Search

Wheat can tolerate a mild water deficit, but prolonged drought causes a number of detrimental physiological changes resulting in a substantial decrease in productivity. The present study evaluates the potential of the natural plant growth regulator melatonin to alleviate the negative effects of moderate drought in two Bulgarian winter wheat cultivars at the early vegetative stage. Melatonin doses of 75 µM were root-supplemented 24 h before or after the stress period. The levels of several biometric parameters, osmolyte content and stress indicators as well as the expression of genes coding for key enzymes of the proline biosynthesis pathway were analyzed in leaves at the end of the drought stress and after two and four days of recovery. Applied alone, melatonin did not exert significant effects on most of the monitored parameters. Water deprivation negatively affected seedlings' fresh weight and water content and increased the stress markers and osmolyte levels. These were accompanied by a high accumulation of TaP5CS and TaP5CR transcripts coding for the enzymes Δ-pyrroline-5-carboxylate synthase and Δ-pyrroline-5-carboxylate reductase, respectively. The effect of melatonin in reducing drought stress was similar whether applied before or after exposure, though slightly more effective when used as a pre-treatment. [ABSTRACT FROM AUTHOR]

Leishmania spp. commonly infects phagocytic cells of the immune system, particularly macrophages, employing various immune evasion strategies that enable their survival by altering the intracellular environment. In mammals, these parasites establish persistent infections by modulating gene expression in macrophages, thus interfering with immune signaling and response pathways, ultimately creating a favorable environment for the parasite's survival and reproduction. In this study, our objective was to use data mining and subsequent filtering techniques to identify the genes that play a crucial role in the infection process of Leishmania spp. We aimed to pinpoint genes that have the potential to influence the progression of Leishmania infection. To achieve this, we exploited prior, curated knowledge from major databases and constructed 16 datasets of human molecular information consisting of coding genes and corresponding proteins. We obtained over 400 proteins, identifying approximately 200 genes. The proteins coded by these genes were subsequently used to build a network of protein–protein interactions, which enabled the identification of key players; we named this set Predicted Genes. Then, we selected approximately 10% of Predicted Genes for biological validation. THP-1 cells, a line of human macrophages, were infected with Leishmania major in vitro for the validation process. We observed that L. major has the capacity to impact crucial genes involved in the immune response, resulting in macrophage inactivation and creating a conducive environment for the survival of Leishmania parasites. [ABSTRACT FROM AUTHOR]

Background: Phanera Lour., a genus in the subfamily Cercidoideae of the family Leguminosae, is characterized by woody liana habit, tendrils, and distinctive bilobate or bifoliolate leaves. The genus holds important medicinal value and constitutes a complex group characterized by morphological diversity and unstable taxonomic boundaries. However, limited information on the chloroplast genomes of this genus currently available constrains our understanding of its species diversity. Hence, it is necessary to obtain more chloroplast genome information to uncover the genetic characteristics of this genus. Methods: We collected and assembled the complete chloroplast genomes of nine representative Phanera plants, including Phanera erythropoda, Phanera vahlii, Phanera aureifolia, Phanera bidentata, Phanera japonica, Phanera saigonensis, Phanera championii, Phanera yunnanensis, and Phanera apertilobata. We then conducted a comparative analysis of these genomes and constructed phylogenetic trees. Results: These species are each characterized by a typical quadripartite structure. A total of 130–135 genes were annotated, and the GC content ranged from 39.25–42.58%. Codon usage analysis indicated that codons encoding alanine were dominant. We found 82–126 simple sequence repeats, along with 5448 dispersed repeats, mostly in the form of forward repeats. Phylogenetic analysis revealed that 16 Phanera species form a well-supported monophyletic group, suggesting a possible monophyletic genus. Furthermore, 10 hypervariable regions were detected for identification and evolutionary studies. Conclusions: We focused on comparing chloroplast genome characteristics among nine Phanera species and conducted phylogenetic analyses, laying the foundation for further phylogenetic research and species identification of Phanera. [ABSTRACT FROM AUTHOR]

Rice (Oryza) is a genus in the Gramineae family, which has grown widely all over the world and is a staple food source for people's survival. The genetic information of rice has garnered significant attention in recent years, prompting numerous researchers to conduct extensive investigations in this field. But rice mitochondrial codon usage patterns have received little attention. The present study systematically analyzed the codon usage patterns and sources of variance in the mitochondrial genome sequences of five rice species by the CodonW and R software programs. Our results revealed that the GC content of codons in rice mitochondrial genome genes was determined to be 43.60%. Notably, the individual codon positions exhibited distinct GC contents: 48.00% for position 1, 42.65% for position 2, and 40.16% for position 3. These findings suggest the preference of the rice mitochondrial genome for codons ending in A or U. A weak codon bias was observed, with the effective number of codons (ENC) varying between 40.02 and 61.00, with an average value of 54.34. Subsequently, we identified 25 identical high-frequency codons in five rice mitochondrial genomes, with 11 codons ending in A and 12 codons ending in U. The regression lines in the neutrality plot exhibited slopes of less than 0.5 in five rice species, indicating a predominant role of natural selection, while mutation pressure remained relatively insignificant. In the PR2-plot analysis, most of the genes were located in the right half of the plot, indicating that the third base of the synonymous codon was preferred to end in G than C. Additionally, the ENC plot and ENC ratio analysis unveiled that codon preferences in the rice mitochondrial genome were predominantly influenced by natural selection rather than mutational pressure. The analysis of correspondence revealed distinct variations in the codon usage pattern across five rice mitochondrial genomes. Based on the RSCU values of species, a cluster tree was inconsistent with the mitochondrial genetic data, indicating that RSCU data could not be used as a basis for classification at the species level in the Oryza genus. These results will help decide the specific types of natural selection pressures influencing codon usage and improve the expression of exogenous genes in rice mitochondrial genomes by optimizing their codons. [ABSTRACT FROM AUTHOR]

Serrated polyposis syndrome (SPS) is characterized by the development of multiple colorectal serrated polyps and increased predisposition to colorectal cancer (CRC). However, the molecular basis of SPS, especially in cases presenting family history of SPS and/or polyps and/or CRC in first-degree relatives (SPS-FHP/CRC), is still poorly understood. In a previous study, we proposed the existence of two molecular entities amongst SPS-FHP/CRC families, proximal/whole-colon and distal SPS-FHP/CRC, according to the preferential location of lesions and somatic events involved in tumor initiation. In the present study, we aimed to investigate these distinct subgroups of SPS patients in a larger cohort at the germline level and to identify the genetic defects underlying an inherited susceptibility for these two entities. Next-generation sequencing was performed using multigene analysis with a custom-designed panel in a Miseq platform in 60 SPS patients (with and without/unknown FHP/CRC). We found germline pathogenic variants in 6/60 patients (ATM, FANCM, MITF, RAD50, RAD51C, and RNF43). We also found variants of unknown significance (VUS), with prediction of probable damaging effect in 23/60 patients (ATM, BLM, BRCA1, FAN1, ERCC2, ERCC3, FANCA, FANCD2, FANCL, MSH2, MSH6, NTHL1, PALB2, PDGFRA, PMS2, PTCH1, RAD51C, RAD51D, RECQL4, TSC2, WRN, and XRCC5 genes). Most variants were detected in gene coding for proteins of the Fanconi Anemia (FA) pathway involved in the DNA Interstrand-Cross Link repair (ICLR). Notably, variants in ICLR genes were significantly more frequent in the proximal/whole-colon than in the distal subgroup [15/44 (34%) vs 1/16 (6%), p = 0.025], as opposed to the non-ICLR genes that were slightly more frequent in the distal group [8/44 (18%) vs. 5/16 (31%), p > 0.05]. Germline defects in the DNA-ICLR genes may contribute to increased serrated colorectal polyps/carcinoma risk in SPS patients, particularly in proximal/whole-colon SPS. The inclusion of DNA-ICLR genes in the genetic diagnosis of SPS patients, mainly in those with proximal/whole-colon lesions, should be considered and validated by other studies. In addition, patients with germline defects in the DNA-ICLR genes may be more sensitive to treatment with platinum-based therapeutics, which can have implications in the clinical management of these patients. [ABSTRACT FROM AUTHOR]

Codon bias analysis of SARS-CoV-2 reveals suboptimal adaptation for translation in human cells it infects. The detailed examination of the codons preferentially used by SARS-CoV-2 shows a strong preference for LysAAA, GlnCAA, GluGAA, and ArgAGA, which are infrequently used in human genes. In the absence of an adapted tRNA pool, efficient decoding of these codons requires a 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2) modification at the U34 wobble position of the corresponding tRNAs (tLysUUU; tGlnUUG; tGluUUC; tArgUCU). The optimal translation of SARS-CoV-2 open reading frames (ORFs) may therefore require several adjustments to the host's translation machinery, enabling the highly biased viral genome to achieve a more favorable "Ready-to-Translate" state in human cells. Experimental approaches based on LC-MS/MS quantification of tRNA modifications and on alteration of enzymatic tRNA modification pathways provide strong evidence to support the hypothesis that SARS-CoV-2 induces U34 tRNA modifications and relies on these modifications for its lifecycle. The conclusions emphasize the need for future studies on the evolution of SARS-CoV-2 codon bias and its ability to alter the host tRNA pool through the manipulation of RNA modifications. [ABSTRACT FROM AUTHOR]

The rise of antibiotic-resistant bacteria in clinical settings has become a significant global concern. Among these bacteria, Acinetobacter baumannii stands out due to its remarkable ability to acquire resistance genes and persist in hospital environments, leading to some of the most challenging infections. Horizontal gene transfer (HGT) plays a crucial role in the evolution of this pathogen. The A. baumannii AMA205 strain, belonging to sequence type ST79, was isolated from a COVID-19 patient in Argentina in 2021. This strain's antimicrobial resistance profile is notable as it harbors multiple resistance genes, some of which had not been previously described in this species. The AmpC family β-lactamase blaCMY-6, commonly found in Enterobacterales, had never been detected in A. baumannii before. Furthermore, this is the first ST79 strain known to carry the carbapenemase blaNDM-1 gene. Other acquired resistance genes include the carbapenemase blaOXA-23, further complicating treatment. Susceptibility testing revealed high resistance to most antibiotic families, including cefiderocol, with significant contributions from blaCMY-6 and blaNDM-1 genes to the cephalosporin and carbapenem resistance profiles. The A. baumannii AMA205 genome also contains genetic traits coding for 111 potential virulence factors, such as the iron-uptake system and biofilm-associated proteins. This study underscores A. baumannii's ability to acquire multiple resistance genes and highlights the need for alternative therapies and effective antimicrobial stewardship to control the spread of these highly resistant strains. [ABSTRACT FROM AUTHOR]

The olive fruit is a drupe whose development and ripening takes several months from flowering to full maturation. During this period, several biochemical and physiological changes occur that affect the skin color, texture, composition, and size of the mesocarp. The final result is a fruit rich in fatty acids, phenolic compounds, tocopherols, pigments, sterols, terpenoids, and other compounds of nutritional interest. In this work, a transcriptomic analysis was performed using flowers (T0) and mesocarp tissue at seven different stages during olive fruit development and ripening (T1–T7) of the 'Picual' cultivar. A total of 1755 genes overexpressed at any time with respect to the flowering stage were further analyzed. These genes were grouped into eight clusters based on their expression profile. The gene enrichment analysis revealed the most relevant biological process of every cluster. Highlighting the important role of hormones at very early stages of fruit development (T1, Cluster 1), whereas genes involved in fatty acid biosynthesis were relevant throughout the fruit developmental process. Hence, genes coding for different fatty acid desaturase (SAD, FAD2, FAD3, FAD4, FAD5, FAD6, and FAD7) enzymes received special attention. In particular, 26 genes coding for different fatty acid desaturase enzymes were identified in the 'Picual' genome, contributing to the improvement of the genome annotation. The expression pattern of these genes during fruit development corroborated their role in determining fatty acid composition. [ABSTRACT FROM AUTHOR]

Integrating Artificial Intelligence (AI) into Precision Medicine (PM) is redefining healthcare, enabling personalized treatments tailored to individual patients based on their genetic code, environment, and lifestyle. AI's ability to analyze vast and complex datasets, including genomics and medical records, facilitates the identification of hidden patterns and correlations, which are critical for developing personalized treatment plans. Unsupervised Learning (UL) is particularly valuable in PM as it can analyze unstructured and unlabeled data to uncover novel disease subtypes, biomarkers, and patient stratifications. By revealing patterns that are not explicitly labeled, unsupervised algorithms enable the discovery of new insights into disease mechanisms and patient variability, advancing our understanding of individual responses to treatment. However, the integration of AI into PM presents some challenges, including concerns about data privacy and the rigorous validation of AI models in clinical practice. Despite these challenges, AI holds immense potential to revolutionize PM, offering a more personalized, efficient, and effective approach to healthcare. Collaboration among AI developers and clinicians is essential to fully realize this potential and ensure ethical and reliable implementation in medical practice. This review will explore the latest emerging UL technologies in the biomedical field with a particular focus on PM applications and their impact on human health and well-being. [ABSTRACT FROM AUTHOR]

The common assumption is that genetic information is built on a four-symbol alphabet, i.e., DNA nucleotides, the smallest meaningful blocks of genomes are codon triplets, and the record of genetic information does not contain any asserted symbols playing the role of the space. It is, however, well known that some nucleotides in some codons are redundant. Our study, therefore, tests the alternative scenario. As the same nucleotide may play various semiotic roles, the genomic alphabet actually contains seven semiotic symbols. Consequently, the meaningful fragments of genomes (words) can be of different sizes, and there are asserted symbols in the record of genomic information. If this is true, then, similarly to natural languages, the frequency-range of these genomic words should follow the power-law distribution. The presented hypothesis was tested, in comparison to competitive (codon-based and n-tuple) forms of tokenization, on a wide range of genomic texts. [ABSTRACT FROM AUTHOR]

A better understanding of protein–protein interaction (PPI) networks representing physical interactions between proteins could be beneficial for evolutionary insights as well as for practical applications such as drug development. As a statistical model for PPI networks, duplication–divergence models have been proposed, but they suffer from resulting in either very sparse networks in which most of the proteins are isolated, or in networks which are much denser than what is usually observed, having almost no isolated proteins. Moreover, in real networks, where a gene codes a protein, gene loss may occur. The loss of nodes has not been captured in duplication–divergence models to date. Here, we introduce a new duplication–divergence model which includes node loss. This mechanism results in networks in which the proportion of isolated proteins can take on values which are strictly between 0 and 1. To understand this new model, we apply strong and weak attacks to networks from duplication–divergence models with and without node loss, and compare the results to those obtained when carrying out similar attacks on two real PPI networks of E. coli and of S. cerevisiae. We find that the new model more closely reflects the damage caused by strong and weak attacks found in the PPI networks. [ABSTRACT FROM AUTHOR]

The 18-exon human TKFC gene codes for dual-activity triokinase and FMN cyclase (TKFC) in an ORF, spanning from exon 2 to exon 18. In addition to TKFC-coding transcripts (classified as tkfc type by their intron-17 splice), databases contain evidence for alternative TKFC transcripts, but none of them has been expressed, studied, and reported in the literature. A novel full-ORF transcript was cloned from brain cDNA and sequenced (accession no. DQ344550). It results from an alternative 3′ splice-site in intron 17. The cloned cDNA contains an ORF also spanning from exon 2 to exon 18 of the TKFC gene but with a 56-nt insertion between exons 17 and 18 (classified as tkfc_ins56 type). This insertion introduces an in-frame stop, and the resulting ORF codes for a shorter TKFC variant, which, after expression, is enzymatically inactive. TKFC intron-17 splicing was found to be differentially expressed in human tissues. In a multiple-tissue northern blot using oligonucleotide probes, the liver showed a strong expression of the tkfc-like splice of intron 17, and the heart preferentially expressed the tkfc_ins56-like splice. Through a comparison to global expression data from massive-expression studies of human tissues, it was inferred that the intestine preferentially expresses TKFC transcripts that contain neither of those splices. An analysis of transcript levels quantified by RNA-Seq in the GTEX database revealed an exception to this picture due to the occurrence of a non-coding short transcript with a tkfc-like splice. Altogether, the results support the occurrence of potentially relevant transcript variants of the TKFC gene, differentially expressed in human tissues. (This work is dedicated in memoriam to Professor Antonio Sillero, 1938–2024, for his lifelong mentoring and his pioneering work on triokinase). [ABSTRACT FROM AUTHOR]

Simple Summary: Large crickets in the family Anostostomatidae, which are locally known as wētā, are a prominent feature of New Zealand endemic diversity and ecology. However, their systematics are poorly resolved, which reflects the wider uncertainty about the treatment on this orthopteran family. We examined the relationships among the New Zealand genera with representatives of the fauna from nearby Australia and New Caledonia by using a DNA dataset. We found that the New Zealand genera comprised four distinct lineages that were each more closely related to taxa outside New Zealand. We also found that the most speciose genus in New Zealand comprised two paraphyletic taxa. The Anostostomatidae of Aotearoa New Zealand are well-characterized at the genus and species level, but the higher-level systematics of the family as a whole remain poorly resolved. We tested the hypothesis that the New Zealand anaostostomatid fauna consists of a single monophyletic group consistent with a single common ancestor. For phylogenetic analysis, we sampled the genera in Aotearoa New Zealand as well as representatives of the family from Australia and New Caledonia. Maximum likelihood analyses including topological comparison statistics with a DNA alignment of thirteen mitochondrial and four nuclear protein coding genes rejected the monophyly of lineages in New Zealand. We found phylogenetic support for four separate New Zealand lineages; three with their closest relatives in Australia and one in New Caledonia. The New Zealand genus Hemiandrus is paraphyletic and the establishment of a morphologically distinct genus is justified. We determined that six of the valid species previously placed in Hemiandrus form a distinct clade that we designated here as Anderus gen. nov. The putative Hemiandrus that we sampled from Australia was sister to neither of the New Zealand lineages. [ABSTRACT FROM AUTHOR]

Malanin is a new type II ribosome-inactivating protein (RIP) purified from Malania oleifera, a rare, endangered tree is only found in the southwest of Guangxi Province and the southeast of Yunnan Province, China. The gene coding sequence of malanin was found from the cDNA library of M. oleifera seeds by employing the ten N-terminal amino acid sequences of malanin, DYPKLTFTTS for chain-A and DETXTDEEFN (X was commonly C) for chain-B. The results showed a 65% amino acid sequence homology between malanin and ricin by DNAMAN 9.0 software, the active sites of the two proteins were consistent, and the four disulfide bonds were in the same positions. The primary sequence and three-dimensional structures of malanin and ricin are likely to be very similar. Our studies suggest that the mechanism of action of malanin is expected to be analogous to ricin, indicating that it is a member of the type II ribosome-inactivating proteins. This result lays the foundation for further study of the anti-tumor activities of malanin, and for the application of malanin as a therapeutic agent against cancers. [ABSTRACT FROM AUTHOR]

Pathogenic variants localized in the gene coding for the Fukutin-Related Protein (FKRP) are responsible for Limb-Girdle Muscular Dystrophy type 9 (LGMDR9), Congenital Muscular Dystrophies type 1C (MDC1C), Walker–Warburg Syndrome (WWS), and Muscle–Eye–Brain diseases (MEBs). LGMDR9 is the fourth most common hereditary Limb Girdle Muscular Dystrophy in Italy. LGMDR9 patients with severe disease show an overlapping Duchenne/Becker phenotype and may have secondary dystrophin reduction on muscle biopsy. We conducted a molecular analysis of the FKRP gene by direct sequencing in 153 patients from Southern Italy (Calabria) with Duchenne/Becker-like phenotypes without confirmed genetic diagnosis. Mutational screening of the patients (112 men and 41 women, aged between 5 and 84 years), revealed pathogenic variants in 16 subjects. The most frequent variants identified were c.427C > A, p.R143S, and c.826C > A, p.L276I (NM_024301.5). The results obtained show that the Duchenne/Becker-like phenotype is frequently determined by mutations in the FKRP gene in our cohort and highlight the importance of considering LGMDR9 in the differential diagnosis of dystrophinopathies in Calabria. Finally, this study, which, to our knowledge, is the first conducted on Calabrian subjects, will contribute to the rapid identification and management of LGMDR9 patients. [ABSTRACT FROM AUTHOR]

Alternative splicing (AS) is a crucial post-transcriptional regulatory mechanism that contributes to proteome complexity and versatility in different plant species. However, detailed AS exploration in diploid cotton during fiber development has not been reported. In this study, we comparatively analyzed G. arboreum and G. raimondii AS events during fiber development using transcriptome data and identified 9690 and 7617 AS events that were distributed in 6483 and 4859 genes, respectively. G. arboreum had more AS genes and AS events than G. raimondii, and most AS genes were distributed at both ends of all 13 chromosomes in both diploid cotton species. Four major AS types, including IR, SE, A3SS, and A5SS, were all experimentally validated through RT-PCR assays. G. arboreum and G. raimondii had only 1888 AS genes in common, accounting for one-third and one-half of the total number of AS genes, respectively. Furthermore, we found a lysine-specific demethylase coding gene with a different AS mechanism in G. arboreum and G. raimondii, in which AS isoforms lacked part of a key conserved domain. Our findings may provide new directions for the discovery of functional genes involved in cotton species differentiation. [ABSTRACT FROM AUTHOR]

Caliciviruses have positive-sense RNA genomes, typically with short 5′-untranslated regions (5′UTRs) that precede the long open reading frame 1 (ORF1). Exceptionally, some avian caliciviruses have long 5′UTRs containing a picornavirus-like internal ribosomal entry site (IRES), which was likely acquired by horizontal gene transfer. Here, we identified numerous additional avian calicivirus genomes with IRESs, predominantly type 2, and determined that many of these genomes contain a ~200–300 codon-long ORF (designated ORF1*) that overlaps the 5′-terminal region of ORF1. The activity of representative type 2 IRESs from grey teal calicivirus (GTCV) and Caliciviridae sp. isolate yc-13 (RaCV1) was confirmed by in vitro translation. Toeprinting showed that in cell-free extracts and in vitro reconstituted reactions, ribosomal initiation complexes assembled on the ORF1* initiation codon and at one or two AUG codons in ORF1 at the 3′-border and/or downstream of the IRES. Initiation at all three sites required eIF4A and eIF4G, which bound to a conserved region of the IRES; initiation on the ORF1* and principal ORF1 initiation codons involved eIF1/eIF1A-dependent scanning from the IRES's 3′-border. Initiation on these IRESs was enhanced by the IRES trans-acting factors (ITAFs) Ebp1/ITAF45, which bound to the apical subdomain Id of the IRES, and PTB (GTCV) or PCBP2 (RaCV1). [ABSTRACT FROM AUTHOR]

Until now, research has not taken into consideration the physicochemical purine–pyrimidine symmetries of the genetic code in the transcription and translation processes of proteinogenesis. Our Supersymmetry Genetic Code table, developed in 2022, is common and unique for all RNA and DNA living species. Its basic structure is a purine–pyrimidine symmetry net with double mirror symmetry. Accordingly, the symmetry of the genetic code directly shows its organisation based on the principle of nucleotide Watson–Crick and codon–anticodon pairing. The maximal purine–pyrimidine symmetries of codons show that each codon has a strictly defined and unchangeable position within the genetic code. We discovered that the physicochemical symmetries of the genetic code play a fundamental role in recognising and differentiating codons from mRNA and the anticodon tRNA and aminoacyl-tRNA synthetases in the transcription and translation processes. These symmetries also support the wobble hypothesis with non-Watson–Crick pairing interactions between the translation process from mRNA to tRNA. The Supersymmetry Genetic Code table shows a specific arrangement of the second base of codons, according to which it is possible that an anticodon from tRNA recognises whether a codon from mRNA belongs to an amino acid with two or four codons, which is very important in the purposeful use of the wobble pairing process. Therefore, we show that canonical and wobble pairings essentially do not lead to misreading and errors during translation, and we point out the role of physicochemical purine–pyrimidine symmetries in decreasing disorder according to error minimisation and preserving the integrity of biological processes during proteinogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: As a zoonotic pathogen, the exploration of new virulence-related genes and the functional identification of Streptococcus suis are of positive significance in revealing the pathogenic mechanism of the strain and developing new vaccines. This study provides evidence that the sugC gene is a virulence-related gene of the Streptococcus suis serotype 2 strain and plays a crucial role in regulating its adhesion and invasion. The sugC gene is a coding gene for the ATP-binding transporter-associated protein, which has been reported to exist in the highly virulent Streptococcus suis. In order to reveal the effect of the sugC gene on the virulence of Streptococcus suis serotype 2, TJS75, a wild-type strain, was used as a parent strain, and a knockout sugC strain and complementary strain were successfully constructed via homologous recombination technology. We found that the adhesion and invasion abilities of the knockout sugC strain in PK-15 cells were decreased. Most importantly, the knockout of the sugC gene could reduce the incidence rate, mortality and LD50 value of TJS75 in BALB/c mice. These results provide a reference for us to further study the pathogenic mechanism of Streptococcus suis. The sugC gene of Streptococcus suis (S. suis) is a coding gene for the ATP-binding transporter-associated protein with strong pathogenicity. In order to reveal the effect of the sugC gene on the virulence of S. suis serotype 2, a wild-type strain of TJS75, isolated from fattening pigs' brain tissue samples, was used as a parent strain, and a knockout sugC gene (ΔsugC) and complementary strain (CΔsugC) were successfully constructed via homologous recombination technology. The biological characteristics of TJS75, ΔsugC and CΔsugC were compared and analyzed through growth curves, biochemical characteristics, hemolysis characteristics, cell infection tests and pathogenicity tests on BALB/c mice. The results of the growth characteristic experiments in vitro showed that the plateau stage growth period of ΔsugC was delayed compared to the TJS75 strain, but there was no difference in the total number of bacteria. The biochemical characteristics and hemolysis ability of ΔsugC in sheep blood had no difference compared with TJS75, but its adhesion and invasion abilities in PK-15 cells were decreased. Knockout of the sugC gene had no impact on the expression levels of adhesion-related genes in TJS75 in real-time PCR analysis. In addition, the LD50 of ΔsugC in BALB/c mice was 1.47 × 108 CFU, seven times higher than that of TJS75 (LD50 = 2.15 × 107 CFU). These results illustrate that the deletion of sugC reduced the virulence of TJS75 to BALB/c mice, but its role in the adhesion and invasion of PK-15 cells in this strain needs to be further explored. In summary, this study provides evidence that the sugC gene is a virulence-related gene in the S. suis serotype 2 strain and plays a crucial role in the adhesion and invasion of S. suis. This study lays a foundation for the further exploration of the potential virulence factors and pathogenesis of S. suis. [ABSTRACT FROM AUTHOR]

Circadian rhythms are endogenous behavioral or physiological cycles that are driven by a daily biological clock that persists in the absence of geophysical or environmental temporal cues. Circadian rhythm-related genes code for clock proteins that rise and fall in rhythmic patterns driving biochemical signals of biological processes from metabolism to physiology and behavior. Clock proteins have a pivotal role in liver metabolism and homeostasis, and their disturbances are implicated in various liver disease processes. Encoded genes play critical roles in the initiation and progression of metabolic dysfunction-associated steatohepatitis (MASH) to hepatocellular carcinoma (HCC) and their proteins may become diagnostic markers as well as therapeutic targets. Understanding molecular and metabolic mechanisms underlying circadian rhythms will aid in therapeutic interventions and may have broader clinical applications. The present review provides an overview of the role of the liver's circadian rhythm in metabolic processes in health and disease, emphasizing MASH progression and the oncogenic associations that lead to HCC. [ABSTRACT FROM AUTHOR]

Variations in the genetic code for proteins are considered to confer traits and underlying disease. Identifying the functional consequences of these genetic variants is a challenging endeavor. There are online databases that contain variant information. Many publications also have described variants in detail. Furthermore, there are tools that allow for the prediction of the pathogenicity of variants. However, navigating these disparate sources is time-consuming and sometimes complex. Finally, text mining and large language models offer promising approaches to understanding the textual form of this knowledge. This review discusses these challenges and the online resources and tools available to facilitate this process. Furthermore, a computational framework is suggested to accelerate and facilitate the process of identifying the phenotype caused by a particular genetic variant. This framework demonstrates a way to gather and understand the knowledge about variants more efficiently and effectively. [ABSTRACT FROM AUTHOR]

The codon usage bias (CUB) of genes encoded by different species' genomes varies greatly. The analysis of codon usage patterns enriches our comprehension of genetic and evolutionary characteristics across diverse species. In this study, we performed a genome-wide analysis of CUB and its influencing factors in six sequenced Eimeria species that cause coccidiosis in poultry: Eimeria acervulina, Eimeria necatrix, Eimeria brunetti, Eimeria tenella, Eimeria praecox, and Eimeria maxima. The GC content of protein-coding genes varies between 52.67% and 58.24% among the six Eimeria species. The distribution trend of GC content at different codon positions follows GC1 > GC3 > GC2. Most high-frequency codons tend to end with C/G, except in E. maxima. Additionally, there is a positive correlation between GC3 content and GC3s/C3s, but a significantly negative correlation with A3s. Analysis of the ENC-Plot, neutrality plot, and PR2-bias plot suggests that selection pressure has a stronger influence than mutational pressure on CUB in the six Eimeria genomes. Finally, we identified from 11 to 15 optimal codons, with GCA, CAG, and AGC being the most commonly used optimal codons across these species. This study offers a thorough exploration of the relationships between CUB and selection pressures within the protein-coding genes of Eimeria species. Genetic evolution in these species appears to be influenced by mutations and selection pressures. Additionally, the findings shed light on unique characteristics and evolutionary traits specific to the six Eimeria species. [ABSTRACT FROM AUTHOR]

It is known that the presence of CAA codons in the CAG tract affects the nature and time of disease onset caused by the expansion of trinucleotide repeats. The mechanisms leading to the occurrence of these diseases should be sought not only at the level of the physiological role of the ATXN2 protein, but also at the DNA level. These mechanisms are associated with non-canonical configurations (hairpins) that can form in the CAG tract. The tendency of hairpins to slide along the corresponding threads is usually considered important to explain the expansion of the CAG tract. At the same time, hairpins occur in areas of open states. Previous studies on the role of CAA interruptions have suggested that, under certain conditions, they can stabilize the dynamics of the hairpin, preventing the expansion of the CAG tract. We calculated the probability of additional open state zones occurrence in the CAG tract using an angular mathematical model of DNA. The calculations made it possible to establish that CAA interruptions affect the stability of the CAG tract, and this influence, depending on the localization of the interruption, can both increase and decrease the stability of the CAG tract. [ABSTRACT FROM AUTHOR]

The human–computer interaction attribute of the interactive genetic algorithm (IGA) allows users to participate in the product design process for which the product needs to be evaluated, and requiring a large number of evaluations would lead to user fatigue. To address this issue, this paper utilizes an XGBoost proxy model modified by particle swarm optimization and the graphical interaction mechanism (GIM) to construct an improved interactive genetic algorithm (PXG-IGA), and then the PXG-IGA is applied to 3D vase design. Firstly, the 3D vase shape has been designed by using a bicubic Bézier surface, and the individual genetic code is binary and includes three parts: the vase control points, the vase height, and the texture picture. Secondly, the XGBoost evaluation of the proxy model has been constructed by collecting user online evaluation data, and the particle swarm optimization algorithm has been used to optimize the hyperparameters of XGBoost. Finally, the GIM has been introduced after several generations, allowing users to change product styles independently to better meet users' expectations. Based on the PXG-IGA, an online 3D vase design platform has been developed and compared to the traditional IGA, KD tree, random forest, and standard XGBoost proxy models. Compared with the traditional IGA, the number of evaluations has been reduced by 58.3% and the evaluation time has been reduced by 46.4%. Compared with other proxy models, the accuracy of predictions has been improved up from 1.3% to 20.2%. To a certain extent, the PXG-IGA reduces users' operation fatigue and provides new ideas for improving user experience and product design efficiency. [ABSTRACT FROM AUTHOR]

The spurge Euphorbia characias is known for its latex, which is rich in antioxidant enzymes and anti-phytopathogen molecules. In this study, we identified a novel polyubiquitin protein in the latex and leaves, leading to the first molecular characterization of its coding gene and expressed protein in E. characias. Using consensus-degenerate hybrid oligonucleotide primers (CODEHOP) and rapid amplification of cDNA ends (5′/3′-RACE), we reconstructed the entire open reading frame (ORF) and noncoding regions. Our analysis revealed that the polyubiquitin gene encodes five tandemly repeated sequences, each coding for a ubiquitin monomer with amino acid variations in four of the five repeats. In silico studies have suggested functional differences among monomers. Gene expression peaked during the summer, correlating with high temperatures and suggesting a role in heat stress response. Western blotting confirmed the presence of polyubiquitin in the latex and leaf tissues, indicating active ubiquitination processes. These findings enhance our understanding of polyubiquitin's regulatory mechanisms and functions in E. characias, highlighting its unique structural and functional features. [ABSTRACT FROM AUTHOR]

Styrax japonicus is a medicinal and ornamental shrub belonging to the Styracaceae family. To explore the diversity and characteristics of the chloroplast genome of S. japonicus, we conducted sequencing and comparison of the chloroplast genomes of four naturally distributed S. japonicus. The results demonstrated that the four chloroplast genomes (157,914–157,962 bp) exhibited a typical quadripartite structure consisting of a large single copy (LSC) region, a small single copy (SSC) region, and a pair of reverse repeats (IRa and IRb), and the structure was highly conserved. DNA polymorphism analysis revealed that three coding genes (infA, psbK, and rpl33) and five intergene regions (petA-psbJ, trnC-petN, trnD-trnY, trnE-trnT, and trnY-trnE) were identified as mutation hotspots. These genetic fragments have the potential to be utilized as DNA barcodes for future identification purposes. When comparing the boundary genes, a small contraction was observed in the IR region of four S. japonicus. Selection pressure analysis indicated positive selection for ycf1 and ndhD. These findings collectively suggest the adaptive evolution of S. japonicus. The phylogenetic structure revealed conflicting relationships among several S. japonicus, indicating divergent evolutionary paths within this species. Our study concludes by uncovering the genetic traits of the chloroplast genome in the differentiation of S. japonicus variety, offering fresh perspectives on the evolutionary lineage of this species. [ABSTRACT FROM AUTHOR]

Dryas octopetala var. asiatica, a dwarf shrub belonging to the Rosaceae family and native to Asia, exhibits notable plasticity in photosynthesis in response to temperature variations. However, the codon usage patterns and factors influencing them in the chloroplast genome of this species have not yet been documented. This study sequenced and assembled the complete genome of D. octopetala var. asiatica. The annotated genes in the chloroplast genome were analyzed for codon composition through multivariate statistical methods including a neutrality plot, a parity rule 2 (PR2) bias plot, and an effective number of codons (ENC) plot using CodonW 1.4.2 software. The results indicated that the mean GC content of 53 CDSs was 38.08%, with the average GC content at the third codon base position being 27.80%, suggesting a preference for A/U(T) at the third codon position in chloroplast genes. Additionally, the chloroplast genes exhibited a weak overall codon usage bias (CUB) based on ENC values and other indicators. Correlation analysis showed a significant negative correlation between ENC value and GC2, an extremely positive correlation with GC3, but no correlation with GC1 content. These findings highlight the importance of the codon composition at the third position in influencing codon usage bias. Furthermore, our analysis indicated that the CUB of the chloroplast genome of D. octopetala var. asiatica was primarily influenced by natural selection and other factors. Finally, this study identified UCA, CCU, GCU, AAU, GAU, and GGU as the optimal codons. These results offer a foundational understanding for genetic modification and evolutionary dynamics of the chloroplast genome of D. octopetala var. asiatica. [ABSTRACT FROM AUTHOR]

The latest research shows that ferns and lycophytes have distinct evolutionary lineages. The codon usage patterns of lycophytes and ferns have not yet been documented. To investigate the gene expression profiles across various plant lineages with respect to codon usage, analyze the disparities and determinants of gene evolution in primitive plant species, and identify appropriate exogenous gene expression platforms, the whole-genome sequences of four distinct species were retrieved from the NCBI database. The findings indicated that Ceratopteris richardii, Adiantum capillus-veneris, and Selaginella moellendorffii exhibited an elevated A/U content in their codon base composition and a tendency to end with A/U. Additionally, S. capillus-veneris had more C/G in its codons and a tendency to end with C/G. The ENC values derived from both ENC-plot and ENC-ratio analyses deviated significantly from the standard curves, suggesting that the codon usage preferences of these four species were primarily influenced by genetic mutations and natural selection, with natural selection exerting a more prominent influence. This finding was further supported by PR2-Plot, neutrality plot analysis, and COA. A combination of RSCU and ENC values was used as a reference criterion to rank the codons and further identify the optimal codons. The study identified 24 high-frequency codons in C. richardii, A. capillus-veneris, and Diphasiastrum complanatum, with no shared optimal codons among the four species. Arabidopsis thaliana and Ginkgo biloba exhibited similar codon preferences to the three species, except for S. moellendorffii. This research offers a theoretical framework at the genomic codon level for investigating the phylogenetic relationships between lycophytes and ferns, shedding light on gene codon optimization and its implications for genetic engineering in breeding. [ABSTRACT FROM AUTHOR]

Pitaya canker, caused by Neoscytalidium dimidiatum, is a destructive disease that significantly threatens the safety of the pitaya industry. The authors of previous studies have mainly focused on its biological characteristics and chemical control. However, there are no molecular markers available thus far that can be used for the population genetics study of this pathogen. In the present study, a draft genome of N. dimidiatum with a total length of 41.46 MB was assembled in which 9863 coding genes were predicted and annotated. In particular, the microsatellite sequences in the draft genome were investigated. To improve the successful screening rate of potentially polymorphic microsatellite makers, another five N. dimidiatum isolates were resequenced and assembled. A total of eight pairs of polymorphic microsatellite primers were screened out based on the polymorphic microsatellite loci after investigating the sequencing and resequencing assemblies of the six isolates. A total of thirteen representative isolates sampled from different pitaya plantations were genotyped in order to validate the polymorphism of the resulting eight markers. The results indicated that these markers were able to distinguish the isolates well. Lastly, a neighbor-joining tree of 35 isolates, sampled from different pitaya plantations located in different regions, was constructed according to the genotypes of the eight molecular markers. The developed tree indicated that these molecular markers had sufficient genotyping capabilities for our test panel of isolates. In summary, we developed a set of polymorphic microsatellite markers in the following study that can effectively genotype and distinguish N. dimidiatum isolates and be utilized in the population genetics study of N. dimidiatum. [ABSTRACT FROM AUTHOR]

Congenital heart disease is one of the most common congenital malformations and thus represents a considerable public health burden. Hence, the identification of individuals and families with an increased genetic predisposition to congenital heart disease (CHD) and its possible prevention is important. Even though CHD is associated with the lack of folate during early pregnancy, the genetic background of folate and methionine metabolism perturbations and their influence on CHD risk is not clear. While some genes, such as those coding for cytosolic enzymes of folate/methionine cycles, have been extensively studied, genetic studies of folate transporters (de)glutamation enzymes and mitochondrial enzymes of the folate cycle are lacking. Among genes coding for cytoplasmic enzymes of the folate cycle, MTHFR, MTHFD1, MTR, and MTRR have the strongest association with CHD, while among genes for enzymes of the methionine cycle BHMT and BHMT2 are the most prominent. Among mitochondrial folate cycle enzymes, MTHFD2 plays the most important role in CHD formation, while FPGS was identified as important in the group of (de)glutamation enzymes. Among transporters, the strongest association with CHD was demonstrated for SLC19A1. [ABSTRACT FROM AUTHOR]

Salinispirillum sp. LH 10-3-1 was newly isolated from the alkali lake water samples collected in Inner Mongolia. In this study, a gene coding for D-lactate dehydrogenase from the strain LH 10-3-1 (SaLDH) was cloned and characterized. The recombinant enzyme was a tetramer with a native molecular mass of 146.2 kDa. The optimal conditions for SaLDH to reduce pyruvate and oxidize D-lactic acid were pH 8.0 and pH 5.0, at 25 °C. Cu2+ and Ca2+ slightly promoted the oxidation and reduction activities of SaLDH, respectively. To improve the stability of SaLDH, the enzyme was immobilized on Cu3(PO4)2-based inorganic hybrid nanoflowers. The results showed that the reduction activity of the hybrid nanoflowers disappeared, and the optimum temperature, specific activity, thermostability, and storage stability of the immobilized SaLDH were significantly improved. In addition, the biotransformation of D-lactic acid to pyruvate catalyzed by SaLDH and the hybrid nanoflowers was investigated. The maximum conversion of D-lactic acid catalyzed by the immobilized SaLDH was 25.7% higher than by free enzymes, and the immobilized SaLDH could maintain 84% of its initial activity after six cycles. [ABSTRACT FROM AUTHOR]

The text discusses the mystery of the origins of life on Earth and the possibility of life existing elsewhere, exploring scientific, philosophical, societal, and religious perspectives. A Special Issue on the origins of life (OoL) research was created to showcase diverse viewpoints and the interdisciplinary nature of the field. Contributions in the issue cover topics such as the formation of amino acids, tRNA evolution, autocatalytic networks, genetic code origin, and the role of non-canonical amino acids, among others, highlighting the complexity and importance of incorporating various perspectives in understanding OoL. [Extracted from the article]

Background: This computational analysis investigated sequence complementarities between the TRIM33 gene and human noncoding (nc)RNAs and characterized their interactions in the context of paraneoplastic dermatomyositis. Methods: TRIM33 FASTA sequence (NCBI Reference Sequence: NC_000001.11) was used for BLASTN analysis against Human GRCh38 in the Ensembl.org database. Retrieved ncRNAs showing hits to TRIM33 were searched in the GeneCards.org database and further analyzed through RNAInter, QmRLFS-finder, Spliceator, and NcPath enrichment analysis. Results: A total of 100 hits were found, involving the lncRNAs NNT-AS1, MKLN1-AS, LINC01206, and PAXBP1-AS1, whose dysregulation has been reported in either cancer or dermatomyositis. Additionally, the lncRNAs NNT-AS1 and PAXBP1-AS1 may interact with microRNA-142-3p, reducing its expression and increasing that of TRIM33. Sequence complementarity affected only TRIM33 intron 1, possibly resulting in alternatively spliced isoforms of TIF1γ with increased immunogenicity. The results also revealed nucleotide alignment between TRIM33 and the gene regulatory elements of 28 ncRNA genes involved in immune pathways. Conclusions: This pivotal study demonstrates sequence complementarity between TRIM33 and human ncRNAs dysregulated in cancer and dermatomyositis. This scenario may lead to the overproduction of more immunogenic TIF1γ variants in tumors and the stimulation of autoimmunity. Further experimental analyses using targeted methods such as Western blot or Chip-Seq are required to confirm these data. [ABSTRACT FROM AUTHOR]

Antibiotic-resistant strains of Staphylococcus aureus are being viewed as a serious threat by various public health agencies. Identifying novel targets in this important pathogen is crucial to the development of new effective antibacterial formulations. We investigated the antibacterial effect of a colloidal nanosilver formulation, Silversol®, against an antibiotic-resistant strain of S. aureus using appropriate in vitro assays. Moreover, we deciphered the molecular mechanisms underlying this formulation's anti-S. aureus activity using whole transcriptome analysis. Lower concentrations of the test formulation exerted a bacteriostatic effect against this pathogen, and higher concentrations exerted a bactericidal effect. Silversol® at sub-lethal concentration was found to disturb multiple physiological traits of S. aureus such as growth, antibiotic susceptibility, membrane permeability, efflux, protein synthesis and export, biofilm and exopolysaccharide production, etc. Transcriptome data revealed that the genes coding for transcriptional regulators, efflux machinery, transferases, β-lactam resistance, oxidoreductases, metal homeostasis, virulence factors, and arginine biosynthesis are expressed differently under the influence of the test formulation. Genes (argG and argH) involved in arginine biosynthesis emerged among the major targets of Silversol®'s antibacterial activity against S. aureus. [ABSTRACT FROM AUTHOR]

Simple Summary: To complement the genetic information of the pencilfish, a popular aquarium ornamental fish, we sequenced the mitochondrial genomes of four common pencilfish species. Their genome structure, nucleotide composition, codon usage, and phylogeny were comparatively analyzed. The results indicate that the four mitogenomes exhibited a typical circular structure. The gene order of the four Nannostomus pencilfish was similar to that of other fish. Our phylogenetic analyses support the current classification of the family Lebiasinidae. This study provides new data for the breeding and study of pencilfish. Although the pencilfish is a globally popular economic fish in the aquarium market, its taxonomic classification could be further refined. In order to understand the taxonomy of species of the genus Nannostomus (Characiformes, Lebiasinidae) and their phylogenetic position within the order Characiformes, in this study, we characterized mitochondrial genomes (mitogenomes) from four Nannostomus species for the first time. The four mitogenomes exhibited the typical circular structure, with overall sizes varying from 16,661 bp to 16,690 bp. They contained 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and 1 control region (CR). Nucleotide composition analysis suggested that the mitochondrial sequences were biased toward A and T. Bayesian inference and maximum likelihood analyses based on PCGs support the family Lebiasinidae classification, described using four Nannostomus species, clustering together with Lebiasina multimaculata from the same family. The results of this study support the current taxonomic classification of the family Lebiasinidae. Phylogenetic analysis also suggested that gene rearrangement would not significantly impact the phylogenetic relationships within the order Characiformes. These results might provide new data regarding the phylogeny and classification of the order Characiformes, thus providing a theoretical basis for the economic development of aquarium fish markets. [ABSTRACT FROM AUTHOR]

The central dogma treats the ribosome as a molecular machine that reads one mRNA codon at a time as it adds each amino acid to its growing peptide chain. However, this and previous studies suggest that ribosomes actually perceive pairs of adjacent codons as they take three-nucleotide steps along the mRNA. We examined GNN codons, which we find are surprisingly overrepresented in eukaryote protein-coding open reading frames (ORFs), especially immediately after NNU codons. Ribosome profiling experiments in yeast revealed that ribosomes with NNU at their aminoacyl (A) site have particularly elevated densities when NNU is immediately followed (3′) by a GNN codon, indicating slower mRNA threading of the NNU codon from the ribosome's A to peptidyl (P) sites. Moreover, if the assessment was limited to ribosomes that have only recently arrived at the next codon, by examining 21-nucleotide ribosome footprints (21-nt RFPs), elevated densities were observed for multiple codon classes when followed by GNN. This striking translation slowdown at adjacent 5′-NNN GNN codon pairs is likely mediated, in part, by the ribosome's CAR surface, which acts as an extension of the A-site tRNA anticodon during ribosome translocation and interacts through hydrogen bonding and pi stacking with the GNN codon. The functional consequences of 5′-NNN GNN codon adjacency are expected to influence the evolution of protein coding sequences. [ABSTRACT FROM AUTHOR]

The enzymatic hydrolysis of the non-reducing disaccharide trehalose in yeasts is carried out by trehalase, a highly specific α –glucosidase. Two types of such trehalase activity are present in yeasts, and are referred to as neutral and acid enzymes. They are encoded by distinct genes (NTH1 and ATH1, respectively) and exhibit strong differences in their biochemical and physiological properties as well as different subcellular location and regulatory mechanisms. Whereas a single gene ATH1 codes for acid trehalase, the genome of some yeasts appears to predict the existence of a second redundant neutral trehalase, encoded by the NTH2 gene, a paralog of NTH1. In S. cerevisiae the corresponding two proteins share 77% amino acid identity, leading to the suggestion that NTH2 codes for a functional trehalase activity. However, Nth2p lacks any measurable neutral trehalase activity and disruption of NTH2 gene has no effect on this activity compared to a parental strain. Likewise, single nth1 Δ and double nth1 Δ /nth2 Δ null mutants display no detectable neutral activity. Furthermore, disruption of NTH2 does not cause any apparent phenotype apart from a slight involvement in thermotolerance. To date, no evidence of a duplicated NTH gene has been recorded in other archetypical yeasts, like C. albicans or C. parapsilosis, and a possible regulatory mechanism of Nth2p remains unknown. Therefore, although genomic analysis points to the existence, in some yeasts, of two distinct genes encoding trehalase activities, the large body of biochemical and physiological evidence gathered from NTH2 gene does not support this proposal. Indeed, much more experimental evidence would be necessary to firmly validate this hypothesis. [ABSTRACT FROM AUTHOR]

The identification of targets that are expressed on the cell membrane is a main goal in cancer research. The Lymphocyte Antigen 6 Family Member G6D (LY6G6D) gene codes for a protein that is mainly present on the surface of colorectal cancer (CRC) cells. Therapeutic strategies against this protein like the development of T cell engagers (TCE) are currently in the early clinical stage. In the present work, we interrogated public genomic datasets including TCGA to evaluate the genomic and immunologic cell profile present in tumors with high expression of LY6G6D. We used data from TCGA, among others, and the Tumor Immune Estimation Resource (TIMER2.0) platform for immune cell estimations and Spearman correlation tests. LY6G6D expression was exclusively present in CRC, particularly in the microsatellite stable (MSS) subtype, and was associated with left-side tumors and the canonical genomic subgroup. Tumors with mutations of APC and p53 expressed elevated levels of LY6G6D. This protein was expressed in tumors with an inert immune microenvironment with an absence of immune cells and co-inhibitory molecules. In conclusion, we described clinical, genomic and immune-pathologic characteristics that can be used to optimize the clinical development of agents against this target. Future studies should be performed to confirm these findings and potentially explore the suggested clinical development options. [ABSTRACT FROM AUTHOR]

The rapid development of high-throughput technology has generated a large amount of protein–protein interaction (PPI) data, which provide a large amount of data support for constructing dynamic protein–protein interaction networks (PPINs). Constructing dynamic PPINs and applying them to recognize protein complexes has become a hot research topic. Most existing methods for complex recognition cannot fully mine the information of PPINs. To address this problem, we propose a construction method of dynamic weighted protein network by multi-level embedding (DWPNMLE). It can reflect the protein network's dynamics and the protein network's higher-order proximity. Firstly, the protein active period is calculated to divide the protein subnetworks at different time points. Then, the connection probability is used for the proteins possessing the same time points to judge whether there is an interaction relationship between them. Then, the corresponding protein subnetworks (multiple adjacency matrices) are constructed. Secondly, the multiple feature matrices are constructed using one-hot coding with the gene ontology (GO) information. Next, the first embedding is performed using variational graph auto-encoders (VGAEs) to aggregate features efficiently, followed by the second embedding using deep attributed network embedding (DANE) to strengthen the node representations learned in the first embedding and to maintain the first-order and higher-order proximity of the original network; finally, we compute the cosine similarity to obtain the final dynamic weighted PPIN. To evaluate the effectiveness of DWPNMLE, we apply four classical protein-complex-recognition algorithms on the DWPNMLE and compare them with two other dynamic protein network construction methods. The experimental results demonstrate that DWPNMLE significantly enhances the accuracy of complex recognition with high robustness, and the algorithms' efficiency is also within a reasonable range. [ABSTRACT FROM AUTHOR]

The genus Rorippa belongs to the family Brassicaceae, and its members usually have high medicinal value. The genus consists of approximately 75 species and mainly grows in the Northern Hemisphere, occurring in every continent except Antarctica. The taxonomy and phylogenetic relationships of Rorippa are still unsettled, largely due to complex morphological variations in Rorippa, which were caused by frequent hybridization events. Here, we sequenced four complete plastid genomes of Rorippa species by Illumina paired-end sequencing. The four new plastid genomes of Rorippa ranged in total size from 154,671 bp for R. palustris to 154,894 bp for R. sylvestris. There are 130 genes in the four plastomes, embodying 8 rRNA, 37 tRNA, and 85 protein-coding genes. Combining with six published plastid genomes, we carried on comparative and phylogenetic analyses. We found that the ten Rorippa plastid genomes were conservative in gene number and order, total size, genomic structure, codon usage, long repeat sequence, and SSR. Fourteen mutational hotspot regions could be selected as candidate DNA barcoding to distinguish Rorippa plants. The phylogenetic trees clearly identified that ten Rorippa species displayed monophyletic relationships within the tribe Cardamineae based on plastomes and nrDNA ITS sequences. However, there are significant cytonuclear discordances in the interspecific relationships within Rorippa, as well as the intergeneric relationships between Rorippa and its related genera. We inferred that the cytonuclear discordance is most likely a result of interspecific hybridization within Rorippa, as well as intergeneric hybridization with its related genera. These plastid genomes can offer precious information for studies of species authentication, evolutionary history, and the phylogeny of Rorippa. [ABSTRACT FROM AUTHOR]

There are many species of Lepidoptera, but few complete mitochondrial genomes of Lepidoptera have been included in databases. Here, the complete mitochondrial genome sequence of Salassa thespis was isolated and characterized. It was 15,302 bp in length and contained 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and an A + T-rich region. Among the 13 PCGs, the initiation codon of cytochrome c oxidase subunit 1 (cox1) was CGA, and the rest were ATN. The cox1 and cox2 genes had an incomplete stop codon T, while the rest terminated with TAA. Codon usage analysis showed that Phe, Ile, Leu and Asn were the most frequent amino acids, while Trp was the least. Like other Lepidopterans, some conserved motifs were found in the A + T-rich region, including a 17 bp poly-T guided by ATAGA, the AT-rich area and a poly-A element. Bayesian inference and maximum likelihood phylogenetic tree analysis based on 13 PCGs of S. thespis confirmed that it belonged to the Saturniidae family and showed the following relationship: (S. thespis + (Rhodinia fugax + Samia canningi)). The enrichment of mitochondrial DNA provides reference information for the study of the evolution and diversity of Lepidoptera insects. [ABSTRACT FROM AUTHOR]

Krascheninnikovia ewersmanniana is a dominant desert shrub in Xinjiang, China, with high economic and ecological value. However, molecular systematics research on K. ewersmanniana is lacking. To resolve the genetic composition of K. ewersmanniana within Amaranthaceae and its systematic relationship with related genera, we used a second-generation Illumina sequencing system to detect the chloroplast genome of K. ewersmanniana and analyze its assembly, annotation, and phylogenetics. Total length of the chloroplast genome of K. ewersmanniana reached 152,287 bp, with 84 protein-coding genes, 36 tRNAs, and eight rRNAs. Codon usage analysis showed the majority of codons ending with base A/U. Mononucleotide repeats were the most common (85.42%) of the four identified simple sequence repeats. A comparison with chloroplast genomes of six other Amaranthaceae species indicated contraction and expansion of the inverted repeat boundary region in K. ewersmanniana, with some genes (rps19, ndhF, ycf1) differing in length and distribution. Among the seven species, the variation in non-coding regions was greater. Phylogenetic analysis revealed Krascheninnikovia ceratoides, Dysphania ambrosioides, Dysphania pumilio, and Dysphania botrys to have a close monophyletic relationship. By sequencing the K. ewersmanniana chloroplast genome, this research resolves the relatedness among 35 Amaranthaceae species, providing molecular insights for germplasm utilization, and theoretical support for studying evolutionary relationships. [ABSTRACT FROM AUTHOR]

Aroma is an important factor in the measurement of the quality and market value of oolong tea. However, it is hard to develop an oolong tea with good aroma quality using unsuitable tea varieties. To explore the key factors of tea varieties in the formation of oolong tea aromas, the fresh leaves of the Chungui variety (CG, suitable for oolong tea, Camellia sinensis (L.) O. Kuntze) and the Fuyun No. 6 variety (F6, unsuitable for oolong tea, Camellia sinensis (L.) O. Kuntze) were harvested and treated by withering and mechanical stress in order. Then, aroma, transcriptome, and jasmonate (JA) contents, and weighted gene co-expression network analysis (WGCNA), of samples were investigated. The contents of characteristic oolong tea aromas, including indole, (E)-β-ocimene, (E)-nerolidol, α-farnesene, and jasmine lactone, were all accumulated in much higher quantities in the CG variety after withering and mechanical stress. Accordingly, the coding genes of aroma formation synthases TSB2, OCS, NES, AFS, and LOX1, and related genes in MVA, MEP, and ALA pathways, were all much more highly activated. These differential reactions are mainly caused by the higher accumulation of jasmonates, especially methyl jasmonate, a type of important plant signal chemical, in CG after mechanical stress. WGCNA analysis indicated 34 different transcription factors from different families are predicted to be involved in this jasmonate-responsive reaction. [ABSTRACT FROM AUTHOR]

This study investigates codon usage bias within the chloroplast genomes of 18 Taraxacum species, focusing on the base composition and various metrics including GC content, Relative Synonymous Codon Usage (RSCU), Effective Number of Codons (ENc), and GC3s. Our analysis revealed a pronounced preference for A/T-ending codons across Taraxacum species, with GC content across the first, second, and third positions of the codons (GC1, GC2, GC3) and the average GC content consistently below 50%. A detailed examination using the RSCU metric identified 29 commonly preferred A/T-ending codons, indicating a strong codon usage bias towards these endings. Specifically, the codon for leucine (UUA) emerged as highly preferred, while the codon for serine (AGC) was least favored. Through the ENc–GC3s plot analysis, we explored the forces shaping this bias, finding evidence that both mutation pressure and natural selection significantly influence codon preference, with most coding sequences showing weak bias. The PR2 plot analysis further confirmed the role of these factors by demonstrating a higher frequency of T over A and C over G at the third codon position, pointing towards a mutation bias complemented by natural selection. Collectively, our findings highlight a consistent pattern of codon usage bias in the chloroplast genomes of Taraxacum species, influenced by a combination of mutation pressure, natural selection, and possibly other unidentified factors. [ABSTRACT FROM AUTHOR]

The Plateau Hongliu (Myricaria elegans Royle.) is a woody shrub halophyte that thrives in arid areas of western Tibet, in the Himalayan Mountains. It is acclaimed as superior in saline stress acclimation and as a critical pharmaceutical resource of the Tibetan traditional herb. Nevertheless, the mitogenome in the genus Myricaria remains unknown. Here, using the Illumina and PacBio sequencing assays, the first complete mitogenome of the M. elegans revealed a multi-branched skeleton with a total length of 416,354 bp and GC content of 44.33%, comprising two circular molecules (M1 and 2). The complete mitogenome annotates 31 unique protein-encoding genes (PEGs), fifteen tRNAs, and three rRNA genes. The UAA exhibits the most prominent codon usage preference as a termination, followed by UUA codons for leucine. The mitogenome contains 99 simple sequence repeats and 353 pairs of dispersed repeats, displaying the most frequent in palindromic repeats. Gene transfer analyses identified 8438 bp of 18 homologous fragments from the plastome, accounting for 2.03% of the total length. Using the PREP suite, 350 C-U RNA editing sites were predicted, of which nad4 and ccmB were on the top frequency. Syntenic and phylogenetic analyses suggested weakly conserved patterns of M. elegans in Caryophyllales owing to the genome rearrangement. In summary, the deciphered unique features and complexities of the mitogenome in M. elegans provide novel insights into understanding the evolution and biological conservation underlying climate resilience in halophytes. [ABSTRACT FROM AUTHOR]

Background: Aeromonas hydrophila is a widely recognized broad-spectrum pathogen that primarily targets the gastrointestinal tract. Type IV pili (T4P) are proteinaceous nano-machines located on the bacterial cell surface, playing a crucial role in host colonization and infection. Regrettably, the T4P systems of A. hydrophila remain largely underexplored. Methods: A. hydrophila genomes with complete genome assembly and annotation reports up to 31 March 2023, were obtained from the NCBI Genome database or KEGG genome database, followed by a global search for T4P secretion system genes. Protein sequences of these manually curetted genes were used as secondary quarry for Synteny analysis. Protein–protein interaction analysis was performed by string analysis and in silico study of genomic islands. Results: We identified 27 orthologs of type IV pili (T4P) nano-machine components in A. hydrophila. These orthologs are primarily distributed across three operons: pilABCD, pilMNOPQ, and pilVWXY. While the first two operons are commonly found in all experimental genomes, the presence of the pilVWXY operon, coding for 11 orthologs, is reported here for the first time in A. hydrophila. Notably, the complete pilVWXY operon is absent in nonvirulent strains. A genomic islands study between a nonvirulent and hypervirulent strain also confirms absence of most of the genes coded by pilVWXY in nonvirulent strain. Interestingly, among the 51 experimental genomes analyzed, the pilVWXY operon was completely absent in 10 strains, most of which are categorized as nonvirulent; Conclusions: The distribution of two major type IV pili (T4P) nano-machines, PilABCDMNOPQ and PilVWXY, is reported here for the first time in A. hydrophila. Additionally, this study suggests a potential role for the PilVWXY nano-machine in establishing human disease. [ABSTRACT FROM AUTHOR]

HIV-1 typically infects cells via the CD4 receptor and CCR5 or CXCR4 co-receptors. Maraviroc is a CCR5-specific viral entry inhibitor; knowledge of viral co-receptor specificity is important prior to usage. We developed and validated an economical V3-env Illumina-based assay to detect and quantify the frequency of viruses utilizing each co-receptor. Plasma from 54 HIV+ participants (subtype B) was tested. The viral template cDNA was generated from plasma RNA with unique molecular identifiers (UMIs). The sequences were aligned and collapsed by the UMIs with a custom bioinformatics pipeline. Co-receptor usage, determined by codon analysis and online phenotype predictors PSSM and Geno2pheno, were compared to existing Trofile® data. The cost of V3-UMI was tallied. The sequences interpreted by Geno2pheno using the most conservative cut-off, a 2% false-positive-rate (FPR), predicted CXCR4 usage with the greatest sensitivity (76%) and specificity (100%); PSSM and codon analysis had similar sensitivity and lower specificity. Discordant Trofile® and genotypic results were more common when participants had specimens from different dates analyzed by either assay. V3-UMI reagents cost USD$62/specimen. A batch of ≤20 specimens required 5 h of technical time across 1.5 days. V3-UMI predicts HIV tropism at a sensitivity and specificity similar to those of Trofile®, is relatively inexpensive, and could be performed by most central laboratories. The adoption of V3-UMI could expand HIV drug therapeutic options in lower-resource settings that currently do not have access to phenotypic HIV tropism testing. [ABSTRACT FROM AUTHOR]

Schlafen (SLFN) is a family of proteins upregulated by type I interferons with a regulatory role in translation. Intriguingly, SLFN14 associates with the ribosome and can degrade rRNA, tRNA, and mRNA in vitro, but a role in translation is still unknown. Ribosomes are important regulatory hubs during translation elongation of mRNAs rich in rare codons. Therefore, we evaluated the potential role of SLFN14 in the expression of mRNAs enriched in rare codons, using HIV-1 genes as a model. We found that, in a variety of cell types, including primary immune cells, SLFN14 regulates the expression of HIV-1 and non-viral genes based on their codon adaptation index, a measurement of the synonymous codon usage bias; consequently, SLFN14 inhibits the replication of HIV-1. The potent inhibitory effect of SLFN14 on the expression of the rare codon-rich transcript HIV-1 Gag was minimized by codon optimization. Mechanistically, we found that the endoribonuclease activity of SLFN14 is required, and that ribosomal RNA degradation is involved. Therefore, we propose that SLFN14 impairs the expression of HIV-1 transcripts rich in rare codons, in a catalytic-dependent manner. [ABSTRACT FROM AUTHOR]

Simple Summary: The mitochondrial genome of insects has been widely used in studies of molecular evolution, population genetics, phylogenetics, and species identification due to its small size (approximately 14–20 kb), relatively high evolutionary rate, low levels of recombination, and high genome copy numbers. In this study, 13 complete mitogenomes of Chiasmini, a diverse group of grassland leafhoppers, were sequenced and analyzed for the first time. The phylogenetic position of Chiasmini within leafhoppers and the phylogenetic relationships among Chiasmini genera were reconstructed. The results show that all 13 mitogenomes are composed of a circular, double-stranded molecule that consists of 37 genes with a total length ranging from 14,805 to 16,269 bp and a variable number of non-coding A + T-rich regions. The gene size, order, arrangement, base composition, codon usage, and secondary structure of tRNAs in these newly sequenced mitogenomes of 13 species are highly conserved in Chiasmini. Phylogenetic analysis of the newly sequenced genomes plus representatives of other tribes and subfamilies of Cicadellidae recover all included subfamilies of Cicadellidae and tribes of Deltocephalinae as monophyletic, except Athysanini and Opsiini in Deltocephalinae, which are paraphyletic in agreement with some other recent studies. Chiasmini form a monophyletic group consisting of seven monophyletic genera arranged as follows: ((Zahniserius + (Gurawa + (Doratura + Aconurella))) + (Leofa + (Exitianus + Nephotettix))). The grassland leafhopper tribe Chiasmini (Cicadellidae: Deltocephalinae) presently comprises 324 described species worldwide, with the highest species diversity occurring in the Nearctic region but a greater diversity of genera occurring in the Old World. In China, this tribe comprises 39 described species in 11 genera, but the fauna remains understudied. The complete mitogenomes of three species of this tribe have been sequenced previously. In order to better understand the phylogenetic position of Chiasmini within the subfamily Deltocephalinae and to investigate relationships among Chiasmini genera and species, we sequenced and analyzed the complete mitogenomes of 13 species belonging to seven genera from China. Comparison of the newly sequenced mitogenomes reveals a closed circular double-stranded structure containing 37 genes with a total length of 14,805 to 16,269 bp and a variable number of non-coding A + T-rich regions. The gene size, gene order, gene arrangement, base composition, codon usage, and secondary structure of tRNAs of the newly sequenced mitogenomes of these 13 species are highly conserved in Chiasmini. The ATN codon is commonly used as the start codon in protein-coding genes (PCGs), except for ND5 in Doratura sp. and ATP6 in Nephotettix nigropictus, which use the rare GTG start codon. Most protein-coding genes have TAA or TAG as the stop codon, but some genes have an incomplete T stop codon. Except for the tRNA for serine (trnS1(AGN)), the secondary structure of the other 21 tRNAs is a typical cloverleaf structure. In addition to the primary type of G–U mismatch, five other types of tRNA mismatches were observed: A–A, A–C, A–G, U–C, and U–U. Chiasmini mitochondrial genomes exhibit gene overlaps with three relatively stable regions: the overlapping sequence between trnW and trnC is AAGTCTTA, the overlapping sequence between ATP8 and ATP6 is generally ATGATTA, and the overlapping sequence between ND4 and ND4L is generally TTATCAT. The largest non-coding region is the control region, which exhibits significant length and compositional variation among species. Some Chiasmini have tandem repeat structures within their control regions. Unlike some other deltocephaline leafhoppers, the sequenced Chiasmini lack mitochondrial gene rearrangements. Phylogenetic analyses of different combinations of protein-coding and ribosomal genes using maximum likelihood and Bayesian methods under different models, using either amino acid or nucleotide sequences, are generally consistent and also agree with results of prior analyses of nuclear and partial mitochondrial gene sequence data, indicating that complete mitochondrial genomes are phylogenetically informative at different levels of divergence within Chiasmini and among leafhoppers in general. Apart from Athysanini and Opsiini, most of the deltocephaline tribes are recovered as monophyletic. The results of ML and BI analyses show that Chiasmini is a monophyletic group with seven monophyletic genera arranged as follows: ((Zahniserius + (Gurawa + (Doratura + Aconurella))) + (Leofa + (Exitianus + Nephotettix))). [ABSTRACT FROM AUTHOR]

Different bacterial species have dramatically different generation times, from 20–30 min in Escherichia coli to about two weeks in Mycobacterium leprae. The translation machinery in a cell needs to synthesize all proteins for a new cell in each generation. The three subprocesses of translation, i.e., initiation, elongation, and termination, are expected to be under stronger selection pressure to optimize in short-generation bacteria (SGB) such as Vibrio natriegens than in the long-generation Mycobacterium leprae. The initiation efficiency depends on the start codon decoded by the initiation tRNA, the optimal Shine–Dalgarno (SD) decoded by the anti-SD (aSD) sequence on small subunit rRNA, and the secondary structure that may embed the initiation signals and prevent them from being decoded. The elongation efficiency depends on the tRNA pool and codon usage. The termination efficiency in bacteria depends mainly on the nature of the stop codon and the nucleotide immediately downstream of the stop codon. By contrasting SGB with long-generation bacteria (LGB), we predict (1) SGB to have more ribosome RNA operons to produce ribosomes, and more tRNA genes for carrying amino acids to ribosomes, (2) SGB to have a higher percentage of genes using AUG as the start codon and UAA as the stop codon than LGB, (3) SGB to exhibit better codon and anticodon adaptation than LGB, and (4) SGB to have a weaker secondary structure near the translation initiation signals than LGB. These differences between SGB and LGB should be more pronounced in highly expressed genes than the rest of the genes. We present empirical evidence in support of these predictions. [ABSTRACT FROM AUTHOR]