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Background and Objectives: Phyllodes tumors are rare breast neoplasms with limited therapeutic options and poorly understood molecular characteristics. This study aimed to analyze genomic alterations and treatment outcomes in advanced phyllodes tumors using Japan’s national clinical genomic testing registry (C-CAT database) to identify potential therapeutic targets and predictive markers. Materials and Methods: We conducted a retrospective analysis of 60 phyllodes tumor cases from 80,329 patients registered in the C-CAT database between June 2019 and August 2024. Comprehensive genomic profiling was performed using multiple platforms including FoundationOne CDx, NCC OncoPanel, and other approved tests. Treatment responses were evaluated according to RECIST criteria, and pathogenic variants were assessed using established databases including ClinVar and OncoKB. Results: The cohort’s median age was 54 years (range: 13–79), with TERT promoter variants (70%), MED12 (52%), and TP53 (50%) mutations being the most frequent alterations. Forty patients received first-line chemotherapy, predominantly anthracycline-based regimens (n = 29). Although not reaching statistical significance, cases with CDKN2A and TERT alterations showed trends toward treatment resistance (OR > 3.0). One patient with a high tumor mutational burden (37/Mb) responded to pembrolizumab. Potential germline variants were identified in two cases (3.3%), involving MSH6 and TP53 alterations. Notably, no cases with CDKN2B alterations demonstrated treatment response (p = 0.09). Conclusions: Our findings suggest distinct molecular patterns in phyllodes tumors compared to other soft tissue sarcomas, with potential implications for treatment selection. The identification of specific genetic alterations associated with treatment resistance may guide therapeutic decision-making, while the presence of actionable mutations in select cases indicates potential opportunities for targeted therapy approaches. Full article

Nosema is a diverse fungal genus of unicellular, obligate symbionts infecting various arthropods. We performed comparative genomic analyses of seven Nosema species that infect bees, wasps, moths, butterflies, and amphipods. As intracellular parasites, these species exhibit significant genome reduction, retaining only about half of the genes found in free-living yeast genomes. Notably, genes related to oxidative phosphorylation are entirely absent (p < 0.001), and those associated with endocytosis are significantly diminished compared to other pathways (p < 0.05). All seven Nosema genomes display significantly lower G-C content compared to their microsporidian outgroup. Species-specific 5~12 bp motifs were identified immediately upstream of start codons for coding genes in all species (p ≤ 1.6 × 10⁻⁷²). Our RNA-seq data from Nosema muscidifuracis showed that this motif is enriched in highly expressed genes but depleted in lowly expressed ones (p < 0.05), suggesting it functions as a cis-regulatory element in gene expression. We also discovered diverse telomeric repeats within the genus. Phylogenomic analyses revealed two major Nosema clades and incongruency between the Nosema species tree and their hosts’ phylogeny, indicating potential host switch events (100% bootstrap values). This study advances the understanding of genomic architecture, gene regulation, and evolution of Nosema, offering valuable insights for developing strategies to control these microbial pathogens. Full article

The makapuno coconut endosperm is distinguished by its soft and irregular texture, in contrast to the solid endosperm of regular coconuts. To establish a scientific foundation for studying makapuno coconuts, callus was induced from makapuno endosperm using a combination of plant growth regulators. The induction was successful, and the resulting callus was subsequently subcultured for further study. Transcriptome sequencing of the makapuno callus identified 429 differentially expressed genes (DEGs), with 273 upregulated and 156 downregulated, compared to callus derived from regular coconut endosperm. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that these DEGs were involved in key metabolic pathways, including fructose and mannose metabolism, carbon fixation in photosynthetic organisms, galactose metabolism, and amino sugar and nucleotide sugar metabolism. Furthermore, lipid content analysis of the makapuno callus revealed a significantly higher total lipid level compared to regular callus, with notable differences in the levels of specific fatty acids, such as myristic acid, palmitic acid, and linoleic acid. This study establishes a novel platform for molecular biological research on makapuno coconuts and provides valuable insights into the molecular mechanisms underlying the formation of makapuno callus tissue. The findings also lay the groundwork for future research aimed at elucidating the unique properties of makapuno endosperm and exploring its potential applications. Full article

Background: Zingiber Mill., a morphologically diverse herbaceous perennial genus of Zingiberaceae, is distributed mainly in tropical to warm-temperate Asia. In China, species of Zingiber have crucial medicinal, edible, and horticultural values; however, their phylogenetic relationships remain unclear. Methods: To address this issue, the complete plastomes of the 29 Zingiber accessions were assembled and characterized. Comparative plastome analysis and phylogenetic analysis were conducted to develop genomic resources and elucidate the intraspecific phylogeny of Zingiber. Results: The newly reported plastomes ranged from 161,495 to 163,880 bp in length with highly conserved structure. Results of comparative analysis suggested that IR expansions/contractions and changes of repeats were the main reasons that influenced the genome size of the Zingiber plastome. A large number of SSRs and six highly variable regions (rpl20, clpP, ycf1, petA-psbJ, rbcL-accD, and rpl32-trnL) have been identified, which could serve as potential DNA markers for future population genetics or phylogeographic studies on this genus. The well-resolved plastome phylogeny suggested that Zingiber could be divided into three clades, corresponding to sect. Pleuranthesis (sect. Zingiber + sect. Dymczewiczia) and sect. Cryptanthium. Conclusions: Overall, this study provided a robust phylogeny of Zingiber plants in China, and the newly reported plastome data and plastome-derived markers will be of great significance for the accurate identification, protection, and agricultural management of Zingiber resources in the future. Full article

Linkage disequilibrium (LD) maps are fundamental tools for exploring the genetic basis of traits of interest in any species. Quantifying LD patterns in cattle breeds has been made possible due to the availability of huge quantities of SNPs through modern sequencing technology. The present research aims to determine and compare linkage disequilibrium levels at different distances on the genome of Sistani domestic cattle and subspecies of Bos taurus and Bos indicus based on genome SNP data. A total of 60 Bos indicus Sahiwal (dairy) and Nellore (beef), Bos taurus Hereford (beef) and Holstein (dairy), and Sistani cattle were sampled and genotyped using Illumina Bovine HD 770 k chip. To ensure the caliber of the sequencing, 10 samples (genetically sequenced cattle) were randomly chosen among all breeds represented. LD was evaluated at distances of 1–50 Kb, 50–100 Kb, 100–500 Kb, and 0.5–1 Mb, and average r² values for all autosomes were calculated within distance classes. For all breeds, the average r² was over 0.2 at distances less than 100 Kb, while for Sistani, Nellore, and Sahiwal, the average r² was above 0.2 between 100 and 500 Kb. Furthermore, for all breeds, the average r² exceeding 0.3 was noted at distances smaller than 50 Kb, while this amount for Holstein and Hereford was observed at distances between 50 and 100 Kb. In various breeds, greater changes in LD levels were observed (at <10 Kb distance). In this study, the Sistani breed showed LD decay patterns similar to indicine cattle (Nellore and Sahiwal), which may be due to the geographic proximity of the Sistan and Baluchestan province to Pakistan, the origin of indicine breeds (they may have had genetic or kinship relationships over a long historical period), or due to ascertainment bias in the SNP chips used. Full article

Background/Objectives: Due to the high frequency and severity of upper respiratory bacterial infections, probiotics could offer a new medical approach. We explored the antibacterial and anti-inflammatory properties of the new strain Lactiplantibacillus plantarum BIA and formulated a nasal spray. Methods: L. plantarum BIA was isolated from orange peel and taxonomically identified through 16S rRNA gene sequencing. Its antibacterial activity was tested against Pseudomonas aeruginosa, Streptococcus pyogenes, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus, while anti-inflammatory potential was evaluated by Griess assay. BIA genome was fully sequenced and analyzed to assess its safety. BIA was formulated in a freeze-dried matrix, containing prebiotics and cryoprotectants, to be reconstituted with a polymer solution. Solutions containing two types of hydroxypropyl methylcellulose (HPMC) and hyaluronic acid were evaluated as resuspending media and compared in terms of pH, viscosity, and mucoadhesion ability. The biological activity of BIA formulated as nasal spray was verified together with the stability of the selected formulations. Results: L. plantarum BIA inhibited human pathogens’ growth and showed anti-inflammatory activity and a safe profile. In the best-performing formulation, the probiotic is lyophilized in 10% fructooligosaccharides, 0.1% ascorbic acid, and 0.5% lactose and reconstituted with HPMC high viscosity 1% w/v. This composition ensured the probiotic’s viability for up to six months in its dried form and one week after reconstitution. It also allowed interaction with the nasal mucosa, preserving its antimicrobial and anti-inflammatory activities. Conclusion: The developed nasal spray could become a promising formulation in the field of nasal infectious and inflammatory diseases. Full article

The gut microbiota plays a crucial role in modulating the immune response during COVID-19, with several studies reporting significant alterations in specific bacterial genera, including Akkermansia, Bacteroides, Bifidobacterium, Faecalibacterium, Lactobacillus, Oscillospira, and Ruminococcus. These genera are symbionts of the gut microbiota and contribute to host health. However, comparing results across studies is challenging due to differences in analysis methods and reference databases. We screened 16S rRNA raw datasets available in public databases on COVID-19, focusing on the V3–V4 region of the bacterial genome. In total, seven studies were included. All samples underwent the same bioinformatics pipeline, evaluating the differential abundance of these seven bacterial genera at each level of severity. The reanalysis identified significant changes in differential abundance. Bifidobacterium emerged as a potential biomarker of disease severity and a therapeutic target. Bacteroides presented a complex pattern, possibly related to disease-associated inflammation or opportunistic pathogen growth. Lactobacillus showed significant changes in abundance across the COVID-19 stages. On the other hand, Akkermansia and Faecalibacterium did not show significant differences, while Oscillospira and Ruminococcus produced statistically significant results but with limited relevance to COVID-19 severity. Our findings reveal new insights into the differential abundance of key bacterial genera in COVID-19, particularly Bifidobacterium and Bacteroides. Full article

The genus Vitis, known for its economically important fruit—grape—is divided into three geographical groups, American, East Asian, and Eurasian, along with a hybrid group. However, previous studies on grape phylogeny using chloroplast genomes have been hindered by limited sample sizes and inconsistent methodologies, resulting in inaccuracies. In this study, we employed the GetOrganelle software with consistent parameters to assemble the chloroplast genomes of 21 grape cultivars, ensuring comprehensive representation across four distinct groups. A comparative analysis of the 21 grape cultivars revealed structural variation, showing chloroplast genome sizes ranging from 160,813 bp to 161,275 bp. In 21 Vitis cultivars, genome annotation revealed 134 to 136 genes, comprising 89 to 91 protein-coding genes (PCGs), 37 tRNAs, and 8 rRNAs. Our observations have pinpointed specific occurrences of contraction and expansion phenomena at the interfaces between inverted repeat (IR) regions and single-copy (SC) regions, particularly in the vicinity of the rpl2, ycf1, ndhF, and trnN genes. Meanwhile, a total of 193 to 198 SSRs were identified in chloroplast genomes. The diversification pattern of chloroplast genomes exhibited strong concordance with the phylogenetic relationships of the Euvitis subgenera. Phylogenetic analysis based on conserved chloroplast genome strongly clustered the grape varieties according to their geographical origins. In conclusion, these findings enhance our understanding of chloroplast genome variation in Vitis populations and have important implications for cultivar selection, breeding, and conservation efforts. Full article

Cancer remains a leading cause of death worldwide. Also threatening the public is the emergence of antibiotic resistance to existing medicines. Despite the challenge to produce viable natural products to market, there continues to be a need within public health to provide new chemotherapeutic drugs such as those exhibiting cytotoxicity and tumor cell growth-inhibitory properties. As marine genomic research advances, it is apparent that marine-derived sediment harbors uniquely potent bioactive compounds compared to their terrestrial counterparts. The Streptomyces genus in particular produces more than 30% of all secondary metabolites currently approved for human health, thus harboring unexplored reservoirs of chemotherapeutic and antibiotic agents to combat emerging disease. The present study identifies the presence of Streptomyces hygroscopicus and rapamycinicus in environmental sediment at locations within the U.S. Stellwagen Bank National Marine Sanctuary (SBNMS) from 2017 to 2022. Sequencing and bioinformatics methods catalogued biosynthetic gene clusters (BGCs) that drive cytotoxic and antibiotic biochemical processes in samples collected from sites permittable and protected to fishing activity. Poisson regression models confirmed that Sites 1 and 3 had significantly higher occurrences of rapamycinicus than other sites (p < 0.01). Poisson regression models confirmed that Sites 1, 2 and 3 had significantly higher occurrence for Streptomyces hygroscopicus across sites (p < 0.05). Interestingly, permitted fishing sites showed a greater prevalence of both species. Statistical analyses showed a significant difference in aligned hits with polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) by site and between species with hygroscopicus showing a greater quantity than rapamycinicus among Streptomyces spp. (p < 0.05; F = 4.7 > F crit). Full article

Autolysis in the sea cucumber Apostichopus japonicus is typically triggered by degradation caused by microorganisms within their bodies. However, information on this topic remains limited. Recently, we isolated and purified a bacterial strain from hydrolyzed instant sea cucumber samples. To investigate its potential role in the autolysis process, this study employed whole-genome sequencing and metabolomics to explore its genetic and metabolic characteristics. The identified strain was classified as Lysinibacillus xylanilyticus and designated with the number XL-2024. Its genome size is 5,075,210 bp with a GC content of 37.33%, encoding 5275 genes. Functional database comparisons revealed that the protein-coding genes were distributed among glucose metabolism hydrolase, metal hydrolase, lysozyme, cell wall hydrolase, and CAZymes. Compared to 20 closely related strains, L. xylanilyticus XL-2024 shared 1502 core homologous genes and had 707 specific genes. These specific genes were mainly involved in the carbohydrate metabolism pathway and exhibited glycosyl bond hydrolase activity. Metabolomic analysis showed that L. xlanilyticus XL-2024 produced several metabolites related to polysaccharide degradation, including peptidase, glucanase, and pectinase. Additionally, the presence of antibacterial metabolites such as propionic acid and ginkgo acid among its metabolites may enhance the stability of the sea cucumber hydrolysate. In summary, L. xylanilyticus XL-2024 may play a pivotal role in the autolysis of A. japonicus. The results of this study provide a strong foundation for understanding how to prevent autolysis in A. japonicus and for better utilizing L. xylanilyticus XL-2024. Full article

Recent findings indicate that human microbiota can excrete trace amines, dopamine, and serotonin. These neurotransmitters (NTs) can either affect classical neurotransmitter signaling or directly trigger trace amine-associated receptors (TAARs), with still unclear consequences for host physiology. Compared to gut microbiota, less information is available on the role of skin microbiota in NT production. To explore this, 1909 skin isolates, mainly from the genera Staphylococcus, Bacillus, and Corynebacterium, were tested for NT production. Only 6.7% of the isolates were capable of producing NTs, all of which belonged to the Staphylococcus genus. Based on substrate specificity, we identified two distinct profiles among the NT producers. One group primarily produced tryptamine (TRY) and phenylethylamine (PEA), while the other mainly produced tyramine (TYM) and dopamine (Dopa). These differing production profiles could be attributed to the activity of two distinct aromatic amino acid decarboxylase enzymes, SadA and TDC, responsible for generating the TRY/PEA and TYM/Dopa product spectra, respectively. SadA and TDC orthologues differ in structure and size; SadA has approximately 475 amino acids, whereas the TDC type consists of about 620 amino acids. The genomic localization of the respective genes also varies: tdc genes are typically found in small, conserved gene clusters, while sadA genes are not. The heterologous expression of sadA and tdc in Escherichia coli yielded the same product spectrum as the parent strains. The possible effects of skin microbiota-derived NTs on neuroreceptor signaling in the human host remain to be investigated. Full article

The cosmopolitan genus Hedysarum L. (Fabaceae) is divided into sections Hedysarum, Stracheya, and Multicaulia. This genus includes many valuable medicinal, melliferous, and forage species. The species taxonomy and genome relationships within the sections are still unclear. We examined intra- and interspecific diversity in the section (sect.) Hedysarum based on repeatome analyses using NGS data, bioinformatic technologies, and chromosome FISH mapping of 35S rDNA, 5S rDNA, and the identified satellite DNA families (satDNAs). A comparison of repeatomes of H. alpinum, H. theinum, and H. flavescens revealed differences in their composition. However, similarity in sequences of most satDNAs indicated a close relationship between genomes within sect. Hedysarum. New effective satDNA chromosomal markers were detected, which is important for karyotype analyses within Hedysarum. Intra- and interspecific variability in the chromosomal distribution patterns of the studied markers were revealed, and species karyograms were constructed. These results provided new insight into the karyotype structures and genomic diversity within sect. Hedysarum, clarified the systematic position of H. sachalinense and H. arcticum, and confirmed the distant genomic relationships between species from sections Hedysarum and Multicaulia. Our findings are important for further comparative genome studies within the genus Hedysarum. Full article

Background: MicroRNAs are well established as master regulators of carcinogenesis and potential biomarkers in breast cancer (BC). In a preliminary effort, we found miR-27a-5p to be significantly downregulated in experimentally derived mammospheres and BC patients from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset. Objectives. Herein, we sought to investigate the putative involvement of miR-27a-5p in promoting a migratory phenotype of breast cancer cells, and establish whether miR-27a-5p is associated with patient clinicopathological characteristics. Methods: miR-27a-5p capability of inducing a metastasis-prone cell phenotype was analyzed in SUM159 and MDA-MB-231, both representing the triple negative BC subtype. miR-27a-5p expression profile was carried out in a cohort of 232 BC patients and normal breast tissues (NBTs) by RT-qPCR. Results: Transient miR-27a-5p inhibition did not affect cell proliferation but led to a significant increase of cell migration in knocked-down compared to control cells. Following quantification in the patient cohort, miR-27a-5p was found higher in NBTs (Median 2.28, IQR 1.50–5.40) and pre-invasive breast lesions (Median 3.32, IQR 1.68–4.32) compared to tumors. In particular, miR-27a-5p was less expressed in patients with synchronous (Median 1.03, IQR 0.83–1.58) or metachronous (Median 1.83, IQR 1.29–3.17) metastases than in patients free from metastases after a 5-year follow-up (Median 2.17, IQR 1.19–3.64), suggesting that miR-27a-5p expression is negatively correlated with breast pathology evolution (R = −0.13, p = 0.038). However, time-to-event analysis did not highlight significant associations with patient outcome in either our internal cohort or TCGA-BRCA dataset. Conclusions: Our study suggests a potential role of miR-27a-5p as tumor suppressor miRNA in breast cancer. Further investigations may help define its biomarker potential in each breast cancer subtype, and identify other molecular partners as targets for new interventions. Full article

Acinetobacter baumannii is a Gram-negative opportunistic pathogen responsible for severe hospital-associated infections. Owing to its ability to develop resistance to a wide range of antibiotics, novel therapeutic strategies are urgently needed. One promising approach is to target bacterial carbonic anhydrases (CAs; EC 4.2.1.1), which are enzymes critical for various metabolic processes. The genome of A. baumannii encodes a β-CA (βAbauCA), which is essential for producing bicarbonate ions required in the early stages of uridine triphosphate (UTP) synthesis, a precursor for the synthesis of peptidoglycans, which are vital components of the bacterial cell wall. This study aimed to inhibit βAbauCA in vitro, with the potential to impair the vitality of the pathogen in vivo. We conducted sequence and structural analyses of βAbauCA to explore its differences from those of human CAs. Additionally, kinetic and inhibition studies were performed to investigate the catalytic efficiency of βAbauCAβ and its interactions with sulfonamides and their bioisosteres, classical CA inhibitors. Our results showed that βAbauCA has a turnover rate higher than that of hCA I but lower than that of hCA II and displays distinct inhibition profiles compared to human α-CAs. Based on the obtained data, there are notable differences between the inhibition profiles of the human isoforms CA I and CA II and bacterial βAbauCA. This could open the door to designing inhibitors that selectively target bacterial β-CAs without affecting human α-CAs, as well as offer a novel strategy to weaken A. baumannii and other multidrug-resistant pathogens. Full article

Background: The Neuro-2a cell line, derived from a murine neuroblastoma (NB), was established as early as 1969 and originates from a transplantable tumor that arose spontaneously in an A/Jax male mouse in 1940. Since then, it has been applied in over 10,000 studies and is used by the World Organization for Animal Health for the routine diagnosis of rabies. Surprisingly, however, Neuro-2a has never been genetically characterized in detail; this study fills that gap. Methods: The Neuro-2a cell line and two of its derivatives, Neuro-2a TR-alpha and Neuro-2a TR-beta, were analyzed for their chromosomal constitution using molecular cytogenetic approaches. Array comparative genomic hybridization was performed to characterize copy number alterations. Results: Neuro-2A has a hyper-tetraploid karyotype with 70 to 97 chromosomes per cell, and the karyotypes of its two examined derivatives were quite similar. Neither of them had a Y-chromosome. The complex karyotype of Neuro-2a includes mitotically stable dicentres, neocentrics, and complex rearrangements resembling chromothripsis events. Although no amplification of euchromatin or oncogenes was detected, there are five derivative chromosomes with the amplification of centromere-near heterochromatic material and 1–5 additional derivatives consisting only of such material. Conclusions: Since satellite DNA amplification has recently been found in advanced human tumors, this finding may be the corresponding equivalent in mice. An in silico translation of the obtained results into the human genome indicated that Neuro-2A is suitable as a model for advanced human NB. Full article