Mitotic spindle positioning protein (MISP) preferentially binds to aged F-actin.

Actin bundling proteins crosslink filaments into polarized structures that shape and support membrane protrusions including filopodia, microvilli, and stereocilia. In the case of epithelial microvilli, mitotic spindle positioning protein (MISP) is an actin bundler that localizes specifically to the basal rootlets, where the pointed ends of core bundle filaments converge. Previous studies established that MISP is prevented from binding more distal segments of the core bundle by competition with other actin-binding proteins. Yet whether MISP holds a preference for binding directly to rootlet actin remains an open question. By immunostaining native intestinal tissue sections, we found that microvillar rootlets are decorated with the severing protein, cofilin, suggesting high levels of ADP-actin in these structures. Using total internal reflection fluorescence microscopy assays, we also found that purified MISP exhibits a binding preference for ADP- versus ADP-Pi-actin-containing filaments. Consistent with this, assays with actively growing actin filaments revealed that MISP binds at or near their pointed ends. Moreover, although substrate attached MISP assembles filament bundles in parallel and antiparallel configurations, in solution MISP assembles parallel bundles consisting of multiple filaments exhibiting uniform polarity. These discoveries highlight nucleotide state sensing as a mechanism for sorting actin bundlers along filaments and driving their accumulation near filament ends. Such localized binding might drive parallel bundle formation and/or locally modulate bundle mechanical properties in microvilli and related protrusions.

[Family planning in men and women with multiple sclerosis. Analysis of the Andalusian Registry (2018-2022)]. / Planificación familiar en hombres y mujeres con esclerosis múltiple. Análisis del Registro Andaluz (2018-2022).

INTRODUCTION: The Andalusian Registry of Pregnancies in patients with multiple sclerosis is the largest Spanish registry on multiple sclerosis (MS) and family planning. For the first time, it includes information on the fertility of men with MS. The influence of the use of a disease-modifying treatment (DMT) on the health of the foetus/newborn and the impact of breastfeeding on MS are also analysed. SUBJECTS AND METHODS: This is a multicentre, prospective and observational study. Recruitment of patients took place between December 2018 and December 2020. Women were followed up for one year after delivery. Altogether 100 women and 16 men were included, with a total of 103 newborn infants. RESULTS: The annualised relapse rate of the women with MS decreased significantly during pregnancy (from 0.23 to 0.065). A total of 11.2% of patients resorted to assisted reproductive techniques in order to conceive a child. No association was found between the use of a DMT at conception and/or pregnancy and the risk of miscarriage, prematurity or low birth weight. Over half the women with MS (54.2%) chose to breastfeed (26.7% of them while on a DMT). CONCLUSIONS: MS does not affect the fertility of men. Neither does the use of a DMT at the time of conception affect their fertility or their children's health. Assisted reproductive techniques did not have a negative impact on the course of MS. Breastfeeding is a common practice among women with MS and there is no evidence of positive or negative effects on disease progression.

TITLE: Planificación familiar en hombres y mujeres con esclerosis múltiple. Análisis del Registro Andaluz (2018-2022).Introducción. El Registro Andaluz de Embarazos en pacientes con esclerosis múltiple (EM) es el mayor registro español sobre EM y planificación familiar. Por primera vez se incluye información sobre la fertilidad de hombres con EM. También se analizan la influencia del uso de un tratamiento modificador de la enfermedad (TME) en la salud del feto o recién nacido y el impacto de la lactancia materna en la EM. Sujetos y métodos. Es un estudio observacional, prospectivo y multicéntrico. El reclutamiento de pacientes se hizo entre diciembre de 2018 y diciembre de 2020. El seguimiento de las mujeres tras el parto fue de un año. Se incluyó a 100 mujeres y 16 hombres, con un total de 103 recién nacidos. Resultados. La tasa anualizada de brotes de las mujeres con EM descendió durante el embarazo de forma significativa (de 0,23 a 0,065). Un 11,2% de los pacientes recurrieron a técnicas de reproducción asistida para conseguir la gestación. No se encontró relación entre el uso de un TME en la concepción y/o embarazo y el riesgo de aborto, prematuridad o bajo peso al nacer. El 54,2% de las mujeres con EM optaron por dar lactancia (el 26,7% de ellas usando un TME). Conclusiones. La EM no afecta a la fertilidad de los hombres. Tampoco influye en ésta, ni en la salud de sus hijos, el uso de un TME en el momento de la concepción. Las técnicas de reproducción asistida no impactaron negativamente en la evolución de la EM. La lactancia se impone como una práctica habitual entre las mujeres con EM y no se evidencian efectos positivos o negativos sobre la evolución de la enfermedad.

Planificación familiar en hombres y mujeres con esclerosis múltiple. Análisis del Registro Andaluz (2018-2022) / Family planning in men and women with multiple sclerosis. Analysis of the Andalusian Registry (2018-2022)

Introducción: El Registro Andaluz de Embarazos en pacientes con esclerosis múltiple (EM) es el mayor registro español sobre EM y planificación familiar. Por primera vez se incluye información sobre la fertilidad de hombres con EM. También se analizan la influencia del uso de un tratamiento modificador de la enfermedad (TME) en la salud del feto o recién nacido y el impacto de la lactancia materna en la EM. Sujetos y métodos: Es un estudio observacional, prospectivo y multicéntrico. El reclutamiento de pacientes se hizo entre diciembre de 2018 y diciembre de 2020. El seguimiento de las mujeres tras el parto fue de un año. Se incluyó a 100 mujeres y 16 hombres, con un total de 103 recién nacidos. Resultados: La tasa anualizada de brotes de las mujeres con EM descendió durante el embarazo de forma significativa (de 0,23 a 0,065). Un 11,2% de los pacientes recurrieron a técnicas de reproducción asistida para conseguir la gestación. No se encontró relación entre el uso de un TME en la concepción y/o embarazo y el riesgo de aborto, prematuridad o bajo peso al nacer. El 54,2% de las mujeres con EM optaron por dar lactancia (el 26,7% de ellas usando un TME). Conclusiones: La EM no afecta a la fertilidad de los hombres. Tampoco influye en ésta, ni en la salud de sus hijos, el uso de un TME en el momento de la concepción. Las técnicas de reproducción asistida no impactaron negativamente en la evolución de la EM. La lactancia se impone como una práctica habitual entre las mujeres con EM y no se evidencian efectos positivos o negativos sobre la evolución de la enfermedad.(AU)

Introduction: The Andalusian Registry of Pregnancies in patients with multiple sclerosis is the largest Spanish registry on multiple sclerosis (MS) and family planning. For the first time, it includes information on the fertility of men with MS. The influence of the use of a disease-modifying treatment (DMT) on the health of the foetus/newborn and the impact of breastfeeding on MS are also analysed. Subjects and methods: This is a multicentre, prospective and observational study. Recruitment of patients took place between December 2018 and December 2020. Women were followed up for one year after delivery. Altogether 100 women and 16 men were included, with a total of 103 newborn infants. Results: The annualised relapse rate of the women with MS decreased significantly during pregnancy (from 0.23 to 0.065). A total of 11.2% of patients resorted to assisted reproductive techniques in order to conceive a child. No association was found between the use of a DMT at conception and/or pregnancy and the risk of miscarriage, prematurity or low birth weight. Over half the women with MS (54.2%) chose to breastfeed (26.7% of them while on a DMT). Conclusions: MS does not affect the fertility of men. Neither does the use of a DMT at the time of conception affect their fertility or their children’s health. Assisted reproductive techniques did not have a negative impact on the course of MS. Breastfeeding is a common practice among women with MS and there is no evidence of positive or negative effects on disease progression.(AU)

Influence of shell thickness on the thermal stability and melting-like behavior of Al@Fe core-shell nanoparticles from atomistic simulations: a structural and dynamic description.

Core-shell nanoparticles (CSNPs) are a class of functional materials that have received important attention nowadays due to their adjustable properties by a controlled tuning of the core or shell. Understanding the thermal response and structural properties of these CSNPs is relevant to carrying out an analysis regarding their synthesis and application at the nanoscale. The present work is aimed to investigate the shell thickness effect on thermal stability and melting behavior of Al@Fe CSNPs by using molecular dynamics simulations. The results are discussed considering the influence of the Fe shell on the Al nanoparticle and analyzing the effect of different shell thicknesses in Al@Fe CSNPs. In general, calorific curves show a smooth energy decline for temperatures greater than room temperature for different shell thicknesses and sizes, corresponding to the inward and outward atomic movement of Al and Fe atoms, respectively, that produce a mixed Al-Fe nanoalloy. Here, the thermal stability of the Al@Fe nanoparticle is gradually lost passing to a liquid-Al@solid-Fe configuration and reaching a mixed Al-Fe state by an exothermic mechanism. Combining quantities of the atomic diffusion and structural identification, a stepped structural transition of the system is subsequently observed, where the melting-like point was estimated. Furthermore, it is observed that the Al@Fe CSNPs with greater stability are obtained with a thick shell and a large size. The ability to control shell thickness and vary the size opens up attractive opportunities to synthesize a broad range of new materials with tunable catalytic properties.

Mitotic spindle positioning protein (MISP) is an actin bundler that senses ADP-actin and binds near the pointed ends of filaments.

Actin bundling proteins crosslink filaments into polarized structures that shape and support membrane protrusions including filopodia, microvilli, and stereocilia. In the case of epithelial microvilli, mitotic spindle positioning protein (MISP) is an actin bundler that localizes specifically to the basal rootlets, where the pointed ends of core bundle filaments converge. Previous studies established that MISP is prevented from binding more distal segments of the core bundle by competition with other actin binding proteins. Yet whether MISP holds a preference for binding directly to rootlet actin remains an open question. Using in vitro TIRF microscopy assays, we found that MISP exhibits a clear binding preference for filaments enriched in ADP-actin monomers. Consistent with this, assays with actively growing actin filaments revealed that MISP binds at or near their pointed ends. Moreover, although substrate attached MISP assembles filament bundles in parallel and antiparallel configurations, in solution MISP assembles parallel bundles consisting of multiple filaments exhibiting uniform polarity. These discoveries highlight nucleotide state sensing as a mechanism for sorting actin bundlers along filaments and driving their accumulation near filament ends. Such localized binding might drive parallel bundle formation and/or locally modulate bundle mechanical properties in microvilli and related protrusions.

Building the brush border, one microvillus at a time.

Microvilli are actin bundle-supported surface protrusions assembled by diverse cell types to mediate biochemical and physical interactions with the external environment. Found on the surface of some of the earliest animal cells, primordial microvilli likely contributed to bacterial entrapment and feeding. Although millions of years of evolution have repurposed these protrusions to fulfill diverse roles such as detection of mechanical or visual stimuli in inner ear hair cells or retinal pigmented epithelial cells, respectively, solute uptake remains a key essential function linked to these structures. In this mini review, we offer a brief overview of the composition and structure of epithelial microvilli, highlight recent discoveries on the growth of these protrusions early in differentiation, and point to fundamental questions surrounding microvilli biogenesis that remain open for future studies.

Giant valley-Zeeman coupling in the surface layer of an intercalated transition metal dichalcogenide.

Spin-valley locking is ubiquitous among transition metal dichalcogenides with local or global inversion asymmetry, in turn stabilizing properties such as Ising superconductivity, and opening routes towards 'valleytronics'. The underlying valley-spin splitting is set by spin-orbit coupling but can be tuned via the application of external magnetic fields or through proximity coupling. However, only modest changes have been realized to date. Here, we investigate the electronic structure of the V-intercalated transition metal dichalcogenide V1/3NbS2 using microscopic-area spatially resolved and angle-resolved photoemission spectroscopy. Our measurements and corresponding density functional theory calculations reveal that the bulk magnetic order induces a giant valley-selective Ising coupling exceeding 50 meV in the surface NbS2 layer, equivalent to application of a ~250 T magnetic field. This energy scale is of comparable magnitude to the intrinsic spin-orbit splittings, and indicates how coupling of local magnetic moments to itinerant states of a transition metal dichalcogenide monolayer provides a powerful route to controlling their valley-spin splittings.

Searching for a prognostic index in lupus nephritis.

BACKGROUND: Currently we do not have an ideal biomarker in lupus nephritis (LN) that should help us to identify those patients with SLE at risk of developing LN or to determine those patients at risk of renal progression. We aimed to evaluate the development of a prognostic index for LN, through the evaluation of clinical, analytical and histological factors used in a cohort of lupus. We have proposed to determine which factors, 6 months after the diagnosis of LN, could help us to define which patients will have a worse evolution of the disease and may be, more aggressive treatment and closer follow-up. METHODS: A retrospective study to identify prognostic factors was carried out. We have included patients over 18 years of age with a clinical diagnosis of systemic lupus erythematosus (SLE) and kidney involvement confirmed by biopsy, who are followed up in our centre during the last 20 years. A multi-step statistical approach will be used in order to obtain a limited set of parameters, optimally selected and weighted, that show a satisfactory ability to discriminate between patients with different levels of prognosis. RESULTS: We analysed 92 patients with LN, although only 73 have been able to be classified according to whether or not they have presented poor renal evolution. The age of onset (44 vs. 32; p = 0.024), the value of serum creatinine (1.41 vs. 1.04; p = 0.041), greater frequency of thrombocytopenia (30 vs. 7%; p = 0.038), higher score in the renal chronicity index (2.47 vs. 1.04; p = 0.015), proliferative histological type (100%) and higher frequency of interstitial fibrosis (67 vs. 32%; p = 0.017) and tubular atrophy (67 vs. 32%; p = 0.018) was observed between two groups. The multivariate analysis allowed us to select the best predictive model for poor outcome at 6 months based on different adjustment and discrimination parameters. CONCLUSION: We have developed a prognostic index of poor renal evolution in patients with LN that combines demographic, clinical, analytical and histopathological factors, easy to use in routine clinical practice and that could be an effective tool in the early detection and management.

Mitotic Spindle Positioning (MISP) is an actin bundler that selectively stabilizes the rootlets of epithelial microvilli.

Microvilli are conserved actin-based surface protrusions that have been repurposed throughout evolution to fulfill diverse cell functions. In the case of transporting epithelia, microvilli are supported by a core of actin filaments bundled in parallel by villin, fimbrin, and espin. Remarkably, microvilli biogenesis persists in mice lacking all three of these factors, suggesting the existence of unknown bundlers. We identified Mitotic Spindle Positioning (MISP) as an actin-binding factor that localizes specifically to the rootlet end of the microvillus. MISP promotes rootlet elongation in cells, and purified MISP exhibits potent filament bundling activity in vitro. MISP-bundled filaments also recruit fimbrin, which further elongates and stabilizes bundles. MISP confinement to the rootlet is enforced by ezrin, which prevents decoration of the membrane-wrapped distal end of the core bundle. These discoveries reveal how epithelial cells optimize apical membrane surface area and offer insight on the remarkable robustness of microvilli biogenesis.

Genetic regulation of the ompX porin of Salmonella Typhimurium in response to hydrogen peroxide stress.

BACKGROUND: Salmonella Typhimurium is a Gram-negative pathogen that causes a systemic disease in mice resembling typhoid fever. During its infective cycle, S. Typhimurium is phagocytized by macrophages and proliferates inside a Salmonella-containing vacuole where Salmonella is exposed and survives oxidative stress induced by H2O2 through modulation of gene expression. After exposure of Salmonella to H2O2, the expression of the porin-encoding gene ompX increases, as previously shown by microarray analysis. Expression of ompX mRNA is regulated at a post-transcriptional level by MicA and CyaR sRNAs in aerobiosis. In addition, sequence analysis predicts a site for OxyS sRNA in ompX mRNA. RESULTS: In this work we sought to evaluate the transcriptional and post-transcriptional regulation of ompX under H2O2 stress. We demonstrate that ompX expression is induced at the transcriptional level in S. Typhimurium under such conditions. Unexpectedly, an increase in ompX gene transcript and promoter activity after challenges with H2O2 does not translate into increased protein levels in the wild-type strain, suggesting that ompX mRNA is also regulated at a post-transcriptional level, at least under oxidative stress. In silico gene sequence analysis predicted that sRNAs CyaR, MicA, and OxyS could regulate ompX mRNA levels. Using rifampicin to inhibit mRNA expression, we show that the sRNAs (MicA, CyaR and OxyS) and the sRNA:mRNA chaperone Hfq positively modulate ompX mRNA levels under H2O2-induced stress in Salmonella during the exponential growth phase in Lennox broth. CONCLUSIONS: Our results demonstrate that ompX mRNA is regulated in response to H2O2 by the sRNAs CyaR, MicA and OxyS is Salmonella Typhimurium.

Genetic regulation of the ompX porin of Salmonella Typhimurium in response to hydrogen peroxide stress

BACKGROUND: Salmonella Typhimurium is a Gram negative pathogen that causes a systemic disease in mice resembling typhoid fever. During its infective cycle, S. Typhimurium is phagocytized by macrophages and proliferates inside a Salmonella containing vacuole where Salmonella is exposed and survives oxidative stress induced by H2O2 through modulation of gene expression. After exposure of Salmonella to H2O2, the expression of the porin encoding gene ompX increases, as previously shown by microarray analysis. Expression of ompX mRNA is regulated at a post transcriptional level by MicA and CyaR sRNAs in aerobiosis. In addition, sequence analysis predicts a site for OxyS sRNA in ompX mRNA. RESULTS: In this work we sought to evaluate the transcriptional and post transcriptional regulation of ompX under H2O2 stress. We demonstrate that ompX expression is induced at the transcriptional level in S . Typhimurium under such conditions. Unexpectedly, an increase in ompX gene transcript and promoter activity after challenges with H2O2 does not translate into increased protein levels in the wild type strain, suggesting that ompX mRNA is also regulated at a post transcriptional level, at least under oxidative stress. In silico gene sequence analysis predicted that sRNAs CyaR, MicA, and OxyS could regulate ompX mRNA levels. Using rifampicin to inhibit mRNA expression, we show that the sRNAs (MicA, CyaR and OxyS) and the sRNA:mRNA chaperone Hfq positively modulate ompX mRNA levels under H2O2 induced stress in Salmonella during the exponential growth phase in Lennox broth. CONCLUSIONS: Our results demonstrate that ompX mRNA is regulated in response to H2O2 by the sRNAs CyaR, MicA and OxyS is Salmonella Typhimurium.

SARS-CoV-2 induces mitochondrial dysfunction and cell death by oxidative stress/inflammation in leukocytes of COVID-19 patients.

The inflammation and activation of the immune system induced by SARS-CoV-2 are mediated by a pro-oxidant microenvironment that can induce cytotoxic effects that enhance tissue damage, favoring organic deterioration. We investigated whether the induction of oxidative stress and inflammation by COVID-19 infection could inhibit mitochondrial function and cause cellular damage in leukocytes. We evaluated levels of oxidative/inflammation markers and their correlation with mitochondrial function and leukocyte cell death in COVID-19 patients at two moments: viremia and severe sepsis with multi-organ failure. COVID-19 induces increased oxidative stress and inflammation markers that activate cellular damage processes. In the viremia stage, an increase in peroxide, nitric oxide, carbonylated proteins, and IL-6 was observed, which was correlated with a marked inhibition of mitochondrial function, decreased cell viability, early apoptosis, necrosis, and leukocytes-reactivity. The severe sepsis stage with multi-organ failure also showed a further increase in levels of peroxide, carbonylated proteins, and IL-6, with a slight decrease in nitric oxide. This oxidative process and inflammation were correlated with less inhibition of mitochondrial function, decreased cell viability and an increase in late apoptosis, and morphology changes evidencing damage in the leukocytes. SARS-CoV-2 induced damage promotes levels of oxidative stress and inflammation markers and mitochondrial dysfunction that potentiate morphological changes and cell death in leukocytes. These processes explain the rapid changes in the immune system, and that present an initial over-activation and early massive death due to SARS-CoV-2 infection, promoting endothelial-alveolar damage that would cause multi-organ failure, sustained by oxidative stress and inflammation.

Brachial-ankle pulse wave velocity with a custom device.

BACKGROUND AND OBJECTIVES: The brachial-ankle pulse wave velocity (baPWV) is one of the most widely used arterial stiffness variables for assessing vascular risk. The abiPWV is a device that calculates various PWVs and the blood pressure ankle-brachial index (ABI). The device can also determine baPWV. The aim of this study was to calculate the baPWV with abiPWV, validate it with a reference device (VaSera) and study its clinical usefulness. PATIENTS AND METHODS: We studied 113 patients (mean age, 53 ±â€¯12 years), 59 (52%) of whom were women, and 10 (8.8%) of whom had a previous cardiovascular event. The participants were classified according to cardiovascular risk factors (CRFs) into group I (none), group II (1 or 2 CRFs) and group III (3 or more CRFs). The patients with a previous cardiovascular event were included in group III. All participants had their baPWV measured with abiPWV and VaSera. RESULTS: The baPWV correlation between the 2 devices was r = 0.93 (p < .001), and the percentage error calculated with the Bland-Altman analysis was 4.5%. The baPWV measured with abiPWV (in m/s) was as follows: group I, 10.5 ±â€¯1.6; group II, 13.8 ±â€¯2.9 (p < .001 when compared with group I); and group III, 14.1 ±â€¯2.7 (p < .001 when compared with group I). There were no differences between groups II and III. The results with VaSera were comparable to those of abiPWV. CONCLUSIONS: Measuring baPWV with the abiPWV is safe and has a similar clinical utility to that of VaSera. Incorporating this function into the options of abiPWV makes it a complete device for assessing arterial stiffness.

Velocidad de onda de pulso brazo-tobillo con un dispositivo propio / Brachial-ankle pulse wave velocity with a custom device

Antecedentes y objetivos La velocidad de onda de pulso brazo-tobillo (VOPbt) es una de las variables de rigidez arterial más empleada en la valoración del riesgo vascular. VOPITB es un dispositivo que calcula distintas VOP y el índice tobillo-brazo de presión arterial (ITB). Además, con sus registros se podría determinar la VOPbt. El objetivo de este estudio fue: calcular la VOPbt con VOPITB, validarlo con un equipo de referencia (VaSera) y estudiar su utilidad clínica. Pacientes y métodos Se estudiaron 113 pacientes, con edad media de 53±12años; 59 (52%) eran mujeres y 10 (8,8%) presentaban evento cardiovascular previo. Los participantes se estatificaron según factores de riesgo vascular (FRV) en: grupoI, ninguno; grupoII, uno o 2; y grupoIII, 3 o más FRV. Los pacientes con algún evento vascular previo se incluyeron en el grupoIII. A todos se les midió la VOPbt con VOPITB y VaSera. Resultados La correlación de VOPbt entre ambos equipos fue r=0,93 (p<0,001) y el porcentaje de error calculado con análisis de Bland-Altman: 4,5%. La VOPbt con VOPITB fue (m/s): grupoI, 10,5±1,6 comparado con grupoII, 13,8±2,9 (p<0,001) y grupoIII, 14,1±2,7 (p<0,001). No se observaron diferencias entre gruposII y III. Los resultados obtenidos con VaSera fueron equiparables a los de VOPITB. Conclusiones La medición de la VOPbt con el equipo VOPITB es segura y de utilidad clínica similar a la realizada con VaSera. La incorporación de esta función a las prestaciones de VOPITB lo convertirá en un dispositivo completo para valorar la rigidez arterial (AU)

Background and objectives The brachial-ankle pulse wave velocity (baPWV) is one of the most widely used arterial stiffness variables for assessing vascular risk. The abiPWV is a device that calculates various PWVs and the blood pressure ankle-brachial index (ABI). The device can also determine baPWV. The aim of this study was to calculate the baPWV with abiPWV, validate it with a reference device (VaSera) and study its clinical usefulness. Patients and methods We studied 113 patients (mean age, 53±12years), 59 (52%) of whom were women, and 10 (8.8%) of whom had a previous cardiovascular event. The participants were classified according to cardiovascular risk factors (CRFs) into groupI (none), groupII (1 or 2 CRFs) and groupIII (3 or more CRFs). The patients with a previous cardiovascular event were included in groupIII. All participants had their baPWV measured with abiPWV and VaSera. Results The baPWV correlation between the 2 devices was r=0.93 (P<.001), and the percentage error calculated with the Bland-Altman analysis was 4.5%. The baPWV measured with abiPWV (in m/s) was as follows: groupI, 10.5±1.6; groupII, 13.8±2.9 (P<.001 when compared with groupI); and groupIII, 14.1±2.7 (P<.001 when compared with groupI). There were no differences between groupsII and III. The results with VaSera were comparable to those of abiPWV. Conclusions Measuring baPWV with the abiPWV is safe and has a similar clinical utility to that of VaSera. Incorporating this function into the options of abiPWV makes it a complete device for assessing arterial stiffness (AU)

Respuestas morfofuncionales de larvas de mosquito Aedes aegypti a la Tetrametrina-Real-ZZ® / Aedes aegypti mosquito larvae morphofunctional responses to Tetrametrina-Real-ZZ®

El mayor conocimiento que se tiene sobre la larva del mosquito Aedes aegypti es sobre su eliminación cómo una estrategia para el control de la transmisión de numerosas arbovirosis de las cuales es el principal vector transmisor. Sin embargo, su uso como un posible modelo para ensayos en la toxicología experimental, ha sido poco explotado. En el presente trabajo se muestra un estudio de la toxicidad del insecticida Tetrametrina, presente en un producto comercial de uso doméstico “Real ZZ” ®, sobre larvas de Aedes aegypti, con el objeto de demostrar la utilidad de éstas como un posible modelo alternativo en la toxicología experimental. Se usaron larvas provenientes de un reservorio de agua de lluvia estancada, las cuales fueron tratadas con distintas concentraciones del insecticida, 0, 0.1, 0.2, 0.3, 0.4. y 0.5 %. Se determinó la CL50 y se describió la respuesta funcional y la morfológica, comparando controles y tratados. El ensayo de toxicidad bajo la acción de la CL50, fue valorado en términos de un estudio diagnóstico, haciendo uso de sus herramientas de interpretación como son la Sensibilidad (S) y la Especificidad (E), parámetros representados en una curva ROC, en donde el ABC fue utilizado como como índice de exactitud de la prueba de toxicidad. La respuesta funcional y la morfológica fueron analizadas a través del programa Video Tracker e ImageJ-Fiji respectivamente. Todos los datos fueron procesados en el programa GraphPad Prims. La CL50 fue de 0,33 %, con un índice de exactitud de la prueba de toxicidad del 79,17± 14 %. La velocidad angular del desplazamiento larvario se redujo en un 29,63% y la morfología de la región cefálica y branquial mostro irregularidades topográficas, con relieves entrantes y salientes de diferentes pendientes, con diferencias estadísticamente significativas, p<0.001. Todos los cambios atribuidos probablemente a la acción neurotóxica de la tetrametrina... (AU)

The best knowledge about the larvae of the Aedes aegypti mosquito is about its elimination as a strategy to control the transmission of numerous arborvirus infections, of which it is the main transmitting vector. However, its incorporation as a possible model for tests in experimental toxicology has been little exploited. This work shows a study of the toxicity of the insecticide Tetramethrin, present in a commercial product for domestic use «Real ZZ» ® on Aedes aegypti larvae, in order to demonstrate their usefulness as a possible alternative model in experimental toxicology. Larvae from a stagnant rainwater reservoir were used, which were treated with different concentrations of the insecticide, 0, 0.1, 0.2, 0.3, 0.4. and 0.5%. The LC50 was determined and the functional and morphological response was described, comparing controls and treated. The toxicity test under the action of LC50 was evaluated in terms of a diagnostic study, making use of its interpretation tools such as Sensitivity (S) and Specificity (E), parameters represented in a ROC curve, where ABC was used as an index of accuracy of the toxicity test. The functional and morphological responses were analyzed through the Video Tracker and ImageJ-Fiji programs respectively. All data were processed in the GraphPad Prims program. The LC50 was 0.33%, with an accuracy index of the toxicity test of 79.17 ± 14%. The angular velocity of larval displacement was reduced by 29.63% and the morphology of the cephalic and branchial region showed topographic irregularities, with incoming and outgoing reliefs of different slopes, with statistically significant differences, p <0.001. All changes probably attributed to the neurotoxic action of tetramethrin. It is concluded that Aedes aegypti mosquito larvae, being good emitters of easily measurable and quantifiable physiological responses, could be considered as a biomodel with great potential in toxicological research... (AU)

Brachial-ankle pulse wave velocity with a custom device. / Velocidad de onda de pulso brazo-tobillo con un dispositivo propio.

BACKGROUND AND OBJECTIVES: The brachial-ankle pulse wave velocity (baPWV) is one of the most widely used arterial stiffness variables for assessing vascular risk. The abiPWV is a device that calculates various PWVs and the blood pressure ankle-brachial index (ABI). The device can also determine baPWV. The aim of this study was to calculate the baPWV with abiPWV, validate it with a reference device (VaSera) and study its clinical usefulness. PATIENTS AND METHODS: We studied 113 patients (mean age, 53±12years), 59 (52%) of whom were women, and 10 (8.8%) of whom had a previous cardiovascular event. The participants were classified according to cardiovascular risk factors (CRFs) into groupI (none), groupII (1 or 2 CRFs) and groupIII (3 or more CRFs). The patients with a previous cardiovascular event were included in groupIII. All participants had their baPWV measured with abiPWV and VaSera. RESULTS: The baPWV correlation between the 2 devices was r=0.93 (P<.001), and the percentage error calculated with the Bland-Altman analysis was 4.5%. The baPWV measured with abiPWV (in m/s) was as follows: groupI, 10.5±1.6; groupII, 13.8±2.9 (P<.001 when compared with groupI); and groupIII, 14.1±2.7 (P<.001 when compared with groupI). There were no differences between groupsII and III. The results with VaSera were comparable to those of abiPWV. CONCLUSIONS: Measuring baPWV with the abiPWV is safe and has a similar clinical utility to that of VaSera. Incorporating this function into the options of abiPWV makes it a complete device for assessing arterial stiffness.

Review: Ruminal microbiome and microbial metabolome: effects of diet and ruminant host.

The rumen contains a great diversity of prokaryotic and eukaryotic microorganisms that allow the ruminant to utilize ligno-cellulose material and to convert non-protein nitrogen into microbial protein to obtain energy and amino acids. However, rumen fermentation also has potential deleterious consequences associated with the emissions of greenhouse gases, excessive nitrogen excreted in manure and may also adversely influence the nutritional value of ruminant products. While several strategies for optimizing the energy and nitrogen use by ruminants have been suggested, a better understanding of the key microorganisms involved and their activities is essential to manipulate rumen processes successfully. Diet is the most obvious factor influencing the rumen microbiome and fermentation. Among dietary interventions, the ban of antimicrobial growth promoters in animal production systems has led to an increasing interest in the use of plant extracts to manipulate the rumen. Plant extracts (e.g. saponins, polyphenol compounds, essential oils) have shown potential to decrease methane emissions and improve the efficiency of nitrogen utilization; however, there are limitations such as inconsistency, transient and adverse effects for their use as feed additives for ruminants. It has been proved that the host animal may also influence the rumen microbial population both as a heritable trait and through the effect of early-life nutrition on microbial population structure and function in adult ruminants. Recent developments have allowed phylogenetic information to be upscaled to metabolic information; however, research effort on cultivation of microorganisms for an in-depth study and characterization is needed. The introduction and integration of metagenomic, transcriptomic, proteomic and metabolomic techniques is offering the greatest potential of reaching a truly systems-level understanding of the rumen; studies have been focused on the prokaryotic population and a broader approach needs to be considered.

Not all saponins have a greater antiprotozoal activity than their related sapogenins.

The antiprotozoal effect of saponins varies according to both the structure of the sapogenin and the composition and linkage of the sugar moieties to the sapogenin. The effect of saponins on protozoa has been considered to be transient as it was thought that when saponins were deglycosilated to sapogenins in the rumen they became inactive; however, no studies have yet evaluated the antiprotozoal effect of sapogenins compared to their related saponins. The aims of this study were to evaluate the antiprotozoal effect of eighteen commercially available triterpenoid and steroid saponins and sapogenins in vitro, to investigate the effect of variations in the sugar moiety of related saponins and to compare different sapogenins bearing identical sugar moieties. Our results show that antiprotozoal activity is not an inherent feature of all saponins and that small variations in the structure of a compound can have a significant influence on their biological activity. Some sapogenins (20(S)-protopanaxatriol, asiatic acid and madecassic acid) inhibited protozoa activity to a greater extent than their corresponding saponins (Re and Rh1 and asiaticoside and madecassoside), thus the original hypothesis that the transient nature of the antiprotozoal action of saponins is due to the deglycosilation of saponins needs to be revisited.