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João Ricardo Sato Claudinei Eduardo Biazoli Ana Paula Arantes Bueno Arthur Caye Pedro Mario Pan Marcos Santoro Jessica Honorato-Mauer Giovanni Abrahão Salum Marcelo Queiroz Hoexter Rodrigo Affonseca Bressan Andrea Parolin Jackowski Euripedes Constantino Miguel Sintia Belangero Luis Augusto Rohde 《Genes, Brain & Behavior》2023,22(2):e12838
144.
Darcy S. O. Mora Madeline Cox Forgivemore Magunda Ashley B. Williams Lyndsey Linke 《Engineering in Life Science》2023,23(3):e2200037
There is an unmet need for delivery platforms that realize the full potential of next-generation nucleic acid therapeutics. The in vivo usefulness of current delivery systems is limited by numerous weaknesses, including poor targeting specificity, inefficient access to target cell cytoplasm, immune activation, off-target effects, small therapeutic windows, limited genetic encoding and cargo capacity, and manufacturing challenges. Here we characterize the safety and efficacy of a delivery platform comprising engineered live, tissue-targeting, non-pathogenic bacteria (Escherichia coli SVC1) for intracellular cargo delivery. SVC1 bacteria are engineered to specifically bind to epithelial cells via a surface-expressed targeting ligand, to allow escape of their cargo from the phagosome, and to have minimal immunogenicity. We describe SVC1's ability to deliver short hairpin RNA (shRNA), localized SVC1 administration to various tissues, and its minimal immunogenicity. To validate the therapeutic potential of SVC1, we used it to deliver influenza-targeting antiviral shRNAs to respiratory tissues in vivo. These data are the first to establish the safety and efficacy of this bacteria-based delivery platform for use in multiple tissue types and as an antiviral in the mammalian respiratory tract. We expect that this optimized delivery platform will enable a variety of advanced therapeutic approaches. 相似文献
145.
Roberto de la Herrán Miguel Hermida Juan Andres Rubiolo Jèssica Gómez-Garrido Fernando Cruz Francisca Robles Rafael Navajas-Pérez Andres Blanco Paula Rodriguez Villamayor Dorinda Torres Pablo Sánchez-Quinteiro Daniel Ramirez Maria Esther Rodríguez Alberto Arias-Pérez Ismael Cross Neil Duncan Teresa Martínez-Peña Ana Riaza Adrian Millán M. Cristina De Rosa Davide Pirolli Marta Gut Carmen Bouza Diego Robledo Laureana Rebordinos Tyler Alioto Carmelo Ruíz-Rejón Paulino Martínez 《Molecular ecology resources》2023,23(4):886-904
Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long- and short-read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.9% of the assembly. Further, we established the correspondence between the assembly and the 21 chromosomes by using BAC-FISH. Whole genome resequencing of six males and six females enabled the identification of 41 single nucleotide polymorphism variants in the follicle stimulating hormone receptor (fshr) consistent with an XX/XY SD system. The observed sex association was validated in a broader independent sample, providing a novel molecular sexing tool. The fshr gene displayed differential expression between male and female gonads from 86 days post-fertilization, when the gonad is still an undifferentiated primordium, concomitant with the activation of amh and cyp19a1a, testis and ovary marker genes, respectively, in males and females. The Y-linked fshr allele, which included 24 nonsynonymous variants and showed a highly divergent 3D protein structure, was overexpressed in males compared to the X-linked allele at all stages of gonadal differentiation. We hypothesize a mechanism hampering the action of the follicle stimulating hormone driving the undifferentiated gonad toward testis. 相似文献
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J. Fábregas E. D. Morales N. Polanco M. Patiño A. Otero J. F. Tobar 《World journal of microbiology & biotechnology》1996,12(1):47-49
The marine microalga Phaeodactylum tricornutum was cultivated in semi-continuous culture under mixotrophic conditions with the soluble fractions of potato, rye and wheat flours that had been naturally fermented, at 2% or 4% (w/v). The rye flour produced the highest microalgal cellular density of 90×106 cells.ml-1 when supplemented with NaNO3 and NaH2PO4. The autotrophic control only gave 57×106 cells.ml-1. The value of agricultural surpluses, such as rye flour, can therefore be increased by its use in the production of valuable, microalgal biomass which is rich in protein, pigments and fatty acids. 相似文献
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M. Palacín C. Mora J. Chillarón M. J. Calonge R. Estévez D. Torrents X. Testar A. Zorzano V. Nunes J. Purroy X. Estivill P. Gasparini L. Bisceglia L. Zelante 《Amino acids》1996,11(2):225-246
Summary The cDNAs of mammalian amino acid transporters already identified could be grouped into four families. One of these protein families is composed of the protein rBAT and the heavy chain of the cell surface antigen 4F2 (4F2hc). The cRNAs of rBAT and 4F2hc induce amino acid transport activity via systems b0,+ -like and y+L -like inXenopus oocytes respectively. Surprisingly, neither rBAT nor 4F2hc is very hydrophobic, and they seem to be unable to form a pore in the plasma membrane. This prompted the hypothesis that rBAT and 4F2hc are subunits or modulators of the corresponding amino acid transporters. The association of rBAT with a light subunit of ~40kDa has been suggested, and such an association has been demonstrated for 4F2hc.The b0,+-like system expressed in oocytes by rBAT cRNA transports L-cystine, L-dibasic and L-neutral amino acids with high-affinity. This transport system shows exchange of amino acids through the plasma membrane ofXenopus oocytes, suggesting a tertiary active transport mechanism. The rBAT gene is mainly expressed in the outer stripe of the outer medulla of the kidney and in the mucosa of the small intestine. The protein localizes to the microvilli of the proximal straight tubules (S3 segment) of the nephron and the mucosa of the small intestine. All this suggested the participation of rBAT in a high-affinity reabsorption system of cystine and dibasic amino acids in kidney and intestine, and indicated rBAT (named SLC3A1 in Gene Data Bank) as a good candidate gene for cystinuria. This is an inherited aminoaciduria due to defective renal and intestinal reabsorption of cystine and dibasic amino acids. The poor solubility of cystine causes the formation of renal cystine calculi. Mutational analysis of the rBAT gene of patients with cystinuria is revealing a growing number (~20) of cystinuria-specific mutations, including missense, nonsense, deletions and insertions. Mutations M467T (substitution of methionine 467 residue for threonine) and R270X (stop codon at arginine residue 270) represent approximately half of the cystinuric chromosomes where mutations have been found. Mutation M467T reduces transport activity of rBAT in oocytes. All this demonstrates that mutations in the rBAT gene cause cystinuria.Three types of cystinuria (types, I, II and III) have been described on the basis of the genetic, biochemical and clinical manifestations of the disease. Type I cystinuria has a complete recessive inheritance; type I heterozygotes are totally silent. In contrast, type II and III heterozygotes show, respectively, high or moderate hyperaminoaciduria of cystine and dibasic amino acids. Type III homozygotes show moderate, if any, alteration of intestinal absorption of cystine and dibasic amino acids; type II homozygotes clearly show defective intestinal absorption of these amino acids. To date, all the rBAT cystinuria-specific mutations we have found are associated with type I cystinuria (~70% of the chromosomes studied) but not to types II or III. This strongly suggests genetic heterogeneity for cystinuria. Genetic linkage analysis with markers of the genomic region of rBAT in chromosome 2 (G band 2p16.3) and intragenic markers of rBAT have demonstrated genetic heterogeneity for cystinuria; the rBAT gene is linked to type I cystinuria, but not to type III. Biochemical, genetic and clinical studies are needed to identify the additional cystinuria genes; a low-affinity cystine reabsortion system and the putative light subunit of rBAT are additional candidate genes for cystinuria. 相似文献
150.