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Primary familial brain calcification (PFBC, OMIM#213600), also known as Fahr's disease, is a rare autosomal dominant or recessive neurodegenerative disorder characterized by bilateral and symmetrical microvascular calcifications affecting multiple brain regions, particularly the basal ganglia (globus pallidus, caudate nucleus, and putamen) and thalamus. The most common clinical manifestations include cognitive impairment, neuropsychiatric signs, and movement disorders. Loss-of-function mutations in

are the major genetic causes of PFBC.

This study aimed to investigate whether

knockout mice could recapitulate the dynamic processes and patterns of brain calcification and neurological symptoms in patients with PFBC. We comprehensively evaluated brain calcifications and PFBC-related behavioral abnormalities in

-deficient mice.

Brain calcifications were analyzed using classic calcium-phosphate staining methods. The Morris water maze, Y-maze, and fear conditioning paradigms were used to evaluate long-tferent between

-HO and wild-type mice after adjusting for body weight, which was a major confounding factor in our motor function evaluations.

The human PFBC-related phenotypes were highly similar to those in

-HO mice. Therefore,

-HO mice might be suitable for the future evaluation of neuropharmacological intervention strategies targeting cognitive and neuropsychiatric impairments.

The human PFBC-related phenotypes were highly similar to those in Slc20a2-HO mice. Therefore, Slc20a2-HO mice might be suitable for the future evaluation of neuropharmacological intervention strategies targeting cognitive and neuropsychiatric impairments.In the current era, one of biggest challenges is to shorten the breeding cycle for rapid generation of a new crop variety having high yield capacity, disease resistance, high nutrient content, etc. Advances in the "-omics" technology have revolutionized the discovery of genes and bio-molecules with remarkable precision, resulting in significant development of plant-focused metabolic databases and resources. Metabolomics has been widely used in several model plants and crop species to examine metabolic drift and changes in metabolic composition during various developmental stages and in response to stimuli. Over the last few decades, these efforts have resulted in a significantly improved understanding of the metabolic pathways of plants through identification of several unknown intermediates. This has assisted in developing several new metabolically engineered important crops with desirable agronomic traits, and has facilitated the de novo domestication of new crops for sustainable agriculture and food security. In this review, we discuss how "omics" technologies, particularly metabolomics, has enhanced our understanding of important traits and allowed speedy domestication of novel crop plants.Many works have reported that protein folding rates are influenced by the characteristics of amino acid sequences and protein structures. However, few reports on the problem of whether the corresponding mRNA sequences are related to the protein folding rates can be found. An mRNA sequence is regarded as a kind of genetic language, and its vocabulary and phraseology must provide influential information regarding the protein folding rate. In the present work, linear regressions on the parameters of the vocabulary and phraseology of mRNA sequences and the corresponding protein folding rates were analyzed. The results indicated that D 2 (the adjacent base-related information redundancy) values and the GC content values of the corresponding mRNA sequences exhibit significant negative relations with the protein folding rates, but D 1 (the single base information redundancy) values exhibit significant positive relations with the protein folding rates. In addition, the results show that the relationships between the parameters of the genetic language and the corresponding protein folding rates are obviously different for different protein groups. Some useful parameters that are related to protein folding rates were found. The results indicate that when predicting protein folding rates, the information from protein structures and their amino acid sequences is insufficient, and some information for regulating the protein folding rates must be derived from the mRNA sequences.Schima superba (Theaceae) is a subtropical evergreen tree and is used widely for forest firebreaks and gardening. Asciminib nmr It is a plant that tolerates salt and typically accumulates elevated amounts of manganese in the leaves. With large ecological amplitude, this tree species grows quickly. Due to its substantial biomass, it has a great potential for soil remediation. To evaluate the thorough framework of the mRNA, we employed PacBio sequencing technology for the first time to generate S. Superba transcriptome. In this analysis, overall, 511,759 full length non-chimeric reads were acquired, and 163,834 high-quality full-length reads were obtained. Overall, 93,362 open reading frames were obtained, of which 78,255 were complete. In gene annotation analyses, the Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Genes (COG), Gene Ontology (GO), and Non-Redundant (Nr) databases were allocated 91,082, 71,839, 38,914, and 38,376 transcripts, respectively. To identify long non-coding RNAs (lncRNAs), we utilized four computational methods associated with protein families (Pfam), Cooperative Data Classification (CPC), Coding Assessing Potential Tool (CPAT), and Coding Non-Coding Index (CNCI) databases and observed 8,551, 9,174, 20,720, and 18,669 lncRNAs, respectively. Moreover, nine genes were randomly selected for the expression analysis, which showed the highest expression of Gene 6 (Na_Ca_ex gene), and CAX (CAX-interacting protein 4) was higher in manganese (Mn)-treated group. This work provided significant number of full-length transcripts and refined the annotation of the reference genome, which will ease advanced genetic analyses of S. superba.Gene editing of the mitochondrial genome using the CRISPR-Cas9 system is highly challenging mainly due to sub-efficient delivery of guide RNA and Cas9 enzyme complexes into the mitochondria. In this study, we were able to perform gene editing in the mitochondrial DNA by appending an NADH-ubiquinone oxidoreductase chain 4 (ND4) targeting guide RNA to an RNA transport-derived stem loop element (RP-loop) and expressing the Cas9 enzyme with a preceding mitochondrial localization sequence. We observe mitochondrial colocalization of RP-loop gRNA and a marked reduction of ND4 expression in the cells carrying a 11205G variant in their ND4 sequence coincidently decreasing the mtDNA levels. This proof-of-concept study suggests that a stem-loop element added sgRNA can be transported to the mitochondria and functionally interact with Cas9 to mediate sequence-specific mtDNA cleavage. Using this novel approach to target the mtDNA, our results provide further evidence that CRISPR-Cas9-mediated gene editing might potentially be used to treat mitochondrial-related diseases.

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