Species-specific FMRP regulation of RACK1 is critical for prenatal cortical development.

Fragile X messenger ribonucleoprotein 1 protein (FMRP) deficiency leads to fragile X syndrome (FXS), an autism spectrum disorder. The role of FMRP in prenatal human brain development remains unclear. Here, we show that FMRP is important for human and macaque prenatal brain development. Both FMRP-deficient neurons in human fetal cortical slices and FXS patient stem cell-derived neurons exhibit mitochondrial dysfunctions and hyperexcitability. Using multiomics analyses, we have identified both FMRP-bound mRNAs and FMRP-interacting proteins in human neurons and unveiled a previously unknown role of FMRP in regulating essential genes during human prenatal development. We demonstrate that FMRP interaction with CNOT1 maintains the levels of receptor for activated C kinase 1 (RACK1), a species-specific FMRP target. Genetic reduction of RACK1 leads to both mitochondrial dysfunctions and hyperexcitability, resembling FXS neurons. Finally, enhancing mitochondrial functions rescues deficits of FMRP-deficient cortical neurons during prenatal development, demonstrating targeting mitochondrial dysfunction as a potential treatment.

BOMA, a machine-learning framework for comparative gene expression analysis across brains and organoids.

Our machine-learning framework, brain and organoid manifold alignment (BOMA), first performs a global alignment of developmental gene expression data between brains and organoids. It then applies manifold learning to locally refine the alignment, revealing conserved and specific developmental trajectories across brains and organoids. Using BOMA, we found that human cortical organoids better align with certain brain cortical regions than with other non-cortical regions, implying organoid-preserved developmental gene expression programs specific to brain regions. Additionally, our alignment of non-human primate and human brains reveals highly conserved gene expression around birth. Also, we integrated and analyzed developmental single-cell RNA sequencing (scRNA-seq) data of human brains and organoids, showing conserved and specific cell trajectories and clusters. Further identification of expressed genes of such clusters and enrichment analyses reveal brain- or organoid-specific developmental functions and pathways. Finally, we experimentally validated important specific expressed genes through the use of immunofluorescence. BOMA is open-source available as a web tool for community use.

Elaboration of reference material for cadmium and arsenic in hydrobiological products, for the purpose of being used in a laboratory intercomparation program / Elaboración de un material de referencia para cadmio y arsénico en productos hidrobiológicos, para propósito de ser utilizado en un programa de intercomparación de laboratorios

Reference materials (RM) are tools used in the comparability and traceability of measurements. They are widely used by laboratories for method validation and quality control of assay. Chile must evaluate theperformance of laboratories that analyzing metals in fishery products, despite RM have high prices and are scarce. For that reason, a RM in a hydrobiological product was developed. Reference values for arsenic and cadmium elements for a fishmeal were assigned. The measurement methods for characterization of the material were Inductively Coupled Plasma Mass Spectrometry, Atomic Absorption Spectrometry and Neutron Activation Analysis. Reference values with their expanded uncertainty (U) were established for arsenic 2.64 ± 0.42 mg/kg (U; k = 2) and for cadmium 0.86 ± 0.16 mg/kg (U; k = 2). Homogeneity and stability of the RM allowed its use in a proficiency test for eleven food control laboratories. Results for median were 2.114 mg/kg for arsenic, and 0.863 mg/kg for cadmium. The performance values of the participants were evaluated with a z score obtaining 60% satisfaction for arsenic and 73% for cadmium.The material demonstrated to be suitable for use in interlaboratory proficiency assay. (AU)

Materiales de referencia (MR) son herramientas utilizadas en la comparabilidad y trazabilidad entre mediciones. Laboratorios los utilizan ampliamente en validación de métodos y control de calidad. Chile debe evaluar el desempeño de los laboratorios que analizan metales en productos pesqueros, a pesar de los altos precios y escasez del MR. Por esa razón, se desarrolló un MR en producto hidrobiológico. Se asignaron valores de referencia para arsénico y cadmio en harina de pescado. Los métodos de medición para la caracterización del material fueron Espectrometría de Masas de Plasma Acoplado Inductivamente, Espectrometría de Absorción Atómica y Análisis de Activación de Neutrones. Se establecieron valores de referencia con su incertidumbre (U) para arsénico 2.64 ± 0.42 mg/kg (U; k = 2) y para cadmio 0.86 ± 0.16 mg/kg (U; k = 2). La homogeneidad y estabilidad del MR permitieron su uso en una prueba de aptitud para once laboratorios de control de alimentos. Las medianas fueron 2,114 mg/kg para arsénico y 0,863 mg/kg para cadmio. Se evaluaron los rendimientos de los participantes con un estadístico de puntaje z satisfactorio del 60% para el arsénico y 73% para el cadmio. El material demostró ser adecuado para uso en ensayo de aptitud de intercomparación. (AU)

Contenido de humedad, proteínas y minerales en diez variedades de quínoa chilena cultivadas en distintas zonas geográficas / Moisture, protein and mineral content of ten varieties of Chilean quinoa grown in different geographic zones

RESUMEN El consumo de quínoa (Chenopodium quínoa Willd) ha aumentado, renovando el interés en su composición y valor nutricional. El objetivo del estudio fue determinar los contenidos de humedad, cenizas, proteínas y algunos minerales (Fe, Zn y Cu) de 10 variedades de quínoa chilena cultivadas en cuatro zonas geográficas, utilizando metodologías analíticas validadas. Las muestras (n=10) de quínoa cultivada en Vallenar, Los Tilos, Hidango y Santa Rosa fueron analizadas en triplicado. Los métodos normalizados aplicados fueron: humedad; cenizas; proteínas; hierro, zinc y cobre, bajo los requisitos de ISO/IEC 17025:2017. Los datos se analizaron usando análisis de varianza para comparar variedades y zonas de cultivo. Las muestras contienen en promedio 16,6 g de proteínas/100 g (14,4-17,5), 8,97 mg de hierro/100 g (7,71-10,76), 3,38 mg de zinc/100 g (2,17-5,30), y 0,83 mg de cobre/100 g (0,60-1,10). Las variedades cultivadas en Vallenar, Los Tilos e Hidango mostraron mayor contenido proteico que las de Santa Rosa (p<0,05). Todas las variedades tienen un contenido destacado de los microminerales cobre, zinc y hierro. Los resultados aportan información relevante sobre el valor nutricional de la quínoa chilena, entregando datos para la actualización de las Tablas de Composición Química de alimentos.

ABSTRACT The intake of quinoa (Chenopodium quinoa Willd) has increased worldwide. Its revival has renewed interest in its composition and nutritional value. The aim of this study was to determine the contents of moisture, ash, protein, and some minerals (Fe, Zn and Cu) of ten varieties of Chilean quinoa grown in various geographical zones, using validated analytical methods under rule ISO/IEC 17025:2017. Grains grown in Vallenar, Los Tilos, Hidango, and Santa Rosa were analyzed in triplicates, using previously validated analytical methodologies and certified reference materials. The normalized methods used were: moisture; ash; protein; mineral, under the ISO/IEC 17025:2017 norm. Data were analyzed using ANOVA to compare varieties and growth zones. The analyzed quinoa grains contain a mean of 16.6 g proteins/100 g (range 14.4-17.5), 8.97 mg iron/100 g (range 7.71-10.76), 3.38 mg zinc/100 g, and 0.83 mg copper/100 g (range 0.60-1.10). The varieties grown in Vallenar, Los Tilos and Hidango showed higher protein content compared to Santa Rosa (p<0.05). All varieties exhibit considerable microminerals content, such as copper, zinc, and iron. These results provide relevant information about the nutritional value of Chilean quinoa and updated reliable data for Food Composition Tables.