Related Sequences Research Articles

CrptAC: Find the Attack Chain with Multiple Encrypted System Logs

Clandestine assailants infiltrate intelligent systems in smart cities and homes for different purposes. These attacks leave clues behind in multiple logs. Systems usually upload their local syslogs as encrypted files to the cloud for longterm storage and resource saving. Therefore, the identification of pre-attack steps through log investigation is crucial for proactive system protection. Current methodologies involve system diagnosis using logs, often relying on datasets for feature training. Furthermore, the prevalence of mass encrypted logs in the cloud introduces a new layer of complexity to this domain. To tackle these challenges, we introduce CrptAC, a system for Multiple Encrypted Log Correlated Analysis, aimed at reconstructing attack chains to prevent further attacks securely. CrptAC initiates by searching and downloading relevant log files from encrypted logs stored in an untrusted cloud environment. Utilizing the obtained logs, it addresses the challenge of discovering event relationships to establish the attack provenance. The system employs various logs to construct event sequences leading up to an attack. Subsequently, we utilize Weighted Graphs and the Longest Common Subsequences algorithm to identify regular steps preceding an attack without the need for third-party training datasets. This approach enables the proactive identification of pre-attack steps by analyzing related log sequences. We apply our methodology to predict attacks in cloud computing and router breach provenance environments. Finally, we validate the proposed method, demonstrating its effectiveness in constructing attack steps and conclusively identifying corresponding syslogs.

A triple-amplified electrochemical-photoelectrochemical dual-mode biosensing platform for viral gene assay based on catalytic hairpin assembly, CRISPR-Cas12a and liposome-entrapped bifunctional methylene blue

Taking SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) gene as the model due to the great destructiveness of COVID-19 in the past years, a triple-amplified electrochemical-photoelectrochemical (EC-PEC) dual-mode biosensing platform was constructed for viral gene assay based on catalytic hairpin assembly (CHA), CRISPR-Cas12a and liposome-entrapped bifunctional methylene blue. Firstly, the SARS-CoV-2 RdRp gene triggered CHA nonenzymatic amplification process to produce large amounts of double-stranded DNA (dsDNA) that could activate CRISPR-Cas12a trans-cleavage ability. Subsequently, the activated CRISPR-Cas12a trans-cleaved nearby ssDNA carrying methylene blue (MB)-encapsulated liposome sphere (MELS) and streptavidin-modified magnetic bead (SMB), and lots of MELS were released. After magnetic separation, MELS was lysed by Triton X-100, releasing a large quantity of bifunctional MB molecules that not only generate an obvious EC signal originated from the electro-oxidation of MB, but also effectively induce the photocurrent-polarity-switching of the Sb2S3 NRs-modified photoelectrode from cathodic photocurrent to anodic photocurrent and generate a large anodic photocurrent. Based on the combination of the above triple amplification processes with MB-induced photocurrent-polarity-switching and EC-PEC dual-mode sensing strategies, the SARS CoV-2 RdRp gene was sensitively, selectively and accurately assayed with a linear response range of 0.1 fM – 10nM (1 aM – 10nM) and a detection limit of 69.6 aM (0.11 aM) for EC (PEC) method. The proposed EC-PEC dual-mode biosensor is also easily extended to the analysis of other viral nucleic acid by changing the related sequences of H1 and H2 DNAs, providing a new way in the early diagnosis and epidemic control of diseases caused by viruses.

Improving the performance of supervised deep learning for regulatory genomics using phylogenetic augmentation.

Supervised deep learning is used to model the complex relationship between genomic sequence and regulatory function. Understanding how these models make predictions can provide biological insight into regulatory functions. Given the complexity of the sequence to regulatory function mapping (the cis-regulatory code), it has been suggested that the genome contains insufficient sequence variation to train models with suitable complexity. Data augmentation is a widely used approach to increase the data variation available for model training, however current data augmentation methods for genomic sequence data are limited. Inspired by the success of comparative genomics, we show that augmenting genomic sequences with evolutionarily related sequences from other species, which we term phylogenetic augmentation, improves the performance of deep learning models trained on regulatory genomic sequences to predict high-throughput functional assay measurements. Additionally, we show that phylogenetic augmentation can rescue model performance when the training set is down-sampled and permits deep learning on a real-world small dataset, demonstrating that this approach improves data efficiency. Overall, this data augmentation method represents a solution for improving model performance that is applicable to many supervised deep-learning problems in genomics. The open-source GitHub repository agduncan94/phylogenetic_augmentation_paper includes the code for rerunning the analyses here and recreating the figures.

Identification of Inhibitors of the Disease-Associated Protein Phosphatase Scp1 Using Antibody Mimetic Molecules.

Protein phosphorylation is a prevalent translational modification, and its dysregulation has been implicated in various diseases, including cancer. Despite its significance, there is a lack of specific inhibitors of the FCP/SCP-type Ser/Thr protein phosphatase Scp1, characterized by high specificity and affinity. In this study, we focused on adnectin, an antibody-mimetic protein, aiming to identify Scp1-specific binding molecules with a broad binding surface that target the substrate-recognition site of Scp1. Biopanning of Scp1 was performed using an adnectin-presenting phage library with a randomized FG loop. We succeeded in identifying FG-1Adn, which showed high affinity and specificity for Scp1. Ala scanning analysis of the Scp1-binding sequence in relation to the FG-1 peptide revealed that hydrophobic residues, including aromatic amino acids, play important roles in Scp1 recognition. Furthermore, FG-1Adn was found to co-localize with Scp1 in cells, especially on the plasma membrane. In addition, Western blotting analysis showed that FG-1Adn increased the phosphorylation level of the target protein of Scp1 in cells, indicating that FG-1Adn can inhibit the function of Scp1. These results suggest that FG-1Adn can be used as a specific inhibitor of Scp1.

Discovery and characterization of sgRNA-sequence-independent DNA cleavage from CRISPR/Cas9 in mouse embryos

The CRISPR/Cas9 system can induce off-target effects in programmed gene editing, but there have been few reports on cleavage detection and their affection in embryo development. To study these events, sgRNAs with different off-target rates were designed and compared after micro-injected into mouse zygotes, and γH2AX was used for DNA cleavage sites analysis by immunostaining and CUT&Tag. Although the low off-target sgRNA were usually selected for production gene editing animals, γH2AX immunofluorescence indicated that there was a relative DSB peak at 15 h after Cas9 system injection, and the number of γH2AX foci at the peak was significantly higher in the low off-target sgRNA-injected group than in the control group. Further, the result of CUT&Tag sequencing analysis showed more double-strand breaks (DSBs) related sequences were detected in low off-target sgRNA-injected group than control and the distribution of DSB related sequences had no chromosome specificity. Gene Ontology (GO) annotation analysis of the DSB related sequences showed that these sequences were mainly concentrated at genes associated with some important biological processes, molecular functions, and cell components. In a conclusion, there are many sgRNA-sequence-independent DSBs in early mouse embryos when the Cas9 system is used for gene editing and the DSB related sequence could be detected and characterized in the genome. These results and method should also be considered in using or optimizing the Cas9 system.

Mottle: Accurate pairwise substitution distance at high divergence through the exploitation of short-read mappers and gradient descent.

Current tools for estimating the substitution distance between two related sequences struggle to remain accurate at a high divergence. Difficulties at distant homologies, such as false seeding and over-alignment, create a high barrier for the development of a stable estimator. This is especially true for viral genomes, which carry a high rate of mutation, small size, and sparse taxonomy. Developing an accurate substitution distance measure would help to elucidate the relationship between highly divergent sequences, interrogate their evolutionary history, and better facilitate the discovery of new viral genomes. To tackle these problems, we propose an approach that uses short-read mappers to create whole-genome maps, and gradient descent to isolate the homologous fraction and calculate the final distance value. We implement this approach as Mottle. With the use of simulated and biological sequences, Mottle was able to remain stable to 0.66-0.96 substitutions per base pair and identify viral outgroup genomes with 95% accuracy at the family-order level. Our results indicate that Mottle performs as well as existing programs in identifying taxonomic relationships, with more accurate numerical estimation of genomic distance over greater divergences. By contrast, one limitation is a reduced numerical accuracy at low divergences, and on genomes where insertions and deletions are uncommon, when compared to alternative approaches. We propose that Mottle may therefore be of particular interest in the study of viruses, viral relationships, and notably for viral discovery platforms, helping in benchmarking of homology search tools and defining the limits of taxonomic classification methods. The code for Mottle is available at https://github.com/tphoward/Mottle_Repo.

Enantioselective propargylic amination and related tandem sequences to α-tertiary ethynylamines and azacycles.

Chiral α-tertiary amines and related azacycles are sought-after compounds for drug development. Despite progress in the catalytic asymmetric construction of aza-quaternary stereocentres, enantioselective synthesis of multifunctional α-tertiary amines remains underdeveloped. Enantioenriched α-disubstituted α-ethynylamines are attractive synthons for constructing chiral α-tertiary amines and azacycles, but methods for their catalytic enantioselective synthesis need to be expanded. Here we describe an enantioselective asymmetric Cu(I)-catalysed propargylic amination (ACPA) of simple ketone-derived propargylic carbonates to give both α-dialkylated and α-alkyl-α-aryl α-tertiary ethynylamines. Sterically confined pyridinebisoxazoline (PYBOX) ligands, with a C4 shielding group and relaying groups, play a key role in achieving excellent enantioselectivity. The syntheses of quaternary 2,5-dihydropyrroles, dihydroquinines, dihydrobenzoquinolines and dihydroquinolino[1,2-α]quinolines are reported, and the synthetic value is further demonstrated by the enantioselective catalytic total synthesis of a selective multi-target β-secretase inhibitor. Enantioselective Cu-catalysed propargylic substitutions with O- and C-centred nucleophiles are also realized, further demonstrating the potential of the PYBOX ligand.

Testing scale-dependent temporal and spatial biases in relative chronology using AMS 14C dating: A case study of Early–Middle Cucuteni-Tripolye sites in Southeastern Europe

Aiming at developing a syncretic chronology for Eneolithic sites in Romania, Moldova and Ukraine, this paper tests the hypothesis that relative material culture sequences will be preserved within lower-order taxonomic units and collapse within higher-order units. We examine relative sequences for sub-groups of the Cucuteni-Tripolye cultural complex (ca. 5050–2950 BCE) using Bayesian sequencing of extant and newly obtained radiocarbon dates. The traditional archaeological perspective holds that the space-time expansion of this cultural complex occurred in rapidly disseminated horizons, with little cross-regional variability in dating. Absolute dating efforts from the 1960s–2000s did little to clarify the situation, especially in the upper section of the Dniester river valley in Ukraine, where numerous older radiometric 14C dates present an improbably early chronology for sites of the Early and early Middle Tripolye periods (Tripolye A and BI). Here we present 21 new AMS 14C dates from early settlements in Southwestern Ukraine and Moldova, with results dating to the latter half of the fifth millennium and the beginning of the fourth millennium BCE. Eschewing the concept of monolithic horizons, we compile both old and new data into regionally distinct sequences, enabling a more nuanced examination of material synchronization and cross-regional settlement dynamics.

On weighted generator of triple sequences and its Tauberian conditions

This paper presents a new perspective on the relationship between the (N, p, q, r) method and P-convergence for triple sequences.Our primary goal is to derive Tauberian conditions that dictate the behavior of the weighted generator sequence (zlmn) in relation to the sequences (Pl), (Qm), and (Rn), with the intention of establishing a fresh interpretation. These conditions control the OL- and O-oscillatory properties and establish a connection from ( N, p, q, r) summability to P-convergence, subject to certain restrictions on the weight sequences. Furthermore, we demonstrate that specific cases, such as the OL-condition of Landau type and the O-condition of Hardy type with respect to (Pl), (Qm) and (Rn), serve as Tauberian conditions for (N, p, q, r) summability under additional conditions. Consequently, our findings encompass all the classical Tauberian theorems, including conditions related to slow decrease and slow oscillation in specific contexts.

Mersenne Matrix Operator and Its Application in $p-$Summable Sequence Space

In this study, it is introduced the regular Mersenne matrix operator which is obtained by using Mersenne numbers and examined sequence spaces described as the domain of this matrix in the space of $p$-summable sequences for $1\leq p \leq \infty$. After that, it investigated some properties and inclusion relations, established the Schauder basis, and stated $\alpha-$, $\beta-$, and $\gamma-$duals of the aforementioned spaces. Additionally, it is characterized by the matrix classes from newly described spaces to classical sequence spaces. Finally, we studied the compactness of matrix operators on related sequence spaces.

Younger Dryas and Early Holocene ice‐margin dynamics in northwest Russia

Younger Dryas and Early Holocene ice‐margin dynamics in northwest Russia

DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma

Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in FLC is its driver mutation, a conserved DNAJB1-PRKACA gene fusion that could be an ideal target neoantigen for immunotherapy. In this study, we aim to define endogenous CD8 Tcell responses to this fusion in FLC patients and evaluate fusion-specific Tcell receptors (TCRs) for use in cellular immunotherapies. We observe that fusion-specific CD8 Tcells are rare and that FLC patient TCR repertoires lack large clusters of related TCR sequences characteristic of potent antigen-specific responses, potentially explaining why endogenous immune responses are insufficient to clear FLC tumors. Nevertheless, we define two functional fusion-specific TCRs, one of which has strong anti-tumor activity invivo. Together, our results provide insights into the fragmented nature of neoantigen-specific repertoires in humans and indicate routes for clinical development of successful immunotherapies for FLC.

CNCA aligns small annotated genomes

BackgroundTo explore the evolutionary history of sequences, a sequence alignment is a first and necessary step, and its quality is crucial. In the context of the study of the proximal origins of SARS-CoV-2 coronavirus, we wanted to construct an alignment of genomes closely related to SARS-CoV-2 using both coding and non-coding sequences. To our knowledge, there is no tool that can be used to construct this type of alignment, which motivated the creation of CNCA.ResultsCNCA is a web tool that aligns annotated genomes from GenBank files. It generates a nucleotide alignment that is then updated based on the protein sequence alignment. The output final nucleotide alignment matches the protein alignment and guarantees no frameshift. CNCA was designed to align closely related small genome sequences up to 50 kb (typically viruses) for which the gene order is conserved.ConclusionsCNCA constructs multiple alignments of small genomes by integrating both coding and non-coding sequences. This preserves regions traditionally ignored in conventional back-translation methods, such as non-coding regions.

Determining growth rates of heterotrophic bacteria from 16S rRNA gene sequence-based analyses of dilution experiments

Vital rates, including growth responses to environmental variability, are poorly characterized for the diverse taxa of heterotrophic bacteria (HBact) in marine ecosystems. Here, we evaluated the potential for combining molecular analyses with dilution experiments to assess taxon-specific growth (cell division) and net growth rates of HBact in natural waters. Two-treatment dilution experiments were conducted with in situ incubations under 3 environmental conditions in the California Current Ecosystem, at offshore and inshore sites during a warm upwelling-suppressed year (2014) and for normal inshore upwelling, representing a 33-fold primary production range. Relative sequence reads from 16S rRNA metabarcoding were normalized to total HBact counts from flow cytometry for community abundance and rate calculations. Composition varied from dominance of Alphaproteobacteria (56%) in oligotrophic offshore (SAR11) and mesotrophic inshore waters (SAR11 and Rhodobacteria) to Bacteriodes/Flavobacteria dominance (64%) and mixed sub-taxon importance (Polaribacter, Rhodobacteria, Formosa) during upwelling. Net growth rates in bottles, validated by comparison to ambient community net growth following a satellite-tracked drifter, varied from near steady state for offshore and inshore conditions to dynamic community changes during upwelling. Mean growth rates doubled (0.33 to 0.62 d-1) over the productivity range, and taxon estimates varied from -0.17 d-1 (Formosa, offshore) to 1.53 d-1 (SAR11, upwelling). Increasing growth of Flavobacteria and Rhodobacteria paralleled their abundance and dominance increases with productivity. SAR11 growth remained higher than average with increasing production, despite declining abundances. We highlight possible PCR or 16S rRNA gene copy biases of growth rate estimates as research needs for further applications of this approach.

Bioinformatics Analysis of Immunoglobulin ε (IgE) Heavy Chain

Immunoglobulin ε is a key immunoglobulin that plays an important role in the immune system. IgE is usually associated with allergic reactions such as food allergies, allergic rhinitis, and allergic dermatitis. In this project, this article Use NCBI or https://www.uniprot.org/ Website to obtain immunoglobulins ε Heavy chain related nucleotide sequences. Using relevant websites and software to analyze and predict immunoglobulins using bioinformatics methods ε Bioinformatics analysis of heavy chains includes physical and chemical properties, structural functions, positional expression, phylogenetic relationships, protein interactions, etc. Understanding the bioinformatics analysis of IgE can help reveal its function in the immune system and its relationship with allergies and other diseases, promote the improvement of diagnosis and treatment methods for allergic diseases, and advance in the field of immunotherapy.

Zelda’s Role in Controlling Gene Expression in the Early Embryo

Much research investigates the influence of Zelda (Zinc-finger early Drosophila Embryo activator, Zld) on early embryo development. CAGGTAG and related sequences are common in the early transcribed genes in Drosophila. These are all referred to as sites that can activate transcription and are responsible for maternal RNA degradation (as cited in Liang et al., 2008). However, it is still unknown whether other activators can help gene expression. Here, we analyze the effect of Zld on specific genes, such as Halo, by chromatin immunoprecipitation assays. One result is that the gene expression is low in the absence of Zld, which could suggest that Zld plays an important role in the activation of early development of the Drosophila embryo.

Outbreaks of bovine mastitis caused by specific Mycoplasma bovis strains recurring at multi-year intervals.

Mycoplasma bovis is a major cause of bovine mastitis. Intermittent shedding of the organism for many months is a feature of cows with intramammary infection. A dairy farm in Japan experienced a mastitis outbreak caused by M. bovis in 2016, as well as 2 additional outbreaks and 1 case in 2020-2021. The causative strains in the 3 outbreaks shared a common and identical genetic feature, the insertion of a transposase gene at the same site within the phosphate acetyltransferase-2 gene. Additionally, all isolates were genotyped to closely related sequence types (ST21 and ST141) by multilocus sequence typing, and had similar pulsopatterns by pulsed-field gel electrophoresis. Our results indicate that infection with the same causative strain remained in this herd and environment for 4 y. Treatment with fluoroquinolones, guided by antimicrobial susceptibility test results, eliminated M. bovis from 16 of 20 M. bovis-infected cows, as confirmed by culture and somatic cell counts. However, mastitis caused by other bacteria occurred in 9 M. bovis-free cows within 2 mo of the last treatment.

Insight into planktonic protistan and fungal communities across the nutrient-depleted environment of the South Pacific Subtropical Gyre.

Ocean microorganisms constitute ~70% of the marine biomass, contribute to ~50% of the Earth's primary production, and play a vital role in global biogeochemical cycles. The marine heterotrophic and mixotrophic protistan and fungal communities have often been overlooked mainly due to limitations in morphological species identification. Despite the accumulation of studies on biogeographic patterns observed in microbial communities, our understanding of the abundance and distribution patterns within the microbial community of the largest subtropical gyre, the South Pacific Gyre (SPG), remains incomplete. Here, we investigated the diversity and vertical composition of protistan and fungal communities in the water column of the ultra-oligotrophic SPG. Our results showed apparent differences in protistan community diversity in the photic and aphotic regions. The entire protistan community diversity was significantly affected by temperature, salinity, oxygen, and nutrient concentrations, while the parasitic community diversity was also affected by chlorophyll a concentration. The parasitic protists were assigned to the class Syndiniales accounting for over 98% of the total parasitic protists, exhibiting higher relative sequence abundance along the water depth and displaying consistent patterns among different sampling stations. In contrast to the protistan community, the fungal community along the SPG primarily clustered based on the sampling station and pelagic zones. In particular, our study reveals a significant presence of parasitic protists and functionally diverse fungi in SPG and their potential impact on carbon cycling in the gyre.IMPORTANCEOur findings carry important implications for understanding the distribution patterns of the previously unrecognized occurrence of parasitic protists and functionally diverse fungi in the nutrient-limited South Pacific Gyre. In particular, our study reveals a significant presence of parasitic Syndiniales, predominantly abundant in the upper 300 m of the aphotic zone in the gyre, and a distinct presence of fungal communities in the aphotic zone at the central part of the gyre. These findings strongly suggest that these communities play a substantial role in yet insufficiently described microbial food web. Moreover, our research enhances our understanding of their contribution to the dynamics of the food webs in oligotrophic gyres and is valuable for projecting the ecological consequences of future climate warming.

Lauda Sion as Doxological Compendium of St. Thomas’s Eucharistic Theology

AbstractIn 1264 in the town of Orvieto, St. Thomas Aquinas composed the Lauda Sion as the Mass sequence for Pope Urban IV’s new universal solemnity of the Body and Blood of our Lord Jesus Christ, the feast of Corpus Christi. The present paper will consider this text of St. Thomas’s liturgical sequence in relation to the eucharistic theology that he teaches in the Summa Theologiae. Just as, according to the Dionysian Aquinas, the Psalms contain all the doctrines revealed in the rest of scripture but transposed into the highest literary genre of praise, so the Lauda Sion contains all the essential eucharistic doctrines of the Summa Theologiae, now set in that same laudatory genre as the Psalter. The paper is divided into ten sections, corresponding to the questions in St. Thomas’s treatment of the Holy Eucharist in the Tertia Pars. Proceeding one topic at a time, this paper will show how the Lauda Sion serves as a doxological compendium of St. Thomas Aquinas’s whole eucharistic theology.

A new HaCV-EBHSV recombinant lagovirus circulating in European brown hares (Lepus europaeus) from Catalonia, Spain

In 2020/2021, several European brown hare syndrome virus (EBHSV) outbreaks were recorded in European hares (Lepus europaeus) from Catalonia, Spain. Recombination analysis combined with phylogenetic reconstruction and estimation of genetic distances of the complete coding sequences revealed that 5 strains were recombinants. The recombination breakpoint is located within the non-structural protein 2C-like RNA helicase (nucleotide position ~ 1889). For the genomic fragment upstream of the breakpoint, a non-pathogenic EBHSV-related strain (hare calicivirus, HaCV; GII.2) was the most closely related sequence; for the rest of the genome, the most similar strains were the European brown hare syndrome virus (EBHSV) strains recovered from the same 2020/2021 outbreaks, suggesting a recent origin. While the functional impact of the atypical recombination breakpoint remains undetermined, the novel recombinant strain was detected in different European brown hare populations from Catalonia, located 20–100 km apart, and seems to have caused a fatal disease both in juvenile and adult animals, confirming its viability and ability to spread and establish infection. This is the first report of a recombination event involving HaCV and EBHSV and, despite the recombination with a non-pathogenic strain, it appears to be associated with mortality in European brown hares, which warrants close monitoring.