Optogenetic Peripheral Nerve Immunogenicity

Optogenetic technologies have been the subject of great excitement within the scientific community for their ability to demystify complex neurophysiological pathways in the central (CNS) and peripheral nervous systems (PNS). The excitement surrounding optogenetics has also extended to the clinic with a trial for ChR2 in the treatment of retinitis pigmentosa currently underway and additional trials anticipated for the near future. In this work, we identify the cause of loss-of-expression in response to transdermal illumination of an optogenetically active peroneal nerve following an anterior compartment (AC) injection of AAV6-hSyn-ChR2(H134R) with and without a fluorescent reporter. Using Sprague Dawley Rag2−/− rats and appropriate controls, we discover optogenetic loss-of-expression is chiefly elicited by ChR2-mediated immunogenicity in the spinal cord, resulting in both CNS motor neuron death and ipsilateral muscle atrophy in both low and high Adeno-Associated Virus (AAV) dosages. We further employ pharmacological immunosuppression using a slow-release tacrolimus pellet to demonstrate sustained transdermal optogenetic expression up to 12 weeks. These results suggest that all dosages of AAV-mediated optogenetic expression within the PNS may be unsafe. Clinical optogenetics for both PNS and CNS applications should take extreme caution when employing opsins to treat disease and may require concurrent immunosuppression. Future work in optogenetics should focus on designing opsins with lesser immunogenicity.MIT Media Lab Consortiu

Investigation of selected genomic deletions and duplications in a cohort of 338 patients presenting with syndromic obesity by multiplex ligation-dependent probe amplification using synthetic probes

Background: Certain rare syndromes with developmental delay or intellectual disability caused by genomic copy number variants (CNVs), either deletions or duplications, are associated with higher rates of obesity. Current strategies to diagnose these syndromes typically rely on phenotype-driven investigation. However, the strong phenotypic overlap between syndromic forms of obesity poses challenges to accurate diagnosis, and many different individual cytogenetic and molecular approaches may be required. Multiplex ligation-dependent probe amplification (MLPA) enables the simultaneous analysis of multiple targeted loci in a single test, and serves as an important screening tool for large cohorts of patients in whom deletions and duplications involving specific loci are suspected. Our aim was to design a synthetic probe set for MLPA analysis to investigate in a cohort of 338 patients with syndromic obesity deletions and duplications in genomic regions that can cause this phenotype.Results: We identified 18 patients harboring copy number imbalances; 18 deletions and 5 duplications. the alterations in ten patients were delineated by chromosomal microarrays, and in the remaining cases by additional MLPA probes incorporated into commercial kits. Nine patients showed deletions in regions of known microdeletion syndromes with obesity as a clinical feature: in 2q37 (4 cases), 9q34 (1 case) and 17p11.2 (4 cases). Four patients harbored CNVs in the DiGeorge syndrome locus at 22q11.2. Two other patients had deletions within the 22q11.2 'distal' locus associated with a variable clinical phenotype and obesity in some individuals. the other three patients had a recurrent CNV of one of three susceptibility loci: at 1q21.1 'distal', 16p11.2 'distal', and 16p11.2 'proximal'.Conclusions: Our study demonstrates the utility of an MLPA-based first line screening test to the evaluation of obese patients presenting with syndromic features. the overall detection rate with the synthetic MLPA probe set was about 5.3% (18 out of 338). Our experience leads us to suggest that MLPA could serve as an effective alternative first line screening test to chromosomal microarrays for diagnosis of syndromic obesity, allowing for a number of loci (e.g., 1p36, 2p25, 2q37, 6q16, 9q34, 11p14, 16p11.2, 17p11.2), known to be clinically relevant for this patient population, to be interrogated simultaneously.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Human Genome & Stem Cell Ctr, São Paulo, BrazilUniv São Paulo, Sch Med, Children Inst, Genet Unit,Dept Pediat, São Paulo, BrazilUniv São Paulo, Sch Med, Dept Med Genet, Neurogenet Unit, BR-14049 Ribeirao Preto, BrazilUniversidade Federal de São Paulo, Ctr Med Genet, Dept Morphol, São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Med Genet, Dept Morphol, São Paulo, BrazilFAPESP: 09/52523-1FAPESP: 1998/14254-2CNPq: 304381/2007-1Web of Scienc

La producción científica sobre países latinoamericanos: una aproximación a su estudio desde la perspectiva bibliométrica y su relación con indicadores del contexto económico y social : PICT 2015-2744

Objetivos de la investigación - Contribuir al conocimiento de la configuración disciplinar y geográfica de la investigación sobre países de América Latina, producida tanto por países de la región como de otras regiones del mundo. - Contribuir al conocimiento de las prácticas de comunicación científica de la producción sobre países de la región latinoamericana a partir del estudio comparativo de la relación entre indicadores bibliométricos. - Contrastar los patrones encontrados en el estudio del caso argentino con los resultados obtenidos para el contexto latinoamericano. - Explorar relaciones entre Indicadores bibliométricos de la producción científica sobre países latinoamericanos e indicadores del contexto económico y social.Pósters presentadosDepartamento de Bibliotecologí

Curso modelado de nicho ecológico, version 1.0

The suite of ideas, protocols, and software tools that has come to be known as “Ecological Niche Modeling” (ENM) — as well as those for the related “Species Distribution Modeling” (SDM)—has seen intensive exploration and research attention in recent decades. In spite of at least four syntheses, the field has grown so much in complexity that it is rather difficult to access for newcomers. Until now, accessibility to this field was achieved by in-person courses organized by universities or research centers, in some of which we have participated as instructors. However, the access to these specialized courses is limited, on one hand because they are not offered in all universities, and on the other because normally they are taught in English. To expand the access to a wider community of Spanish-speaking researchers, here we offer an entirely digital and free-of-charge course in Spanish, which was presented over 23 weeks via Internet in 2018. Although intrinsic Internet-related barriers may limit access to course materials, we have made them available in diverse formats (video, audio, pdf) in order to eliminate most of these problems.El conjunto de ideas, métodos y programas informáticos que se conoce como “Modelado de Nicho Ecológico” (MNE)—y el relacionado “Modelado de Distribución de Especies” (MDS)—han sido objeto de intensa exploración e investigación en las últimas décadas. A pesar de existir al menos cuatro síntesis publicadas, este campo ha crecido tanto en complejidad, que la formación de nuevos investigadores es difícil. Hasta ahora, dicha formación se ha hecho de manera presencial en cursos organizados por universidades o centros de investigación, de los que hemos formado parte como instructores. Sin embargo, el acceso a este tipo de cursos especializados es restringido, por un lado, porque los cursos no se ofrecen en todas las universidades, y por otro, porque normalmente se imparten en inglés. Para facilitar el acceso a una mayor comunidad de científicos de habla hispana, presentamos un curso en español, completamente digital y de acceso gratuito, que se realizó vía Internet durante 23 semanas consecutivas en 2018. Aunque las barreras intrínsecas al uso de Internet pueden dificultar la accesibilidad a los materiales del curso, hemos usado diversos formatos para la divulgación de los contenidos académicos (video, audio, pdf) con el objetivo de eliminar la mayor parte de estos problemas

J-PLUS: A first glimpse at spectrophotometry of asteroids -- The MOOJa catalog

Context: The Javalambre Photometric Local Universe Survey (J-PLUS) is an observational campaign that aims to obtain photometry in 12 ultraviolet-visible filters (0.3-1 {\mu}m) of approximately 8 500 deg{^2} of the sky observable from Javalambre (Teruel, Spain). Due to its characteristics and strategy of observation, this survey will let us analyze a great number of Solar System small bodies, with improved spectrophotometric resolution with respect to previous large-area photometric surveys in optical wavelengths. Aims: The main goal of this work is to present here the first catalog of magnitudes and colors of minor bodies of the Solar System compiled using the first data release (DR1) of the J-PLUS observational campaign: the Moving Objects Observed from Javalambre (MOOJa) catalog. Methods: Using the compiled photometric data we obtained very-low-resolution reflectance (photospectra) spectra of the asteroids. We first used a {\sigma}-clipping algorithm in order to remove outliers and clean the data. We then devised a method to select the optimal solar colors in the J-PLUS photometric system. These solar colors were computed using two different approaches: on one hand, we used different spectra of the Sun, convolved with the filter transmissions of the J-PLUS system, and on the other, we selected a group of solar-type stars in the J-PLUS DR1, according to their computed stellar parameters. Finally, we used the solar colors to obtain the reflectance spectra of the asteroids. Results: We present photometric data in the J-PLUS filters for a total of 3 122 minor bodies (3 666 before outlier removal), and we discuss the main issues of the data, as well as some guidelines to solve the

Influence of antisynthetase antibodies specificities on antisynthetase syndrome clinical spectrum time course

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The "ex-novo" occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies' positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe