Viruses: Friends and Foes

In this chapter, we will review how viruses can be used to positively affect joints and cartilage of their hosts. Many viruses are arthrogenic, and cause persistent and debilitating arthritis. Even those viruses that are not typically arthrogenic can also cause bone lesions as secondary pathogenesis. Some of these foes include members of the alphaviruses, like chikungunya and Ross River viruses, the rubiviruses, such as rubella, and erythoparvoviruses, like parvovirus B19. Some more uncommon viruses, which can occasionally have detrimental effects on their hosts’ joints, include herpes simplex virus, varicella zoster, mumps, human cytomegalovirus, avian orthoreovirus, and caprine arthritis-encephalitis virus. Despite some viruses having negative impacts on cartilage and joints, others have been used as an effective means of gene therapy for bone and cartilage repair. We will take an in-depth look at the current therapeutic strategies for treating arthritis using various viral vectors

Mannose binding lectin is required for alphavirus-induced arthritis/myositis

Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within the muscle and joints, and prior studies have demonstrated that the host complement system contributes to development of disease. In this study, we have used a mouse model of RRV-induced disease to identify and characterize which complement activation pathways mediate disease progression after infection, and we have identified the mannose binding lectin (MBL) pathway, but not the classical or alternative complement activation pathways, as essential for development of RRV-induced disease. MBL deposition was enhanced in RRV infected muscle tissue from wild type mice and RRV infected MBL deficient mice exhibited reduced disease, tissue damage, and complement deposition compared to wild-type mice. In contrast, mice deficient for key components of the classical or alternative complement activation pathways still developed severe RRV-induced disease. Further characterization of MBL deficient mice demonstrated that similar to C3(-/-) mice, viral replication and inflammatory cell recruitment were equivalent to wild type animals, suggesting that RRV-mediated induction of complement dependent immune pathology is largely MBL dependent. Consistent with these findings, human patients diagnosed with RRV disease had elevated serum MBL levels compared to healthy controls, and MBL levels in the serum and synovial fluid correlated with severity of disease. These findings demonstrate a role for MBL in promoting RRV-induced disease in both mice and humans and suggest that the MBL pathway of complement activation may be an effective target for therapeutic intervention for humans suffering from RRV-induced arthritis and myositis.This work was supported by NIH/NIAMS R01 AR 047190 awarded to MTH

Nanotribology and electrical properties of carbon nanotubes hybridized with covalent organic frameworks

Nanomanipulation of molecular materials such as carbon nanotubes (CNTs) or new covalent organic frameworks (COFs) is key not only for the study of their fundamental physicochemical properties, but also for building and probing nanodevices. Therefore, we have investigated the tribological properties of oxidized MWCNTs (ox-MWCNTs) and their hybridization with COF building blocks (ox-MWCNTs@COF) adsorbed on a mica surface. We used the AFM tip to apply torsional forces on individual nanotubes. Depending on the manipulation parameters, the lateral displacements of the AFM tip slide and/or bend nanotubes enabling the direct quantification of the nanotube-mica adhesion. We found striking changes in the behaviour of the lateral force needed to manipulate each carbon nanotube variant which indicates an increased adhesion of ox-MWCNTs@COF with respect to ox-MWCNTs (∼10x). In addition, the use of the AFM tip as a mobile electrode enabled the measurement of electrical transport through individual nanotubes that revealed a rectifying behaviour of the ox-MWCNTs@COF with high resistivity, which was in contrast with the near ohmic performance of ox-MWCNTsP. J.d.P. acknowledges support by grants from the Ministerio de Ciencia e Innovacion (FIS2017- 89549-R; “Maria de Maeztu” Program for Units of Excellence in R&D MDM2014-0377; and FIS2017-90701- REDT) and the Human Frontiers Science Program (HFSPO RGP0012/ 2018). R. M. ackowledges support by grant PID2019-110637RB-10

Characterisation of neuronal and glial populations of the visual system during zebrafish lifespan

[EN] During visual system morphogenesis, several cell populations arise at different time points correlating with the expression of specific molecular markers We have analysed the distribution pattern of three molecular markers (zn-1, calretinin and glial fibrillary acidic protein) which are involved in the development of zebrafish retina and optic tectum. Zn-1 is a neural antigen expressed in the developing zebrafish central nervous system. Calretinin is the first calcium-binding protein expressed in the central nervous system of vertebrates and it is widely distributed in different neuronal populations of vertebrate retina, being a valuable marker for its early and late development. Glial fibrillary acidic protein (GFAP), which is an astroglial marker, is a useful tool for characterising the glial environment in which the optic axons develop. We describe the expression profile changes in these three markers throughout the zebrafish lifespan with special attention to ganglion cells and their projections. Zn-1 is expressed in the first postmitotic ganglion cells of the retina. Calretinin is observed in the ganglion and amacrine cells of the retina in neurons of different tectal bands and in axons of retinofugal projections. GFAP is localised in the endfeet of Müller cells and in radial processes of the optic tectum after hatching. A transient expression of GFAP in the optic nerve, coinciding with the arrival of the first calretinin-immunoreactive optic axons, is observed. As axonal growth occurs in these regions of the zebrafish visual pathway (retina and optic tectum)throughout the lifespan, a relationship between GFAP expression and the correct arrangement of the first optic axons may exist. In conclusion we provide valuable neuroanatomical data about the best characterised sensorial pathway to be used in further studies such as teratology and toxicology

Localization of mRNA of two types of somatolactin, growth hormone, and prolactin in the pituitary of gilthead seabream Sparus auratus L., 1758

The mRNA expression of two types of somatolactin (SL1 and SL2), growth hormone (GH), and prolactin (PRL) were analysed by in situ non-radioactive hybridization (ISH) in the pituitary of gilthead sea bream Sparus auratus L., 1758. The different SL probes used, 5' end labelled with biotin or dioxygenin, showed a strong signal, mainly in the pars intermedia (PI) of the pituitary gland. We found, for the first time, cells that co-express both SL forms. Furthermore, the GH and PRL oligoprobes showed signs of hybridization in the proximal pars distalis (PPD) and rostral pars distalis (RPD), respectively. Moreover, the study of specimens of three ages and different sizes, produced by asynchronic growth of the S. aurata under commercial farming conditions, found no qualitative differences in the levels of expression of these two SL forms.Se analizó, por hibridación in situ (HIS) no radiactiva, la expresión de ARNm de los dos tipos de somatolactina (SL1 y SL2), hormona de crecimiento (GH) y prolactina (PRL) en hipófisis de dorada Sparus auratus L., 1758. Las distintas oligosondas de somatolactina (SL) empleadas, marcadas en su extremo 5' con biotina o digoxigenina, presentaron una fuerte señal, fundamentalmente en la pars intermedia (PI) de la glándula pituitaria, detectándose, por primera vez, células que coexpresan ambas formas. Por otra parte, las oligosondas de GH y PRL mostraron señales de hibridación en la proximal pars distalis (PPD) y rostral pars distalis (RPD), respectivamente. Además, en el estudio de animales con tres edades y tallas diferentes, producidos por el crecimiento asincrónico de la dorada en cultivo industrial, no se observaron diferencias cualitativas en los niveles de expresión de estas dos formas de SL.Instituto Español de Oceanografí

Mutation of a Conserved Nuclear Export Sequence in Chikungunya Virus Capsid Protein Disrupts Host Cell Nuclear Import

Transmitted by mosquitoes; chikungunya virus (CHIKV) is responsible for frequent outbreaks of arthritic disease in humans. CHIKV is an arthritogenic alphavirus of the Togaviridae family. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleus. In encephalitic alphaviruses nuclear translocation induces host cell shut off; however, the role of capsid protein nuclear localisation in arthritogenic alphaviruses remains unclear. Using replicon systems, we investigated a nuclear export sequence (NES) in the N-terminal region of capsid protein; analogous to that found in encephalitic alphavirus capsid but uncharacterised in CHIKV. The chromosomal maintenance 1 (CRM1) export adaptor protein mediated CHIKV capsid protein export from the nucleus and a region within the N-terminal part of CHIKV capsid protein was required for active nuclear targeting. In contrast to encephalitic alphaviruses, CHIKV capsid protein did not inhibit host nuclear import; however, mutating the NES of capsid protein (∆NES) blocked host protein access to the nucleus. Interactions between capsid protein and the nucleus warrant further investigation

Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen

Re-emergence of chikungunya virus, a mosquito-transmitted pathogen, is of serious public health concern. In the past 15 years, after decades of infrequent, sporadic outbreaks, the virus has caused major epidemic outbreaks in Africa, Asia, the Indian Ocean, and more recently the Caribbean and the Americas. Chikungunya virus is mainly transmitted by Aedes aegypti mosquitoes in tropical and subtropical regions, but the potential exists for further spread because of genetic adaptation of the virus to Aedes albopictus, a species that thrives in temperate regions. Chikungunya virus represents a substantial health burden to affected populations, with symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. The inflammatory response coincides with raised levels of immune mediators and infiltration of immune cells into infected joints and surrounding tissues. Animal models have provided insights into disease pathology and immune responses. Although host innate and adaptive responses have a role in viral clearance and protection, they can also contribute to virus-induced immune pathology. Understanding the mechanisms of host immune responses is essential for the development of treatments and vaccines. Inhibitory compounds targeting key inflammatory pathways, as well as attenuated virus vaccines, have shown some success in animal models, including an attenuated vaccine strain based on an isolate from La Reunion incorporating an internal ribosome entry sequence that prevents the virus from infecting mosquitoes and a vaccine based on virus-like particles expressing envelope proteins. However, immune correlates of protection, as well as the safety of prophylactic and therapeutic candidates, are important to consider for their application in chikungunya infections. In this Review, we provide an update on chikungunya virus with regard to its epidemiology, molecular virology, virus-host interactions, immunological responses, animal models, and potential antiviral therapies and vaccines

Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation

10.1371/journal.ppat.1004649PLoS Pathogens11

Solar energetic electron events measured by MESSENGER and Solar Orbiter. Peak intensity and energy spectrum radial dependences: statistical analysis

Context/Aims: We present a list of 61 solar energetic electron (SEE) events measured by the MESSENGER mission and the radial dependences of the electron peak intensity and the peak-intensity energy spectrum. The analysis comprises the period from 2010 to 2015, when MESSENGER heliocentric distance varied between 0.31 and 0.47 au. We also show the radial dependencies for a shorter list of 12 SEE events measured in February and March 2022 by spacecraft near 1 au and by Solar Orbiter around its first close perihelion at 0.32 au. Results: Due to the elevated background intensity level of the particle instrument on board MESSENGER, the SEE events measured by this mission are necessarily large and intense; most of them accompanied by a CME-driven shock, being widespread in heliolongitude, and displaying relativistic ($\sim$1 MeV) electron intensity enhancements. The two main conclusions derived from the analysis of the large SEE events measured by MESSENGER, which are generally supported by Solar Orbiter's data results, are: (1) There is a wide variability in the radial dependence of the electron peak intensity between $\sim$0.3 au and $\sim$1 au, but the peak intensities of the energetic electrons decrease with radial distance from the Sun in 27 out of 28 events. On average and within the uncertainties, we find a radial dependence consistent with $R^{-3}$. (2) The electron spectral index found in the energy range around 200 keV ($\delta$200) of the backward-scattered population near 0.3 au measured by MESSENGER is harder in 19 out of 20 (15 out of 18) events by a median factor of $\sim$20% ($\sim$10%) when comparing to the anti-sunward propagating beam (backward-scattered population) near 1 au.Comment: 20 pages, 13 figure

Chatbots in social networks for the timely support of university students with attention-deficit/hyperactivity disorder symptoms

Se estima que la prevalencia del trastorno por déficit de atención con hiperactividad (TDAH) en estudiantes universitarios es del 2 al 4.5% pero varía de una universidad a otra. Sin embargo, muchos estudiantes evitan acudir a tratamiento por ansiedad, temor al estigma, porque sienten que los problemas de los otros son mayores que los propios o bien desconocen la sintomatología del TDAH. En esta contribución se presenta el diseño e implementación de un chatbot para la aplicación del cuestionario Adult Self Report Scale-Versión 1.1 (EATDAH-A) así como los resultados de la aplicación del mismo y la opinión de los usuarios en cuanto a su utilidad y experiencia como usuario.It is estimated that the prevalence of Attention Deficit Hyperactivity Disorder (ADHD) in university students is from 2 to 4.53% but varies from one university to another. However, many students avoid therapies due to grief, nervousness, fear, or because they feel that the problems of others are greater than their own or they are unaware of the symptoms of ADHD. This contribution presents the design and implementation of a chatbot for the application of the Adult Self Report Scale-Version 1.1 (ASRS v1.1) questionnaire as well as the results of its application and the opinion of users regarding its usefulness and user experience.Facultad de Informátic