN) y menor actividad de ECA y niveles de Ang II en ratas Lewis (L). La interregulación entre ECA, ECA2 y su relación con remodelamiento aórtico hipertensivo no ha sido explorada Objetivo: Determinar la expresión de ECA y ECA2 y los parámetros de remodelamiento vascular hipertensivo en la aorta de ratas con niveles genéticamente determinados de ECA. Métodos: A ratas macho homocigotas de 150 grs BN y LL, se les indujo HTA por 6 semanas por el procedimiento Goldblatt (GB, 2 K-1clip). Ratas pseudo-operadas se usaron como controles (sham). Se determinó la presión arterial sistólica (PAS), el grosor de la túnica media (GTM), área de la TM (ATM), expresión génica deECA, ECA2 ,TGF-beta, PAI-1 y MCP-1 por RT-PCR y también proteica de ECA y ECA2 por Western Blot. Resultados: La masa cardiaca relativa y la PAS aumentaron significativamente en los grupos GB respecto a sus controles Sham, sin diferencias por efecto del polimorfismo de la ECA. En condiciones de normotensión las ratas BN mostraron que la pared aórtica expresa mayores niveles génicos y proteicos de la ECA(60% y 134%, respectivamente) y menores de ECA2 (74% y 73%, respectivamente) respecto de las ratas L(p<0.05). Estos resultados se asociaron con mayores GTM y ATM como en los niveles de mRNA de TGF-beta y, PAI-1 en las aortas de ratas BN respecto de las ratas L (p<0,05). En respuesta a un estrés hipertensivo las ratas con mayores niveles de ECA y menores niveles de ECA2 mostraron mayor GTM (p<0,05, respecto de GB-L), sin diferencias en los otros parámetros evaluados...

Background: Angiotensin I converting enzyme (ACE) polymorphism determines increased ACE and Ang IIlevels in Brown Norway rats (BN) and decreased ACE and Ang II levels in Lewis (L) rats. The interactionbetween ACE and ACE2 in relation to aortic remodeling associated to hypertension has not been explored. Aim: to determine the expression of ACE and ACE2 along with parameters of remodeling in hypertensive rats with genetically determined levels of ACE. Methods: BN and L rats weighing 150 g were made hypertensive by the Goldblatt procedure (GB, 2K-1 clip). Sham operated rats were used as controls. Systolic blood pressure (SBP), media thickness (MT), and MT area were measured. RT-PCR was used to determine the genetic expression of ACE, ACE2, TGF-beta, PAI-1 and MCP-1. Western Blot was used to measure the protein fraction of ACE and ACE2 Results: Relative cardiac mass and SBP increases significantly in GB rats compared to controls; ACE polymorphism did not influence this effect. The aortic wall of normotensive BN rats expressed increased genic and protein levels of ACE (60% and 134%, respectively) and decreased levels of ACE2 (74% and 73%, respectively) compared to L rats (p<0.05). These findings were associated to increased MT and MT area as well as increased mRNA for TGF-beta and PAI 1 in BN rats compared to L rats (p<0.05). In response to hypertensive stress, rats with increased ACE and decreased ACE2 levels developed increased MT compared to GB-L rats; other parameters of remodeling were not affected...

El aumento de la actividad y expresión de la enzima convertidora de angiotensina I homóloga (ECA2) inducido por enalapril se asocia a menor fibrosis e hipertrofia ventricular izquierda post infarto al miocardio en la rata / Enalapril induced increase in Homologous Angiotensin I converting enzyme (ECA2) is associated to decreased fibrosis and decreased left ventricular hypertrophy post myocardial infarction in rats

Recientemente se ha descubierto el gen de una nueva enzima convertidora de angiotensina I- homóloga a ECA y denominada ECA-2 que finalmente lleva a producir angiotensina 1-7. Esta segunda vía del sistema reninaangiotensina (SRA), con la ECA-2 tendría acciones opuestas a la ECA. Objetivo y Métodos: Determinar la actividad y expresión de la ECA2 en el tratamiento de la hipertrofia y fibrosis ventricular izquierda tardía post IAM en la rata. Se usaron ratas Sprague Dawley 200 +/- 10 g sometidas a ligadura de la coronaria izquierda. Como controles se usaron ratas sham (S). 48 hrs. post cirugía, un grupo de ratas IAM recibió enalapril (IAM-ENA; 10 mg/kg, gavage). A las 8 semanas post-operatorias se determinó la presión arterial sistólica (PAS), masa corporal(MC), masa cardíaca relativa (MCR, mg VI/100 g MC, expresión proteica de la cadena pesada de la miosina beta(betaMHC) por Western blot, mRNA por RT-PCR, las actividades enzimáticas de ECA y de ECA-2 por fluorimetría tanto circulante como en ventrículo izquierdo (VI), el contenido de colágeno total por rojo picrosirio y la actividad de metaloproteasa 2 (MMP-2) por zimografía. Conclusión: El aumento de la actividad y expresión de la ECA2 (a nivel circulante y tisular cardíaco) se asocia a menor fibrosis e hipertrofia ventricular izquierda, lo que podría aumentar – en ese periodo - el efecto cardioprotector de Ang-(1-7).

Background. Recently the gene of a new angiotensin-1 converting homologous enzyme (ACE-2) which leads to the production of angiotensin 1-7 (Ang (1-7) has been reported. This new pathway of the renin-angiotensin system(RAS) is supposed to have opposite effects to those of ACE. Aim: To determine the activity and expression of ACE-2 in the development of left ventricular hypertrophy and fibrosis late after induced myocardial infarction (AMI) in rats. Methods: 200 +/- 10g Sprague-Dawley rats were submitted to left coronary artery ligation. Sham operated rats were used as controls. 48 hr after surgery, one group of AMI rats received enalapril (AMI-En), 10mg/Kg. 8 weeks after surgery the systolic blood pressure (SBP), body mass (BM) and relative cardiac mass (RCM, mg/100g BM) were measured. The protein expression of heavy weight chain beta myosin (beta HCM) was determined by Western Blot, mRNA through RT-PCR, circulating and left ventricular ACE and ACE-2 activities through fluorometry, total collagen content by the pycrosirius red method and metaloproteinase-2 (MMP-2) through zymography were determined. Conclusion: The increased activity and expression of ACE-2 both in plasma and the LV is associated to less fibrosis and left ventricular hypertrophy after AMI. This could temporarily boost the cardioproctive effect of Ang (1-7).

Enalapril attenuates downregulation of Angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in myocardial infarcted rat.

The early and long-term effects of coronary artery ligation on the plasma and left ventricular angiotensin-converting enzyme (ACE and ACE2) activities, ACE and ACE2 mRNA levels, circulating angiotensin (Ang) levels [Ang I, Ang-(1-7), Ang-(1-9), and Ang II], and cardiac function were evaluated 1 and 8 weeks after experimental myocardial infarction in adult Sprague Dawley rats. Sham-operated rats were used as controls. Coronary artery ligation caused myocardial infarction, hypertrophy, and dysfunction 8 weeks after surgery. At week 1, circulating Ang II and Ang-(1-9) levels as well as left ventricular and plasma ACE and ACE2 activities increased in myocardial-infarcted rats as compared with controls. At 8 weeks post-myocardial infarction, circulating ACE activity, ACE mRNA levels, and Ang II levels remained higher, but plasma and left ventricular ACE2 activities and mRNA levels and circulating levels of Ang-(1-9) were lower than in controls. No changes in plasma Ang-(1-7) levels were observed at any time. Enalapril prevented cardiac hypertrophy and dysfunction as well as the changes in left ventricular ACE, left ventricular and plasmatic ACE2, and circulating levels of Ang II and Ang-(1-9) after 8 weeks postinfarction. Thus, the decrease in ACE2 expression and activity and circulating Ang-(1-9) levels in late ventricular dysfunction post-myocardial infarction were prevented with enalapril. These findings suggest that in this second arm of the renin-angiotensin system, ACE2 may act through Ang-(1-9), rather than Ang-(1-7), as a counterregulator of the first arm, where ACE catalyzes the formation of Ang II.