Neuroinflammation and Neurodegeneration

Pathophysiological processes of neurodegenerative diseases are not clearly defined. However, an important body of evidence points toward the role of various inflammatory processes. The microglial cell is the main representative of the immune system in the central nervous system (CNS). This cell type can sense foreign or harmful pathogens and trigger its own activation and the generation of neuroinflammatory processes through phagocytosis and the release of cytokines, in order to maintain the cellular microenvironment. However, after maintaining a permanent state of activation due to sustained stimulation over time, microglial cells may generate a focus of persistent inflammation that in some cases precedes or enhances the neurodegenerative process. Thus, neuroinflammatory microenvironment becomes toxic and harmful for the neuronal cell, which degenerates and releases various factors that in turn activate the inflammatory response of microglia, potentiating the neurodegenerative cycle. In this chapter, we discuss the evidence on the role of microglial cell activation in neurodegenerative conditions and the association between neuroinflammatory processes and age-related neurological diseases. Finally, we outline how this new approach can help us to find new ways to understand neurodegenerative processes and to orientate the search for new therapies

The Trans-Neptunian Object (84922) 2003 VS2 through Stellar Occultations

We present results from three world-wide campaigns that resulted in the detections of two single-chord and one multi-chord stellar occultations by the plutino object (84922) 2003 VS2. From the single-chord occultations in 2013 and 2014 we obtained accurate astrometric positions for the object, while from the multi-chord occultation on 2014 November 7, we obtained the parameters of the best-fitting ellipse to the limb of the body at the time of occultation. We also obtained short-term photometry data for the body in order to derive its rotational phase during the occultation. The rotational light curve present a peak-to-peak amplitude of 0.141 ± 0.009 mag. This allows us to reconstruct the 3D shape of the body, with principal semi-axes of a = 313.8 ± 7.1 km, = - + b 265.5 9.8 8.8 km, and = - + c 247.3 43.6 26.6 km, which is not consistent with a Jacobi triaxial equilibrium figure. The derived spherical volume equivalent diameter of - + 548.3 44.6 29.5 km is about 5% larger than the radiometric diameter of 2003 VS2 derived from Herschel data of 523 ± 35 km, but still compatible with it within error bars. From those results we can also derive the geometric albedo ( - + 0.123 0.014 0.015) and, under the assumption that the object is a Maclaurin spheroid, the density r = - + 1400 300 1000 for the plutino. The disappearances and reappearances of the star during the occultations do not show any compelling evidence for a global atmosphere considering a pressure upper limit of about 1 microbar for a pure nitrogen atmosphere, nor secondary features (e.g., rings or satellite) around the main body.Fil: Benedetti Rossi, Gustavo. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil. Centre National de la Recherche Scientifique. Observatoire de Paris; Francia. Laboratório Interinstitucional de e-Astronomia; BrasilFil: Santos Sanz, P.. Instituto de Astrofísica de Andalucía; EspañaFil: Ortiz, J. L.. Instituto de Astrofísica de Andalucía; EspañaFil: Assafin, M.. Observatório do Valongo; BrasilFil: Sicardy, B.. Sorbonne University; Francia. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Morales, N.. Instituto de Astrofísica de Andalucía; EspañaFil: Vieira Martins, R.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil. Laboratório Interinstitucional de e-Astronomia; Brasil. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Duffard, R.. Instituto de Astrofísica de Andalucía; EspañaFil: Braga Ribas, F.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil. Laboratório Interinstitucional de e-Astronomia; Brasil. Centre National de la Recherche Scientifique. Observatoire de Paris; Francia. Universidade Tecnologia Federal do Parana; BrasilFil: Rommel, F. L.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil. Laboratório Interinstitucional de e-Astronomia; BrasilFil: Camargo, J. I. B.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil. Laboratório Interinstitucional de e-Astronomia; BrasilFil: Desmars, J.. Instituto de Astrofísica de Andalucía; EspañaFil: Colas, A. F.. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Vachier, F.. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Alvarez Candal, A.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; BrasilFil: Fernández Valenzuela, E.. University of Central Florida; Estados UnidosFil: Almenares, L.. Universidad de la Republica; UruguayFil: Artola, R.. Estación Astrofísica de Bosque Alegre; ArgentinaFil: Baum, T. P.. Observatoire Astronomique des Makes; FranciaFil: Behrend, R.. Observatoire de Genève; ItaliaFil: Bérard, D.. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Bianco, F. B.. University of Delaware; Estados Unidos. University of New York; Estados UnidosFil: Brosch, N.. Universitat Tel Aviv; IsraelFil: Ceretta, A.. Observatorio Astronómico Los Molinos; UruguayFil: Colazo, C. A.. Estación Astrofísica de Bosque Alegre; ArgentinaFil: Gomes Junior, A. R.. Laboratório Interinstitucional de e-Astronomia; Brasil. Universidade Estadual Paulista Julio de Mesquita Filho. Faculdade de Engenharia; BrasilFil: Ivanov, V. D.. Observatorio Europeo del Sur; AlemaniaFil: Jehin, E.. Université de Liège; BélgicaFil: Kaspi, S.. Universitat Tel Aviv; IsraelFil: Gil Hutton, Ricardo Alfredo. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Geofísica y Astronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Complejo Astronómico "El Leoncito". Universidad Nacional de Córdoba. Complejo Astronómico "El Leoncito". Universidad Nacional de la Plata. Complejo Astronómico "El Leoncito". Universidad Nacional de San Juan. Complejo Astronómico "El Leoncito"; Argentin

The effect of an autologous cellular gel-matrix integrated implant system on wound healing

<p>Abstract</p> <p>Background</p> <p>This manuscript reports the production and preclinical studies to examine the tolerance and efficacy of an autologous cellular gel-matrix integrated implant system (IIS) aimed to treat full-thickness skin lesions.</p> <p>Methods</p> <p>The best concentration of fibrinogen and thrombin was experimentally determined by employing 28 formula ratios of thrombin and fibrinogen and checking clot formation and apparent stability. IIS was formed by integrating skin cells by means of the <it>in situ </it>gelification of fibrin into a porous crosslinked scaffold composed of chitosan, gelatin and hyaluronic acid. The <it>in vitro </it>cell proliferation within the IIS was examined by the MTT assay and PCNA expression. An experimental rabbit model consisting of six circular lesions was utilized to test each of the components of the IIS. Then, the IIS was utilized in an animal model to cover a 35% body surface full thickness lesion.</p> <p>Results</p> <p>The preclinical assays in rabbits demonstrated that the IIS was well tolerated and also that IIS-treated rabbit with lesions of 35% of their body surface, exhibited a better survival rate (p = 0,06).</p> <p>Conclusion</p> <p>IIS should be further studied as a new wound dressing which shows promising properties, being the most remarkable its good biological tolerance and cell growth promotion properties.</p

Spectroscopic confirmation of CEERS NIRCam-selected galaxies at z≃8−10\boldsymbol{z \simeq 8-10}

We present JWST/NIRSpec prism spectroscopy of seven galaxies selected from the Cosmic Evolution Early Release Science Survey (CEERS) NIRCam imaging with photometric redshifts z_phot>8. We measure emission line redshifts of z=7.65 and 8.64 for two galaxies, and z=9.77(+0.37,-0.29) and 10.01(+0.14,-0.19) for two others via the detection of continuum breaks consistent with Lyman-alpha opacity from a mostly neutral intergalactic medium. The presence (absense) of strong breaks (strong emission lines) give high confidence that these two galaxies are at z>9.6, but the break-derived redshifts have large uncertainties given the low spectral resolution and relatively low signal-to-noise of the CEERS NIRSpec prism data. The two z~10 sources are relatively luminous (M_UV<-20), with blue continua (-2.3<beta<-1.9) and low dust attenuation (A_V=0.15(+0.3,-0.1)); and at least one of them has high stellar mass for a galaxy at that redshift (log(M_*/M_sol)=9.3(+0.2,-0.3)). Considered together with spectroscopic observations of other CEERS NIRCam-selected high-z galaxy candidates in the literature, we find a high rate of redshift confirmation and low rate of confirmed interlopers (8.3%). Ten out of 34 z>8 candidates with CEERS NIRSpec spectroscopy do not have secure redshifts, but the absence of emission lines in their spectra is consistent with redshifts z>9.6. We find that z>8 photometric redshifts are generally in agreement (within uncertainties) with the spectroscopic values. However, the photometric redshifts tend to be slightly overestimated (average Delta(z)=0.50+/-0.12), suggesting that current templates do not fully describe the spectra of very high-z sources. Overall, our results solidifies photometric evidence for a high space density of bright galaxies at z>8 compared to theoretical model predictions, and further disfavors an accelerated decline in the integrated UV luminosity density at z>8.Comment: Submitted to ApJL. 24 pages, 9 figures, 7 tables. File with Table 6 included in source .tar fil

Multiplex Real-Time PCR Assay Using TaqMan Probes for the Identification of Trypanosoma cruzi DTUs in Biological and Clinical Samples

Background: Trypanosoma cruzi has been classified into six Discrete Typing Units (DTUs), designated as TcI–TcVI. In order to effectively use this standardized nomenclature, a reproducible genotyping strategy is imperative. Several typing schemes have been developed with variable levels of complexity, selectivity and analytical sensitivity. Most of them can be only applied to cultured stocks. In this context, we aimed to develop a multiplex Real-Time PCR method to identify the six T. cruzi DTUs using TaqMan probes (MTq-PCR).Methods/Principal Findings: The MTq-PCR has been evaluated in 39 cultured stocks and 307 biological samples from vectors, reservoirs and patients from different geographical regions and transmission cycles in comparison with a multi-locus conventional PCR algorithm. The MTq-PCR was inclusive for laboratory stocks and natural isolates and sensitive for direct typing of different biological samples from vectors, reservoirs and patients with acute, congenital infection or Chagas reactivation. The first round SL-IR MTq-PCR detected 1 fg DNA/reaction tube of TcI, TcII and TcIII and 1 pg DNA/reaction tube of TcIV, TcV and TcVI reference strains. The MTq-PCR was able to characterize DTUs in 83% of triatomine and 96% of reservoir samples that had been typed by conventional PCR methods. Regarding clinical samples, 100% of those derived from acute infected patients, 62.5% from congenitally infected children and 50% from patients with clinical reactivation could be genotyped. Sensitivity for direct typing of blood samples from chronic Chagas disease patients (32.8% from asymptomatic and 22.2% from symptomatic patients) and mixed infections was lower than that of the conventional PCR algorithm.Conclusions/Significance: Typing is resolved after a single or a second round of Real-Time PCR, depending on the DTU. This format reduces carryover contamination and is amenable to quantification, automation and kit production.This work received financial support from the Ministry of Science and Technology of Argentina [PICT 2011-0207 to AGS] and the National Scientific and Technical Research Council in Argentina (CONICET) [PIP 112 2011-010-0974 to AGS]. Work related to evaluation of biological samples was partially sponsored by the Pan-American Health Organization (PAHO) [Small Grants Program PAHO-TDR]; the Drugs and Neglected Diseases Initiative (DNDi, Geneva, Switzerland), Wellcome Trust (London, United Kingdom), SANOFI-AVENTIS (Buenos Aires, Argentina) and the National Council for Science and Technology in Mexico (CONACYT) [FONSEC 161405 to JMR]

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio

Combination of novel and public RNA-seq datasets to generate an mRNA expression atlas for the domestic chicken

Background: The domestic chicken (Gallus gallus) is widely used as a model in developmental biology and is also an important livestock species. We describe a novel approach to data integration to generate an mRNA expression atlas for the chicken spanning major tissue types and developmental stages, using a diverse range of publicly-archived RNA-seq datasets and new data derived from immune cells and tissues. Results: Randomly down-sampling RNA-seq datasets to a common depth and quantifying expression against a reference transcriptome using the mRNA quantitation tool Kallisto ensured that disparate datasets explored comparable transcriptomic space. The network analysis tool Graphia was used to extract clusters of co-expressed genes from the resulting expression atlas, many of which were tissue or cell-type restricted, contained transcription factors that have previously been implicated in their regulation, or were otherwise associated with biological processes, such as the cell cycle. The atlas provides a resource for the functional annotation of genes that currently have only a locus ID. We cross-referenced the RNA-seq atlas to a publicly available embryonic Cap Analysis of Gene Expression (CAGE) dataset to infer the developmental time course of organ systems, and to identify a signature of the expansion of tissue macrophage populations during development. Conclusion: Expression profiles obtained from public RNA-seq datasets - despite being generated by different laboratories using different methodologies - can be made comparable to each other. This meta-analytic approach to RNA-seq can be extended with new datasets from novel tissues, and is applicable to any species

BrAPI-an application programming interface for plant breeding applications

Motivation: Modern genomic breeding methods rely heavily on very large amounts of phenotyping and genotyping data, presenting new challenges in effective data management and integration. Recently, the size and complexity of datasets have increased significantly, with the result that data are often stored on multiple systems. As analyses of interest increasingly require aggregation of datasets from diverse sources, data exchange between disparate systems becomes a challenge. Results: To facilitate interoperability among breeding applications, we present the public plant Breeding Application Programming Interface (BrAPI). BrAPI is a standardized web service API specification. The development of BrAPI is a collaborative, community-based initiative involving a growing global community of over a hundred participants representing several dozen institutions and companies. Development of such a standard is recognized as critical to a number of important large breeding system initiatives as a foundational technology. The focus of the first version of the API is on providing services for connecting systems and retrieving basic breeding data including germplasm, study, observation, and marker data. A number of BrAPI-enabled applications, termed BrAPPs, have been written, that take advantage of the emerging support of BrAPI by many databases

Constraints on the structure and seasonal variations of Triton's atmosphere from the 5 October 2017 stellar occultation and previous observations

Context. A stellar occultation by Neptune's main satellite, Triton, was observed on 5 October 2017 from Europe, North Africa, and the USA. We derived 90 light curves from this event, 42 of which yielded a central flash detection. Aims. We aimed at constraining Triton's atmospheric structure and the seasonal variations of its atmospheric pressure since the Voyager 2 epoch (1989). We also derived the shape of the lower atmosphere from central flash analysis. Methods. We used Abel inversions and direct ray-tracing code to provide the density, pressure, and temperature profiles in the altitude range similar to 8 km to similar to 190 km, corresponding to pressure levels from 9 mu bar down to a few nanobars. Results. (i) A pressure of 1.18 +/- 0.03 mu bar is found at a reference radius of 1400 km (47 km altitude). (ii) A new analysis of the Voyager 2 radio science occultation shows that this is consistent with an extrapolation of pressure down to the surface pressure obtained in 1989. (iii) A survey of occultations obtained between 1989 and 2017 suggests that an enhancement in surface pressure as reported during the 1990s might be real, but debatable, due to very few high S/N light curves and data accessible for reanalysis. The volatile transport model analysed supports a moderate increase in surface pressure, with a maximum value around 2005-2015 no higher than 23 mu bar. The pressures observed in 1995-1997 and 2017 appear mutually inconsistent with the volatile transport model presented here. (iv) The central flash structure does not show evidence of an atmospheric distortion. We find an upper limit of 0.0011 for the apparent oblateness of the atmosphere near the 8 km altitude.J.M.O. acknowledges financial support from the Portuguese Foundation for Science and Technology (FCT) and the European Social Fund (ESF) through the PhD grant SFRH/BD/131700/2017. The work leading to these results has received funding from the European Research Council under the European Community's H2020 2014-2021 ERC grant Agreement nffi 669416 "Lucky Star". We thank S. Para who supported some travels to observe the 5 October 2017 occultation. T.B. was supported for this research by an appointment to the National Aeronautics and Space Administration (NASA) Post-Doctoral Program at the Ames Research Center administered by Universities Space Research Association (USRA) through a contract with NASA. We acknowledge useful exchanges with Mark Gurwell on the ALMA CO observations. This work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, https://www.cosmos.esa.int/web/gaia/dpac/consortium).Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement. J.L.O., P.S.-S., N.M. and R.D. acknowledge financial support from the State Agency for Research of the Spanish MCIU through the "Center of Excellence Severo Ochoa" award to the Instituto de Astrofisica de Andalucia (SEV-2017-0709), they also acknowledge the financial support by the Spanish grant AYA-2017-84637-R and the Proyecto de Excelencia de la Junta de Andalucia J.A. 2012-FQM1776. The research leading to these results has received funding from the European Union's Horizon 2020 Research and Innovation Programme, under Grant Agreement no. 687378, as part of the project "Small Bodies Near and Far" (SBNAF). P.S.-S. acknowledges financial support by the Spanish grant AYA-RTI2018-098657-J-I00 "LEO-SBNAF". The work was partially based on observations made at the Laboratorio Nacional de Astrofisica (LNA), Itajuba-MG, Brazil. The following authors acknowledge the respective CNPq grants: F.B.-R. 309578/2017-5; R.V.-M. 304544/2017-5, 401903/2016-8; J.I.B.C. 308150/2016-3 and 305917/2019-6; M.A. 427700/20183, 310683/2017-3, 473002/2013-2. This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (CAPES) -Finance Code 001 and the National Institute of Science and Technology of the e-Universe project (INCT do e-Universo, CNPq grant 465376/2014-2). G.B.R. acknowledges CAPES-FAPERJ/PAPDRJ grant E26/203.173/2016 and CAPES-PRINT/UNESP grant 88887.571156/2020-00, M.A. FAPERJ grant E26/111.488/2013 and A.R.G.Jr. FAPESP grant 2018/11239-8. B.E.M. thanks CNPq 150612/2020-6 and CAPES/Cofecub-394/2016-05 grants. Part of the photometric data used in this study were collected in the frame of the photometric observations with the robotic and remotely controlled telescope at the University of Athens Observatory (UOAO; Gazeas 2016). The 2.3 m Aristarchos telescope is operated on Helmos Observatory by the Institute for Astronomy, Astrophysics, Space Applications and Remote Sensing of the National Observatory of Athens. Observations with the 2.3 m Aristarchos telescope were carried out under OPTICON programme. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 730890. This material reflects only the authors views and the Commission is not liable for any use that may be made of the information contained therein. The 1. 2m Kryoneri telescope is operated by the Institute for Astronomy, Astrophysics, Space Applications and Remote Sensing of the National Observatory of Athens. The Astronomical Observatory of the Autonomous Region of the Aosta Valley (OAVdA) is managed by the Fondazione Clement Fillietroz-ONLUS, which is supported by the Regional Government of the Aosta Valley, the Town Municipality of Nus and the "Unite des Communes valdotaines Mont-Emilius". The 0.81 m Main Telescope at the OAVdA was upgraded thanks to a Shoemaker NEO Grant 2013 from The Planetary Society. D.C. and J.M.C. acknowledge funds from a 2017 'Research and Education' grant from Fondazione CRT-Cassa di Risparmio di Torino. P.M. acknowledges support from the Portuguese Fundacao para a Ciencia e a Tecnologia ref. PTDC/FISAST/29942/2017 through national funds and by FEDER through COMPETE 2020 (ref. POCI010145 FEDER007672). F.J. acknowledges Jean Luc Plouvier for his help. S.J.F. and C.A. would like to thank the UCL student support observers: Helen Dai, Elise Darragh-Ford, Ross Dobson, Max Hipperson, Edward Kerr-Dineen, Isaac Langley, Emese Meder, Roman Gerasimov, Javier Sanjuan, and Manasvee Saraf. We are grateful to the CAHA, OSN and La Hita Observatory staffs. This research is partially based on observations collected at Centro Astronomico HispanoAleman (CAHA) at Calar Alto, operated jointly by Junta de Andalucia and Consejo Superior de Investigaciones Cientificas (IAA-CSIC). This research was also partially based on observation carried out at the Observatorio de Sierra Nevada (OSN) operated by Instituto de Astrofisica de Andalucia (CSIC). This article is also based on observations made with the Liverpool Telescope operated on the island of La Palma by Liverpool John Moores University in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias with financial support from the UK Science and Technology Facilities Council. Partially based on observations made with the Tx40 and Excalibur telescopes at the Observatorio Astrofisico de Javalambre in Teruel, a Spanish Infraestructura Cientifico-Tecnica Singular (ICTS) owned, managed and operated by the Centro de Estudios de Fisica del Cosmos de Aragon (CEFCA). Tx40 and Excalibur are funded with the Fondos de Inversiones de Teruel (FITE). A.R.R. would like to thank Gustavo Roman for the mechanical adaptation of the camera to the telescope to allow for the observation to be recorded. R.H., J.F.R., S.P.H. and A.S.L. have been supported by the Spanish projects AYA2015-65041P and PID2019-109467GB-100 (MINECO/FEDER, UE) and Grupos Gobierno Vasco IT1366-19. Our great thanks to Omar Hila and their collaborators in Atlas Golf Marrakech Observatory for providing access to the T60cm telescope. TRAPPIST is a project funded by the Belgian Fonds (National) de la Recherche Scientifique (F.R.S.-FNRS) under grant PDR T.0120.21. TRAPPIST-North is a project funded by the University of Liege, and performed in collaboration with Cadi Ayyad University of Marrakesh. E.J. is a FNRS Senior Research Associate