Search

Translation fidelity relies on accurate aminoacylation of transfer RNAs (tRNAs) by aminoacyl-tRNA synthetases (AARSs). AARSs specific for alanine (Ala), leucine (Leu), serine, and pyrrolysine do not recognize the anticodon bases. Single nucleotide anticodon variants in their cognate tRNAs can lead to mistranslation. Human genomes include both rare and more common mistranslating tRNA variants. We investigated three rare human tRNALeu variants that mis-incorporate Leu at phenylalanine or tryptophan codons. Expression of each tRNALeu anticodon variant in neuroblastoma cells caused defects in fluorescent protein production without significantly increased cytotoxicity under normal conditions or in the context of proteasome inhibition. Using tRNA sequencing and mass spectrometry we confirmed that each tRNALeu variant was expressed and generated mistranslation with Leu. To probe the flexibility of the entire genetic code towards Leu mis-incorporation, we created 64 yeast strains to express all possible tRNALeu anticodon variants in a doxycycline-inducible system. While some variants showed mild or no growth defects, many anticodon variants, enriched with G/C at positions 35 and 36, including those replacing Leu for proline, arginine, alanine, or glycine, caused dramatic reductions in growth. Differential phenotypic defects were observed for tRNALeu mutants with synonymous anticodons and for different tRNALeu isoacceptors with the same anticodon. A comparison to tRNAAla anticodon variants demonstrates that Ala mis-incorporation is more tolerable than Leu at nearly every codon. The data show that the nature of the amino acid substitution, the tRNA gene, and the anticodon are each important factors that influence the ability of cells to tolerate mistranslating tRNAs.

Modern life is essentially homochiral, containing D-sugars in nucleic acid backbones and L-amino acids in proteins. Since coded proteins are theorized to have developed from a prebiotic RNA World, the homochirality of L-amino acids observed in all known life presumably resulted from chiral transfer from a homochiral D-RNA World. This transfer would have been mediated by aminoacyl-RNAs defining the genetic code. Previous work on aminoacyl transfer using tRNA mimics has suggested that aminoacylation using D-RNA may be inherently biased toward reactivity with L-amino acids, implying a deterministic path from a D-RNA World to L-proteins. Using a model system of self-aminoacylating D-ribozymes and epimerizable activated amino acid analogs, we test the chiral selectivity of 15 ribozymes derived from an exhaustive search of sequence space. All of the ribozymes exhibit detectable selectivity, and a substantial fraction react preferentially to produce the D-enantiomer of the product. Furthermore, chiral preference is conserved within sequence families. These results are consistent with the transfer of chiral information from RNA to proteins but do not support an intrinsic bias of D-RNA for L-amino acids. Different aminoacylation structures result in different directions of chiral selectivity, such that L-proteins need not emerge from a D-RNA World.

Summary: Root morphogenesis is crucial for water and nutrient acquisition, but many aspects of root morphogenesis in crops are not well‐understood.Here, we cloned and functionally characterized a key gene for root morphogenesis in rice (Oryza sativa) based on mutant analysis. The stop root morphogenesis 1 (srm1) mutant lacks crown roots (CRs) and lateral roots (LRs) and carries a point mutation in the t‐SNARE coding gene SYNTAXIN OF PLANTS 132 (OsSYP132), leading to a premature stop codon and ablating the post‐transmembrane (PTM) region of OsSYP132.We identified the functional SNARE complex OsSYP132–OsNPSN13–OsSYP71–OsVAMP721/722 and determined that the integrity of the PTM region of OsSYP132 is essential for OsSYP132‐based SNARE complex‐mediated fusion of OsVAMP721/722 vesicles with the plasma membrane.The loss of this region in srm1 disrupts the intercellular trafficking and plasma membrane localization of OsPIN1b, preventing proper auxin distribution in the primordia of CRs and LRs and inhibiting their outgrowth. [ABSTRACT FROM AUTHOR]

The aminoacyl‐tRNA synthetases (aaRS) are a large group of enzymes that implement the genetic code in all known biological systems. They attach amino acids to their cognate tRNAs, moonlight in various translational and non‐translational activities beyond aminoacylation, and are linked to many genetic disorders. The aaRS have a subtle ontology characterized by structural and functional idiosyncrasies that vary from organism to organism, and protein to protein. Across the tree of life, the 22 coded amino acids are handled by 16 evolutionary families of Class I aaRS and 21 families of Class II aaRS. We introduce AARS Online, an interactive Wikipedia‐like tool curated by an international consortium of field experts. This platform systematizes existing knowledge about the aaRS by showcasing a taxonomically diverse selection of aaRS sequences and structures. Through its graphical user interface, AARS Online facilitates a seamless exploration between protein sequence and structure, providing a friendly introduction to the material for non‐experts and a useful resource for experts. Curated multiple sequence alignments can be extracted for downstream analyses. Accessible at www.aars.online, AARS Online is a free resource to delve into the world of the aaRS. [ABSTRACT FROM AUTHOR]

tRNAs are not only essential for decoding the genetic code, but their abundance also has a strong impact on the rate of protein production, folding, and on the stability of the translated messenger RNAs. Plasmodium expresses a unique surface protein called tRip, involved in the import of exogenous tRNAs into the parasite. Comparative proteomic analysis of the blood stage of wild‐type and tRip‐KO variant of P. berghei parasites revealed that downregulated proteins in the mutant parasite are distinguished by a bias in their asparagine content. Furthermore, the demonstration of the possibility of charging host tRNAs with Plasmodium aminoacyl‐tRNA synthetases led us to propose that imported host tRNAs participate in parasite protein synthesis. These results also suggest a novel mechanism of translational control in which import of host tRNAs emerge as regulators of gene expression in the Plasmodium developmental cycle and pathogenesis, by enabling the synthesis of asparagine‐rich regulatory proteins that efficiently and selectively control the parasite infectivity. [ABSTRACT FROM AUTHOR]

In modern medical diagnostics, where analytical chemistry plays a key role, fast and accurate identification of pathogens is becoming increasingly important. Infectious diseases pose a growing threat to public health due to population growth, international air travel, bacterial resistance to antibiotics, and other factors. For instance, the detection of SARS-CoV-2 in patient samples is a key tool to monitor the spread of the disease. While there are several techniques for identifying pathogens by their genetic code, most of these methods are too expensive or slow to effectively analyze clinical and environmental samples that may contain hundreds or even thousands of different microbes. Standard approaches (e.g., culture media and biochemical assays) are known to be very time- and labor-intensive. The purpose of this review paper is to highlight the problems associated with the analysis and identification of pathogens that cause many serious infections. Special attention was paid to the description of mechanisms and the explanation of the phenomena and processes occurring on the surface of pathogens as biocolloids (charge distribution). This review also highlights the importance of electromigration techniques and demonstrates their potential for pathogen pre-separation and fractionation and demonstrates the use of spectrometric methods, such as MALDI-TOF MS, for their detection and identification. [ABSTRACT FROM AUTHOR]

Reversible protein phosphorylation is a ubiquitous phenomenon essential for eukaryotic cellular processes. Recent advancements in research about neurodevelopmental disorders have prompted investigations into the intricate relationship between protein phosphatases, particularly phosphoprotein phosphatases (PPPs), and neurodevelopment. Notably, variants in 10 coding genes spanning four PPP family members have been implicated in neurodevelopmental disorders. Here, we provide a comprehensive overview of the clinical phenotypes, genotypes, and pathogenic mechanisms observed in affected patients. Our analysis reveals challenges in subsequent statistical analyses due to inconsistent clinical phenotypic descriptions and a lack of large multicenter studies, hampering analysis about genotype–phenotype correlations. The scarcity of follow‐up data poses a significant obstacle to prognostic counseling for nearly all rare diseases. Presently, symptomatic treatment strategies are employed for patients with variants, as definitive cures remain elusive. Future research may explore protein phosphatase regulators as potential therapeutic targets. Furthermore, it is imperative not to overlook other members of the protein phosphatase family or coding genes with undiscovered variants. Insights gleaned from the temporal and spatial distribution of proteins, along with observations from animal model phenotypes, may provide valuable directions for uncovering novel pathogenic genes. [ABSTRACT FROM AUTHOR]

To construct a derivative of the avirulent Pseudomonas aeruginosa ATCC 9027 that produces high levels of di-rhamnolipid, that has better physico-chemical characteristics for biotechnological applications than mono-rhamnolipid, which is the sole type produced by ATCC 9027. We used plasmids expressing the rhlC gene, which encodes for rhamnosyl transferase II that transforms mono- to di-rhamnolipids under different promoters and in combination with the gene coding for the RhlR quorum sensing regulator, or the mono-rhamnolipid biosynthetic rhlAB operon. The plasmids tested carrying the rhlC gene under the lac promoter were plasmid prhlC and prhlRC, while prhlAB-R–C expressed this gene from the rhlA promoter, forming part of the artificially constructed rhlAB-R–C operon. We measured rhamnolipds concentrations using the orcinol method and determined the proportion of mono-rhamnolipids and di-rhamnolipids by UPLC/MS/MS. We found that the expression of rhlC in P. aeruginosa ATCC 9027 caused the production of di-rhamnolipids and that the derivative carrying plasmid prhlAB-R–C gives the best results considering total rhamnolipids and a higher proportion of di-rhamnolipids. A P. aeruginosa ATCC 9027 derivative with increased di-rhamnolipids production was developed by expressing plasmid prhlAB-R–C, that produces similar rhamnolipids levels as PAO1 type-strain and presented a higher proportion of di-rhamnolipids than this type-strain. [ABSTRACT FROM AUTHOR]

Clinopodium gracile is an important medicinal herb in the Lamiaceae family. This species lacks corresponding genomic resources, which significantly limits the study of its active compound synthesis pathways, breeding practices, and assessment of natural genetic variations. We assembled the chromosomal-level genome of C. gracile using Oxford Nanopore (ONT) technology and Hi-C sequence. The assembled genome is 307.3 Mb in size and consists of 9 chromosomes. The scaffold N50 was 36.3 Mb. The BUSCO completeness (Embryophyta_db10) of the genome was 97.2%. The genome annotates 40,083 protein coding genes. C. gracile and S. miltiorrhiza diverged approximately 30.615 million years ago. C. gracile has not undergone recent species-specific WGD events. A high proportion of young LTRs indicates a recent transposable element (TE) transposition burst in C. gracile. [ABSTRACT FROM AUTHOR]

Sulfur fluoride exchange (SuFEx) and phosphorus fluoride exchange (PFEx) click chemistries are advancing research across multiple disciplines. By genetically incorporating latent bioreactive unnatural amino acids (Uaas), these chemistries have been integrated into proteins, enabling precise covalent linkages with biological macromolecules and paving the way for new applications. However, their suboptimal reaction rates in proteins limit effectiveness, and traditional catalytic methods for small molecules are often incompatible with biological systems or in vivo applications. We demonstrated that introducing an arginine adjacent to the latent bioreactive Uaa significantly boosts SuFEx and PFEx reaction rates between proteins. This method is effective across various Uaas, target residues, and protein environments. Notably, it also enables efficient SuFEx reactions in acidic conditions, common in certain cellular compartments and tumor microenvironments, which typically hinder SuFEx reactions. Furthermore, we developed the first covalent cell engager that substantially enhances natural killer cell activation through improved covalent interaction facilitated by arginine. These findings provide mechanistic insights and offer a biocompatible strategy to harness these robust chemistries for advancing biological research and developing new biotherapeutics. [ABSTRACT FROM AUTHOR]

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]

Metal‐mediated chemical transformations are promising approaches to manipulate and regulate proteins in fundamental biological research and therapeutic development. Nevertheless, unlike bond‐forming reactions, the exploration of selective bond cleavage reactions catalyzed by metals that are fully compatible with proteins and living systems remains relatively limited. Here, it is reported that Copper(II)/tris(3‐hydroxypropyltriazolylmethyl)amine (THPTA), commonly used in copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) reaction, can be repurposed as a new bioorthogonal catalyst for thiazolidine (Thz) bond cleavage. This process liberates an α‐oxo‐aldehyde group under physiological conditions, without requiring additional additives. To showcase the utility of this method, this simple catalyst system is coupled with genetic code expansion technology to achieve on‐demand activation of genetically encoded Thz‐caged α‐oxo‐aldehydes, enabling further functionalization of proteins. For the first time, this cell‐compatible Thz uncaging reaction allows for the site‐specific installation of α‐oxo‐aldehydes at the internal positions of proteins in phage and bacterial surface display systems, expanding the chemical space of proteins. Overall, this study expands the toolkit of bioorthogonal catalysts and paves the way for metal‐promoted chemical reactions in living systems, potentially benefiting various applications in the future. [ABSTRACT FROM AUTHOR]

Unspecific peroxygenases (UPOs) are regarded as a "dream catalyst" for selective oxyfunctionalization reactions like oxygenations. We present the display of the model UPO rAaeUPO (PaDa−I) on the cell surface of the heterologous production host Komagataella phaffii as a one‐step production and immobilization process. The coding sequence for PaDa−I was combined with genes coding for cell wall proteins from Saccharomyces cerevisiae and transformed into K. phaffii. The fusion proteins were compared among each other and with secreted, free PaDa−I. One system in particular, a C‐terminal fusion of PaDa−I and Sag1 yielded near identical activity per volume culture broth to the secreted PaDa−I with ~90 % of the activity being at the cell wall. The surface display simplifies downstream processing and includes immobilization on a cheap, retainable and replaceable matrix, that is the production host itself. The enzymes remained active in a repeated batch process for 10 batches and 200 h of catalysis. [ABSTRACT FROM AUTHOR]

DNA deamination occurs constantly in a cell and causes DNA damage. As this damage can be deleterious, organisms have evolved many systems to eliminate it, such as Endonuclease V (Endo V). DUF99 family protein contains a domain of unknown function similar to Endo V but has not been experimentally characterized to date. Here, we show that DUF99 family proteins cleave the 30-side of deoxyuridine (dU) on DNA substrates. Based on phylogenetic analysis, we designated this new protein family as Endonuclease dU (Endo_dU). We also observed that Endo_dU coding gene frequently colocalizes with that of uracil-DNA glycosylase (UDG) in halophilic archaea, and we further performed gene knockout of Endo_dU gene on Haloferax volcanii. The transcription level of UDG gene on Endo_dU knockout strain was increased when induced by sodium bisulfite. Thus, we hypothesize that Endo_dU establishes a new endonuclease family with broad phylogenetic distribution and may participate in DNA repair. [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]

In domesticated sable population, after almost 100 years of selective breeding, individuals with colored fur began to be recorded. In particular, in the offspring of a pair of sables with black coat color, a puppy with pastel coat color was identified. In the TYRP1 gene that determines this sable coat color, single nucleotide insertion was determined, and the trait inheritance mode was recessive. In 2022, in this population, puppies with white coat color were born simultaneously to the representatives of two sable lines. In most mammalian species, albinism is caused by the mutations in the TYR gene, which encodes the tyrosinase enzyme. In the present study, the sable TYR gene was analyzed as a functional candidate gene for albinism. Sequence analysis of the TYR gene coding region and splicing sites did not reveal any differences of white sables from standard colored sables, which suggested that the studied phenotype was caused by genetic variants in other genes. [ABSTRACT FROM AUTHOR]

The Gram-negative marine bacterium Vibrio anguillarum is able to cause vibriosis with hemorrhagic septicemia in many fish species, and iron acquisition is a critical step for virulence. Despite the fact that genes specific to certain processes of iron transport have been studied, the iron-regulated circuits of the V. anguillarum strains remain poorly understood. In this study, we showed that in V. anguillarum strain 775, iron could affect the expression of a number of critical metabolic pathways and virulence factors. The global iron uptake regulator VaFur is the major actor to control these processes for the bacterium to respond to different iron conditions. A VaFur binding motif was identified to distinguish directly and indirectly regulated targets. The absence of VaFur resulted in the aberrant expression of most iron acquisition determinants under rich-iron conditions. A similar regulation pattern was also observed in the transcription of genes coding for the type VI secretion system. The expression of peroxidase genes is positively controlled by VaFur to prevent iron toxicity, and the deletion of Vafur caused impaired growth in the presence of iron and H2O2. VaFur also upregulates some virulence factors under limited-iron conditions, including metalloprotease EmpA and motility, which are likely critical for the high virulence of V. anguillarum 775. The deletion of VaFur led to reduced swimming motility and decreased extracellular protease activity under limited-iron conditions, thereby leading to attenuated pathogenicity. Our study provides more evidence to better understand the VaFur regulon and its role in the pathogenesis of V. anguillarum. IMPORTANCEVibriosis, the most common disease caused by marine bacteria belonging to the genus Vibrio, leads to massive mortality of economical aquatic organisms in Asia. Iron is one of the most important trace elements, and its acquisition is a critical battle occurring between the host and the pathogen. However, excess iron is harmful to cells, so iron utilization needs to be strictly controlled to adapt to different conditions. This process is mediated by the global iron uptake regulator Fur, which acts as a repressor when iron is replete. On the other hand, free iron in the host is limited, so the reduced virulence of the Δfur mutant should not be directly caused by abnormally regulated iron uptake. The significance of this work lies in uncovering the mechanism by which the deletion of Fur causes reduced virulence in Vibrio anguillarum and identifying the critical virulence factors that function under limited-iron conditions. [ABSTRACT FROM AUTHOR]

Codon usage bias, or the unequal use of synonymous codons, is observed across genes, genomes, and between species. It has been implicated in many cellular functions, such as translation dynamics and transcript stability, but can also be shaped by neutral forces. We characterized codon usage across 1,154 strains from 1,051 species from the fungal subphylum Saccharomycotina to gain insight into the biases, molecular mechanisms, evolution, and genomic features contributing to codon usage patterns. We found a general preference for A/T-ending codons and correlations between codon usage bias, GC content, and tRNA-ome size. Codon usage bias is distinct between the 12 orders to such a degree that yeasts can be classified with an accuracy >90% using a machine learning algorithm. We also characterized the degree to which codon usage bias is impacted by translational selection. We found it was influenced by a combination of features, including the number of coding sequences, BUSCO count, and genome length. Our analysis also revealed an extreme bias in codon usage in the Saccharomycodales associated with a lack of predicted arginine tRNAs that decode CGN codons, leaving only the AGN codons to encode arginine. Analysis of Saccharomycodales gene expression, tRNA sequences, and codon evolution suggests that avoidance of the CGN codons is associated with a decline in arginine tRNA function. Consistent with previous findings, codon usage bias within the Saccharomycotina is shaped by genomic features and GC bias. However, we find cases of extreme codon usage preference and avoidance along yeast lineages, suggesting additional forces may be shaping the evolution of specific 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]

Excessive extracellular matrix deposition and increased intrahepatic angiogenesis are prominent features of cirrhosis. β-arrestin2 is thought to be involved in the pathological processes of various fibrotic diseases. This study aimed to investigate the role and possible mechanism of β-arrestin2 in the angiogenesis of cirrhosis. Firstly, β-arrestin2 expression in liver tissues of cirrhotic patients was detected, and the correlation between β-arrestin2 and α-SMA, CD-31, PDGF, and VEGF indexes was analyzed. Then, after liver cirrhosis induced by CCL 4 in Arrb2-KO mice (β-arrestin2 coding gene), liver histopathological changes were observed, and the expressions of α-SMA, CD-31, PDGF, VEGF, and VEGFR2 were detected. Finally, VEGF-A was used to treat human liver sinusoidal endothelial cells (LSECs) to simulate pathological conditions. After transfection with si-ARRB2, the cell activity, MDA and GSH-PX activities, cell invasion, angiogenesis, and the expressions of α-SMA, CD-31, and VEGF/VEGFR2 pathway were detected. Results showed that β-arrestin2 expression in the liver increased significantly during cirrhosis and was positively correlated with angiogenesis. In vivo , Arrb2-KO significantly inhibited fibrosis and angiogenesis in cirrhotic mice, and decreased the expressions of α-SMA, CD31, PDGF, VEGF, and VEGFR2. Studies using LSECs in vitro showed that after intervention of ARRB2, the activity of LSECs and the number of invasions and tubule formations were significantly reduced. Similarly, after transfection with si-ARRB2, the expressions of α-SMA, CD31, PDGF, VEGF, and VEGFR2 in LSECs were significantly decreased. Collectively, β-arrestin2 aggravated cirrhosis by promoting the angiogenesis of LSECs. Blocking β-arrestin2 may be an important target against angiogenesis and fibrosis in cirrhosis. [Display omitted] • β-arrestin2 expression was increased in cirrhosis and correlated with angiogenesis. • Knockout Arrb2 inhibited the progression of liver cirrhosis, reduce angiogenesis. • ARRB2 intervention inhibited the proliferation, invasion and angiogenesis of LSECs. • β-arrestin2 (Arrb2) promoted LSECs angiogenesis through the VEGF/VEGFR2 pathway. [ABSTRACT FROM AUTHOR]

Nitrate is a nutrient and signal that regulates gene expression. The nitrate response has been extensively characterized at the organism, organ, and cell‐type‐specific levels, but intracellular mRNA dynamics remain unexplored. To characterize nuclear and cytoplasmic transcriptome dynamics in response to nitrate, we performed a time‐course expression analysis after nitrate treatment in isolated nuclei, cytoplasm, and whole roots. We identified 402 differentially localized transcripts (DLTs) in response to nitrate treatment. Induced DLT genes showed rapid and transient recruitment of the RNA polymerase II, together with an increase in the mRNA turnover rates. DLTs code for genes involved in metabolic processes, localization, and response to stimulus indicating DLTs include genes with relevant functions for the nitrate response that have not been previously identified. Using single‐molecule RNA FISH, we observed early nuclear accumulation of the NITRATE REDUCTASE 1 (NIA1) transcripts in their transcription sites. We found that transcription of NIA1, a gene showing delayed cytoplasmic accumulation, is rapidly and transiently activated; however, its transcripts become unstable when they reach the cytoplasm. Our study reveals the dynamic localization of mRNAs between the nucleus and cytoplasm as an emerging feature in the temporal control of gene expression in response to nitrate treatment in Arabidopsis roots. Summary statement: Transcriptome analysis of nuclear and cytoplasmic fractions in response to nitrate revealed transcripts with specific subcellular localization, revealing a novel layer of gene regulation. The dynamic interplay between mRNA localization, synthesis, and decay is crucial for the adaptive response of Arabidopsis roots to nitrate. [ABSTRACT FROM AUTHOR]

Background/Aim: The serine proteinase inhibitor 1 (SERPINE1) gene codes for the plasminogen activator inhibitor 1 (PAI1) protein and is thought to play a tumor supportive role in various cancers. In this work we aimed to uncover the role PAI1 plays in the proliferation, migration, and invasion of vulvar cancer (VC), and define the protein’s function as an oncogene or tumor suppressor. Materials and Methods: Through treatment with an agonist (G1) and antagonist (G36) of G-coupled estrogen receptor 1 (GPER1), an upstream regulator of SERPINE1 expression, and a forward transfection knockdown protocol, the expression of SERPINE1/PAI1 in VC cells was altered. The effects these altered SERPINE1/PAI1 levels had on tumor cell functions were then examined. Proliferation was analyzed using the resazurin assay, while migration was studied via the gap closure assay. Through colony- and tumor sphere- formation assays clonogenicity was tested, and western blots showed protein expression. Results: In A431 VC cells, when the levels of PAI1 were reduced via knockdown or treatment with G1, migration, proliferation, and colony growth was reduced. Treatment with G36 increased expression of PAI1 and increased migration and colony size in CAL39 cells. Conclusion: Based on the findings in this study, suppressing PAI1 expression in VC cells appears to reduce their progression and tumorigenic potential. Therefore, PAI1 could possibly function as an oncogene in VC. GPER1 appears to be a suitable target for suppressing PAI1 in VC. [ABSTRACT FROM AUTHOR]

The duration of flowering and maturity is an important agricultural trait determining the suitability of a variety for cultivation in the target region. In the present study, we used genome-wide association analysis (GWAS) to search for loci associated with soybean flowering and maturity in the Central and West Siberian regions of Russia. A field experiment was conducted in 2021/2022 at two locations (Orel and Novosibirsk). A germplasm collection of 180 accessions was genotyped using SoySNP50K Illumina Infinium Bead-Chip. From the initial collection, we selected 129 unrelated accessions and conducted GWAS on this dataset using two multi-locus models: FarmCPU and BLINK. As a result, we identified 13 loci previously reported to be associated with duration of soybean development, and 17 new loci. 33 candidate genes were detected in these loci using analysis of co-expression, gene ontology, and literature data, with the best candidates being Glyma.03G177500, Glyma.13G177400, and Glyma.06G213100. These candidate genes code the Arabidopis orthologs TOE1 (TARGET OF EAT 1), SPL3 (SQUAMOSA PROMOTER BINDING PROTEIN LIKE 3), the DELLA protein, respectively. In these three genes, we found haplotypes which may be associated with the length of soybean flowering and maturity, providing soybean adaptation to a northern latitudes. [ABSTRACT FROM AUTHOR]

CHASERR encodes a human long nor}coding RNA (IncRNA) adjacent to CHDZ, decoding gene in which de novo loss-of-function variants cause developmental and epileptic encephalopathy. Here, we report our findings in three unrelated children with a syndromic, early-onset neurodevelopmental disorder, each of whOm had de novo deletion in the CHASERR locus. The children had severe encephalopathy, shared facial dysmorphisms, cortical atrophy, and cerebral hypomyelination - phenotype that is distinct from the phenotypes of patients with CHD2 haploinsuf ficiency. We found that the CHASERR deletion results in increased CHD2 protein abundance in patient-derived celllines and increased expression of the CHD2 transcript in cis. These findings indicate that CHD2 has bidirectional dosage sensitivity in human disease, and we recommend that other IncRNA-encoding genes be evaluated, particularly those upstream of genes associated with mendelian disorders. [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]

SUMMARY: Plant long noncoding RNAs (lncRNAs) exhibit features such as tissue‐specific expression, spatiotemporal regulation, and stress responsiveness. Although diverse studies support the regulatory role of lncRNAs in model plants, our knowledge about lncRNAs in crops is limited. We employ a custom pipeline on a dataset of over 1000 RNA‐seq samples across nine representative species of the family Cucurbitaceae to predict 91 209 nonredundant lncRNAs. The lncRNAs were characterized according to three confidence levels and classified by their genomic context into intergenic, natural antisense, intronic, and sense‐overlapping. Compared with protein‐coding genes, lncRNAs were, on average, expressed at low levels and displayed significantly higher specificity when considering tissue, developmental stages, and stress responsiveness. The evolutionary analysis indicates higher positional conservation than sequence conservation, probably linked to the conserved modular motifs within syntenic lncRNAs. Moreover, a positive correlation between the expression of intergenic/natural antisense lncRNAs and their closest/parental gene was observed. For those intergenic, the correlation decreases with the distance to the neighboring gene, supporting that their potential cis‐regulatory effect is within a short‐range. Furthermore, the analysis of developmental studies showed that a conserved NAT‐lncRNA family is differentially expressed in a coordinated way with their cognate sense protein‐coding genes. These genes code for proteins associated with phloem development, thus providing insights about the potential involvement of some of the identified lncRNAs in a developmental process. We expect that this extensive inventory will constitute a valuable resource for further research lines focused on elucidating the regulatory mechanisms mediated by lncRNAs in cucurbits. [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]

Three billion years of evolution have produced a vast variety of protein molecules, whose functions are directly dependent on their ability to assume and maintain specific shapes. Proteins are defined by the sequence and chemical characteristics of their amino acids, which dictate their 3D shape and function, ranging from enzymatic activity to immune responses. Here, we explore a synthetic form of linear structure that can be bent in a programmable way into various specific 3D shapes inspired by the way functional proteins are defined using genetic codes. This synthetic structure is based on non‐circular multistable corrugated tubes, which can be fabricated at various length scales and cross‐sectional shapes, thus enabling the modification of their properties. Additionally, the cross‐section shape can be rewritten multiple times, allowing for the repair of structural damage and the rewriting of the properties of the structure's multi‐stability. A numerical model is used to describe the bending energy landscape of different cross‐sections. The proposed reprogrammable 3D shapes of a rewritable 1D metamaterial are promising candidates for futuristic robotic systems, complex deployable structures, catheter devices, and energy absorption and harvesting. [ABSTRACT FROM AUTHOR]

The Halimedineae are marine green macroalgae that play crucial roles as primary producers in various habitats, including coral reefs, rocky shores, embayments, lagoons, and seagrass beds. Several tropical species have calcified thalli, which contribute significantly to the formation of coral reefs. In this study, we investigated the codon usage patterns and the main factors influencing codon usage bias in 16 chloroplast genomes of the suborder Halimedineae. Nucleotide composition analysis revealed that the codons of these species were enriched in A/U bases and preferred to end in A/U bases, and the distribution of GC content followed a trend of GC1 > GC2 > GC3. 30 optimal codons encoding 17 amino acids were identified, and most of the optimal codons and all of the over-expressed codons preferentially ended with A/U. The neutrality plot, effective number of codons (ENc) plot, and parity rule 2 (PR2) plot analysis indicated that natural selection played a major role in shaping codon usage bias of the most Halimedineae species. The genetic relationships based on their RSCU values and chloroplast protein-coding genes showed the closely related species have similar codon usage patterns. This study describes, for the first time, the codon usage patterns and characterization of Halimedineae chloroplast genomes, and provides new insights into the evolution of this suborder. [ABSTRACT FROM AUTHOR]

Aminoacyl-tRNA synthetases hold the key to the genetic code and assign nucleic acid-based codons to amino acids, the building blocks of proteins. In their ability to recognize identity elements on transfer RNAs (tRNAs), some as simple as a single base pair, they ensure that the same proteins are formed each time information embedded in DNA is transcribed into messenger RNA (mRNA) and translated into proteins (Figure 1A). Thus, aminoacyl-tRNA synthetase active sites are conserved; however, since their evolutionary origin, their functions have been co-opted, expanded on and played novel roles during evolution. Below, we provide an overview of the many functions of aminoacyl-tRNA synthetases — from their role in translation, one of the most fundamental processes of all life, to newly discovered, diverse functions. Rasangi Tennakoon and Haissi Cui introduce aminoacyl-tRNA synthetases, the class of enzymes that load amino acids onto tRNAs and thus interpret the genetic code. [ABSTRACT FROM AUTHOR]

Carioca and black bean groups play a significant role in Latin American common bean (Phaseolus vulgaris) consumption, serving as excellent sources of nutrients. One of the most significant threats for common bean production is common bacterial blight (CBB), a disease caused by the gram‐negative bacteria Xanthomonas phaseoli pv. phaseoli (Xpp) and Xanthomonas citri pv. fuscans (Xcf). An effective method for managing this disease is the use of plant genetic resistance. However, it is not known whether the same or overlapping sets of genes are associated with resistance to both pathogens. This study aimed to identify a repertoire of genes potentially associated with resistance to Xpp and compare it with that previously reported for Xcf. Eighty carioca and black common bean cultivars that had previously been challenged with Xcf were inoculated with a strain of Xpp, and a genome‐wide association study (GWAS) using single‐nucleotide polymorphisms (SNPs) and disease severity data was conducted. Three carioca and three black bean cultivars exhibited high levels of resistance to Xpp. Five SNPs with the highest −log10(p) values unveiled genes coding for diverse putative biochemical functions, including a light‐regulated Lir1 protein, a proton‐dependent oligopeptide transporter family protein, a metallo‐dependent phosphatase‐like protein, a WPP domain‐interacting tail‐anchored protein 2 and a pectin lyase‐like superfamily protein. No overlap between this repertoire of genes with that reported for Xcf was found. These findings provide important insights into genes potentially involved in the P. vulgaris resistance to Xpp and the complexity of the resistance response to CBB. [ABSTRACT FROM AUTHOR]

Codon‐based analyses of the PPARGC1A gene across 38 vertebrate species were deployed to elucidate patterns of evolutionary change. Employing maximum likelihood assessments through MEGA, we scrutinized 447 codon positions addressing the entire coding region, excluding positions mired by gaps or missing data. Distinct codons manifested variance in selection pressures, particularly codons 4, 11, 66, and 123, which exhibited positive dN‐dS values suggestive of positive selection. Codon 137 displayed the most pronounced dN‐dS value, signifying intensified selective advantage. Meanwhile, codons 30 and 90 portrayed near‐neutral scores, indicative of purifying selection. Complementary computational methods (IFEL, REL, FUBAR, and SLAC) confirmed positive selection at specific codon sites, with varying degrees of corroboration. The integration of mixed‐effect modeling (MEME) identified episodic diversifying selection, pinpointing codons that underwent selection episodes in certain lineages. Refined codon model selection lent insight into substitution rates, revealing nuanced degrees of evolutionary conservation among different codons. Supporting these genetic insights, the phylogenetic analysis highlighted relationships among the PPARGC1A sequences and domain analysis confirmed conserved features across species, while protein–protein interaction networks suggested a complex web of functional interdependencies. These findings advance our understanding of the PPARGC1A gene's evolutionary trajectory and underscore the gene's potential adaptive significance within diverse vertebrate lineages. [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]

Purpose: The vagal sensory nerve (VSN) is an essential interoceptive pathway that is connected to every level of the body. Its intricate genetic coding provides sustenance for physiological processes, including controlling blood pressure and respiration. Electroacupuncture (EA) is a proven surface stimulation therapy that can regulate vagal nerve activity, which can effectively prevent cardiovascular diseases. A growing number of studies have concentrated on the mapping of VSN codes, but little is known, and the physiological background of how EA influences interoceptive has not been fully explored. Method: Here, we incorporate the hypothesized interaction among EA targets, VSNs, and the heart. This offers suggestions for using a versatile and focused EA strategy to modify vagal interoceptive awareness to enhance cardiovascular conditions. We first clarified the major role of vagal nerve in the control of cardiac activity. Additionally, we clarified the multidimensional coding pattern in the VSNs, revealing that the targeted control of multimodal interoceptive is the functional basis of the synchronization of cardiovascular system. Finding: We propose a strategy in which EA of the VSNs is employed to activate the interoceptive loop and reduce the risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Finnhorse is Finland's native and national horse breed and it has genetic affinities to northern European and Asian horses. It has historical importance for agriculture, forest work and transport and as a war horse. Finnhorse has four breeding sections in the studbook and is under conservation and characterisation efforts. We sequenced and annotated the genome of a Finnhorse mare from the working horse section using PacBio and Omni‐C data. This genome can complement the existing Thoroughbred reference genome (EquCab 3.0) and facilitate genetic studies of horses from northern Eurasia. We assembled 2.4 Gb of the genome with an N50 scaffold length of 83.8 Mb and the genome annotation resulted in a total of 19 748 protein coding genes of which 1200 were Finnhorse specific. The assembly has high quality and synteny with the current horse reference genome. We manually curated five genes of interest and deposited the final assembly in the European Nucleotide Archive under the accession no. PRJEB71364. [ABSTRACT FROM AUTHOR]

New methods are enabling comprehensive transcriptome-wide poly(A) tail analysis. Cytoplasmic dynamics involving the deadenylation and polyadenylation of poly(A) tails regulate gene expression. Non-A residues are prevalent in the 3′ ends and the internal body of poly(A) tails, where they may play crucial roles in RNA regulation. Poly(A) tails potentially encode vital epigenetic regulatory information. The poly(A) tail is an essential structural component of mRNA required for the latter's stability and translation. Recent technologies have enabled transcriptome-wide profiling of the length and composition of poly(A) tails, shedding light on their overlooked regulatory capacities. Notably, poly(A) tails contain not only adenine but also uracil, cytosine, and guanine residues. These findings strongly suggest that poly(A) tails could encode a wealth of regulatory information, similar to known reversible RNA chemical modifications. This review aims to succinctly summarize our current knowledge on the composition, dynamics, and regulatory functions of RNA poly(A) tails. Given their capacity to carry rich regulatory information beyond the genetic code, we propose the concept of 'poly(A) tail epigenetic information' as a new layer of RNA epigenetic regulation. [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]

In order to solve the problem that the formation and assignment of space launch crew mainly rely on mission experience and lack of theoretical support, firstly, the formation of space launch crew is briefly designed based on the principles of space launch crew allocation, including technical support team, launch team and test team. Secondly, on the basis of the work benefit value of space launch crew in the three teams, the personnel allocation model is constructed with the maximum work benefit as the optimization objective based on the traditional assignment model. Finally, the calculation method for the personnel allocation model is given through the decimal bit string coding of genetic algorithm. For a concrete example, the result of personnel allocation is given, proving the feasibility and effectiveness of the method. [ABSTRACT FROM AUTHOR]

Human cytoplasmic tRNAs contain dihydrouridine modifications at positions 16 and 17 (D16/D17). The enzyme responsible for D16/D17 formation and its cellular roles remain elusive. Here, we identify DUS1L as the human tRNA D16/D17 writer. DUS1L knockout in the glioblastoma cell lines LNZ308 and U87 causes loss of D16/D17. D formation is reconstituted in vitro using recombinant DUS1L in the presence of NADPH or NADH. DUS1L knockout/overexpression in LNZ308 cells shows that DUS1L supports cell growth. Moreover, higher DUS1L expression in glioma patients is associated with poorer prognosis. Upon vector-mediated DUS1L overexpression in LNZ308 cells, 5′ and 3′ processing of precursor tRNATyr(GUA) is inhibited, resulting in a reduced mature tRNATyr(GUA) level, reduced translation of the tyrosine codons UAC and UAU, and reduced translational readthrough of the near-cognate stop codons UAA and UAG. Moreover, DUS1L overexpression increases the amounts of several D16/D17-containing tRNAs and total cellular translation. Our study identifies a human dihydrouridine writer, providing the foundation to study its roles in health and disease. DUS1L was identified as the human tRNA dihydrouridine writer for positions 16 and 17. DUS1L overexpression changes the amount of several D16/D17-containing tRNAs and increases total cellular translation and cell growth in glioblastoma cells. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome of the Parotis chlorochroalis was sequenced, revaeling a length of 15239 bp with 37 genes and an A + T-rich region. All c13 PCGs begin with typical ATN codons, except COI gene, which starts with CGA. Eleven genes terminate with TAA, two with T–. All 22 tRNA genes exhibit typical cloverleaf structure except for trnS1 P. chlorochroalis has two relatively conserved intergenic regions and two relatively conserved overlapping regions. Phylogenetic analysis support P. chlorochroalis belongs to subfamily Spilomelinae, the topologies of Crambidae are highly congruent with previous studies. This newly sequences mitochondrial genome provides valuable resources for taxonomic inference and evolutionary studies of genus Parotis. [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]

It is unclear how patterns of regional genetic differentiation in the UK and Ireland might impact the protein-coding fraction of the genome. We exploit UK Biobank (UKB) and Viking Genes whole exome sequencing data to study regional genetic differentiation across the UK and Ireland in protein coding genes, encompassing 44,696 unrelated individuals from 20 regions of origin. We demonstrate substantial exonic differentiation among Shetlanders, Orcadians, individuals with full or partial Ashkenazi Jewish ancestry and in several mainland regions (particularly north and south Wales, southeast Scotland and Ireland). With stringent filtering criteria, we find 67 regionally enriched (≥5-fold) variants likely to have adverse biomedical consequences in homozygous individuals. Here, we show that regional genetic variation across the UK and Ireland should be considered in the design of genetic studies and may inform effective genetic screening and counselling. The genetic variants present in humans often reflect the geographical origins of their ancestors. This study shows that people from different UK regions tend to carry different rare variants in their exomes, with potential biomedical consequences. [ABSTRACT FROM AUTHOR]