The Global Phosphorylation Landscape of SARS-CoV-2 Infection.

The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.

Clinical applications of allografts in foot and ankle surgery.

PURPOSE: The purpose of this review is to systematically analyse current literature on the use of allografts in the surgical treatment of foot and ankle disorders in adult patients. Based on this study, we propose evidence-based recommendations. METHODS: The database for PubMed was searched for all published articles. No timeframe restrictions were applied. Clinical studies eligible for inclusion met the following criteria: performed on patients over 18 years old; subject to surgical treatment of foot and ankle disorders; with report on the outcome of the use of allografts; with a report and assessment of pain and function, or equivalent; minimum follow-up of 1 year was required. Two reviewers independently screened and selected studies for full-text analysis from title and abstract. 107 studies were included from 1113 records. Studies were grouped according to surgical indications into ten categories: musculoskeletal tumours (n = 16), chronic ankle instability (n = 15), ankle arthritis (n = 14), osteochondral lesions of the talus (n = 12), Achilles tendon defects (n = 11), other tendon defects (n = 9), fusions (n = 9), fractures (n = 8), hallux rigidus (n = 3) and other indications (n = 10). RESULTS: Most studies displayed evidence level of IV (n = 57) and V (n = 39). There was one level I, one level II and nine level III studies. Most studies reported allografting as a good option (n = 99; 92.5%). Overall complication rate was 17% (n = 202). CONCLUSIONS: Fair evidence (Grade B) was found in favour of the use of allografts in lateral ankle ligament reconstruction or treatment of intra-articular calcaneal fracture. Fair evidence (Grade B) was found against the use of allogeneic MSCs in tibiotalar fusions. LEVEL OF EVIDENCE: V.

A disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects.

Failure of septation of the interventricular septum (IVS) is the most common congenital heart defect (CHD), but mechanisms for patterning the IVS are largely unknown. We show that a Tbx5+/Mef2cAHF+ progenitor lineage forms a compartment boundary bisecting the IVS. This coordinated population originates at a first- and second heart field interface, subsequently forming a morphogenetic nexus. Ablation of Tbx5+/Mef2cAHF+ progenitors cause IVS disorganization, right ventricular hypoplasia and mixing of IVS lineages. Reduced dosage of the CHD transcription factor TBX5 disrupts boundary position and integrity, resulting in ventricular septation defects (VSDs) and patterning defects, including Slit2 and Ntn1 misexpression. Reducing NTN1 dosage partly rescues cardiac defects in Tbx5 mutant embryos. Loss of Slit2 or Ntn1 causes VSDs and perturbed septal lineage distributions. Thus, we identify essential cues that direct progenitors to pattern a compartment boundary for proper cardiac septation, revealing new mechanisms for cardiac birth defects.

Zinc accumulation in Atriplex lentiformis is driven by plant genes and the soil microbiome.

Successful phytoremediation of acidic metal-contaminated mine tailings requires amendments to condition tailings properties prior to plant establishment. This conditioning process is complex and includes multiple changes in tailings bio-physico-chemical properties. The objective of this project is to identify relationships between tailings properties, the soil microbiome, and plant stress response genes during growth of Atriplex lentiformis in compost-amended (10 %, 15 %, 20 % w/w) mine tailings. Analyses include RNA-Seq for plant root gene expression, 16S rRNA amplicon sequencing for bacterial/archaeal communities, metal concentrations in both tailings and plant organs, and phenotypic measures of plant stress. Zn accumulation in A. lentiformis leaves varied with compost levels and was the highest in the intermediate treatment (15 %, TC15). Microbial analysis identified Alicyclobacillus, Hydrotalea, and Pseudolabrys taxa with the highest relative abundance in TC15, and these taxa were strongly associated with Zn accumulation. Furthermore, we identified 190 root genes with significant gene expression changes. These root genes were associated with different pathways including, abscisic acid and auxin signaling, defense responses, ion channels, metal ion binding, oxidative stress, transcription regulation, and transmembrane transport. However, root gene expression changes were not driven by the increasing levels of compost. For example, there were 15 genes that were up-regulated in TC15, whereas 106 genes were down-regulated in TC15. The variables analyzed explained 86 % of the variance in Zn accumulation in A. lentiformis leaves. Importantly, Zn accumulation was driven by Zn shoot concentrations, leaf stress symptoms, plant root genes, and microbial taxa. Therefore, our results suggest there are strong plant-microbiome associations that drive Zn accumulation in A. lentiformis and different plant gene pathways are involved in alleviating varying levels of metal stress. Future work is needed to gain a mechanistic understanding of these plant-microbiome interactions to optimize phytoremediation strategies as they will govern the success or failure of the revegetation process.

Mental health consequences of the COVID-19 pandemic associated with social isolation / Consecuencias de la pandemia de la COVID-19 en la salud mental asociadas al aislamiento social

Abstract The 2019 coronavirus pandemic (COVID-19) is a public health emergency of international concern, which poses a major challenge to mental health as a result of its unprecedented impact in this 21st century. Research in past epidemics has revealed a deep and wide range of psychosocial consequences at the individual and collective level. There are multiple associated psychological disturbances, ranging from isolated symptoms to complex disorders with marked impairment of functionality, such as insomnia, anxiety, depression, and post-traumatic stress disorder. Therefore, it is necessary for mental health services to develop strategies that allow them to react skillfully and provide support to health workers and the affected population so as to reduce the psychological impact as well as the development of psychiatric symptoms. The purpose of this reflection article is to show the possible consequences on the mental health of the population as a result of social isolation due to the COVID-19 pandemic.

Resumen La pandemia por coronavirus 2019 (COVID-19) es una emergencia de salud pública de preocupación internacional, con impactos sin precedentes en el siglo XXI y hoy representa un gran desafío a la salud mental. Estudios en epidemias anteriores han revelado una profunda y amplia gama de consecuencias psicosociales a nivel individual y comunitario durante los brotes. Son múltiples las alteraciones psicológicas asociadas, que van desde síntomas aislados hasta trastornos complejos, con un deterioro marcado de la funcionalidad, como insomnio, ansiedad, depresión y trastorno por estrés postraumático. En este contexto es necesario que las entidades de salud mental desarrollen estrategias que permitan reaccionar con destreza y que logren un soporte al personal de salud y a la población afectada, en aras de reducir el impacto psicológico y de los síntomas psiquiátricos. Este artículo de reflexión tiene por objetivo mostrar las posibles consecuencias en la salud mental de la población, como resultado del aislamiento social debido a la pandemia de la COVID-19.

Biotenodesis con tensor de fascia lata. técnica extraarticular / Biotenodesis with fascia lata tensor

Las biotenodesis con tensor de fascia lata para el tratamiento de las inestabilidades por insuficiencia del ligamento cruzado anterior han sido utilizadas con muy buenos resultados durante muchísimos años. Tuvieron su máximo apogeo entre los años 1975 y 1985, siendo prácticamente olvidadas por la mayoría de los cirujanos con la llegada de las técnicas de reconstrucción intraarticulares artroscópicas. En los últimos años luego de la descripción de un “viejo-nuevo” ligamento anterolateral de la rodilla, han tenido un nuevo auge si bien debe mencionarse claramente que la técnica de Lemaire no reconstruye este ligamento. Esta técnica resulta sumamente útil cuando se la asocia con plásticas intraarticulares en revisiones o insuficiencias luego de una plástica primaria del LCA, o como procedimiento único en pacientes de más de 50 años con bajo nivel de exigencia física, en virtud que presentan una muy baja morbilidad y una rehabilitación más rápida en relación a las plásticas intraarticulares. Tipo de estudio: Técnica Quirúrgica. Nivel de evidencia: V.

The biotenodesis with fascia lata tensor for the treatment of instabilities due to insufficiency of the anterior cruciate ligament have been used with very good results for many years. In recent years after the description of an “old-new” anterolateral ligament of the knee have had a new boom although it should be clearly stated that the technique of Lemaire does not reconstruct this ligament. Anatomical repairs and details of surgical technique are described. This technique is extremely useful when it is associated with intraarticular plastics in revisions or insufficiencies after primary plastic surgery of the ACL or as a single procedure in patients over 50 years of age with a low level of physical requirement because they present a very low morbidity and one Rehabilitation in relation to intra-articular plastic. Type of study: Surgical Technique. Level of Evidence: V.