Identical Substitutions Research Articles

Whole Snake Genomes from Eighteen Families of Snakes (Serpentes: Caenophidia) and Their Applications to Systematics.

We present genome assemblies for 18 snake species representing 18 families (Serpentes: Caenophidia): Acrochordus granulatus, Aparallactus werneri, Boaedon fuliginosus, Calamaria suluensis, Cerberus rynchops, Grayia smithii, Imantodes cenchoa, Mimophis mahfalensis, Oxyrhabdium leporinum, Pareas carinatus, Psammodynastes pulverulentus, Pseudoxenodon macrops, Pseudoxyrhopus heterurus, Sibynophis collaris, Stegonotus admiraltiensis, Toxicocalamus goodenoughensis, Trimeresurus albolabris, and Tropidonophis doriae. From these new genome assemblies, we extracted thousands of loci commonly used in systematic and phylogenomic studies on snakes, including target-capture datasets composed of UCEs and AHEs, as well as traditional Sanger loci. Phylogenies inferred from the two target-capture loci datasets were identical with each other, and strongly congruent with previously published snake phylogenies. To show additional utility of these non-model genomes for investigative evolutionary research, we mined the genome assemblies of two New Guinea island endemics in our dataset (Stegonotus admiraltiensis and Tropidonophis doriae) for the ATP1a3 gene, a thoroughly researched indicator of resistance to toad toxin ingestion by squamates. We find that both these snakes possess the genotype for toad toxin resistance despite their endemism to New Guinea, a region absent of any toads until the human-mediated introduction of Cane Toads in the 1930s. These species possess identical substitutions that suggest the same bufotoxin resistance as their Australian congenerics (Stegonotus cucullatus and Tropidonophis mairii) which forage on invasive Cane Toads. Herein, we show the utility of short-read high coverage genomes, as well as improving the deficit of available squamate genomes with associated voucher specimens.

The Molecular detection and pathotypic characterization of Genotype VII.2 of Newcastle Disease Virus Isolated from Imported Cockatiels in Iran

Genotype VII of Newcastle disease virus (NDV), the most prevalent genotype of avian paramyxovirus I (APMV-1) in Asia, is rapidly spreading worldwide. The emergence of new sub-genotype VII.2 in different countries raises questions about the evolutionary patterns of these isolates. Despite the devastating effects of NDV on endangered parrot species and the major role of the psittacines in the cross-species transmission of the virus, there have not been any phylogenetic studies on the NDVs circulation in these populations in Iran. In this regard, a brain sample obtained from three dead cockatiels of a suspected NDV flock with an 80% mortality rate was implemented for further molecular, pathogenicity, and phylogenetic analysis of the fusion gene and deduced amino acid sequences. Pathogenicity indices and Cleavage site investigation revealed the high virulence (112RRQKRF117) of the virus. Phylogenetic studies clustered our isolate (SR0077) among VII.2 sequences from Pakistan, Indonesia, China, Jordan, and Malaysia. Moreover, the nucleotide distances between the studied isolate and VII.2 strains reported from Pakistan were less than 0.01. However, non-VII.2 isolates previously reported from Iran were phylogenetically distinct from our isolate. Taken together, these findings, along with some identical substitutions at functional domains of the F protein, highlight the risk of introducing VII.2 strains to other countries and the possible incidence of new panzootics. Finally, based on history and molecular analyses, it seems that bird trade from Pakistan is the main cause of the development of new VII.2 NDV strains in Iran.

Molecular Bulkiness ofa Single Amino Acid inthe F1 α-Subunit Determines the Robustness ofCyanobacterial ATP Synthase.

Cyanobacteria are promising photosynthetic organisms owing to their ease of genetic manipulation. Among them, Synechococcus elongatus UTEX 2973 exhibits faster growth, higher biomass production efficiency and more robust stress tolerance compared with S. elongatus PCC 7942. This is due to specific genetic differences, including four single-nucleotide polymorphisms (SNPs) in three genes. One of these SNPs alters an amino acid at position 252 of the FoF1 ATP synthase α-subunit from Tyr to Cys (αY252C) in S. elongatus 7942. This change has been shown to significantly affect growth rate and stress tolerance, specifically in S. elongatus. Furthermore, experimental substitutions with several other amino acids have been shown to alter the ATP synthesis rate in the cell. In the present study, we introduced identical amino acid substitutions into Synechocystis sp. PCC 6803 at position 252 to elucidate the amino acid's significance and generality across cyanobacteria. We investigated the resulting impact on growth, intracellular enzyme complex levels, intracellular ATP levels and enzyme activity. The results showed that the αY252C substitution decreased growth rate and high-light tolerance. This indicates that a specific bulkiness of this amino acid's side chain is important for maintaining cell growth. Additionally, a remarkable decrease in the membrane-bound enzyme complex level was observed. However, the αY252C substitution did not affect enzyme activity or intracellular ATP levels. Although the mechanism of growth suppression remains unknown, the amino acid at position 252 is expected to play an important role in enzyme complex formation.

Mechanical and durability performance of sustainable concretes containing conventional and emerging supplementary cementitious materials

This paper presents a comparative study on the mechanical and durability properties of concrete mixtures containing conventional supplementary cementitious materials (SCMs) and emerging alternatives (i.e., volcanic ash, volcanic ash-limestone blend, and metakaolin-limestone blend), with an emphasis on the latter. To enable effective comparison, identical volumetric substitution levels (30%) of SCMs along with a constant binder and aggregate volumes were employed. The metakaolin-limestone concrete performs the best among all types of concretes in terms of strength development, water absorption capacity and chloride penetration resistance. The incorporation of volcanic ash though reduces the compressive strength of concrete and increases water absorption capacity considerably compared to the reference Portland cement concrete, and its chloride diffusion coefficient is only about half of that of the reference concrete. In addition, the concretes containing volcanic ash or volcanic ash-limestone show better performance in controlling the potential alkali-silica reaction-induced expansion than the reference concrete and ground granulated blast-furnace slag concrete.

Comparative Analysis of Potential Determinants of Resistance to Aminoglycosides in <i>Burkholderia pseudomallei</i> Strains with Different Level of Sensitivity to Gentamicin

The aim of the study was to identify and compare potential determinants of aminoglycoside resistance in gentamicin susceptible Burkholderia pseudomallei strains.Materials and methods. A bioinformatics analysis of whole genome shotgun sequences of three B. pseudomallei strains having different levels of sensitivity to gentamicin was carried out.Results and discussion. B. pseudomallei is intrinsically resistant to aminoglycosides. Such strains, as a rule, are not taken into account in the classical scheme of isolation and identification. At the same time, there were no significant differences in the clinical manifestations of melioidosis during infection with gentamicin-resistant and sensitive strains. In B. pseudomallei strains of different sequence types (ST70, ST948, and ST1566), point missense mutations were found in the genes of three efflux pumps of the RND family: AmrAB-OprA, BpeAB-OprB, BpeEF-OprC, and one with unknown functions, as well as in the gene aminoglycoside-6’-N-acetyltransferase AAC(6’)-III. All three strains had amino acid substitutions in the AmrA periplasmic linker: ARG160SER, Arg116Gln and Gly237Arg, Thr317Lys, respectively. In moderately sensitive strains (ST948 and ST1566), an identical Val222Met substitution was found in the repressor of the AmrAB-OprA operon, AmrR. It is likely that the intermediate level of sensitivity to gentamicin in the studied strains is mediated by the constitutive expression of the AmrAB-OprA operon, which partially compensates for the structural defects. It is also possible that a dinucleotide deletion in the AAC (6’)-III aminoglycoside-6’-N-acetyltransferase gene, as well as detected mutations in the homologues of the periplasmic linker (BPSL2234) of an uncharacterized efflux operon of the RND family, are involved in the loss of resistance to gentamicin.

Induction of Broad β-lactam Resistance in Achromobacter ruhlandii by Exposure to Ticarcillin Is Primarily Linked to Substitutions in Murein Peptide Ligase Mpl.

Achromobacter species are emerging pathogens in cystic fibrosis with inherent resistance to several classes of antimicrobial agents. We exposed strains with wild-type antimicrobial susceptibility to ticarcillin and generated mutants with broad β-lactam resistance. Within the detection limit of the assay, the capability to develop mutational resistance was strain-specific and reproducible. Mutational resistance was observed for all three tested strains of Achromobacter ruhlandii, for one of seven strains of Achromobacter xylosoxidans, and for none of five strains of Achromobacter insuavis. All mutants were resistant to piperacillin-tazobactam, while minimal inhibitory concentration of several other β-lactams increased 4–32-fold. Whole genome sequencing identified 1–4 non-synonymous mutations in known genes per mutant. All mutants encoded amino acid substitutions in cell wall recycling proteins, primarily Mpl, and the observed resistance is probably caused by hyperproduction of OXA-114-like β-lactamases. Related, but not identical substitutions were detected in clinical strains expressing acquired antimicrobial resistance.

Nucleophilic Substitution at Heteroatoms-Identity Substitution Reactions at Phosphorus and Sulfur Centers: Do They Proceed in a Concerted (SN2) or Stepwise (A-E) Way?

The mechanisms of three selected identity substitution reactions at phosphorus and sulfur occurring with stereospecific inversion have been investigated using density functional theory (DFT). The first identity reaction between methoxyl anion and methyl ethylphenylphosphinate 1 reported in 1963 has been shown to proceed in a stepwise fashion according to the addition–elimination (A–E) mechanism involving formation of a pentacoordinate phosphorus intermediate (TBI-1). In contrast, the results of DFT studies of the identity chloride exchange reaction in (ethoxy)ethylphosphonochloridothionate 3 in acetone solution provided evidence that it proceeds synchronously according to the classical Ingold’s SN2-P mechanism. DFT calculations of the methoxyl–methoxy exchange reaction at sulfur in methyl p-toluenesulfinate 4 catalyzed by trifluoroacetic acid in methanol revealed that it proceeds stepwise (A–E mechanism), involving the formation of the high-coordinate sulfurane intermediate. In both identity transesterification reactions, 1 and 4, the transiently formed trigonal bipyramidal intermediates with the two methoxyl groups occupying apical positions (TBI-1 and TBI-4) have higher free energy barriers for the Berry-type pseudorotation than those for direct decomposition to starting phosphinate and sulfinate ensuring stereospecific inversion of configuration at the phosphinyl and sulfinyl centers. Thus, the DFT method proved its usefulness in the distinction between both mechanisms that are often indistinguishable by kinetic measurements.

Surface residues and nonadditive interactions stabilize a consensus homeodomain protein

Despite the widely reported success of consensus design in producing highly stabilized proteins, little is known about the physical mechanisms underlying this stabilization. Here, we explore the potential sources of stabilization by performing a systematic analysis of the 29 substitutions that we previously found to collectively stabilize a consensus homeodomain compared with an extant homeodomain. By separately introducing groups of consensus substitutions that alter or preserve charge state, occur at varying degrees of residue burial, and occur at positions of varying degrees of conservation, we determine the extent to which these three features contribute to the consensus stability enhancement. Surprisingly, we find that the largest total contribution to stability comes from consensus substitutions on the protein surface and that the largest per substitution contributions come from substitutions that maintain charge state. This finding suggests that, although consensus proteins are often enriched in charged residues, consensus stabilization does not result primarily from interactions involving charged residues. Although consensus substitutions at strongly conserved positions also contribute disproportionately to stabilization, significant stabilization is also contributed from substitutions at weakly conserved positions. Furthermore, we find that identical consensus substitutions show larger stabilizing effects when introduced into the consensus background than when introduced into an extant homeodomain, indicating that synergistic, stabilizing interactions among the consensus residues contribute to consensus stability enhancement of the homeodomain. By measuring DNA binding affinity for the same set of variants, we find that, although consensus design of the homeodomain increases both affinity and folding stability, it does so using a largely nonoverlapping set of substitutions.

40 Factors Influencing Accuracy of Genomic Selection with Sequence Information

Abstract Incorporating the sequence information only marginally increases the accuracy of genomic selection. The purpose of this study was to find out why by examining profiles of Quantitative Trait Nucleotides (QTN). Multiple populations were simulated with different effective population sizes and number of animals. 100 equidistant QTN with identical substitution effects were included in 50k SNP genotypes. Analyses were by single-step GBLUP, with solutions converted to SNP values and subsequently to p-values for each SNP. Manhattan plots for standardized SNP solutions were noisy and were elevated only for few QTNs. Manhattan plots for p-values were similar to those for SNP solutions, indicating little impact of population structure. The number of significant QTN was lower with lower effective population size and increased with larger data; at most about 20% of QTNs were detected. A QTN profile was created by averaging SNP solutions ±100 SNP around each QTN. The profile showed a normal-like response but with a distinct peak for the QTN. While the peak was higher with more data and higher effective population size, the normal-like response was smaller with higher effective population size. QTNs explained little variance because of shrinkage. The accuracy of genomic selection would be 100% if all QTNs are identified and their variances known, to prevent shrinking or inflation. This study allows to see limits of application of QTN from sequence data for genomic selection. If all causative SNP are included in the data, only a fraction of them can be identified even under a very simplistic architecture. As variance of QTN are assumed constant or are crude approximations (like in BayesR), the estimated QTN effects are inaccurate. Additional complications in QTN detection are close-spaced QTN and false QTNs due to imputation. Small effective population size allows the genomic selection by GBLUP but complicates the use of QTNs.

Magneto-structural properties and reliability of (Mn/Ni/Zn) substituted cobalt-copper ferrite heterogeneous catalyst for selective and efficient oxidation of aryl alcohols

Herein, M2+ substituted CoCuFe2O4 (M2+ = Mn, Zn, Ni) ferrites have been synthesized using the sol-gel auto combustion method. The structural, morphological and magnetic studies confirm the phase formation of pure magnetic cubic spinel MCoCuFe2O4 (M2+ = Mn, Zn, Ni) ferrites. The substitution with Mn, Ni and Zn does not show large variation in binding energies obtained from XPS of Cu (2p) that specifies identical copper concentration (Cu0.5) and substitution of only cobalt (Co2+) in Mn-F, Ni-F and Zn-F catalysts. Interestingly, MCoCuFe2O4 magnetic catalysts were explored for selective oxidation of a series of substituted benzyl alcohols. Catalyst Mn-F showed 93% conversion of benzyl alcohol while, Ni-F showed 95% conversion of 4-nitrobenzyl alcohol. Whereas, the catalyst Zn-F was showed 96% conversion for 4-methoxybenzyl alcohol. Additionally the results also indicate an efficient separation and recovery of the magnetic catalysts after four successive reuses without any considerable loss in its catalytic activity.

РЕАЛИЗАЦИЯ НЕЛИНЕЙНОГО ПРЕОБРАЗОВАНИЯ ПОДСТАНОВКИ В ВИДЕ ЭЛЕМЕНТОВ СИСТЕМЫ СЧИСЛЕНИЯ РЯДА ФАКТОРИАЛЬНЫХ МНОЖЕСТВ

The paper investigates a nonlinear substitution transformation, presented as an element of the number system of factorial sets. This approach takes into account the characteristic features of substitutions and al-lows you to minimize the amount of memory for storing. Based on the unambiguous numbering approach for substitutions, three methods of storing in memory are considered: in the form of a vector, in the form of values of cyclic shifts of elements of an identical substitution, and in the form of a decimal substitution number. The results of the analysis of the amount of data required for storing the nonlinear substitution transformation for cryptographic primitives are presented. The complexity of translating the transformed substitutions into the standard form of storage by a vector is determined. The obtained results can be ap-plied in software solutions for ensuring information security using cryptographic primitives containing a nonlinear substitution transformation. The proposed approach to writing in the form of substitution trans-formations is recommended for implementation in complexes with a limited amount of memory.

Distribution of fluoroquinolone resistance determinants in Carbapenem-resistant Klebsiella pneumoniae clinical isolates associated with bloodstream infections in China

BackgroundThe rate of fluoroquinolone (FQ) resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) is high. The present study aimed to investigate the distribution of fluoroquinolone resistance determinants in clinical CRKP isolates associated with bloodstream infections (BSIs).ResultsA total of 149 BSI-associated clinical CRKP isolates collected from 11 Chinese teaching hospitals from 2015 to 2018 were investigated for the prevalence of fluoroquinolone resistance determinants, including plasmid-mediated quinolone resistance (PMQR) genes and spontaneous mutations in the quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes. Among these 149 clinical CRKP isolates, 117 (78.5%) exhibited resistance to ciprofloxacin. The GyrA substitutions (Ser83 → IIe/Phe) and (Asp87 → Gly/Ala) were found among 112 (75.2%) of 149 isolates, while the substitution (Ser80 → IIe) of ParC was found in 111 (74.5%) of the 149 isolates. In total, 70.5% (105/149) of the CRKP isolates had at least two mutations within gyrA as well as a third mutation in parC. No mutations in the QRDRs were found in 31 ciprofloxacin susceptible CRKP isolates. Eighty-nine (56.9%) of 149 were found to carry PMQR genes including qnrS1 (43.0%), aac(6′)-Ib-cr (16.1%), qnrB4 (6.0%), qnrB2 (2.7%), and qnrB1 (1.3%). Nine isolates contained two or more PMQR genes, with one carrying four [aac(6′)-Ib-cr, qnr-S1, qnrB2, and qnrB4]. The co-existence rate of PMQR determinants and mutations in the QRDRs of gyrA and parC reached 68.5% (61/89). Seventy-four (83.1%, 74/89) PMQR-positive isolates harbored extended-spectrum beta-lactamase (ESBL)-encoding genes. Multilocus sequence typing (MLST) analysis demonstrated that the ST11 was the most prevalent STs in our study.ConclusionsMutations in the QRDRs of gyrA and parC were the key factors leading to the high prevalence of fluoroquinolone resistance among BSI-associated CRKP. The co-existence of PMQR genes and mutations in the QRDRs can increase the resistance level of CRKP to fluoroquinolones in clinical settings. ST11 CRKP isolates with identical QRDR substitution patterns were found throughout hospitals in China.

Adaptive introgression of the beta-globin cluster in two Andean waterfowl.

Introgression of beneficial alleles has emerged as an important avenue for genetic adaptation in both plant and animal populations. In vertebrates, adaptation to hypoxic high-altitude environments involves the coordination of multiple molecular and cellular mechanisms, including selection on the hypoxia-inducible factor (HIF) pathway and the blood-O2 transport protein hemoglobin (Hb). In two Andean duck species, a striking DNA sequence similarity reflecting identity by descent is present across the ~20 kb β-globin cluster including both embryonic (HBE) and adult (HBB) paralogs, though it was yet untested whether this is due to independent parallel evolution or adaptive introgression. In this study, we find that identical amino acid substitutions in the β-globin cluster that increase Hb-O2 affinity have likely resulted from historical interbreeding between high-altitude populations of two different distantly-related species. We examined the direction of introgression and discovered that the species with a deeper mtDNA divergence that colonized high altitude earlier in history (Anas flavirostris) transferred adaptive genetic variation to the species with a shallower divergence (A. georgica) that likely colonized high altitude more recently possibly following a range shift into a novel environment. As a consequence, the species that received these β-globin variants through hybridization might have adapted to hypoxic conditions in the high-altitude environment more quickly through acquiring beneficial alleles from the standing, hybrid-origin variation, leading to faster evolution.

CYBERSTALKING: PROBLEMS OF LEGAL PROTECTION

Purpose: to investigate the features and essence of cyberstalking as a crime in the cyber environment, to point out the legal possibilities of protecting victims of such a crime. Research methods: the research was carried out using generally recognized methods of scientific knowledge, such as: analytical, comparative legal, systemic and structural and others. Results: the concept, essence, characteristics of cyberstalking and related categories were investigated, the problems of protecting Internet users in connection with this crime were indicated, recommendations were given to overcome the problem under consideration. Discussion: the discussion in the article touches upon the aspects of finding ways to solve the problem of cyberstalking, the need to improve and supplement the current domestic legislation, its harmonization with international standards. Today, many crimes, both against the state as a whole, and against individual groups and even specific individuals, are committed online using computers and other devices (also known as «gadgets»). Fraud and forgery, identity substitution, personal data leakage, hacking, spamming, harassment - these are just a few of the cyber problems that many of us face on a daily basis. The so-called cyberstalkers, whose activities often lead to dire consequences, have become especially active in recent years. We can say that the actions called cyberstalking include intimidation, harassment, false accusations, defamation, victim tracking and similar acts committed using gadgets connected to the World Wide Web. Many residents of the post-Soviet expanses are sure that cyber-harassment is not so dangerous, because most often it concerns offensive statements and similar «conversational» actions, rather than real, «physical» actions. But this is a huge misconception, because online harassment quite often turns into harassment in real «offline» life. And in most cases women become victims of such stalking. It is very important to know how this issue is settled in Ukraine, what legal norms can help each of us protect ourselves if cyberstalking affects us or our loved ones.

Transgenic mice with an R342X mutation in Phf6 display clinical features of Börjeson-Forssman-Lehmann Syndrome.

The PHF6 mutation c.1024C > T; p.R342X, is a recurrent cause of Börjeson-Forssman-Lehmann Syndrome (BFLS), a neurodevelopmental disorder characterized by moderate-severe intellectual disability, truncal obesity, gynecomastia, hypogonadism, long tapering fingers and large ears (MIM#301900). Here, we generated transgenic mice with the identical substitution (R342X mice) using CRISPR technology. We show that the p.R342X mutation causes a reduction in PHF6 protein levels, in both human and mice, from nonsense-mediated decay and nonsense-associated alternative splicing, respectively. Magnetic resonance imaging studies indicated that R342X mice had a reduced brain volume on a mixed genetic background but developed hydrocephaly and a high incidence of postnatal death on a C57BL/6 background. Cortical development proceeded normally, while hippocampus and hypothalamus relative brain volumes were altered. A hypoplastic anterior pituitary was also observed that likely contributes to the small size of the R342X mice. Behavior testing demonstrated deficits in associative learning, spatial memory and an anxiolytic phenotype. Taken together, the R342X mice represent a good preclinical model of BFLS that will allow further dissection of PHF6 function and disease pathogenesis.

Molecular characterization of cucumber mosaic virus infecting Echinacea purpurea in Ukraine

Cucumber mosaic virus (CMV) is one of the most widespread and harmful viruses infecting Echinacea purpurea. Only three sequences of CMV coneflower isolates are in NCBI Genbank. The aim was to perform phylogenetic analysis of Ukrainian CMV isolate infecting purple coneflower. For the first time, 443 nt CP gene sequence of CMV isolate Р-EP-Ukr-19 infecting coneflower plants in Ukraine was submitted to the NCBI GenBank under Ac.No MT978189. Phylogenetic analysis showed that Р-EP-Ukr-19 clustered into the subgroup IB and shares 93.7% − 99.7% nt and 86.4%-99.2% aa identity. P-EP-Ukr-19 has the highest level of the CP sequence identity with Ukrainian Ukr-8, Ukr-sq13, Ukr-tom2, Ukr-1409 (99.0-99.7% nt and 97.5-99.2% aa) and with Chinese and Korean isolates. In CP region Р-ЕР-Ukr-19 has two identical aa substitutions with these isolates and one unique substitution comparing to other strains. This is the first phylogenetic analysis of CMV isolate infecting purple coneflower plants in Ukraine.

Generalized Normal Forms of the Systems of Ordinary Differential Equations with a Quasi-Homogeneous Polynomial ($$\alpha x_{1}^{2}$$ + x 2, x 1 x 2) in the Unperturbed Part

In this paper, the study of the structural arrangement of generalized normal forms (GNFs) is continued. A planar system that is real-analytic at the origin of coordinates is considered. Its unperturbed part forms a first degree quasi-homogeneous polynomial ( $$\alpha x_{1}^{2}$$ + x2, x1x2) with weight (1, 2), in which parameter α ∈ (–1/2, 0) ∪ (0, 1/2]. For the given values of α, this polynomial is a generatrix in the canonical form of an equivalence class with respect to quasi-homogeneous zero order substitutions into which any first order quasi-homogeneous polynomial with weight (1, 2) should be divided according to the chosen structural principles. It makes sense to reduce to GNF only the systems with different canonical forms in their unperturbed part. The constructive method of resonance equations and sets is used to write the resonance equations with the perturbations of the acquired system satisfying these equations using a formal, almost identical quasi-homogeneous substitution in the original system. The fulfillment of these conditions ensures the formal equivalence of the systems. In addition, the resonance sets of coefficients are specified, which allow obtaining all possible GNF structures and proving that the original system is reducible to a GNF with any of the specified structures. Some examples of characteristic GNFs are presented, including the GNFs with parameter α implying the appearance of an additional resonance equation and the second nonzero coefficient in the appropriate orders of GNFs.

Beaver and Naked Mole Rat Genomes Reveal Common Paths to Longevity

Long-lived rodents have become an attractive model for the studies on aging. To understand evolutionary paths to long life, we prepare chromosome-level genome assemblies of the two longest-lived rodents, Canadian beaver (Castor canadensis) and naked mole rat (NMR, Heterocephalus glaber), which were scaffolded with invitro proximity ligation and chromosome conformation capture data and complemented with long-read sequencing. Our comparative genomic analyses reveal that amino acid substitutions at "disease-causing" sites are widespread in the rodent genomes and that identical substitutions in long-lived rodents are associated with common adaptive phenotypes, e.g., enhanced resistance to DNA damage and cellular stress. By employing a newly developed substitution model and likelihood ratio test, we find that energy and fatty acid metabolism pathways are enriched for signals of positive selection in both long-lived rodents. Thus, the high-quality genome resource of long-lived rodents can assist in the discovery of genetic factors that control longevity and adaptive evolution.

Leibnizian Identity and Paraconsistent Logic

The standard Leibnizian view of identity allows for substitutivity of identicals and validates transitivity of identity within classical semantics. However, in a series of works, Graham Priest argues that Leibnizian identity invalidates both principles when formalized in paraconsistent semantics. This paper aims to show the Leibnizian view of identity validates substitutivity of identicals and transitivity of identity whether the logic is classical or paraconsistent. After presenting Priest's semantics of identity, I show what a semantic expression of Leibnizian identity does amount to. Then, I argue that Priest's semantic definition of identity is not Leibnizian. Finally, I offer a semantics characterization of identity in paraconsistent logic that is truly Leibnizian. I demonstrate that the correct formalization of Leibnizian identity in paraconsistent logic also validates substitutivity of identicals and transitivity of identity.

First outbreak of Haemophilus influenzae clone ST422 with low susceptibility to quinolones in paediatric patients in Japan.

Introduction. Recently, a Haemophilus influenzae clone with low susceptibility to quinolones emerged in paediatric patients in Japan. Isolates of this clone survived for a long time when exposed to the therapeutic concentration of quinolones, despite being classified as 'susceptible' under the criteria of the Clinical and Laboratory Standards Institute. In the present study, we report the first outbreak of this clone in paediatric patients in 2018.Aim. Our aim was to characterise the first outbreak of an H. influenzae clone with low susceptibility to quinolones.Methodology. All H. influenzae isolates (n=62), collected at a Japanese teaching hospital in 2018, were characterized by both antimicrobial susceptibility tests and multilocus sequence typing. In addition, the similarity in genetic backgrounds was analysed by PFGE.Results. Among all the isolates (n=62), quinolone low-susceptible isolates accounted for 19.4 % (n=12). Seven out of 12 isolates were identified as sequence type 422 (ST422) and showed more than 90 % similarity to each other by PFGE analysis. All ST422 isolates exhibited identical amino acid substitutions in both quinolone resistance-determining regions in GyrA and ParC. In addition, all these isolates were from paediatric patients who had been referred by different primary care clinics and had no relationship to each other.Conclusion. In this study, we describe an outbreak of a quinolone low-susceptible ST422 clone in paediatric patients in Japan. Because ST422 isolates have already been reported in at least five other countries, it has the potential to spread worldwide.