Human metapneumovirus: Mechanisms and molecular targets used by the virus to avoid the immune system

Indexación: Scopus.This work was supported by Comisión Nacional de Investigación Científica y Tecnolígica (CONICYT) N◦21151028 and FONDECYT (N◦1070352 and N◦1170964) and the Millennium Institute on Immunology and Immunotherapy (P09/016-F).Human metapneumovirus (hMPV) is a respiratory virus, first reported the year 2001. Since then, it has been described as one of the main etiological agents that causes acute lower respiratory tract infections (ALRTIs), which is characterized by symptoms such as bronchiolitis, wheezing and coughing. Susceptible population to hMPV-infection includes newborn, children, elderly and immunocompromised individuals. This viral agent is a negative-sense, single-stranded RNA enveloped virus, that belongs to the Pneumoviridae family and Metapneumovirus genus. Early reports-previous to 2001-state several cases of respiratory illness without clear identification of the responsible pathogen, which could be related to hMPV. Despite the similarities of hMPV with several other viruses, such as the human respiratory syncytial virus or influenza virus, mechanisms used by hMPV to avoid the host immune system are still unclear. In fact, evidence indicates that hMPV induces a poor innate immune response, thereby affecting the adaptive immunity. Among these mechanisms, is the promotion of an anergic state in T cells, instead of an effective polarization or activation, which could be induced by low levels of cytokine secretion. Further, the evidences support the notion that hMPV interferes with several pattern recognition receptors (PRRs) and cell signaling pathways triggered by interferon-associated genes. However, these mechanisms reported in hMPV are not like the ones reported for hRSV, as the latter has two non-structural proteins that are able to inhibit these pathways. Several reports suggest that viral glycoproteins, such as G and SH, could play immune-modulator roles during infection. In this work, we discuss the state of the art regarding the mechanisms that underlie the poor immunity elicited by hMPV. Importantly, these mechanisms will be compared with those elicited by other common respiratory viruses. © 2018 Frontiers Media S.A. All rights reserved.https://www.frontiersin.org/articles/10.3389/fimmu.2018.02466/ful

Asymmetric synthesis of (1R, 5S)-2-methyl-6, 7-benzomorphan via Aza-Prins reaction

(1R, 5S)-2-Methyl-6, 7-benzomorphan has been synthesised from (R)-(benzyloxy)(phenyl)acetaldehyde. On a 2-mmol scale Bi (OTf)3 promoted Aza-Prins reaction with N-tosylhomoallylamine afforded an 88/12 mixture of 6-oxa-2-azabicyclo[3.2.1]octanes. Major diastereoisomer was converted to enantiomerically pure (2S, 4S)-2-benzyl-1- methylpiperidin-4-ol via a high-yielding sequence hydrogenolysis/N-detosylation/N-methylation. Acid-catalysed intramolecular Friedel-Crafts cyclisation of the piperidinol afforded (1R, 5S)-2-methyl-6, 7-benzomorphan in five steps with a yield of 25%. © 2021 The Authors. Chirality published by Wiley Periodicals LLC

High-performance liquid chromatographic enantioseparation of unusual amino acid derivatives with axial chirality on polysaccharide-based chiral stationary phases

The successfulenantioseparationofaxiallychiralaminoacidderivativescontainingacyclohexylidene moiety onan an alyticalandsemipreparativescalewasachievedforthefirsttimebyHPLCusing polysaccharide-based chiral stationary phases. Racemicmethyl N-benzoylamino esters,easilyobtained by methanoly sisof the corresponding 5(4H)-oxazolones, were subject edtochiralHPLCresolutionusing chiral stationaryphasesbasedonimmobilized3,5-dimethylphenylcarbamatederivativesofamylose (Chiralpak® IA column)orcellulose(Chiralpak® IB column). The behaviour of both selectors under dif-ferent elution conditions was evaluated and compared. The amy los ecolumns howed better performance than the cellulose column for allenantiomers tested. These mi preparative resolution of axially chiral amino acidderivatives with different side chains has been achievedona 250mm×20mmIDChiralpak® IA columnusingtheappropriatemixtureof n-hexane/chlorofom/ethanol aseluent by successive injec-tions of asolution of the sample in chloroform. Using this protocol up to 120 m go feachenan tiomer of the correspondingaxiallychiralaminoacidderivativewereobtainedfrom300mgofracemate.[(Sa)-2a, 105 mg;(Ra)-2a, 60mg,[(Sa)-2b, 105mg;(Ra)-2b, 90mg,[(Sa)-2c, 120mg;(Ra)-2c, 100mg]

Complicaciones de los osteocondromas

Los osteocondromas o exostosis cartilaginosas son los tumores óseos más frecuentes, representando el 10-15 % de la totalidad. Parece ser más bien una alteración del desarrollo óseo más que un tumor verdadero. Suele tener una imagen radiográfica patognomónica. Los osteocondromas pueden ser solitarios o múltiples, estos últimos forman parte del síndrome de exostosis múltiples hereditarias, de transmisión autosómica dominante. Las complicaciones que pueden presentar, pueden ser óseas; deformidad del hueso donde asientan o fracturas del mismo, o de los tejidos que lo rodean, pudiendo provocar trastornos neurológicos, vasculares, bursitis, y la peor complicación, que es su malignización. Existen variantes de los osteocondromas como la exostosis subungueal, la displasia epifisaria hemimielica, y las exostosis en torreta y por tracción. Es importante conocer la apariencia radiológica de todos los tipos de exostosis, para diferenciarlas de sus posibles complicaciones.Osteochondroma, also termed osteocartlaginous exostoses represents the most common bone tumors and is a developmental lesion rather than a true neoplasm. It constitutes 10-15 % of all bone tumors. Its radiologic features are often pathognomonic. Osteochondromas may be solitary or multiple, the latter being associated with the autosomal dominant syndrome, hereditary multiple exostoses. Complications associated with osteochondroma include deformity, fracture, vascular compromise, neurologic sequelae, overlying bursa formation, and malignant transformation. Variant of osteochondroma include subungueal exostosis, dysplasia epiphysealis hemimelica, turret and traction exostoses. Recognition of the radiologic spectrum of appearances of osteochondroma and its variants allow prospective diagnosis and differentiation of the numerous potential complications

MC64-Cluster: Many-Core CPU Cluster Architecture and Performance Analysis in B-Tree Searches

The MC64-Cluster computer platform was designed, based on many-core CPU microprocessors: Tile64. MC64-Cluster architecture was outlined in terms of both hardware and software, including commands available to manage jobs and provided application programming interfaces to communicate and synchronize tiles, making this system easy to use. Massively, concurrent-searches of keys in B-trees, which are used in many applications, including bioinformatics, were used. Remarkable performance improvements were obtained when the cluster resources were combined with those available in host machine (hybrid or heterogeneous environments). These results were even more outstanding when analyzed in terms of performance-per-watt, highlighting their green-computing advantages. Together with the cluster architecture, they represent the main contributions of this work. To our knowledge, this is the first cluster implementation of this kind being developed

MC64-ClustalWP2: A Highly-Parallel Hybrid Strategy to Align Multiple Sequences in Many-Core Architectures

We have developed the MC64-ClustalWP2 as a new implementation of the Clustal W algorithm, integrating a novel parallelization strategy and significantly increasing the performance when aligning long sequences in architectures with many cores. It must be stressed that in such a process, the detailed analysis of both the software and hardware features and peculiarities is of paramount importance to reveal key points to exploit and optimize the full potential of parallelism in many-core CPU systems. The new parallelization approach has focused into the most time-consuming stages of this algorithm. In particular, the so-called progressive alignment has drastically improved the performance, due to a fine-grained approach where the forward and backward loops were unrolled and parallelized. Another key approach has been the implementation of the new algorithm in a hybrid-computing system, integrating both an Intel Xeon multi-core CPU and a Tilera Tile64 many-core card. A comparison with other Clustal W implementations reveals the high-performance of the new algorithm and strategy in many-core CPU architectures, in a scenario where the sequences to align are relatively long (more than 10 kb) and, hence, a many-core GPU hardware cannot be used. Thus, the MC64-ClustalWP2 runs multiple alignments more than 18x than the original Clustal W algorithm, and more than 7x than the best x86 parallel implementation to date, being publicly available through a web service. Besides, these developments have been deployed in cost-effective personal computers and should be useful for life-science researchers, including the identification of identities and differences for mutation/polymorphism analyses, biodiversity and evolutionary studies and for the development of molecular markers for paternity testing, germplasm management and protection, to assist breeding, illegal traffic control, fraud prevention and for the protection of the intellectual property (identification/traceability), including the protected designation of origin, among other applications

Resultados de la reparación quirúrgica Del ligamento deltoideo en las fracturas equivalentes bimaleolares

ObjetivoEl objetivo de este estudio es evaluar los resultados de la reparación quirúrgica del ligamento deltoideo en fracturas equivalente bimaleolares.Material y métodoEntre 2002 y 2009 fueron intervenidos 49 pacientes con fractura del maléolo peroneo y signos clásicos de lesión del ligamento deltoideo; finalmente se recuperaron para la revisión 44 pacientes. Se dividieron en 2 grupos: grupo A con 33 casos, en los que se reparó el ligamento deltoideo, y grupo B con 11 casos, donde el deltoideo fue tratado conservadoramente. Las fracturas fueron clasificadas según Lauge-Hansen y la AO/OTA. Para la valoración clínico-funcional se usó la escala de la American Orthopaedic Foot and Ankle Society (AOFAS) para el tobillo. Se registraron las complicaciones y reintervenciones.ResultadosTras un seguimiento medio de 12 meses, se obtuvo un resultado satisfactorio en ambos grupos, con una puntuación media final de 95 puntos en el grupo A y una de 94 en el grupo B, según la escala AOFAS. Hubo 2 infecciones, 1 intolerancia de la sutura medial, 1 algodistrofia y 4 casos precisaron retirada de material.ConclusionesNuestros resultados sugieren que la lesión del ligamento deltoideo puede ser reparada con buenos resultados funcionales. Y entendemos que, aunque los signos clásicos nos ayudan a sospechar la lesión, no son predictores fiables de la necesidad de reparación del lado medial.PurposeThe purpose of this study is to evaluate the result of surgical repair of deltoid ligament in fracture of the distal fibula upper or at the syndesmotic level.Materials and methodsBetween 2002 and 2009, 49 patients with distal fibula fractures and classical signs of deltoid ligament incompetence were operated, 44 were available for follow-up. Two groups: group A included 33 cases in whom deltoid ligament was treated by surgical repair, and group B, 11 cases who were treated conservatively. All fractures were classified according to Lauge-Hansen and AO/OTA. The AOFAS ankle score was used for clinical and functional evaluation. Complications and reinterventions were recorded.ResultsAt a mean follow-up of 12 months, a satisfactory functional result was obtained in both groups, with a mean final score of 95 points in group A and 94 in group B on the AOFAS scale. There were 2 infection, a medial suture intolerance, an algodystrophy and 4 hardware removed.ConclusionsOur findings suggest that a ruptured deltoid ligament can be repair with goods functional result. And we understand that although the classical signs help us to suspect a torn ligament, are not reliable predictors for surgical revision of the medial side

Design, synthesis and structure-activity evaluation of novel 2-pyridone-based inhibitors of a-synuclein aggregation with potentially improved BBB permeability

The treatment of Parkinson''s disease (PD), the second most common neurodegenerative human disorder, continues to be symptomatic. Development of drugs able to stop or at least slowdown PD progression would benefit several million people worldwide. SynuClean-D is a low molecular weight 2-pyridone-based promising drug candidate that inhibits the aggregation of a-synuclein in human cultured cells and prevents degeneration of dopaminergic neurons in a Caenorhabditis elegans model of PD. Improving SynuClean-D pharmacokinetic/pharmacodynamic properties, performing structure/activity studies and testing its efficacy in mammalian models of PD requires the use of gr-amounts of the compound. However, not enough compound is on sale, and no synthetic route has been reported until now, which hampers the molecule progress towards clinical trials. To circumvent those problems, we describe here an efficient and economical route that enables the synthesis of SynuClean-D with good yields as well as the synthesis of SynuClean-D derivatives. Structure-activity comparison of the new compounds with SynuClean-D reveals the functional groups of the molecule that can be disposed of without activity loss and those that are crucial to interfere with a-synuclein aggregation. Several of the derivatives obtained retain the parent''s compound excellent in vitro anti-aggregative activity, without compromising its low toxicity. Computational predictions and preliminary testing indicate that the blood brain barrier (BBB) permeability of SynuClean-D is low. Importantly, several of the newly designed and obtained active derivatives are predicted to display good BBB permeability. The synthetic route developed here will facilitate their synthesis for BBB permeability determination and for efficacy testing in mammalian models of PD. © 2021 The Author

Integrating local environmental data and information from non-driven citizen science to estimate jellyfish abundance in Costa del Sol (southern Spain)

Tourism, fishing and aquaculture are key economic sectors of Costa del Sol (southern Iberian Peninsula). The management of these activities is sometimes disturbed by the onshore arrival and stranding of jellyfish swarms. In the absence data on the occurrence of these organisms, it may be interesting to explore data from non-driven systems, such as social networks. The present study show how data in text format from a mobile app called Infomedusa can be processed and used to model the relationship between estimated abundance of jellyfish on the beaches and local environmental conditions. The data retrieved from this app using artificial intelligence procedures (transition network or TN algorithm), were used as input for GAM models to estimate the abundance of jellyfish based on wind speed and direction. The analysis of data provided by Infomedusa indicated that only 30.39% of messages provided by the users had information about absence/presence of jellyfishes in the beaches. On the other hand, the TN processing capacity showed an accuracy level to discriminate messages with information on absence/presence of jellyfish slightly higher than 80%. GAM models considering the wind direction and speed of previous day explained between 37% and 77% of the variance of jellyfish abundance estimate from Infomedusa data. In conclusion, this approach may contribute to the development of a system for predicting the onshore arrival of jellyfish in the Costa del Sol.Versión del edito