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BACKGROUND: The relationship between placental pathology and the maternal syndrome of preeclampsia is incompletely characterized. Mismatch between placental nutrient supply and fetal demands induces stress in the syncytiotrophoblast, the layer of placenta in direct contact with maternal blood. Such stress alters the content and increases the release of syncytiotrophoblast extracellular vesicles (STB-EVs) into the maternal circulation. We have previously shown 5′-tRNA fragments (5′-tRFs) constitute the majority of small RNA in STB-EVs in healthy pregnancy. 5′-tRFs are produced in response to stress. We hypothesized STB-EV 5′-tRF release might change in preeclampsia. METHODS: We perfused placentas from 8 women with early-onset preeclampsia and 6 controls, comparing small RNA expression in STB-EVs. We used membrane-affinity columns to isolate maternal plasma vesicles and investigate placental 5′-tRFs in vivo. We quantified 5′-tRFs from circulating STB-EVs using a placental alkaline phosphatase immunoassay. 5′-tRFs and scrambled RNA controls were added to monocyte, macrophage and endothelial cells in culture to investigate transcriptional responses. RESULTS: 5′-tRFs constitute the majority of small RNA in STB-EVs from both preeclampsia and normal pregnancies. More than 900 small RNA fragments are differentially expressed in preeclampsia STB-EVs. Preeclampsia-dysregulated 5′-tRFs are detectable in maternal plasma, where we identified a placentally derived load. 5′-tRF-Glu-CTC, the most abundant preeclampsia-upregulated 5′-tRF in perfusion STB-EVs, is also increased in preeclampsia STB-EVs from maternal plasma. 5′-tRF-Glu-CTC induced inflammation in macrophages but not monocytes. The conditioned media from 5′-tRF-Glu-CTC-activated macrophages reduced eNOS (endothelial NO synthase) expression in endothelial cells. CONCLUSIONS: Increased release of syncytiotrophoblast-derived vesicle-bound 5′-tRF-Glu-CTC contributes to preeclampsia pathophysiology. [ABSTRACT FROM AUTHOR]

As a reference mitogenome, the complete mitochondrial genome of the white-breasted hedgehog, Erinaceus concolor , was firstly presented in this study by employing Long-Range PCR and Next-Generation Sequencing. The total lengths of the mitogenomes were 17.451 bp and 17.455 bp. A total of 37 genes, namely two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), and a non-coding D-loop were encoded in the mitogenome, compatible with the previously reported mitogenomes belonging to representatives of the family Erinaceidae (Mammalia: Eulipotyphla). Maximum Likelihood and Bayesian Inference phylogenetic analyses of Eulipotyphla and Erinaceidae based on the complete mitogenomes revealed a conventional relationship for the relevant organism's groups. Divergence time analyses based on complete mitogenome data revealed that evolutionary divergence events within Erinaceidae began about 58.87 Myr ago corresponding to the early Eocene, and the basal split of Erinaceus dates back to approximately 11.01 Myr ago in the late Miocene. Single cytochrome b -based analyses can be considered weaker, as they produce phylogenies that are relatively inconsistent with the natural classification of Eulipotyphla and put the onset of evolutionary divergence events earlier. The genetic information obtained as a result of this study can be used as a genetic resource for conservation biology studies; it will also undoubtedly contribute to the understanding of molecular evolution of E. concolor and closely related taxa. [ABSTRACT FROM AUTHOR]

We announce complete mitogenomes of four smelts (Osmeridae) of the San Francisco Estuary (SFE): endemic Hypomesus transpacificus , native H. pretiosus and Spirinchus thaleichthys , and non-native H. nipponensis. The genomes each contained 13 protein coding, 2 ribosomal RNA and 22 transfer RNA genes, a control region (D-loop), and a putative origin of replication of the light strand (O L); gene order followed other osmerids. Total genomes were 16,767 base-pairs (bp) for H. transpacificus ; 16,672bp for H. pretiosus ; 16,811bp for S. thaleichthys ; and 16,779bp for H. nipponensis. GC content was from 47.8% (S. thaleichthys) to 49.4% (H. pretiosus). Phylogenetic analyses of mitogenomes placed H. transpacificus sequences within the H. pretiosus [Oregon + SFE] clade and most closely related to H. pretiosus [SFE], whereas affinities of derivative cytochrome b sequences supported a Lake Suwa origin for SFE H. nipponensis. [ABSTRACT FROM AUTHOR]

The first approved RNAi therapeutics, ONPATTRO, in 2017 moves the concept of RNA interference (RNAi) therapy from research to clinical reality, raising the hopes for the treatment of currently incurable diseases. However, RNAi therapeutics are still facing two main challenges—susceptibility to enzymatic degradation and low ability to escape from endo/lysosome into the cytoplasm. Therefore, we developed disulfide-based nanospheres (DBNPs) as universal vehicles to achieve efficient RNA delivery to address these problems. Notably, the DBNPs possess unique and desirable features, including improved resistance to nuclease degradation, direct cytoplasmic delivery through thiol-mediated cellular uptake, and cytosolic environment-responsive release, greatly enhancing the bioavailability of RNA therapeutics. Additionally, DBNPs are superior in terms of overcoming formidable physiological barriers, including vascular barriers and impermeable tumor tissues. Owning to these advantages, the DBNPs exhibit efficient gene silencing effect when delivering either small interfering RNA (siRNA) or microRNA in various cell lines and generate remarkable growth inhibition in the zebrafish and mouse model of pancreatic tumors as compared to traditional delivery vectors, such as PEI. Therefore, DBNPs have potential application prospect in RNAi therapy both in vitro and in vivo. RNA interference (RNAi) therapeutics could target and alter any disease-related mRNA translation, thus have great potential in clinical application. Delivery efficiency of RNA modalities into cell cytoplasm is the main problem that currently limit RNAi therapeutics to release their full potential. Most of the known delivery materials suffer from the endo/lysosomal entrapment and enzymatic degradation during endocytosis-dependent uptake, resulting unsatisfied efficiency of the cytoplasmic release. Here, we developed disulfide-based nanospheres could directly transfer RNA modalities into the cytoplasm and significantly enhance the delivery efficiency, thus holding great potential in RNAi therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Indonesian local rabbit (Oryctolagus cuniculus) is a local breed in Indonesia. We reveal the mitochondrial genome sequence of the Indonesian local Rabbit for the first time. A better understanding of the mechanisms underlying these beneficial aspects of local breeds over imported ones requires detailed genetic investigations, of which mtDNA genome sequencing is of particular importance. Such an investigation will solve the major issues of misidentification with Javanese hares (Lepus nigricollis) and maternal lineage. In addition, this information will guide better statistics on the Indonesian local rabbit breed population and strategies for its conservation and breeding plans. This study aimed to identify and explore the characteristics of the mtDNA genomes of Indonesian local rabbits. Result This study observed that the length of the mtDNA genome is 17,469 bp, consisting of two ribosomal RNA (12S rRNA, 16S rRNA), 22 transfer RNA genes (trnR, trnG, trnK, trnD, trnS, trnY, trnC, trnN, trnA, trnW, trnM, trnQ, trnl, trnL, trnV, trnF, trnP, trnT, trnE, trnL, trnS, trnH), 13 protein-coding genes (PCGs) (ND4l, ND3, COX3, ATP6, ATP8, COX2, COX1, ND2, ND1, CYTB, ND6, ND5, ND4), a replication origin, and a noncoding control region (D-loop). Conclusions mtDNA genome of Indonesian local rabbit was the longest and had the most extended D-loop sequence among the other references of Oryctolagus cuniculus. Other specific differences were also found in the percentage of nucleotides and variation in most of the PCGs when they were aligned with Oryctolagus cuniculus references from GenBank. Indonesian local Rabbits strongly suspected brought from Europe during the colonial period in Indonesia. [ABSTRACT FROM AUTHOR]

l -Ornithine (Orn) is a core amino acid responsible for ammonia detoxification in the body via the hepatic urea cycle. Clinical studies in Orn therapy have focused on interventions for hyperammonemia-associated diseases, such as hepatic encephalopathy (HE), a life-threatening neurological symptom affecting more than 80% of patients with liver cirrhosis. However, its low molecular weight (LMW) causes Orn to diffuse nonspecifically and be rapidly eliminated from the body after oral administration, resulting in unfavorable therapeutic efficacy. Hence, Orn is constantly supplied by intravenous infusion in many clinical settings; however, this treatment inevitably decreases patient compliance and limits its application in long-term management. To improve the performance of Orn, we designed self-assembling polyOrn-based nanoparticles for oral administration through ring-opening polymerization of Orn-N-carboxy anhydride initiated with amino-ended poly(ethylene glycol), followed by acylation of free amino groups in the main chain of the polyOrn segment. The obtained amphiphilic block copolymers, poly(ethylene glycol)- block -polyOrn(acyl) (PEG- block -POrn(acyl)), enabled the formation of stable nanoparticles (NanoOrn(acyl)) in aqueous media. We employed the isobutyryl (i Bu) group for acyl derivatization in this study (NanoOrn(iBu)). In the healthy mice, daily oral administration of NanoOrn(iBu) for one week did not induce any abnormalities. In the mice exhibiting acetaminophen (APAP)-induced acute liver injury, oral pretreatment with NanoOrn(iBu) effectively reduced systemic ammonia and transaminases levels compared to the LMW Orn and untreated groups. The results suggest that the application of NanoOrn(iBu) is of significant clinical value with the feasibility of oral delivery and improvement in APAP-induced hepatic pathogenesis. Liver injury is often accompanied by hyperammonemia, a life-threatening condition characterized by elevated blood ammonia levels. Current clinical treatments for reducing ammonia typically entail the invasive approach of intravenous infusion, involving the administration of l -ornithine (Orn) or a combination of Orn and L -aspartate. This method is employed due to the poor pharmacokinetics associated with these compounds. In our pursuit of enhancing therapy, we have developed an orally administrable nanomedicine based on Orn-based self-assembling nanoparticle (NanoOrn(iBu)), which provides sustained Orn supply to the injured liver. Oral administration of NanoOrn(iBu) to healthy mice did not cause any toxic effects. In a mouse model of acetaminophen-induced acute liver injury, oral administration of NanoOrn(iBu) surpassed Orn in reducing systemic ammonia levels and liver damage, thereby establishing NanoOrn(iBu) as a safe and effective therapeutic option. [Display omitted] [ABSTRACT FROM AUTHOR]

Previous studies have revealed that age‐related hearing loss (AHL) in Cdk5 regulatory subunit‐associated protein 1 (Cdk5rap1)‐knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1‐knockout mice with AHL. Mitochondria in the spiral ganglion neurons (SGNs) and hair cells (HCs) were normal despite senescence; however, the mitochondria of types I, II, and IV spiral ligament fibrocytes were ballooned, damaged, and ballooned, respectively, in the stria vascularis. Our results suggest that the accumulation of dysfunctional mitochondria in the lateral wall, rather than the loss of HCs and SGNs, leads to the onset of AHL. Our results provide valuable information regarding the underlying mechanisms of AHL and the relationship between aberrant tRNA modification‐induced hearing loss and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

RNAs are extremely important molecules inside the cell, which perform many different functions. For example, messenger RNAs, transfer RNAs and ribosomal RNAs are involved in protein synthesis, whereas noncoding RNAs have numerous regulatory roles. Ribonucleases (RNases) are the enzymes responsible for the processing and degradation of all types of RNAs, having multiple roles in every aspect of RNA metabolism. However, the involvement of RNases in disease is still not well understood. This review focuses on the involvement of the RNase II/RNB family of 3′–5′ exoribonucleases in human disease. This can be attributed to direct effects, whereby mutations in the eukaryotic enzymes of this family [defective in sister chromatid joining (Dis3; or Rrp44), Dis3‐like exonuclease 1 (Dis3L1; or Dis3L) and Dis3‐like exonuclease 2 (Dis3L2)] are associated with a disease, or indirect effects, whereby mutations in the prokaryotic counterparts of RNase II/RNB family (RNase II and/or RNase R) affect the physiology and virulence of several human pathogens. In this review, we compare the structural and biochemical characteristics of the members of the RNase II/RNB family of enzymes. The outcomes of mutations impacting enzymatic function are revisited, in terms of both the direct and indirect effects on disease. Furthermore, we also describe the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) viral exoribonuclease and its importance to combat the COVID‐19 pandemic. As a result, RNases may be a good therapeutic target to reduce bacterial and viral pathogenicity. These are the two perspectives on RNase II/RNB family enzymes that are presented in this review. [ABSTRACT FROM AUTHOR]

Ribosomes stall indefinitely at the 3′ end of the mRNAs that lack natural stop codon and also pause anywhere on normal mRNAs during starvation. This pausing traps a considerable population of ribosomes in an inactive state and leads to a deficiency of ribosomes for ongoing protein synthesis. Bacteria possess a special RNA molecule called the tmRNA (a chimera of tRNA and mRNA), which in association with its binding partner SmpB protein, rescues the stalled ribosomes in a complex multistep process called trans-translation. This review aims to discuss the process of trans-translation and its involvement in regulating macromolecular processes in bacteria. [ABSTRACT FROM AUTHOR]

Background: Marine bacteria have recently attracted increasing attention to be harnessed for the production of valuable enzymes, vitamins, and bioactive compounds. Bacteria associated with the surfaces of marine macroalgae, called epibionts, are particularly interesting from ecological and biotechnological points of view, as they often exhibit antimicrobial activities to compete with pathogenic bacteria for nutrients and spaces. In search for biotechnologically potential genes from marine bacteria, we sequenced and analysed the genome of the epibiont HI03-3b, a polysaccharide-degrading bacterium associated with the surface of the Indonesian brown algae Hydroclathrus sp. Results: The algal epibiont HI03-3b has a genome of approximately 4,860,704 bp in size with 42.02 mol% G + C content, consisting of 5655 open reading frames (ORFs), 4409 genes coding for proteins (CDSs), 94 genes for tRNAs, and 32 genes for rRNAs. The genome sequence of HI03-3b was most closely related to that of Cytobacillus firmus NCTC10335 with the average amino acid identity (AAI) of 95.0 %, average nucleotide identity (ANI) of 94.1 %, and a recommended DNA-DNA hybridization (DDH) of 57.60 %. These scores are lower than the most frequently used standard for species demarcation (95% ANI cutoff) and the new species threshold (DDH > 70.0% for the same bacterial species). Some differences in genome features and gene composition were observed between HI03-3b and NCTC10335, such as genes encoding carbohydrate active enzymes. These suggest that HI03-3b is unique and likely a novel species within Cytobacillus genus, and we therefore proposed its name as Cytobacillus wakatobiense HI03-3b. Genome sequence analyses indicated the presence of genes involved not only in polysaccharide and protein degradation but also in vitamin and secondary metabolite biosynthesis. Some of them encode enzymes and compounds with biotechnological interest, such as protease, chitinase, subtilisin, pullulanase, and bacillolysin, which are often associated with antimicrobial or antibiofilm activities. This antimicrobial potential is supported by our finding that the extracellular protein fraction of this epibiont inhibited the growth of the bacterial pathogen Staphylococcus aureus. Conclusion: The epibiont Cytobacillus HI03-3b harbours genes for polysaccharide and protein degradation as well as for natural product biosynthesis, suggesting its potential ecological roles in outcompeting other bacteria during biofilm formation as well as in protecting its algal host from predation. Due to the presence of genes for vitamin biosynthesis, it might also provide the algal host with vitamins for growth and development. Some of these metabolic genes are biotechnologically important, as they could become a platform for bioengineering to generate various seaweed-derived substances sustainably, such as antibiofilm agents and vitamins, which are beneficial for human health. [ABSTRACT FROM AUTHOR]

Sarcocystis cruzi is a member of the genus Sarcocystis, infecting bovine animals such as cattle and bison as intermediate hosts, and canids such as dogs and raccoon dogs as definitive hosts. Acute sarcocystosis of S. cruzi causes occasional symptoms in cattle, including weight loss, reduced milk production, abortions, and death, and similar to other Sarcocystis species can potentially cause food poisoning in humans when raw or undercooked infected cattle meat is consumed. Despite these issues, genetic information on S. cruzi is scarce, and there is no specific quantitative method for the detection and quantification of the parasite in infected cattle. In this study, we aimed to develop a method based on high-throughput sequencing of S. cruzi genome and transcriptome that specifically and quantitatively detects the S. cruzi acetyl-CoA synthetase gene (ScACS). Cardiac muscles were collected from slaughterhouses in Saitama Prefecture to obtain sarcocysts from which DNA and RNA were extracted for the high-throughput sequencing. Using the sequences, we developed a specific quantitative PCR assay which could distinguish S. cruzi ACS from that of Toxoplasma gondii by taking advantage of the differences in their exon/intron organizations and validated the assay with the microscopic counting of the S. cruzi bradyzoites. Thus, this assay will be useful for future studies of S. cruzi pathogenesis in cattle and for the surveillance of infected animals, thereby easing public health concerns. [ABSTRACT FROM AUTHOR]

In this article, a bioinformatics pipeline is proposed that focuses on two types of elements, namely the mobile genetic elements (MGE) and Ribonucleic acids (RNAs). The MGEs are called insertion sequences (ISs) in the prokaryotic domain. The objective of this research work is to study the behaviour of RNAs and MGEs genes, and the effects of their presence around inversions in genome sequences. The proposed pipeline finds the relation between the transposase gene types (e.g., DDE and DEDD) located within insertion sequences according to their IS family and sub-family, and RNAs (tRNA and rRNA) on the one hand, and genomic inversion on the other hand. More precisely, we wonder whether the insertion sequences and RNAs have any effects on the occurrence of inversions. To investigate this, we start by extracting all inversions between every two close isolates of P. aeruginosa from a high supported phylogenetic tree, and we investigate inversion boundaries, to determine the impact of IS elements and RNAs around these inversions. For RNAs genes, we noticed that a high occurrence of these elements are found in what we called InBoundary, while few to zero occurrences have been recorded in OutBoundary. We remark that the NCGM2.S1 genome has the largest amount of tRNAs and inversions comparing to other genomes. For RNA genes, the tRNAs genes (Arg, Ala, Leu) recorded the highest occurrences around the inversions, while there was few occurrences of rRNA genes, within all genomes. For IS elements, we noticed that the family of IS3 has the highest impact on inversions, but sometimes other type of IS elements can also be found with IS3 around the inversions. In this case, these types of ISs shared the same type of transposase gene (DDE). We finally conclude that the distribution of RNA and IS genes has a big impact on the inversions in bacterial genomes. [ABSTRACT FROM AUTHOR]

In this article, a bioinformatics pipeline is proposed that focuses on two types of elements, namely the mobile genetic elements (MGE) and Ribonucleic acids (RNAs). The MGEs are called insertion sequences (ISs) in the prokaryotic domain. The objective of this research work is to study the behaviour of RNAs and MGEs genes, and the effects of their presence around inversions in genome sequences. The proposed pipeline finds the relation between the transposase gene types (e.g., DDE and DEDD) located within insertion sequences according to their IS family and sub-family, and RNAs (tRNA and rRNA) on the one hand, and genomic inversion on the other hand. More precisely, we wonder whether the insertion sequences and RNAs have any effects on the occurrence of inversions. To investigate this, we start by extracting all inversions between every two close isolates of P. aeruginosa from a high supported phylogenetic tree, and we investigate inversion boundaries, to determine the impact of IS elements and RNAs around these inversions. For RNAs genes, we noticed that a high occurrence of these elements are found in what we called InBoundary, while few to zero occurrences have been recorded in OutBoundary. We remark that the NCGM2.S1 genome has the largest amount of tRNAs and inversions comparing to other genomes. For RNA genes, the tRNAs genes (Arg, Ala, Leu) recorded the highest occurrences around the inversions, while there was few occurrences of rRNA genes, within all genomes. For IS elements, we noticed that the family of IS3 has the highest impact on inversions, but sometimes other type of IS elements can also be found with IS3 around the inversions. In this case, these types of ISs shared the same type of transposase gene (DDE). We finally conclude that the distribution of RNA and IS genes has a big impact on the inversions in bacterial genomes. [ABSTRACT FROM AUTHOR]

The genetic variation in the breeding concentrations of spotted seals (Phoca largha) inhabiting the Rimsky-Korsakov Archipelago (Peter the Great Bay, Sea of Japan) was studied using the control region of the mitochondrial genome. A total of 17 haplotypes in the control region and adjacent threonine and proline tRNA genes of 535 bp were identified in 32 largha underyearlings. The haplotype network revealed two mitochondrial lineages of spotted seals separated by fixed mutation steps. An analysis of molecular variation (AMOVA) and phylogenetic reconstruction showed significant genetic differentiation between two groups of individuals from the same pupping sites. The obtained results are compared with available data for other parts of the spotted seal range. Possible events in the last glacial that have led to the sympatry of distinct spotted seal lineages in Peter the Great Bay are discussed. [ABSTRACT FROM AUTHOR]

Saccharomyces cerevisiae has 6 synonymous tRNACCATrp genes encoding the identical sequence, including their intronic region. They are supposed to express tRNACCATrp in the same quality and quantity. Here, we generated single to quintuple deletion strains with all the possible combinations of the synonymous tRNACCATrp genes to analyze whether those individual genes equally contribute cell viability and tRNA production. The quintuple deletion strains that only harbor tW(CCA)J, tW(CCA)M, or tW(CCA)P were viable but almost lethal while the other quintuple deletions showed moderately impaired growth. These growth differences were not obvious among the quadruple deletion strains, which expressed almost one third of mature tRNACCATrp in the wild type. Therefore, no dosage compensation operates for tRNACCATrp amount, and growth variations among the quintuple deletion strains may not simply reflect differences in tRNACCATrp shortage. Yeast may retain the redundancy of tRNACCATrp genes for a noncanonical function(s) beyond the supply of the tRNA to translation. [ABSTRACT FROM AUTHOR]

In this paper, we present a new algorithm to find the optimal proteins generated through DNA synthesis. The algorithm executes in five stages: in the first stage, it takes a DNA sequences and consider it as the initial populations of lions, determined the main positions of each lion and the main distances among lions and goal point then consider this distance as fitness of that lions, after that sort the lions based on their fitness to preparing it to the second stage. The second stage develops lion optimization algorithm (LOA) by adding four new features on it, each feature performance one task, a replacing the kernel of LOA (i.e., searching machnizam) by spirally searching & Bubble net searching to increase the accuracy, at the same time reduce the execution time to reach of the goal achieve by A Smart feature. The main purpose of the third stage is determining lion active or more yauld where each lion in population need update the positions and fitness after each move in searching space to reach of their goal., this achieved through Yauld feature. The fourth stage applies the Cooperative features to convert the active sequence of DNA (i.e., Yauld lion) into mRNA after that built tRNA from it after splitting it into triplet to start to generate the proteins. Synthesis of all triplet of tRNA to generated final proteins result by new optimization algorithm achieved based on deep composite that satisfies the four rules, this feature called Deep feature and represent the final stage of the algorithm. The new algorithm appears as a pragmatic optimization model, it proves their robust to work with dynamic length of DNA sequence. It increases accuracy and reduces execution times. [ABSTRACT FROM AUTHOR]

Poppies are beneficial plants with a variety of applications, including medicinal, edible, ornamental, and industrial purposes. Some Papaver species are forensically significant plants because they contain opium, a narcotic substance. Internationally trafficked species of illegal poppies are being identified by DNA barcoding employing multiple markers in response to their forensic value. However, effective markers for precise species identification of legal and illegal poppies are still under discussion, with research on illegal poppies focusing on Papaver somniferum L., and species identification studies of Papaver bracteatum and Papaver setigerum DC. still lacking. As a result, in order to evaluate the performance of genetic markers and classify their DNA sequences in the genus Papaver , this study developed the first machine learning-based two-layer model, in which the first layer classifies legal and illegal poppies from the given sequence and the second layer identifies species of illegal poppies using their sequences. We constructed the dataset and investigated biological features from four markers, internal transcribed spacer 1 (ITS1), internal transcribed spacer 2 (ITS2), transfer RNA Leucine (trnL), transfer RNA Leucine - transfer RNA Phenylalanine intergenic spacer (trnL–trnF intergenic spacer) and their combination, using four machine learning algorithms, K-nearest neighbor (KNN), Naïve Bayes (NB), extreme gradient boost (XGBoost) and Random Forest (RF). According to our findings, for Layer 1 to classify legal and illegal poppies, KNN-based models using combined ITS region achieved the greatest performance of accuracy 0.846 and 0.889 using training and test sets, respectively. Additionally, for Layer 2 to identify illegal poppy species, KNN-based models using combined ITS region achieved the best performance of 0.833 and 1.000 for using training and test sets, respectively. To validate the model, the combined ITS region, which includes ITS 1 and 2 sequences, from blind poppy samples were used as a case study, with the Layer 1 correctly classifying legal and illegal poppies with over 0.830 accuracy. Layer 2 correctly identified P. setigerum DC., however, only one of the three P. somniferum L. species was accurately identified. Nevertheless, our research shows that machine learning can be used to classify and identify legal and illegal poppy species using DNA barcodes which can then be used as an efficient and effective forensic tool for improved law enforcement and a safer society. [Display omitted] • A two-layer machine learning model was developed for the classification of legal and illegal poppy classification. • The KNN-based model using ITS region exhibited best performance in differentiating legal from illegal poppies, and subsequently identifying specific illegal species. • Machine learning proved effective in classifying and identifying legal and illegal poppy species using DNA barcoding. [ABSTRACT FROM AUTHOR]

Yeast species found in the phyllosphere and rhizospheric soil of plants are acknowledged as proficient biocontrol agents against the soilborne and airborne fungal plant pathogens. The unicellular yeasts are particularly valuable due to their ease of cultivation and effectiveness as biocontrol agents against various yeast genera. This review article thoroughly described the fundamental exploration of yeast biocontrol mechanisms, including myco-parasitism, volatile metabolites, killer toxin production, toxic enzyme secretion, induction resistance in the host plant, and competition for resources on plant surfaces and in the soil. Antagonistic yeasts are highlighted for their productions of killer toxins, that disrupt vulnerable segments of the targeted pathogen, such as cell wall degradation, plasma membrane disruption, tRNA linkage breakage, and DNA mutation. The use of beneficial microbe-based products those derived from yeast is a multifaceted strategy to controlling post-harvest fungal pathogens and enhancing plant health. Commercially available yeast-based products, namely Boni-protect® (Aureobasidium pullulans), Nexy® (Candida oleophilic), Candifruit® (Candida sake), Shemer® (Metschnikowia fructicola), Pantovital® (Pantoea agglomerans), and Romeo® (Saccharomyces cerevisiae)." For example: "Boni-protect® (Aureobasidium pullulans), Nexy® (Candida oleophilic), Candifruit® (Candida sake), Shemer® (Metschnikowia fructicola), Pantovital® (Pantoea agglomerans), and Romeo® (Saccharomyces cerevisiae) are discussed for their efficacy against postharvest fungal pathogens. This review article enhances the understanding of biocontrol mechanism and formulation strategies for yeast based commercial products, supporting future research efforts in fungal pathogen managements. • Yeast species combat soilborne and airborne fungal pathogens. • Ease of cultivation makes unicellular yeasts noteworthy biocontrols. • Exploring yeast biocontrol mechanisms: myco-parasitism and more. • Antagonistic yeasts' killer toxins target pathogen vulnerabilities. • Commercial yeast-based products enhance plant health effectively. [ABSTRACT FROM AUTHOR]

Withdrawal: Urinary exosomal tRNA‐derived small RNA signatures as a predictive biomarker in lung cancer, published in FEBS OPEN BIO, 10.1002/2211‐5463.13716. The above article, published online on 9th October 2023 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the journal Editor in Chief, Miguel De la Rosa, and Wiley Periodicals LLC. The withdrawal has been agreed following no response from the author to requests to sign the Journal's publishing license/to requests to approve their article proof for publication. https://doi.org/10.1002/2211-5463.13716 [ABSTRACT FROM AUTHOR]

Leptospermum is an ecologically and economically important genus with a long unresolved taxonomic issue concerning polyphyly, as indicated from early molecular analysis on two chloroplast regions. To resolve this, we used genome skimming to obtain high‐copy chloroplast and nuclear ribosomal DNA for a comprehensive phylogenomic analysis of 110 accessions comprising of 38 Leptospermum taxa, 6 closely allied genera and 5 outgroup genera. Maximum likelihood and Bayesian analyses resolved congruent clades for the chloroplast (132,143 bp: 80 CDSs, 4 rRNA genes, 29 tRNA genes, 17 introns and 97 IGSs) and nuclear (1219 bp: ITS1, ITS2, ETS, 5.8S) alignments to provide a robust interpretation of evolutionary relationships. Together, these data confirmed extensive polyphyly of Leptospermum that separated the genus into five monophyletic clades spread amongst clades representing six closely allied genera: Agonis, Asteromyrtus, Homalospermum, Kunzea, Neofabricia and Pericalymma. These five Leptospermum clades share some similarities with morphological and genetic groupings identified previously but provide greater resolution to inform a clear pathway to taxonomic revision. The evidence presented here provides support for resolution of the current polyphyly of Leptospermum through the recognition of five genera, while retaining all other genera of Leptospermeae in their current circumscription. [ABSTRACT FROM AUTHOR]

Endonuclease V ( EndoV ) is an inosine-specific endonuclease which is highly conserved in all domains of life: Bacteria, Archaea, and Eukarya; and, therefore, may play an important role in nucleic acid processes. It is currently thought that bacterial EndoVs are involved in DNA repair, while eukaryotic EndoVs are involved in RNA editing based on the differences in substrate preferences. However, the role of EndoV proteins, particularly in the archaeal domain, is still poorly understood. Here, we explored the biochemical properties of EndoV from the hyperthermophilic archaeon Thermococcus kodakarensis ( TkoEndoV ) . We show that TkoEndoV has a strong preference for RNA over DNA. Further, we synthesized 1-methylinosine-containing RNA that is a simple TC loop mimic of archaeal tRNA and found that TkoEndoV discriminates between 1-methylinosine and inosine, and selectively acts on inosine. Our findings suggest a potential role of archaeal EndoV in the regulation of inosine-containing RNA. [ABSTRACT FROM AUTHOR]

We investigated the regulators of the glucose induction ( GI ) of the ECF-sigma genes sigX / M . During further screening of transposon-inserted mutants, we identified several regulators including an RNA component of RNase P ( rnpB ), which is required for tRNA maturation. A depletion of rnpB is known to trigger the stringent response. We showed evidence that the stringent response inhibited GI of sigX/M . [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EV) within the cellular secretome are emerging as modulators of pathological processes involved in tumor growth through their ability to transfer donor‐derived RNA into recipient cells. While the effects of tumor and stromal cell EVs within the tumor microenvironment have been studied, less is known about the contributions of normal, nontransformed cells. We examined the impact of EVs within the cellular secretome from nonmalignant cells on transformed cell growth and behavior in cholangiocarcinoma cells. These effects were enhanced in the presence of the pro‐fibrogenic mediator TGF‐β. We identified miR‐195 as a TGF‐β responsive miRNA in normal cells that can be transferred via EV to tumor cells and regulate cell growth, invasion, and migration. The effects of miR‐195 involve modulation of the epithelial–mesenchymal transition through direct effects on the transcription factor Snail. These studies provide in vitro and in vivo evidence for the impact of normal cellular secretome on transformed cell growth, show the importance of EV RNA transfer, and identify mechanisms of EV‐mediated transfer of miRNA as a contributor to tumor development, which may provide new therapeutic opportunities for targeting human cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

The male of the wolf spider Paratrochosina amica (Mello-Leitão 1941) is redescribed, and the female of this species is described for the first time. Additionally, we evaluate the phylogenetic position of P. amica using the mitochondrial genes cytochrome c oxidase subunit I (cox1), the 12S rRNA (12S) and 16S rRNA (16S), NADH deshydrogenase subunit I (nad1) and the complete tRNA leu (L1). In live specimens we recognized three different morphotypes based on colour patterns. There were no differences in genitalic features of males and females among the three morphotypes. Molecular results through GMYC analyses did not identify independent evolutionary lineages. Genetic and taxonomic results support that the three morphotypes are conspecific. Phylogenetic analysis confirms the position of P. amica in the subfamily Allocosinae. [ABSTRACT FROM AUTHOR]

Ostracoda is a diverse group of tiny crustaceans. Although more than 9330 extant species have been described, whole-mitogenomic data were available for only five species. Here we present a complete mitogenomic sequence for an additional species, the parthenogenetic podocopan ostracod Heterocypris spadix. The mitogenome is 15,205 bp long and contains the typical animal mitogenomic complement of 13 protein coding, two ribosomal RNA, and 22 transfer RNA genes. In a mitogenome-based phylogenetic tree, Myodocopa and Podocopa were each monophyletic. Gene order in Podocopa was much more similar to the pancrustacean ground pattern than was gene order in Myodocopa. Gene order was invariant in the three myodocopan species examined, all in the family Cypridinidae. Within Podocopa, two species from different families (Fabaeformiscandona kushiroensis , Candonidae; H. spadix , Cyprididae) were identical in gene order and differed from the pancrustacean ground pattern by only a single recombination. In Cyprididae, however, Cypridopsis vidua differed from H. spadix by five rearrangements. These conflicting patterns—apparent gene-order conservation within (Cypridinidae) and between families (Cyprididae and Candonidae), but marked divergence within a family (Cyprididae)—suggest that the evolution of gene order in ostracods was more complex than that expected from the cypridinid data. [ABSTRACT FROM AUTHOR]

Genome characterization of California poppy (Eschscholzia californica cv. "Hitoezaki"), which produces pharmaceutically important benzylisoquinoline alkaloids (BIAs), was carried out using the draft genome sequence. The numbers of tRNA and rRNA genes were close to those of the other plant species tested, whereas the frequency of repetitive sequences was distinct from those species. Comparison of the predicted genes with those of Amborella trichopoda, Nelumbo nucifera, Solanum lycopersicum , and Arabidopsis thaliana , and analyses of gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway indicated that the enzyme genes involved in BIA biosynthesis were highly enriched in the California poppy genome. Further comparative analysis using the genome information of Papaver somniferum and Aquilegia coerulea , both BIA-producing plants, revealed that many genes encoding BIA biosynthetic enzymes, transcription factors, transporters, and candidate proteins, possibly related to BIA biosynthesis, were specifically distributed in these plant species. [ABSTRACT FROM AUTHOR]

We sequenced the complete mitochondrial genome of the fishfly species Acanthacorydalis fruhstorferi van der Weele (Megaloptera: Corydalidae). The genome, which was 15,286 bp in length, included a standard set of 13 protein-coding genes, 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and a putative A+T-rich region. The gene arrangement is identical to that of most common Megaloptera mitochondrial genomes. We analyzed the preferred codon usage of the protein-coding genes and predicted the secondary structures of all the RNA transcripts. In addition, a phylogenetic tree was constructed based on the sequences of the 13 protein-coding genes, and the results supported the current view of a close relationship between Megaloptera and Neuroptera. Our analyses suggest that complete mitochondrial genome sequences are a promising method to fully resolve the phylogenetic relationships within Megaloptera. [ABSTRACT FROM AUTHOR]

Objectives: Recent studies have shown that tRNA-derived RNA fragments (tRFs) are novel regulators of post-transcriptional gene expression. However, the expression profiles and their role in post-transcriptional gene regulation in chondrocytes is unknown. Here, we determined tRFs expression profile and explored tRF-3003a role in post-transcriptional gene regulation in IL-1β stimulated chondrocytes.Methods: We used qPCR arrays to determine tRNAs and tRFs expression in age- and sex-matched primary human OA chondrocytes and TC28/I2 cells stimulated with IL-1β. Chondrocytes were transfected with tRNA-CysGCA overexpression plasmid or tRF-3003a mimic and 3'UTR luciferase reporter plasmids of mRNAs harboring predicted tRF target "seed sequence". The AGO-RNA-induced silencing complex (AGO-RISC)-dependent repressive activity of tRF-3003a was determined by siRNA-mediated knockdown of AGO2.Results: IL-1β increased the expression levels of specific tRNAs and of tRF-3003a, a type 3 tRF produced by the cleavage of tRNA-CysGCA. tRF-3003a "seed sequence" was identified in the 3'UTR of JAK3 mRNA and tRNA-CysGCA overexpression or transfection of a tRF-3003a mimic in chondrocytes downregulated JAK3 expression and significantly reduced the activity of the 3'UTR reporter. RIP assay showed enrichment of tRF-3003a into AGO2/RISC in IL-1β treated chondrocytes. The suppressive effect of tRF-3003a on JAK3 3'UTR reporter was abrogated with siRNA-mediated depletion of AGO2.Conclusions: We demonstrate that under pathological conditions chondrocytes display perturbations in the expression profile of specific tRNAs and tRFs. Furthermore, a specific tRF namely tRF-3003a can post-transcriptionally regulate JAK3 expression via AGO/RISC formation in chondrocytes. Identification of this novel mechanism may be of value in the design of precision therapies for OA. [ABSTRACT FROM AUTHOR]

Sea cucumber species are abundant (>1400 species) and widely distributed globally. mtDNA sequencing is frequently used to identify the phylogenetic and evolutionary relationships among species. However, there are no reports on the mitochondrial genome of Phyllophorus liuwutiensis. Here, we performed mtDNA sequencing of P. liuwutiensis to examine its phylogenetic relationships with other echinoderms. Its mitochondrial genome (15 969 bp) contains 37 coding genes, including 13 protein‐coding genes, 22 tRNA genes and 2 rRNA genes. Except for one protein‐coding gene (nad6) and five tRNA genes encoded on the negative strand, all other genes were encoded on the positive strand. The mitochondrial bases of P. liuwutiensis were composed of 29.55% T, 22.16% C, 35.64% A and 12.64% G. The putative control region was 703 bp in length. Seven overlapping regions (1–10 bp) were found. The noncoding region between the genes ranged from 1 to 130 bp in length. One putative control region has been found in the P. liuwutiensis mitogenome. All of the tRNA genes were predicted to fold into a cloverleaf structure. In addition, we compared the gene arrangements of six echinoderms, revealing that the gene order of P. liuwutiensis was a new arrangement. [ABSTRACT FROM AUTHOR]

Two novel cry-type gene homologues, tentatively named cryPp1 and cryPp2, were detected in the genomic DNA of Paenibacillus popilliae ATCC 14706T, both of which were similar to genes encoding Cry18 proteins, suggesting their similar modes of action. Ours is the first report concerning multiple Cry homologues, detected from a sole strain of P. popilliae. In order to characterize the roles of the two Cry homologues in pathogenicity, a trial for the expression of recombinant proteins in Escherichia coli was conducted, which revealed that the optimization of rare codons, such as supplementation of tRNA genes, was necessary. [ABSTRACT FROM AUTHOR]

Thermotolerant strains are critical for low-cost high temperature fermentation. In this study, we carried out the thermal adaptation of A. pasteurianus IFO 3283–32 under acetic acid fermentation conditions using an experimental evolution approach from 37ºC to 40ºC. The adapted strain exhibited an increased growth and acetic acid fermentation ability at high temperatures, however, with the trade-off response of the opposite phenotype at low temperatures. Genome analysis followed by PCR sequencing showed that the most adapted strain had 11 mutations, a single 64-kb large deletion, and a single plasmid loss. Comparative phenotypic analysis showed that at least the large deletion (containing many ribosomal RNAs and tRNAs genes) and a mutation of DNA polymerase (one of the 11 mutations) critically contributed to this thermotolerance. The relationship between the phenotypic changes and the gene mutations are discussed, comparing with another thermally adapted A. pasteurianus strains obtained previously. In vitro thermal adaption of mesophilic Acetic Acid Bacteria generates thermally adapted strains exhibiting both thermotolerance and trade-off response [ABSTRACT FROM AUTHOR]

Echinostoma revolutum is a zoonotic food-borne intestinal trematode that can cause intestinal bleeding, enteritis, and diarrhea in human and birds. To identify a suspected E. revolutum trematode from a red-crowned crane (Grus japonensis) and to reveal the genetic characteristics of its mitochondrial (mt) genome, the internal transcribed spacer (ITS) and complete mt genome sequence of this trematode were amplified. The results identified the trematode as E. revolutum. Its entire mt genome sequence was 15,714 bp in length, including 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and one non-coding region (NCR), with 61.73% A+T base content and a significant AT preference. The length of the 22 tRNA genes ranged from 59 bp to 70 bp, and their secondary structure showed the typical cloverleaf and D-loop structure. The length of the large subunit of rRNA (rrnL) and the small subunit of rRNA (rrnS) gene was 1,011 bp and 742 bp, respectively. Phylogenetic trees showed that E. revolutum and E. miyagawai clustered together, belonging to Echinostomatidae with Hypoderaeum conoideum. This study may enrich the mitochondrial gene database of Echinostoma trematodes and provide valuable data for studying the molecular identification and phylogeny of some digenean trematodes. [ABSTRACT FROM AUTHOR]

5-Aminolevulinic acid (ALA) is an important cellular metabolic intermediate that has broad agricultural and medical applications. Previously, attempts have been made to synthesize ALA by multiple enzymes in cell free systems. Here we report the development of a semi-permeable system for ALA production using stable enzymes. Glucose, sodium polyphosphate, ATP, tRNA, glutamate and NADPH were used as substrates for ALA synthesis by a total of nine enzymes: adenylate kinase, polyphosphate kinase, glucose-6-phosphate dehydrogenase, phosphogluconolactonase, 6-phosphogluconate dehydrogenase, glutamyl-tRNA synthetase and glutamate-1-semialdehyde aminotransferase from E. coli, hexokinase from yeast, as well as glutamyl-tRNA reductase and its stimulator protein glutamyl-tRNA reductase binding protein (GBP) from Arabidopsis in a semi-permeable system. After reaction for 48 h, the glutamate conversion reached about 95%. This semi-permeable system facilitated the reuse of enzymes, and was helpful for the separation and purification of the product. The ALA production could be further improved by process optimization and enzyme engineering. Abbreviations: PPK: polyphosphate kinase; ADK: adenylate kinase; ALA: 5-Aminolevulinic acid; HK: hexokinase; ZWF: glucose-6-phosphatedehydrogenase; PGL: phosphogluconolactonase; GND: 6-phosphogluconate dehydrogenase; GTS: glutamyl-tRNA synthetase; GTR: glutamyl-tRNA reductase; GBP: GTR binding protein; GSAAT: glutamate-1-semialdehyde aminotransferase. The multi-enzyme reactions for 5-aminolevulinic acid (ALA) synthesis through the C5 pathway. [ABSTRACT FROM AUTHOR]

The loss of bone and destruction of bone microstructure due to aging in senile osteoporosis (SOP) significantly impair the health and quality of life of the elderly. The pathogenesis of SOP is primarily related to osteogenic deficiency, attenuation of osteoblast function, insufficient bone formation, and eventual bone loss. While METTL1 is the major reported methyltransferase to catalyze RNA 7-methylguanosine (m7G) methylation, regulating mRNA transcription, miRNA biosynthesis, biological function, tRNA stability, RNA intracellular processing, and maturation, its role in the pathogenesis of SOP and osteogenic differentiation of BMSCs has not been studied. In this research, we found a significant decrease in METTL1 in BMSCs from SOP patients. Deletion of METTL1 significantly inhibited m7G modification of Runx2, impeding osteogenic differentiation of BMSCs in vitro and inducing SOP in vivo. We further developed bone-targeted lipid nanoparticles containing the m7G methylated Runx2 mRNA (ZA-m7G Runx2 mRNA-LNPs), which significantly promoted bone repair and formation in the bone defect mouse model as well as the SOP mouse. This study provides new basic theoretical theory and treatment strategies for the prevention and treatment of SOP by revealing a critical m7G RNA modification mechanism of osteogenic differentiation disorders of BMSCs in the pathogenesis of SOP. [Display omitted] • Knockdown of METTL1 significantly limited the osteogenic differentiation of BMSCs in vitro. • Internal mRNA m7G modification of Runx2 mRNA was significantly up-regulated during BMSCs differentiation. • Loss of METTL1-mediated RUNX2 mRNA 7-methylguanosine methylation modification facilitates senile osteoporosis. • Bone-targeted lipid nanoparticles containing the 7-methylguanosine methylated Runx2 mRNA is a promising bone-targeting therapy strategy for SOP. [ABSTRACT FROM AUTHOR]

Abstract Diabetes mellitus (DM) is a complex endocrine and metabolic disorder for human health and well-being. Deregulated glucose and lipid metabolism are the primary underlying manifestations associated with this disease. Transfer RNAs (tRNAs) are considered to mainly participate in protein translation and may contribute to complex human pathologies. Although the molecular mechanisms remain, for the most part, unknown, accumulating evidence indicates that tRNAs play a vital role in the pathogenesis of DM. This paper reviews different aspects of tRNA-associated dysregulation in DM, such as tRNA mutations, tRNA modifications, tRNA aminoacylation and tRNA derivatives, aiming at a better understanding of the pathogenesis of DM and providing new ideas for the personalized treatment of this metabolism-associated disease. Highlights • tRNA-associated dysregulation played a key role in DM. • tRNA mutations caused severe respiratory chain deficiency and mitochondrial dysfunction in the pathogenesis of DM. • tRNA modifications interfered with proinsulin processing, beta cell apoptosis, and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Abstract We present a complete sequence and describe the organization of the mitochondrial genome of the amoeba Paravannella minima (Amoebooza, Discosea, Vannellida). This tiny species represents a branch at the base of Vannellida tree, to the moment being its earliest-branching lineage. The circular mitochondrial DNA of this species has 53,464 bp in length and contains 30 protein-coding genes, 2 ribosomal RNAs, 23 transfer RNAs, and 15 open reading frames. This genome is significantly longer and contains more protein-coding genes than any yet sequenced mitochondrial genome of vannellid amoebae. Unlike the previously sequenced mitochondrial genomes of Vannellida, which should be translated using the "Table 4" (the mold, protozoan, and coelenterate mitochondrial code), that of P. minima can be properly translated using the universal genetic code. [ABSTRACT FROM AUTHOR]

Abstract Settleability of particles in activated sludge systems can be impaired by an overgrowth of filamentous bacteria, a problem known as bulking. These filaments are often members of the phylum Chloroflexi, sometimes reaching abundances in excess of 30% of the biovolume. The uncultured Chloroflexi phylotype, Candidatus Amarolinea, has been observed in high abundances in Danish full-scale activated sludge systems by 16S rRNA gene amplicon surveys, where it has been associated with bulking. In this study, fluorescence in situ hybridization was applied to confirm their high abundance, filamentous morphology, and contribution to the interfloc bridging that characterizes filamentous bulking. Furthermore, genome-centric metagenomics using both Illumina and Oxford Nanopore sequencing was used to obtain a near complete population genome (5.7 Mbp) of the Ca. Amarolinea phylotype, which belongs to the proposed novel family Amarolineaceae within the order Caldilineales of Chloroflexi. Annotation of the genome indicated that the phylotype is capable of aerobic respiration, fermentation, and dissimilatory nitrate reduction to ammonia. The genome sequence also gives a better insight into the phylogenetic and evolutionary relationships of the organism. The name Candidatus Amarolinea aalborgensis is proposed for the species. [ABSTRACT FROM AUTHOR]

Abstract Candidate bacterial phylum BRC1 has been identified in a broad range of mostly organic-rich oxic and anoxic environments through molecular analysis of microbial communities. None of the members of BRC1 have been cultivated and only a few draft genome sequences have been obtained from metagenomes or as a result of single-cell sequencing. We have reconstructed complete genome of BRC1 bacterium, BY40, from metagenome of the microbial community of a deep subsurface thermal aquifer in the Tomsk Region of the Western Siberia, Russia, and used it for metabolic reconstruction and comparison with existing genomic data. Analysis of 3.3 Mb genome of BY40 bacterium revealed numerous glycoside hydrolases that could enable utilization of carbohydrates, including enzymes of chitin-degradation pathway. The bacterium lacks flagellar machinery but the twitching motility is encoded. The reconstructed central metabolism revealed pathways enabling the fermentation of organic substrates, as well as their complete oxidation through aerobic and anaerobic respiration. Phylogenetic analysis using BY40 genome supported the phylum level classification of BRC1 lineage. Based on phylogenetic and genomic analyses, the novel bacterium is proposed to be classified as Candidatus Sumerlaea chitinivorans, within a candidate phylum Sumerlaeota. [ABSTRACT FROM AUTHOR]

Abstract Enrichment of barcode databases with mitochondrial cytochrome c oxidase subunit I (COI) barcode sequences in different animal taxa has become important for identification of animal source in food samples to prevent commercial fraud. In this study, COI barcode sequence in seventy one river buffalo samples were determined, analyzed and deposited in Genbank barcode database and barcode of life database (BOLD) to contribute for construction of public reference library for COI barcode sequence in river buffalo. Moreover COI barcode sequence was used to identify the closely related buffalo groups: river buffalo, swamp buffalo, lowland anoa and African buffalo. Results indicated the success of the COI barcode in the identification of each of the tested groups. Whereas a suggested sequence of other mitochondrial segment representing two successive transfer RNA (tRNA) genes; tRNA-Threonine (MT-TT) and tRNA-Proline (MT-TP) was failed to be used as a barcode marker for differentiation between the tested buffalo groups. [ABSTRACT FROM AUTHOR]

Benzophenones (BPs) are commonly used in personal care products like sunscreens and are increasingly being released into the environment, raising concerns about their potential ecotoxic effects. BPs as emerging environmental contaminants, little is known about their toxic effects on estuarine organisms. This study firstly investigated the toxic effects of five commonly used BPs on mud crabs (Scylla paramamosain). The crabs were exposed to varying concentrations of BPs for 14 days. The results showed that BPs caused damage to antioxidant systems in crabs. Transcriptome sequencing revealed that BP-3 and BP-1 had a greater impact on the crabs compared to the other BPs. Specifically, BP-1 and BP-3 caused severe damage to organelles and ribosomes. BP affected catalytic activity and hydrolase activity, BP-2 affected phosphoenolpyruate carboxykinase activity, and BP-4 affected tRNA aminoacylation and hydrolase activity. These findings can enhance our understanding of the ecotoxicity of BPs and may help to protect estuarine ecosystems. [Display omitted] • Comparative analysis of five BPs' toxic effects on crabs was firstly conducted. • The five BPs caused different gene response patterns in S. paramamosain. • BP-3 and BP-1 exhibited higher hepatotoxicity on S. paramamosain. • BPs impacted the antioxidant system in S. paramamosain. • BPs influenced the apoptosis signaling in S. paramamosain. [ABSTRACT FROM AUTHOR]

Although boron is an essential element for many organisms, an excess amount of it can cause toxicity, and the mechanism behind this toxicity is not yet fully understood. The Gcn4 transcription factor plays a crucial role in the boron stress response by directly activating the expression of the boron efflux pump Atr1. More than a dozen transcription factors and multiple cell signaling pathways have roles in regulating the Gcn4 transcription factor under various circumstances. However, it is unknown which pathways or factors mediate boron signaling to Gcn4. Using the yeast Saccharomyces cerevisiae as a model, we analyzed the factors that converge on the Gcn4 transcription factor to assess their possible roles in boron stress signaling. Our findings show that the GCN system is activated by uncharged tRNA stress in response to boron treatment and that GCN1 , which plays a role in transferring uncharged tRNAs to Gcn2, is necessary for the kinase activity of Gcn2. The SNF and PKA pathways were not involved in mediating boron stress, even though they interact with Gcn4. Mutations in TOR pathway genes, such as GLN3 and TOR1 , abolished Gcn4 and ATR1 activation in response to boric acid treatment. Therefore, our study suggests that the TOR pathway must be functional to form a proper response against boric acid stress. • Boric acid causes eIF2α phosphorylation in a GCN1 dependent manner. • TOR1 deletion disrupts boron efflux pump (ATR1) induction in response to boric acid treatment. • GLN3 plays role in boron stress response. • The Tor pathway mediates boron stress signaling. [ABSTRACT FROM AUTHOR]

Mitochondria is an important subcellular organelle with the prime function being energy metabolism and supply of energy to the body cells for carrying out the vital functions. Energy is the primary requisite for the reproductive organs of both male and female for carrying out the normal functions. In the present article, we have described how mutation in mitochondrial DNA lead to defects in male and female reproduction. Mitochondria is an integral part of the mid-piece of sperm and also has role in other parts of male reproductive system. Similarly, mitochondrial DNA has role in female reproductive system including ovulation, zygote activation, fertilization, oocyte maturation and embryo development. Mitochondrial defect are collectively named as "mystondria" (mysterious diseases of mitochondria) and may be corrected through mitochondrial replacement therapy, popularly known as three parent baby concept, since there are no other scope for cure or treatment. Two approaches for mitochondrial replacement therapy are pronuclear transfer and spindle transfer. The first three parent baby was developed in April 2016 through mitochondrial replacement therapy. The present review is aimed at functional relevance of three-parent baby concept in animal reproduction. [ABSTRACT FROM AUTHOR]

Transfer RNA (tRNA) molecules are sumptuously decorated with evolutionary conserved post-transcriptional nucleoside modifications that are essential for structural stability and ensure efficient protein translation. The tRNA modification levels change significantly in response to physiological stresses, altering translation in a number of ways. For instance, tRNA hypomodification leads to translational slowdown, disrupting protein homeostasis and reducing cellular fitness. This highlights the importance of proper tRNA modification as a determinant for maintaining cellular function and viability during stress. Furthermore, the expression of several microbial virulence factors is induced by changes in environmental conditions; a process where tRNA 2-thiolation is unequivocal for pathogenicity. In this review, we discuss the multifaceted implications of tRNA modification for infection by examining the roles of nucleoside modification in tRNA biology. Future development of novel methods and combinatory utilization of existing technologies will bring tRNA modification-mediated regulation of cellular immunity and pathogenicity to the limelight. [ABSTRACT FROM AUTHOR]

Purpose In various malignancies RNA fragments are dysregulated. Our study was designed to determine the expression of 4, 5′-tRNA halves in the tissue and serum of patients with clear cell renal cell carcinoma. Materials and Methods Tissue and serum samples of patients with clear cell renal cell carcinoma and nonmalignant disease were collected prospectively in our biobank. We isolated total RNA from 95 clear cell renal cell carcinomas and 50 normal renal tissues as well as serum RNA from 27 patients with clear cell renal cell carcinoma and 13 with nonmalignant urological disease. To specifically determine the expression of 5′-tRNA halves we dephosphorylated and ligated an adaptor nucleotide to the 3′ end of the tRNA halves. The expression levels of 4, 5′-tRNA halves (5′-tRNA-Arg-CCT, 5′-tRNA-Glu-CTC, 5′-tRNA-Leu-CAG and 5′-tRNA-Lys-TTT) were then measured by TaqMan® based quantitative reverse transcription-polymerase chain reaction. Results All studied 5′-tRNA halves were down-regulated in clear cell renal cell carcinoma tissues, indicating a potential role as a tumor suppressor. Furthermore, we noted decreased expression of 5′-tRNA halves in patients with adverse clinicopathological parameters. All 5′-tRNA halves were expressed at lower levels in nonorgan confined clear cell renal cell carcinoma. The 5′-tRNA-Lys-TTT halves inversely correlated with ISUP (International Society of Urological Pathology) grade. In patients with clear cell renal cell carcinoma 5′-tRNA-Arg-CCT, 5′-tRNA-Glu-CTC and 5′-tRNA-Lys-TTT halves circulated at lower levels than in control subjects, indicating relevance as noninvasive biomarkers. Conclusions In patients with clear cell renal cell carcinoma 5′-tRNA halves have potential as diagnostic and prognostic biomarkers. The 5′-tRNA halves may act in a tumor suppressive manner, which requires further research to confirm. [ABSTRACT FROM AUTHOR]

In this paper, we continue investigating the structure of the Primary Language of the human brain introduced by J. von Neumann in 1957. According to our hypothesis, the Primary Language is the Language of Visual Streams (mental movies). Our investigation is focused on the major ancient algorithms essential for the development of humanity, which should have used the Primary Language directly, bypassing human symbolic languages. One of them is the Algorithm of Discovery (AD), the algorithm for inventing new algorithms. We investigate the AD by applying it to the past discoveries. In this paper, we apply it to rediscovering the “mechanics” of protein translation. We emphasize application of mosaic reasoning as one of the means for focusing visual streams in the desired direction. Specifically, we identify the matching rules that are used to link the mRNA and tRNA mosaics. [ABSTRACT FROM AUTHOR]

Unsupervised data mining capable of extracting a wide range of knowledge from big data without prior knowledge or particular models is a timely application in the era of big sequence data accumulation in genome research. By handling oligonucleotide compositions as high-dimensional data, we have previously modified the conventional self-organizing map (SOM) for genome informatics and established BLSOM, which can analyze more than ten million sequences simultaneously. Here, we develop BLSOM specialized for tRNA genes (tDNAs) that can cluster (self-organize) more than one million microbial tDNAs according to their cognate amino acid solely depending on tetra- and pentanucleotide compositions. This unsupervised clustering can reveal combinatorial oligonucleotide motifs that are responsible for the amino acid-dependent clustering, as well as other functionally and structurally important consensus motifs, which have been evolutionarily conserved. BLSOM is also useful for identifying tDNAs as phylogenetic markers for special phylotypes. When we constructed BLSOM with 'species-unknown' tDNAs from metagenomic sequences plus 'species-known' microbial tDNAs, a large portion of metagenomic tDNAs self-organized with species-known tDNAs, yielding information on microbial communities in environmental samples. BLSOM can also enhance accuracy in the tDNA database obtained from big sequence data. This unsupervised data mining should become important for studying numerous functionally unclear RNAs obtained from a wide range of organisms. [ABSTRACT FROM AUTHOR]

Short RNAs derived from the cleavage of tRNA molecules are observed in most organisms. Their occurrence seems to be induced by stress conditions, but still little is known about their biogenesis and functions. We find that the recovery of tRNA fragments depends on the RNA isolation method. Using an optimized RNA extraction protocol and northern blot hybridization technique, we show that the tRNA-derived fragments in yeast are widespread in 12 different growth conditions. We did not observe significant stress-dependent changes in the amounts of tRNA fragments pool. Instead, we show the differential processing of almost all individual tRNAs. We also provide evidence that 3′-part-derived tRNA fragments are as abundant as the 5′- one in Saccharomyces cerevisiae. The resulting set of S. cerevisiae tRNA fragments provides a robust basis for further experimental studies on biological functions of tRFs. [ABSTRACT FROM AUTHOR]

Actinobacterial genus Streptomyces (streptomycetes) represents one of the largest cultivable group of bacteria famous for their ability to produce valuable specialized (secondary) metabolites. Regulation of secondary metabolic pathways inextricably couples the latter to essential cellular processes that determine levels of amino acids, carbohydrates, phosphate, etc. Post-transcriptional tRNA modifications remain one of the least studied aspects of streptomycete physiology, albeit a few of them were recently shown to impact antibiotic production. In this study, we describe the diversity of post-transcriptional tRNA modifications in model strain Streptomyces albus (albidoflavus) J1074 by combining mass spectrometry and genomic data. Our results show that J1074 can produce more chemically distinct tRNA modifications than previously thought. An in silico approach identified orthologs for enzymes governing most of the identified tRNA modifications. Yet, genetic control of certain modifications remained elusive, suggesting early divergence of tRNA modification pathways in Streptomyces from the better studied model bacteria, such as Escherichia coli and Bacillus subtilis. As a first point in case, our data point to the presence of a non-canonical MiaE enzyme performing hydroxylation of prenylated adenosines. A further finding concerns the methylthiotransferase MiaB, which requires previous modification of adenosines by MiaA to i6A for thiomethylation to ms2i6A. We show here that the J1074 ortholog, when overexpressed, yields ms2A in a ΔmiaA background. Our results set the working ground for and justify a more detailed studies of biological significance of tRNA modification pathways in streptomycetes. IMPORTANCE Post-transcriptional tRNA modifications (PTTMs) play an important role in maturation and functionality of tRNAs. Little is known about tRNA modifications in the antibiotic-producing actinobacterial genus Streptomyces, even though peculiar tRNA-based regulatory mechanisms operate in this taxon. We provide a first detailed description of the chemical diversity of PTTMs in the model species, S. albidoflavus J1074, and identify most plausible genes for these PTTMs. Some of the PTTMs are described for the first time for Streptomyces. Production of certain PTTMs in J1074 appears to depend on enzymes that show no sequence similarity to known PTTM enzymes from model species. Our findings are of relevance for interrogation of genetic basis of PTTMs in pathogenic actinobacteria, such as M. tuberculosis. [ABSTRACT FROM AUTHOR]

Alcohol consumption has been shown to disrupt hepatic lipid homeostasis. Long-chain acyl-CoA synthetase 1 (ACSL1) critically regulates hepatic fatty acid metabolism and lipid homeostasis by channeling fatty acids to lipid metabolic pathways. However, it remains unclear how ACSL1 contributes to the development of alcohol-associated liver disease (ALD). We performed chronic alcohol feeding animal studies with hepatocyte-specific ACSL1 knockout (ACSL1Δhep) mice, hepatocyte-specific STAT5 knockout (STAT5Δhep) mice, and ACSL1Δhep based-STAT5B overexpression (Stat5b-OE) mice. Cell studies were conducted to define the causal role of ACSL1 deficiency in the pathogenesis of alcohol-induced liver injury. The clinical relevance of the STAT5-ACSL1 pathway was examined using liver tissues from patients with alcoholic hepatitis (AH) and normal subjects (Normal). We found that chronic alcohol consumption reduced hepatic ACSL1 expression in AH patients and ALD mice. Hepatocyte-specific ACSL1 deletion exacerbated alcohol-induced liver injury by increasing free fatty acids (FFA) accumulation and cell death. Cell studies revealed that FFA elicited the translocation of BAX and p-MLKL to the lysosomal membrane, resulting in lysosomal membrane permeabilization (LMP) and thereby initiating lysosomal-mediated cell death pathway. Furthermore, we identified that the signal transducer and activator of transcription 5 (STAT5) is a novel transcriptional regulator of ACSL1. Deletion of STAT5 exacerbated alcohol-induced liver injury in association with downregulation of ACSL1, and reactivation of ACSL1 by STAT5 overexpression effectively ameliorated alcohol-induced liver injury. In addition, ACSL1 expression was positively correlated with STAT5 and negatively correlated with cell death was also validated in the liver of AH patients. ACSL1 deficiency due to STAT5 inactivation critically mediates alcohol-induced lipotoxicity and cell death in the development of ALD. These findings provide insights into alcohol-induced liver injury. [Display omitted] • ACSL1 deficiency sensitizes hepatocytes to cell death in ALD mice. • BAX binding with p-MLKL mediates lysosomal membrane permeabilization. • STAT5 is a new transcriptional regulator of ACSL1. • STAT5-ACSL1 signaling protects hepatocytes from alcohol-induced liver injury. [ABSTRACT FROM AUTHOR]