Coding Region Research Articles

Complete genome sequence of Escherichia coli O157:H7 phage Φ241.

We report the genome sequence of phage Φ241 infecting Escherichia coli O157:H7. Phage Φ241 was isolated from an industrial cucumber fermentation at high acidity (pH 3.7) and high salinity (5% NaCl). The phage genome consists of a 157,291 bp circular double-stranded DNA with 203 coding regions and 44.96% GC content.

African Swine Fever Virus Protein-Protein Interaction Prediction.

The African swine fever virus (ASFV) is an often deadly disease in swine and poses a threat to swine livestock and swine producers. With its complex genome containing more than 150 coding regions, developing effective vaccines for this virus remains a challenge due to a lack of basic knowledge about viral protein function and protein-protein interactions between viral proteins and between viral and host proteins. In this work, we identified ASFV-ASFV protein-protein interactions (PPIs) using artificial intelligence-powered protein structure prediction tools. We benchmarked our PPI identification workflow on the Vaccinia virus, a widely studied nucleocytoplasmic large DNA virus, and found that it could identify gold-standard PPIs that have been validated in vitro in a genome-wide computational screening. We applied this workflow to more than 18,000 pairwise combinations of ASFV proteins and were able to identify seventeen novel PPIs, many of which have corroborating experimental or bioinformatic evidence for their protein-protein interactions, further validating their relevance. Two protein-protein interactions, I267L and I8L, I267L__I8L, and B175L and DP79L, B175L__DP79L, are novel PPIs involving viral proteins known to modulate host immune response.

'Drifting' Buchnera genomes track the microevolutionary trajectories of their aphid hosts.

Evolution of Buchnera-aphid host symbioses is often studied among species at macroevolutionary scales. Investigations within species offer a different perspective about how eco-evolutionary processes shape patterns of genetic variation at microevolutionary scales. Our study leverages new and publicly available whole-genome sequencing data to study Buchnera-aphid host evolution in Myzus persicae, the peach potato aphid, a globally invasive and polyphagous pest. Across 43 different asexual, clonally reproducing isofemale strains, we examined patterns of genomic covariation between Buchnera and their aphid host and considered the distribution of mutations in protein-coding regions of the Buchnera genome. We found Buchnera polymorphisms within aphid strains, suggesting the presence of genetically different Buchnera strains within the same clonal lineage. Genetic distance between pairs of Buchnera samples was positively correlated to genetic distance between their aphid hosts, indicating shared evolutionary histories. However, there was no segregation of genetic variation for both M. persicae and Buchnera with plant host (Brassicaceae and non-tobacco Solanaceae) and no associations between genetic and geographic distance at global or regional spatial scales. Abundance patterns of non-synonymous mutations were similar to synonymous mutations in the Buchnera genome, and both mutation classes had similar site frequency spectra. We hypothesize that a predominance of neutral processes results in the Buchnera of M. persicae to simply 'drift' with the evolutionary trajectory of their aphid hosts. Our study presents a unique microevolutionary characterization of Buchnera-aphid host genomic covariation across multiple aphid clones. This provides a new perspective on the eco-evolutionary processes generating and maintaining polymorphisms in a major pest aphid species and its obligate primary endosymbiont.

Diverse origins of near-identical antifreeze proteins in unrelated fish lineages provide insights into evolutionary mechanisms of new gene birth and protein sequence convergence.

Determining the origins of novel genes and the genetic mechanisms underlying the emergence of new functions is challenging yet crucial for understanding evolutionary innovations. The convergently evolved fish antifreeze proteins provide excellent opportunities to investigate evolutionary origins and pathways of new genes. Particularly notable is the near-identical type I antifreeze proteins (AFPI) in four phylogenetically divergent fish taxa. This study tested the hypothesis of protein sequence convergence beyond functional convergence in three unrelated AFPI-bearing fish lineages, revealing different paths by which a similar protein arose from diverse genomic resources. Comprehensive comparative analyses of de novo sequenced genome of the winter flounder and grubby sculpin, available high-quality genome of the cunner and 14 other relevant species found that the near-identical AFPI originated from a distinct genetic precursor in each lineage. Each independently evolved a coding region for the novel ice-binding protein while retaining sequence identity in the regulatory regions with their respective ancestor. The deduced evolutionary processes and molecular mechanisms are consistent with the Innovation-Amplification-Divergence (IAD) model applicable to AFPI formation in all three lineages, a new Duplication-Degeneration-Divergence (DDD) model we propose for the sculpin lineage, and a DDD model with gene fission for the cunner lineage. This investigation illustrates the multiple ways by which a novel functional gene with sequence convergence at the protein level could evolve across divergent species, advancing our understanding of the mechanistic intricacies in new gene formation.

Comparative Analysis of Plastome Sequences of Seven Tulipa L. (Liliaceae Juss.) Species from Section Kolpakowskianae Raamsd. Ex Zonn and Veldk.

Tulipa L. is a genus of significant economic, environmental, and cultural importance in several parts of the world. The exact number of species in the genus remains uncertain due to inherent taxonomic challenges. We utilized next-generation sequencing technology to sequence and assemble the plastid genomes of seven Tulipa species collected in Kazakhstan and conducted a comparative analysis. The total number of annotated genes was 136 in all seven studied Tulipa species, 114 of which were unique, including 80 protein-coding, 30 tRNA, and 4 rRNA genes. Nine regions (petD, ndhH, ycf2-ycf3, ndhA, rpl16, clpP, ndhD-ndhF, rpoC2, and ycf1) demonstrated significant nucleotide variability, suggesting their potential as molecular markers. A total of 1388 SSRs were identified in the seven Tulipa plastomes, with mononucleotide repeats being the most abundant (60.09%), followed by dinucleotide (34.44%), tetranucleotide (3.90%), trinucleotide (1.08%), pentanucleotide (0.22%), and hexanucleotide (0.29%). The Ka/Ks values of the protein-coding genes ranged from 0 to 3.9286, with the majority showing values <1. Phylogenetic analysis based on a complete plastid genome and protein-coding gene sequences divided the species into three major clades corresponding to their subgenera. The results obtained in this study may contribute to understanding the phylogenetic relationships and molecular taxonomy of Tulipa species.

Evolution of the regulation of developmental gene expression in blind Mexican cavefish.

Developmental evolution and diversification of morphology can arise through changes in the regulation of gene expression or protein-coding sequence. To unravel mechanisms underlying early developmental evolution in cavefish of the species Astyanax mexicanus, we compared transcriptomes of surface-dwelling and blind cave-adapted morphs at the end of gastrulation. Twenty percent of the transcriptome was differentially expressed. Allelic expression ratios in cave X surface hybrids showed that cis-regulatory changes are the quasi-exclusive contributors to inter-morph variations in gene expression. Among a list of 108 genes with change at the cis-regulatory level, we explored the control of expression of rx3, which is a master eye gene. We discovered that cellular rx3 levels are cis-regulated in a cell-autonomous manner, whereas rx3 domain size depends on non-autonomous Wnt and Bmp signalling. These results highlight how uncoupled mechanisms and regulatory modules control developmental gene expression and shape morphological changes. Finally, a transcriptome-wide search for fixed coding mutations and differential exon use suggested that variations in coding sequence have a minor contribution. Thus, during early embryogenesis, changes in gene expression regulation are the main drivers of cavefish developmental evolution.

Sequencing of Kaposi's Sarcoma Herpesvirus (KSHV) genomes from persons of diverse ethnicities and provenances with KSHV-associated diseases demonstrate multiple infections, novel polymorphisms, and low intra-host variance.

Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. These include near full-length sequence of genomes with KSHV K1 subtypes A, B, C, and F as well as subtype E, for which no full sequence was previously available. High levels of recombination were observed. Fourteen individuals (18%) showed evidence of infection with multiple KSHV variants (from two to four unique genomes). Twenty-six comparisons of sequences, obtained from various sampling sites including PBMC, tissue biopsies, oral fluids, and effusions in the same participants, identified near complete genome conservation between different biological compartments. Polymorphisms were identified in coding and non-coding regions, including indels in the K3 and K15 genes and sequence inversions here reported for the first time. One such polymorphism in KSHV ORF46, specific to the KSHV K1 subtype E2, encoded a mutation in the leucine loop extension of the uracil DNA glycosylase that results in alteration of biochemical functions of this protein. This confirms that KSHV sequence variations can have functional consequences warranting further investigation. This study represents the largest and most diverse analysis of KSHV genome sequences to date among individuals with KAD and provides important new information on global KSHV genomics.

Approach for Phased Sequence-Based Genotyping of the Critical Pharmacogene Dihydropyrimidine Dehydrogenase (DPYD).

Pre-treatment genotyping of four well-characterized toxicity risk-variants in the dihydropyrimidine dehydrogenase gene (DPYD) has been widely implemented in Europe to prevent serious adverse effects in cancer patients treated with fluoropyrimidines. Current genotyping practices are largely limited to selected commonly studied variants and are unable to determine phasing when more than one variant allele is detected. Recent evidence indicates that common DPYD variants modulate the functional impact of deleterious variants in a phase-dependent manner, where a cis- or a trans-configuration translates into different toxicity risks and dosing recommendations. DPYD is a large gene with 23 exons spanning nearly a mega-base of DNA, making it a challenging candidate for full-gene sequencing in the diagnostic setting. Herein, we present a time- and cost-efficient long-read sequencing approach for capturing the complete coding region of DPYD. We demonstrate that this method can reliably produce phased genotypes, overcoming a major limitation with current methods. This method was validated using 21 subjects, including two cancer patients, each of whom carried multiple DPYD variants. Genotype assignments showed complete concordance with conventional approaches. Furthermore, we demonstrate that the method is robust to technical challenges inherent in long-range sequencing of PCR products, including reference alignment bias and PCR chimerism.

Differential expression and genetic polymorphism of DMRT1 and FOXL2 genes in the gonads of Kadaknath chicken

In chicken, the left ovary is functional and the right ovary becomes rudimentary in the later stage of the embryonic development. The expression and genetic polymorphism of the DMRT1 and FOXL2 genes are assessed in order to understand the distinct developing process of gonads in male and female embryonic gonads. In the current study, 19th day Kadaknath chicken gonadal tissue samples were collected from the embryos and RT-PCR analysis and DNA sequencing was done. According to the expression studies, the left ovaries relative expression of FOXL2 was 2.14 and 12.65 factor greater than that of the right ovaries and testes, while the right testis relative expression of DMRT1 was 3.78 and 3.83 fold higher than that of the left and right ovaries. DNA sequence analysis in the left ovary identified a nonsynonymous alteration (c.289C&gt;G) involving histidine to aspartic acid at the 289th position in the FOXL2 coding region. The 51st position of exon 6 of DMRT1 has a G→A transition SNP that is not part of the coding sequence (CDS). Males showed higher levels of the DMRT1 gene than females, while females expressed higher levels of FOXL2. It was found that the DMRT1 and FOXL2 genes are polymorphic. The genetic variability in the gonads and the differences in DMRT1 and FOXL2 gene expression allow learning more about the critical mechanisms underlying chicken gonadal development.

Nexilin in cardiomyopathy: unveiling its diverse roles with special focus on endocardial fibroelastosis.

Cardiac disorders exhibit considerable heterogeneity, and understanding their genetic foundations is crucial for their diagnosis and treatment. Recent genetic analyses involving a growing number of participants have uncovered novel mutations within both coding and non-coding regions of DNA, contributing to the onset of cardiac conditions. The NEXN gene, encoding the Nexilin protein, an actin filament-binding protein, is integral to normal cardiac function. Mutations in this gene have been linked to cardiomyopathies, cardiovascular disorders, and sudden deaths. Heterozygous or homozygous variants of the NEXN gene are associated with the development of endocardial fibroelastosis (EFE), a rare cardiac condition characterized by excessive collagen and elastin deposition in the left ventricular endocardium predominantly affecting infants and young children. EFE occurs both primary and secondary to other conditions and often leads to unfavorable prognoses and outcomes. This review explores the role of NEXN genetic variants in cardiovascular disorders, particularly EFE, revealing that functional mutations are not clustered in a specific domain of Nexilin based on the cardiac disorder phenotype. Our review underscores the importance of understanding genetic mutations for the diagnosis and treatment of cardiac conditions.

Genome assembly, comparative genomics, and identification of genes/pathways underlying plant growth-promoting traits of an actinobacterial strain, Amycolatopsis sp. (BCA-696)

The draft genome sequence of an agriculturally important actinobacterial species Amycolatopsis sp. BCA-696 was developed and characterized in this study. Amycolatopsis BCA-696 is known for its biocontrol properties against charcoal rot and also for plant growth-promotion (PGP) in several crop species. The next-generation sequencing (NGS)-based draft genome of Amycolatopsis sp. BCA-696 comprised of ~ 9.05 Mb linear chromosome with 68.75% GC content. In total, 8716 protein-coding sequences and 61 RNA-coding sequences were predicted in the genome. This newly developed genome sequence has been also characterized for biosynthetic gene clusters (BGCs) and biosynthetic pathways. Furthermore, we have also reported that the Amycolatopsis sp. BCA-696 produces the glycopeptide antibiotic vancomycin that inhibits the growth of pathogenic gram-positive bacteria. A comparative analysis of the BCA-696 genome with publicly available closely related genomes of 14 strains of Amycolatopsis has also been conducted. The comparative analysis has identified a total of 4733 core and 466 unique orthologous genes present in the BCA-696 genome The unique genes present in BCA-696 was enriched with antibiotic biosynthesis and resistance functions. Genome assembly of the BCA-696 has also provided genes involved in key pathways related to PGP and biocontrol traits such as siderophores, chitinase, and cellulase production.

Analysis of a Chinese pedigree with Bw subtype due to a novel variant of α-1,3-N-acetylgalactosaminyltransferase gene

To explore the serological characteristics and genetic variant in a Chinese pedigree with Bw subtype. A 32-year-old female proband who had undergone prenatal examination on December 10, 2020 at the 960th Hospital of the PLA Joint Logistics Support Force and five members from her pedigree were selected as the study subjects. Peripheral blood samples were collected and subjected to ABO blood group phenotyping with serological methods and ABO blood group genotyping with fluorescent PCR. Genetic testing and haplotype analysis were carried out by direct sequencing of the entire coding region of the ABO gene in the proband and cloned sequencing of exons 1-7. The blood type serology of the proband showed Bw, and her ABO blood type genotype determined by fluorescence PCR was B/O. The direct sequencing results showed that the proband had matched the ABO*O.01.01/ABO*B.01 genotype and carried a c.1A>G variant. Cloned sequencing has confirmed the c.1A>G variant to have occurred in the ABO*B.01 allele. Family analysis revealed that the mother of the proband had an O blood type, her husband had a B phenotype, and her three children had a normal B blood type. DNA sequencing showed that the two sons of the proband had a genotype of ABO*B.01 and c.1A>G/ABO*B.01. The daughter of the proband was ABO*O.01.01/ABO*B.01, whilst her mother was ABO*O.01.01/ABO *O.01.02. The novel c.1A>G variant sequence has been registered with the database with a number MZ076785 1. The novel c.1A>G variant of exon 1 of α- 1,3 galactose aminotransferase gene probably underlay the reduced expression of B antigen in this pedigree.

HyperCas12a enables highly-multiplexed epigenome editing screens.

Interactions between multiple genes or cis-regulatory elements (CREs) underlie a wide range of biological processes in both health and disease. High-throughput screens using dCas9 fused to epigenome editing domains have allowed researchers to assess the impact of activation or repression of both coding and non-coding genomic regions on a phenotype of interest, but assessment of genetic interactions between those elements has been limited to pairs. Here, we combine a hyper-efficient version of Lachnospiraceae bacterium dCas12a (dHyperLbCas12a) with RNA Polymerase II expression of long CRISPR RNA (crRNA) arrays to enable efficient highly-multiplexed epigenome editing. We demonstrate that this system is compatible with several activation and repression domains, including the P300 histone acetyltransferase domain and SIN3A interacting domain (SID). We also show that the dCas12a platform can perform simultaneous activation and repression using a single crRNA array via co-expression of multiple dCas12a orthologues. Lastly, demonstrate that the dCas12a system is highly effective for high-throughput screens. We use dHyperLbCas12a-KRAB and a ~19,000-member barcoded library of crRNA arrays containing six crRNAs each to dissect the independent and combinatorial contributions of CREs to the dose-dependent control of gene expression at a glucocorticoid-responsive locus. The tools and methods introduced here create new possibilities for highly multiplexed control of gene expression in a wide variety of biological systems.

The complete chloroplast genome sequences of nine melon varieties (Cucumis melo L.): lights into comparative analysis and phylogenetic relationships.

Melon (Cucumis melo L.) is one of the most extensively grown horticulture crops of the world. Based on the morphological characters, melon was formerly divided into two subspecies, Cucumis melo ssp. melo and C. melo ssp. agrestis. However, the present methods are still inadequate to distinguish between them. The phylogenetic analysis based on chloroplast genome sequences could provide essential evidence for the classification of melon varieties. We sequenced the chloroplast genomes of nine different melon varieties by the Illumina Hiseq and performed bioinformatic analyses including repeat element analysis, genome comparison and phylogenetic analysis. The results showed that the melon chloroplast genome has a typical quadripartite structure that was conserved across the analyzed sequences. Its length ranges between 155, 558 and 156, 569bp, with a total GC content varying from 36.7% to 37%. We found 127-132 genes in melon chloroplast genomes, including 85-87 protein-coding regions, 34-37 tRNA and 6-8 rRNA genes. The molecular structure, gene order, content, codon usage, long repeats, and simple sequence repeats (SSRs) were mostly conserved among the nine sequenced genomes. Phylogenetic analysis showed that the chloroplast genome could clearly distinguish between C. melo ssp. melo and C. melo ssp. agrestis. This study not only provides valuable knowledge on melon chloroplasts, but also offers a theoretical basis and technical support for the genetic breeding of melons.

Bacterial aggregation facilitates internalin-mediated invasion of Listeria monocytogenes.

Dissemination of food-borne L. monocytogenes in the host relies on internalin-mediated invasion, but the underlying invasion strategies remain elusive. Here we use live-cell microscopy to follow single cell interactions between individual human cells and L. monocytogenes and elucidate mechanisms associated with internalin B (InlB)-mediated invasion. We demonstrate that whilst a replicative invasion of nonphagocytic cells is a rare event even at high multiplicities of invasion, L. monocytogenes overcomes this by utilising a strategy relaying on PrfA-mediated ActA-based aggregation. We show that L. monocytogenes forms aggregates in extracellular host cell environment, which promote approximately 5-fold more host cell adhesions than the non-aggregating actA-ΔC mutant (which lacks the C-terminus coding region), with the adhering bacteria inducing 3-fold more intracellular invasions. Aggregation is associated with robust MET tyrosine kinase receptor clustering in the host cells, a hallmark of InlB-mediated invasion, something not observed with the actA-ΔC mutant. Finally, we show via RNA-seq analyses that aggregation involves a global adaptive response to host cell environment (including iron depletion), resulting in metabolic changes in L. monocytogenes and upregulation of the PrfA virulence regulon. Overall, our analyses provide new mechanistic insights into internalin-mediated host-pathogen interactions of L. monocytogenes.

The dynamic behavior of chromatophores marks the transition from bands to spots in leopard geckos

Reptilian skin coloration is spectacular and diverse, yet little is known about the ontogenetic processes that govern its establishment and the molecular signaling pathways that determine it. Here, we focus on the development of the banded pattern of leopard gecko hatchlings and the transition to black spots in the adult. With our histological analyses, we show that iridophores are present in the white and yellow bands of the hatchling and they gradually perish in the adult skin. Furthermore, we demonstrate that melanophores can autonomously form spots in the absence of the other chromatophores both on the regenerated skin of the tail and on the dorsal skin of the Mack Super Snow (MSS) leopard geckos. This color morph is characterized by uniform black coloration in hatchlings and black spots in adulthood; we establish that their skin is devoid of xanthophores and iridophores at both stages. Our genetic analyses identified a 13-nucleotide deletion in the PAX7 transcription factor of MSS geckos, affecting its protein coding sequence. With our single-cell transcriptomics analysis of embryonic skin, we confirm that PAX7 is expressed in iridophores and xanthophores, suggesting that it plays a key role in the differentiation of both chromatophores. Our in situ hybridizations on whole-mount embryos document the dynamics of the skin pattern formation and how it is impacted in the PAX7 mutants. We hypothesize that the melanophores-iridophores interactions give rise to the banded pattern of the hatchlings and black spot formation is an intrinsic capacity of melanophores in the postembryonic skin.

Rapid evolution of promoters from germline-specifically expressed genes including transposon silencing factors

BackgroundThe piRNA pathway in animal gonads functions as an ‘RNA-based immune system’, serving to silence transposable elements and prevent inheritance of novel invaders. In Drosophila, this pathway relies on three gonad-specific Argonaute proteins (Argonaute-3, Aubergine and Piwi) that associate with 23–28 nucleotide piRNAs, directing the silencing of transposon-derived transcripts. Transposons constitute a primary driver of genome evolution, yet the evolution of piRNA pathway factors has not received in-depth exploration. Specifically, channel nuclear pore proteins, which impact piRNA processing, exhibit regions of rapid evolution in their promoters. Consequently, the question arises whether such a mode of evolution is a general feature of transposon silencing pathways.ResultsBy employing genomic analysis of coding and promoter regions within genes that function in transposon silencing in Drosophila, we demonstrate that the promoters of germ cell-specific piRNA factors are undergoing rapid evolution. Our findings indicate that rapid promoter evolution is a common trait among piRNA factors engaged in germline silencing across insect species, potentially contributing to gene expression divergence in closely related taxa. Furthermore, we observe that the promoters of genes exclusively expressed in germ cells generally exhibit rapid evolution, with some divergence in gene expression.ConclusionOur results suggest that increased germline promoter evolution, in partnership with other factors, could contribute to transposon silencing and evolution of species through differential expression of genes driven by invading transposons.

Novel splicing variant and gonadal mosaicism in DYRK1A gene identified by whole-genome sequencing in multiplex autism spectrum disorder families.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with considerable genetic heterogeneity. The disorder is clinically diagnosed based on DSM-5 criteria, featuring deficits in social communication and interaction, along with restricted and repetitive behaviours. Here, we performed whole-genome sequencing (WGS) on four individuals with ASD from two multiplex families (MPX), where more than one individual is affected, to identify potential single nucleotide variants (SNVs) and structural variants (SVs) in coding and non-coding regions. A rigorous bioinformatics pipeline was employed for variant detection, followed by segregation analysis. Our investigation revealed an unreported splicing variant in the DYRK1A gene (c.-77 + 2T > C; IVS1 + 2T > C; NM_001396.5), in heterozygote form in two affected children in one of the families (family B), which was absent in the healthy parents and siblings. This finding suggests the presence of gonadal mosaicism in one of the parents, representing the first documented instance of such inheritance for a variant in the DYRK1A gene associated with ASD. Furthermore, we identified a 50bp deletion in intron 9 of the DLG2 gene in two affected patients from the same family, confirmed by PCR and Sanger sequencing. In Family A, we identified potential candidate variants associated with ASD shared by the two patients. These findings enhance our understanding of the genetic landscape of ASD, particularly in MPX families, and highlight the utility of WGS in uncovering novel genetic contributions to neurodevelopmental disorders.

PET Imaging of Differentiated Thyroid Cancer with TSHR-Targeted [89Zr]Zr-TR1402.

Thyroid cancer is the most common endocrine cancer, with differentiated thyroid cancers (DTCs) accounting for 95% of diagnoses. While most DTC patients are diagnosed and treated with radioiodine (RAI), up to 20% of DTC patients become RAI refractory (RAI-R). RAI-R patients have significantly reduced survival rates compared to patients who remain RAI-avid. This study explores [89Zr]Zr-TR1402 as a thyroid-stimulating hormone receptor (TSHR)-targeted PET radiopharmaceutical for DTC. [89Zr]Zr-TR1402 was synthesized with a molar activity of 25.9 MBq/nmol by conjugating recombinant human TSH (rhTSH) analogue TR1402 to chelator p-SCN-Bn-deferoxamine (DFO) in a molar ratio of 3:1 (DFO/TR1402) and radiolabeling with 89Zr (t1/2 = 78.4 h, β+ = 22.7%). As TSHR is absent in commonly available DTC-derived cell lines, TSHR was reintroduced via stable transduction by delivering a lentivirus containing the full-length coding region of the human TSHR gene. Receptor-mediated uptake of [89Zr]Zr-TR1402 was evaluated in vitro in stably transduced TSHR+ and wild-type TSHR- DTC cell lines. In vivo PET imaging was performed on Days 1-3 postinjection in male and female athymic nude mice bearing TSHR+ and TSHR- xenografts, along with ex vivo biodistribution on Day 3 postinjection. In vitro uptake of 1 nM [89Zr]Zr-TR1402 was significantly higher in TSHR+ THJ529T (P < 0.0001) and FTC133 (P < 0.01) cells than in TSHR- THJ529T and FTC133 cells. This uptake was shown to be specific in both TSHR+ THJ529T (P < 0.0001) and TSHR+ FTC133 (P < 0.0001) cells by blocking uptake with 250 nm DFO-TR1402. In vivo PET imaging showed accumulation of [89Zr]Zr-TR1402 in TSHR+ tumors, which was the highest on Day 1. In the male FTC133 xenograft model, ex vivo biodistribution confirmed a significant difference (P < 0.001) in uptake between FTC133+ (1.3 ± 0.1%ID/g) and FTC133- (0.8 ± 0.1%ID/g) tumors. A significant difference (P < 0.05) in uptake was also seen in the male THJ529T xenograft model between THJ529T+ (1.8 ± 0.6%ID/g) and THJ529T- (0.8 ± 0.4%ID/g) tumors. The in vitro and in vivo accumulation of [89Zr]Zr-TR1402 in TSHR-expressing DTC cell lines support the continued preclinical optimization of this approach.

Cross-Channel Color Image Encryption Scheme Based on Discrete Memristive Coupled Neurons and DWT Compression

To address the consumption and security of color images for transmission and storage, a cross-channel color image encryption scheme based on a discrete memristive coupled neuron model and DWT compression is designed in this article. Firstly, the dynamics of the discrete memristive coupled neuron system are analyzed and found to possess the hyperchaotic phenomenon, which provides sufficient security for the encryption scheme. Secondly, the color image processed by discrete wavelet transform (DWT) has a quarter of the previous capacity. Then, the color image is combined with a Hash function, and the resulting Hash sequence is given the initial value of the hyperchaotic system. Next, a particle swarm foraging algorithm (PSFA) is designed to better disrupt the correlation in the RGB channel. Finally, a complementary DNA coding rule is implemented for the further encryption of color images. Simulation results show that even with DWT lossy compression, the recovered image can be clearly seen. The performance analysis illustrates that under the hyperchaotic system, the proposed encryption algorithm brings higher security for color images.