Relativistic chaotic scattering: Unveiling scaling laws for trapped trajectories.

In this paper we study different types of phase space structures which appear in the context of relativistic chaotic scattering. By using the relativistic version of the Hénon-Heiles Hamiltonian, we numerically study the topology of different kind of exit basins and compare it with the case of low velocities in which the Newtonian version of the system is valid. Specifically, we numerically study the escapes in the phase space, in the energy plane, and in the ß plane, which richly characterize the dynamics of the system. In all cases, fractal structures are present, and the escaping dynamics is characterized. In every case a scaling law is numerically obtained in which the percentage of the trapped trajectories as a function of the relativistic parameter ß and the energy is obtained. Our work could be useful in the context of charged particles which eventually can be trapped in the magnetosphere, where the analysis of these structures can be relevant.

Mental health, subjective experiences and environmental change.

This article responds to Coope's call for the medical humanities to address the climate crisis as a health issue. Coope proposes three areas for progress towards ecological thinking in healthcare, with a focus on ecological mental health. The article emphasises the need to understand the cultural dimensions of mental health and proposes an interdisciplinary approach that integrates insights from the arts and humanities. It examines the impact of climate change on mental health, drawing on The Rockefeller Foundation - Lancet Commission on Planetary Health and recent studies. The discussion focuses on the intersection of mental health, subjective experience and environmental change. Focusing on emotional experiences as constructed from biological and cultural elements, the article proposes a holistic approach to mental health. It proposes two converging lines of research, in constant interaction: first, a historical and cultural research of those concepts, practices and symbols related to the environment, emphasising a cultural history of nature; and second, a synchronous research, drawing on anthropology, sociology and participatory art-based research, to understand how these aforementioned elements influence our current relations with nature. The article concludes by emphasising the urgency of developing narratives and histories that redirect temporal trajectories towards a better future, while respecting and acknowledging diverse narratives of individual experience. It calls for collaborative efforts from the medical humanities to contribute to a more comprehensive understanding of the complex relationship between mental health, nature and ecological crisis.

Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome.

BACKGROUND: Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state. METHODS: We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1C122Y variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments. RESULTS: Kir2.1C122Y mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1C122Y cardiomyocytes showed significantly reduced inwardly rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1C122Y mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and NaV1.5 proteins. CONCLUSIONS: The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.

Modern anthropogenic drought in Central Brazil unprecedented during last 700 years.

A better understanding of the relative roles of internal climate variability and external contributions, from both natural (solar, volcanic) and anthropogenic greenhouse gas forcing, is important to better project future hydrologic changes. Changes in the evaporative demand play a central role in this context, particularly in tropical areas characterized by high precipitation seasonality, such as the tropical savannah and semi-desertic biomes. Here we present a set of geochemical proxies in speleothems from a well-ventilated cave located in central-eastern Brazil which shows that the evaporative demand is no longer being met by precipitation, leading to a hydrological deficit. A marked change in the hydrologic balance in central-eastern Brazil, caused by a severe warming trend, can be identified, starting in the 1970s. Our findings show that the current aridity has no analog over the last 720 years. A detection and attribution study indicates that this trend is mostly driven by anthropogenic forcing and cannot be explained by natural factors alone. These results reinforce the premise of a severe long-term drought in the subtropics of eastern South America that will likely be further exacerbated in the future given its apparent connection to increased greenhouse gas emissions.

The Kir2.1E299V mutation increases atrial fibrillation vulnerability while protecting the ventricles against arrhythmias in a mouse model of short QT syndrome type 3.

AIMS: Short QT syndrome type 3 (SQTS3) is a rare arrhythmogenic disease caused by gain-of-function mutations in KCNJ2, the gene coding the inward rectifier potassium channel Kir2.1. We used a multidisciplinary approach and investigated arrhythmogenic mechanisms in an in-vivo model of de-novo mutation Kir2.1E299V identified in a patient presenting an extremely abbreviated QT interval and paroxysmal atrial fibrillation. METHODS AND RESULTS: We used intravenous adeno-associated virus-mediated gene transfer to generate mouse models, and confirmed cardiac-specific expression of Kir2.1WT or Kir2.1E299V. On ECG, the Kir2.1E299V mouse recapitulated the QT interval shortening and the atrial-specific arrhythmia of the patient. The PR interval was also significantly shorter in Kir2.1E299V mice. Patch-clamping showed extremely abbreviated action potentials in both atrial and ventricular Kir2.1E299V cardiomyocytes due to a lack of inward-going rectification and increased IK1 at voltages positive to -80 mV. Relative to Kir2.1WT, atrial Kir2.1E299V cardiomyocytes had a significantly reduced slope conductance at voltages negative to -80 mV. After confirming a higher proportion of heterotetrameric Kir2.x channels containing Kir2.2 subunits in the atria, in-silico 3D simulations predicted an atrial-specific impairment of polyamine block and reduced pore diameter in the Kir2.1E299V-Kir2.2WT channel. In ventricular cardiomyocytes, the mutation increased excitability by shifting INa activation and inactivation in the hyperpolarizing direction, which protected the ventricle against arrhythmia. Moreover, Purkinje myocytes from Kir2.1E299V mice manifested substantially higher INa density than Kir2.1WT, explaining the abbreviation in the PR interval. CONCLUSION: The first in-vivo mouse model of cardiac-specific SQTS3 recapitulates the electrophysiological phenotype of a patient with the Kir2.1E299V mutation. Kir2.1E299V eliminates rectification in both cardiac chambers but protects against ventricular arrhythmias by increasing excitability in both Purkinje-fiber network and ventricles. Consequently, the predominant arrhythmias are supraventricular likely due to the lack of inward rectification and atrial-specific reduced pore diameter of the Kir2.1E299V-Kir2.2WT heterotetramer.

MYH10 activation rescues contractile defects in arrhythmogenic cardiomyopathy (ACM).

The most prevalent genetic form of inherited arrhythmogenic cardiomyopathy (ACM) is caused by mutations in desmosomal plakophilin-2 (PKP2). By studying pathogenic deletion mutations in the desmosomal protein PKP2, here we identify a general mechanism by which PKP2 delocalization restricts actomyosin network organization and cardiac sarcomeric contraction in this untreatable disease. Computational modeling of PKP2 variants reveals that the carboxy-terminal (CT) domain is required for N-terminal domain stabilization, which determines PKP2 cortical localization and function. In mutant PKP2 cells the expression of the interacting protein MYH10 rescues actomyosin disorganization. Conversely, dominant-negative MYH10 mutant expression mimics the pathogenic CT-deletion PKP2 mutant causing actin network abnormalities and right ventricle systolic dysfunction. A chemical activator of non-muscle myosins, 4-hydroxyacetophenone (4-HAP), also restores normal contractility. Our findings demonstrate that activation of MYH10 corrects the deleterious effect of PKP2 mutant over systolic cardiac contraction, with potential implications for ACM therapy.

Fear of Falling as a Behavioral Symptom in Neurocognitive Impaired Patients: Evidence from an Underrepresented Population.

BACKGROUND: Fear of falling (FoF) is a condition associated with falls, multi-morbidity, and functional impairment. To date it remains unknow which clinical, somatic, socio-demographic, behavioral, and emotional factors are associated with FoF and how these factors interact in people with Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). OBJECTIVE: Identify the association of FoF with clinical, socio-demographic, and neuropsychiatric factors in patients with AD and bvFTD. METHODS: We evaluated 98 participants, 58 with AD and 40 with bvFTD at mild or moderate stages and assess FoF using the Falls Efficacy Scale-International. Additionally, we analyzed cognitive, physical performance variables, functional impairment, and affective and behavioral symptoms associated with FoF using standardized scales and a regression model analysis. RESULTS: The prevalence of FoF in AD and bvFTD was 51% and 40%, respectively. In the AD group, physical performance [F (3, 53) = 4.318, p = 0.009], the behavioral symptoms model [F (19, 38) = 3.314, p = 0.001], and the anxiety model [F (1, 56) = 13.4, p≤0.01] showed statistically significant values. In addition, the presence of hallucinations assessed with the Neuropsychiatric Inventory and social behavior assessed with the Mild Behavioral Impairment Checklist were significant. In contrast, in the bvFTD group, a homologous group of models was evaluated but we did not find any significant results. CONCLUSION: FoF in people with AD was related to physical performance, neuropsychiatric symptoms such as apathy and hallucinations, and affective symptoms such as anxiety. However, this pattern was not seen in the bvFTD group, and therefore further studies are required.

Extracellular cysteine disulfide bond break at Cys122 disrupts PIP2-dependent Kir2.1 channel function and leads to arrhythmias in Andersen-Tawil Syndrome.

Background: Andersen-Tawil Syndrome Type 1 (ATS1) is a rare heritable disease caused by mutations in the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys122-to-Cys154 disulfide bond in the Kir2.1 channel structure is crucial for proper folding, but has not been associated with correct channel function at the membrane. We tested whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing the open state of the channel. Methods and Results: We identified a Kir2.1 loss-of-function mutation in Cys122 (c.366 A>T; p.Cys122Tyr) in a family with ATS1. To study the consequences of this mutation on Kir2.1 function we generated a cardiac specific mouse model expressing the Kir2.1C122Y mutation. Kir2.1C122Y animals recapitulated the abnormal ECG features of ATS1, like QT prolongation, conduction defects, and increased arrhythmia susceptibility. Kir2.1C122Y mouse cardiomyocytes showed significantly reduced inward rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking ability and localization at the sarcolemma and the sarcoplasmic reticulum. Kir2.1C122Y formed heterotetramers with wildtype (WT) subunits. However, molecular dynamic modeling predicted that the Cys122-to-Cys154 disulfide-bond break induced by the C122Y mutation provoked a conformational change over the 2000 ns simulation, characterized by larger loss of the hydrogen bonds between Kir2.1 and phosphatidylinositol-4,5-bisphosphate (PIP2) than WT. Therefore, consistent with the inability of Kir2.1C122Y channels to bind directly to PIP2 in bioluminescence resonance energy transfer experiments, the PIP2 binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch-clamping the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing PIP2 concentrations. Conclusion: The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential to channel function. We demonstrated that ATS1 mutations that break disulfide bonds in the extracellular domain disrupt PIP2-dependent regulation, leading to channel dysfunction and life-threatening arrhythmias.

Iodotyrosines Are Biomarkers for Preclinical Stages of Iodine-Deficient Hypothyroidism in Dehal1-Knockout Mice.

Background: Iodine is required for the synthesis of thyroid hormone (TH), but its natural availability is limited. Dehalogenase1 (Dehal1) recycles iodine from mono- and diiodotyrosines (MIT, DIT) to sustain TH synthesis when iodine supplies are scarce, but its role in the dynamics of storage and conservation of iodine is unknown. Methods: Dehal1-knockout (Dehal1KO) mice were generated by gene trapping. The timing of expression and distribution was investigated by X-Gal staining and immunofluorescence using recombinant Dehal1-beta-galactosidase protein produced in fetuses and adult mice. Adult Dehal1KO and wild-type (Wt) animals were fed normal and iodine-deficient diets for 1 month, and plasma, urine, and tissues were isolated for analyses. TH status was monitored, including thyroxine, triiodothyronine, MIT, DIT, and urinary iodine concentration (UIC) using a novel liquid chromatography with tandem mass spectrometry method and the Sandell-Kolthoff (S-K) technique throughout the experimental period. Results: Dehal1 is highly expressed in the thyroid and is also present in the kidneys, liver, and, unexpectedly, the choroid plexus. In vivo transcription of Dehal1 was induced by iodine deficiency only in the thyroid tissue. Under normal iodine intake, Dehal1KO mice were euthyroid, but they showed negative iodine balance due to a continuous loss of iodotyrosines in the urine. Counterintuitively, the UIC of Dehal1KO mice is twofold higher than that of Wt mice, indicating that S-K measures both inorganic and organic iodine. Under iodine restriction, Dehal1KO mice rapidly develop profound hypothyroidism, while Wt mice remain euthyroid, suggesting reduced retention of iodine in the thyroids of Dehal1KO mice. Urinary and plasma iodotyrosines were continually elevated throughout the life cycles of Dehal1KO mice, including the neonatal period, when pups were still euthyroid. Conclusions: Plasma and urine iodotyrosine elevation occurs in Dehal1-deficient mice throughout life. Therefore, measurement of iodotyrosines predicts an eventual iodine shortage and development of hypothyroidism in the preclinical phase. The prompt establishment of hypothyroidism upon the start of iodine restriction suggests that Dehal1KO mice have low iodine reserves in their thyroid glands, pointing to defective capacity for iodine storage.

Linfoma de células T/natural killer extranodal de tipo nasal enmascarado en una sinusopatia

Introducción: El linfoma de células T citotóxico/natural killer extranodal de tipo nasal es poco frecuente, pero con alta tasa de mortalidad. Las manifestaciones clínicas de la enfermedad pueden simular una infección de senos paranasales. Objetivo: Presentar las manifestaciones clínicas de un paciente de 34 años de edad con diagnóstico de linfoma de células T citotóxico/natural killer extranodal de tipo nasal. Caso clínico: Se presenta un paciente masculino de 34 años de edad con rinorrea verdosa fétida recurrente y obstrucción en fosa nasal derecha. En la evaluación inicial sugiere sinusitis crónica, sin embargo, debido al empeoramiento de las manifestaciones clínicas se realiza una tomografía computarizada que muestra lesiones sugestivas de infiltración neoplásica, una biopsia de la lesión confirma el diagnóstico de linfoma de células T/natural killer extranodal de tipo nasal. Conclusiones: Los linfomas de células T citotóxico/natural killer extranodal de tipo nasal son considerados neoplasias poco frecuentes, caracterizadas por el patrón rápidamente progresivo con afectación ósea; en su etapa inicial presenta manifestaciones clínicas similares a una sinusitis. La tomografía computarizada y la histopatología, son indispensables en el diagnóstico de la enfermedad.

Introduction: Nasal-type extranodal natural killer/cytotoxic T-cell lymphoma is rare but has a high mortality rate. The clinical manifestations of the disease can mimic a paranasal sinus infection. Objective: To present the clinical manifestations of a 34-year-old patient diagnosed with nasal-type extranodal natural killer/cytotoxic T-cell lymphoma. Clinical case: A 34-year-old male patient with recurrent greenish fetid rhinorrhea and obstruction in the right nostril is presented. In the initial evaluation, it suggests chronic sinusitis, however, due to the worsening of the clinical manifestations, a computed tomography is performed that shows lesions suggestive of neoplastic infiltration, a biopsy of the lesion confirms the diagnosis of T-cell lymphoma/extranodal natural killer. Conclusions: Nasal-type extranodal natural killer/cytotoxic T-cell lymphomas are considered rare neoplasms characterized by a rapidly progressive pattern with bone involvement; in its initial stage it presents clinical manifestations similar to sinusitis. Computed tomography and histopathology are essential in the diagnosis of the disease.

Solid supports and supported liquid membranes for different liquid phase microextraction and electromembrane extraction configurations. A review.

Liquid phase microextraction (LPME) and electromembrane microextraction (EME) can be considered as two of the most popular techniques in sample treatment today. Both techniques can be configurated as membrane-assisted techniques to carry out the extraction. These supports provide the required geometry and stability on the contact surface between two phases (donor and acceptor) and improve the reproducibility of sample treatment techniques. These solid support pore space, once is filled with organic solvents, act as a selective barrier acting as a supported liquid membrane (SLM). The SLM nature is a fundamental parameter, and its selection is critical to carry out successful extractions. There are numerous SLMs that have been successfully employed in a wide variety of application fields. The latter is due to the specificity of the selected organic solvents, which allows the extraction of compounds of a very different nature. In the last decade, solid supports and SLM have evolved towards "green" and environmentally friendly materials and solvents. In this review, solid supports implemented in LPME and EME will be discussed and summarized, as well as their applications. Moreover, the advances and modifications of the solid supports and the SLMs to improve the extraction efficiencies, recoveries and enrichment factors are discussed. Hollow fiber and flat membranes, including microfluidic systems, will be considered depending on the technique, configuration, or device used.

Assessment of visual function and the neuroretina in subjects diagnosed with congenital anomaly of color vision.

This cross-sectional and observational study includes 50 eyes of subjects with color blindness and 50 eyes of control subjects. Visual function (visual acuity, contrast sensitivity, and color vision) and neuroretinal structure were assessed in all subjects using optical coherence tomography (OCT). Significant thinning of the retinal nerve fiber layer, ganglion cell layer, and retina were observed in the color blindness group. Significant thinning was also recorded in layers that involve photoreceptor nuclei (between the outer limiting layer and the Bruch membrane and between the outer plexiform layer and the outer limiting membrane). OCT evaluation based on retinal segmentation is a rapid (5-10 minutes) non-invasive technique and seems to be a good biomarker of color blindness.

Beta-3 adrenergic receptor overexpression reverses aortic stenosis-induced heart failure and restores balanced mitochondrial dynamics.

Aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and heart failure (HF). There is a lack of therapies able to prevent/revert AS-induced HF. Beta3 adrenergic receptor (ß3AR) signaling is beneficial in several forms of HF. Here, we studied the potential beneficial effect of ß3AR overexpression on AS-induced HF. Selective ß3AR stimulation had a positive inotropic effect. Transgenic mice constitutively overexpressing human ß3AR in the heart (c-hß3tg) were protected from the development of HF in response to induced AS, and against cardiomyocyte mitochondrial dysfunction (fragmented mitochondria with remodeled cristae and metabolic reprogramming featuring altered substrate use). Similar beneficial effects were observed in wild-type mice inoculated with adeno-associated virus (AAV9) inducing cardiac-specific overexpression of human ß3AR before AS induction. Moreover, AAV9-hß3AR injection into wild-type mice at late disease stages, when cardiac hypertrophy and metabolic reprogramming are already advanced, reversed the HF phenotype and restored balanced mitochondrial dynamics, demonstrating the potential of gene-therapy-mediated ß3AR overexpression in AS. Mice with cardiac specific ablation of Yme1l (cYKO), characterized by fragmented mitochondria, showed an increased mortality upon AS challenge. AAV9-hß3AR injection in these mice before AS induction reverted the fragmented mitochondria phenotype and rescued them from death. In conclusion, our results step out that ß3AR overexpression might have translational potential as a therapeutic strategy in AS-induced HF.

Thyroid hormone regulators in human cerebral cortex development.

Brain development is critically dependent on the timely supply of thyroid hormones. The thyroid hormone transporters are central to the action of thyroid hormones in the brain, facilitating their passage through the blood-brain barrier. Mutations of the monocarboxylate transporter 8 (MCT8) cause the Allan-Herndon-Dudley syndrome, with altered thyroid hormone concentrations in the blood and profound neurological impairment and intellectual deficit. Mouse disease models have revealed interplay between transport, deiodination, and availability of T3 to receptors in specific cells. However, the mouse models are not satisfactory, given the fundamental differences between the mouse and human brains. The goal of the present work is to review human neocortex development in the context of thyroid pathophysiology. Recent developments in single-cell transcriptomic approaches aimed at the human brain make it possible to profile the expression of thyroid hormone regulators in single-cell RNA-Seq datasets of the developing human neocortex. The data provide novel insights into the specific cellular expression of thyroid hormone transporters, deiodinases, and receptors.

Rehabilitación del daño cerebral y unidades de convalecencia / Brain Injury Rehabilitation and Convalescent Units

Existe un consenso generalizado en cuanto que la atención del daño cerebral requiere la existencia de unidades y equipos especializados en dar una atención integral.La realidad es que existe una escasez de recursos para la atención de pacientes con daño cerebral, especialmente en cuanto a laexistencia de unidades específicas de neurorehabilitación o unidades de rehabilitación intensiva. A pesar de que la Congregación de Hermanas Hospitalarias cuenta con la Red Menni de daño cerebral no es suficientepara atender a todos los pacientes. Un número importante de pacientes son atendidos actualmente en unidades de convalecencia (centros afines de la Red Menni), los cuales no todos cuentan con un equipo multidisciplinar ni con la tecnología ni robótica necesaria. (AU)

There is a general consensus that carefor brain damage requires the existence ofunits and teamns specialized in providingcomprehensive care. The reality is that there is a shortage of resources for the care of patients with brain, especially regarding the existence of specific units of neurorehabilitation or intensive rehabilitation units.Even though the Congregation of SistersHospitallers has the Menni Network of brain damage not it is enough to take care of all the patiens.A significant number of patients they are currently cared for in convalescent units (related centers of the Red Menni), nota ll of which have a multidisciplinary tea mor the technology no robotics necessary. (AU)

Atherosclerosis Induced by Adeno-Associated Virus Encoding Gain-of-Function PCSK9.

Induction of atherosclerosis in mice with one or more genetic alterations (e.g., conditional deletion of a gene of interest) has traditionally required crossbreeding with Apoe or Ldlr deficient mice to achieve sufficient hypercholesterolemia. However, this procedure is time consuming and generates a surplus of mice with genotypes that are irrelevant for experiments. Several alternative methods exist that obviate the need to work in mice with germline-encoded hypercholesterolemia. In this chapter, we detail an efficient and increasingly used method to induce hypercholesterolemia in mice through adeno-associated virus-mediated transfer of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene.

Bioaccumulation of heavy metals and As in maize (Zea mays L) grown close to mine tailings strongly impacts plant development.

Potentially toxic metals and metalloids present in mining residues can affect ecosystems, particularly plant growth and development. In this study we evaluated heavy metal (Fe, Zn, Cu, Cd, Pb) and As contents in maize (Zea mays L) plants grown in soils collected near (40 m), at intermediate (400 m) and remote (3000 m) distances from mine tailings near Taxco City, Mexico. Soils sampled near and at intermediate sites from the tailings contained high levels of heavy metals which were 3- to 55-fold higher compared to the control samples. Heavy metal and As content in plants reflected the soil contamination being the greatest for most studied elements in root samples followed by stems, leaves, and kernels. Though plants were capable of completing their life cycle and producing the seeds, high bioaccumulation levels had a strong impact negatively on plant development. Abnormalities in the organs like malformations in reproductive structures (tassel and ear), reduction in the phytomer number and the plant height were present. Microscopic studies and morphometric analyses suggest that strongly affected plant growth result from negative and synergistic action of heavy metals and As in soils on cell growth and cell production. This study showed that maize grown near mine tailings accumulated high levels of heavy metals and As which decrease significantly plant yield and could be dangerous if it is consumed by animals and humans.

Tbx5 variants disrupt Nav1.5 function differently in patients diagnosed with Brugada or Long QT Syndrome.

AIMS: The transcription factor Tbx5 controls cardiogenesis and drives Scn5a expression in mice. We have identified two variants in TBX5 encoding p. D111Y and p. F206L Tbx5, respectively, in two unrelated patients with structurally normal hearts diagnosed with long QT (LQTS) and Brugada (BrS) syndrome. Here, we characterized the consequences of each variant to unravel the underlying disease mechanisms. METHODS AND RESULTS: We combined clinical analysis with in vivo and in vitro electrophysiological and molecular techniques in human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs), HL-1 cells, and cardiomyocytes from mice trans-expressing human wild-type (WT) or mutant proteins. Tbx5 increased transcription of SCN5A encoding cardiac Nav1.5 channels, while repressing CAMK2D and SPTBN4 genes encoding Ca/calmodulin kinase IIδ (CaMKIIδ) and ßIV-spectrin, respectively. These effects significantly increased Na current (INa) in hiPSC-CMs and in cardiomyocytes from mice trans-expressing Tbx5. Consequently, action potential (AP) amplitudes increased and QRS interval narrowed in the mouse electrocardiogram. p. F206L Tbx5 bound to the SCN5A promoter failed to transactivate it, thus precluding the pro-transcriptional effect of WT Tbx5. Therefore, p. F206L markedly decreased INa in hiPSC-CM, HL-1 cells and mouse cardiomyocytes. The INa decrease in p. F206L trans-expressing mice translated into QRS widening and increased flecainide sensitivity. p. D111Y Tbx5 increased SCN5A expression but failed to repress CAMK2D and SPTBN4. The increased CaMKIIδ and ßIV-spectrin significantly augmented the late component of INa (INaL) which, in turn, significantly prolonged AP duration in both hiPSC-CMs and mouse cardiomyocytes. Ranolazine, a selective INaL inhibitor, eliminated the QT and QTc intervals prolongation seen in p. D111Y trans-expressing mice. CONCLUSIONS: In addition to peak INa, Tbx5 critically regulates INaL and the duration of repolarization in human cardiomyocytes. Our original results suggest that TBX5 variants associate with and modulate the intensity of the electrical phenotype in LQTS and BrS patients.

Morphological characteristics and accumulation of arsenic in Argyrochosma formosa (Liebm.) Windham developed in a highly contaminated site with arsenic in Matehuala, SLP, México.

We studied the ability of Argyrochosma formosa growing in an arsenic heavily contaminated site to accumulate this metalloid; morphological characteristics and translocation of arsenic were evaluated in the organs. Population census of wild specimens of A. formosa was done, and 14 samples of ferns and rhizosphere soil were collected randomly. We recorded morphological characteristics with scanning electronic microscopy (SEM); concentrations of As in organs of fern plants (root, rhizome, and fronds) were evaluated with inductively coupled plasma-optic emission spectrometry (ICP-OES). Two hundred ninety-four individuals at different stages of development were identified, indicating the establishment of fern on the site. Morphological characteristics of A. formosa in fern plant organs did not show structural effects, compared with herbarium plants. Arsenic distribution in fern plant tissues was 192.2-763.6 mg/kg, 188-1017 mg/kg, and 113-2008 mg/kg, in roots, rhizomes, and fronds, respectively. The calculated bioaccumulation factor in fronds ranged from 2 to 7 and the translocation factor from 0.6 to 2.1. Our data suggest that A. formosa is an arsenic-tolerant species and propose it for phytoremediation on contaminated sites with As concentrations similar to that of the studied location. Further studies should be performed to evaluate the mechanisms of accumulation of As in plant tissues.