L1 Sequences Research Articles

Genetic variability of human papillomavirus type 18 based on E6, E7 and L1 genes in central China

BackgroundHigh-risk human papillomavirus (HR-HPV) infection is an important factor for the development of cervical cancer. HPV18 is the second most common HR-HPV after HPV16.MethodsIn this study, MEGA11 software was used to analyze the variation and phylogenetic tree of HPV18 E6-E7 and L1 genes. The selective pressure to E6, E7 and L1 genes was estimated using pamlX. In addition, the B cell epitopes of L1 amino acid sequences and T cell epitopes of E6-E7 amino acid sequences in HPV18 were predicted by ABCpred server and IEDB website, respectively.ResultsA total of 9 single nucleotide variants were found in E6-E7 sequences, of which 2 were nonsynonymous variants and 7 were synonymous variants. Twenty single nucleotide variants were identified in L1 sequence, including 11 nonsynonymous variants and 9 synonymous variants. Phylogenetic analysis showed that E6-E7 and L1 sequences were all distributed in A lineage. In HPV18 E6, E7 and L1 sequences, no positively selected site was found. The nonconservative substitution R545C in L1 affected hypothetical B cell epitope. Two nonconservative substitutions, S82A in E6, and R53Q in E7, impacted multiple hypothetical T cell epitopes.ConclusionThe sequence variation data of HPV18 may lay a foundation for the virus diagnosis, further study of cervical cancer and vaccine design in central China.

Task-Specific Alignment and Multiple-level Transformer for few-shot action recognition

In the research field of few-shot learning, the main difference between image-based and video-based is the additional temporal dimension. In recent years, some works have used the Transformer to deal with frames, then get the attention feature and the enhanced prototype, and the results are competitive. However, some video frames may relate little to the action, and only using single frame-level or segment-level features may not mine enough information. We address these problems sequentially through an end-to-end method named “Task-Specific Alignment and Multiple-level Transformer Network (TSA-MLT)”. The first module (TSA) aims to filter the action-irrelevant frames for action duration alignment. Affine Transformation for frame sequence in the time dimension is used for linear sampling. The second module (MLT) focuses on the Multiple-level feature of the support prototype and query sample to mine more information for the alignment, which operates on different level features. We adopt a fusion loss according to a fusion distance that fuses the L2 sequence distance, which focuses on temporal order alignment, and the Optimal Transport distance, which focuses on measuring the gap between the appearance and semantics of the videos. Extensive experiments show our method achieves state-of-the-art results on the HMDB51 and UCF101 datasets and a competitive result on the benchmark of Kinetics and something-2-something V2 datasets. Our code will be available at the URL: https://github.com/cofly2014/tsa-mlt.git.

Determination and Characterization of Novel Papillomavirus and Parvovirus Associated with Mass Mortality of Chinese Tongue Sole (Cynoglossus semilaevis) in China.

A massive mortality event concerning farmed Chinese tongue soles occurred in Tianjin, China, and the causative agent remains unknown. Here, a novel Cynoglossus semilaevis papillomavirus (CsPaV) and parvovirus (CsPV) were simultaneously isolated and identified from diseased fish via electron microscopy, virus isolation, genome sequencing, experimental challenges, and fluorescence in situ hybridization (FISH). Electron microscopy showed large numbers of virus particles present in the tissues of diseased fish. Viruses that were isolated and propagated in flounder gill cells (FG) induced typical cytopathic effects (CPE). The cumulative mortality of fish given intraperitoneal injections reached 100% at 7 dpi. The complete genomes of CsPaV and CsPV comprised 5939 bp and 3663 bp, respectively, and the genomes shared no nucleotide sequence similarities with other viruses. Phylogenetic analysis based on the L1 and NS1 protein sequences revealed that CsPaV and CsPV were novel members of the Papillomaviridae and Parvoviridae families. The FISH results showed positive signals in the spleen tissues of infected fish, and both viruses could co-infect single cells. This study represents the first report where novel papillomavirus and parvovirus are identified in farmed marine cultured fish, and it provides a basis for further studies on the prevention and treatment of emerging viral diseases.

Applications of Supersymmetric Polynomials in Statistical Quantum Physics

We propose a correspondence between the partition functions of ideal gases consisting of both bosons and fermions and the algebraic bases of supersymmetric polynomials on the Banach space of absolutely summable two-sided sequences ℓ1(Z0). Such an approach allows us to interpret some of the combinatorial identities for supersymmetric polynomials from a physical point of view. We consider a relation of equivalence for ℓ1(Z0), induced by the supersymmetric polynomials, and the semi-ring algebraic structures on the quotient set with respect to this relation. The quotient set is a natural model for the set of energy levels of a quantum system. We introduce two different topological semi-ring structures into this set and discuss their possible physical interpretations.

HPV18 L1 and long control region sequences variation and E6/E7 differential expression in nasopharyngeal and cervical cancers: a comparative study

BackgroundThe role of high-risk human papillomaviruses (hr-HPVs) in cervical cancer (CC) pathogenesis has long been established. Knowledge about the involvement of hr-HPVs in the etiology of nasopharyngeal cancers (NPC) was not well appreciated until the early 2000s when a clear link began to emerge. However, it is not clear whether HPV oncogenesis in the different epithelial cancers is associated with L1 gene and long-control region (LCR) sequences variation. This study aimed to investigate the HPV18 L1 gene and LCR sequences variation in cervical and nasopharyngeal biopsies, and assessed E6 and E7 genes expression level in both cancers.MethodFour-hundred and three (403) formalin-fixed paraffin-embedded tissues originating from nasopharyngeal (NPC) (279) and cervical (CC) (124) sites were collected from a pathology laboratory, Pathologist Without Borders, Accra, Ghana. Haematoxylin and eosin staining was carried out to confirm the presence of cancer on prepared biopsy sections. DNA was extracted from the confirmed cancer biopsies, followed by PCR using MY09/GP5+ /6+ primers to detect the presence of HPV and specific primers for the amplification of L1 gene and LCR. Sanger sequencing was carried out to determine HPV genotypes, and L1 and LCR sequences variant of HPV18s in CC and NPC biopsies. The HPV18 E6/E7 mRNA expression pattern in both cancers was determined using RT-qPCR.ResultsMost of the NPC (45%) and CC (55%) biopsies were HPV18 positive. Comparison of HPV18 L1 sequences obtained from cervical and nasopharyngeal cancer tissues, the L1 sequences from the NPC were highly dissimilar with a 59–100% variation among themselves, and in relation to the reference strains. However, the L1 sequences from the CC were more similar with a 91.0–100% variation among the amplified sequences. Also, the LCR sequences from CC were quite different relative to that of NPC. Results for the differential expression of E6/E7 in the two cancers showed a higher fold change in E6 expression in the CC tissues than the NPC tissues while a reverse expression pattern was found for E7 gene.ConclusionThe current study reports for the first-time variations in HPV18 L1 and LCR sequences, and differential expression of E6/E7 genes in NPC compared to CC, suggesting a possible adaptation mechanism of the virus at different cancer sites.

Identification of epigenetically active L1 promoters in the human brain and their relationship with psychiatric disorders

Long interspersed nuclear element-1 (LINE-1, L1) affects the transcriptome landscape in multiple ways. Promoter activity within its 5’UTR plays a critical role in regulating diverse L1 activities. However, the epigenetic status of L1 promoters in adult brain cells and their relationship with psychiatric disorders remain poorly understood. Here, we examined DNA methylation and hydroxymethylation of the full-length L1s in neurons and nonneurons and identified “epigenetically active” L1s. Notably, some of epigenetically active L1s were retrotransposition competent, which even had chimeric transcripts from the antisense promoters at their 5’UTRs. We also identified differentially methylated L1s in the prefrontal cortices of patients with psychiatric disorders. In nonneurons of bipolar disorder patients, one L1 was significantly hypomethylated and showed an inverse correlation with the expression level of the overlapping gene NREP. Finally, we observed that altered DNA methylation levels of L1 in patients with psychiatric disorders were not affected by the surrounding genomic regions but originated from the L1 sequences. These results suggested that altered epigenetic regulation of the L1 5’UTR in the brain was involved in the pathophysiology of psychiatric disorders.

Mice Mutated in the Third Fibronectin Domain of L1 Show Enhanced Hippocampal Neuronal Cell Death, Astrogliosis and Alterations in Behavior.

Adhesion molecules play major roles in cell proliferation, migration, survival, neurite outgrowth and synapse formation during nervous system development and in adulthood. The neural cell adhesion molecule L1 contributes to these functions during development and in synapse formation and synaptic plasticity after trauma in adulthood. Mutations of L1 in humans result in L1 syndrome, which is associated with mild-to-severe brain malformations and mental disabilities. Furthermore, mutations in the extracellular domain were shown to cause a severe phenotype more often than mutations in the intracellular domain. To explore the outcome of a mutation in the extracellular domain, we generated mice with disruption of the dibasic sequences RK and KR that localize to position 858RKHSKR863 in the third fibronectin type III domain of murine L1. These mice exhibit alterations in exploratory behavior and enhanced marble burying activity. Mutant mice display higher numbers of caspase 3-positive neurons, a reduced number of principle neurons in the hippocampus, and an enhanced number of glial cells. Experiments suggest that disruption of the dibasic sequence in L1 results in subtle impairments in brain structure and functions leading to obsessive-like behavior in males and reduced anxiety in females.

MP15-04 PRESENCE OF HPV IN PROSTATE TISSUE FROM PATIENTS SUBMITTED TO PROSTATE BIOPSY

You have accessJournal of UrologyCME1 Apr 2023MP15-04 PRESENCE OF HPV IN PROSTATE TISSUE FROM PATIENTS SUBMITTED TO PROSTATE BIOPSY Nalisson Pereira, Emerson Martins, Mateus Quintela, Arthur Cunha, and Jaques Waisberg Nalisson PereiraNalisson Pereira More articles by this author , Emerson MartinsEmerson Martins More articles by this author , Mateus QuintelaMateus Quintela More articles by this author , Arthur CunhaArthur Cunha More articles by this author , and Jaques WaisbergJaques Waisberg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003235.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is the second most common cancer among men. Environmental and hereditary factors are assumed to play crucial roles in prostate carcinogenesis. In addition, increasing epidemiological evidence, along with molecular research, suggests that viral infection would be a potential cofactor for the development of PCa. Recently, it has been estimated that virus infection represents approximately 10% of the worldwide cancer burden. HPV, one of the most important oncogenic viruses. Based on the genomic sequence of L1, the gene encoding the main capsid protein, more than 200 types of HPV have been identified and characterized, with at least 14 high-risk types which may cause cancer. The aim of this study was to evaluate the presence of HPV in prostate tissue in patients undergoing transrectal ultrasound-guided prostate biopsy and its possible relationship with prostate cancer. METHODS: 157 prostate tissue samples were obtained from patients undergoing screening for PCa by transrectal ultrasound guided biopsy, collected at IOM (Instituto de Oncologia e Mastologia de Macapá, Amapá, Brazil) from December 2018 to January 2021. One fragment was placed in a microcentrifuge tube with 1mL of RNAlater. After collection, the vials were stored at -20C until being processed. Total DNA extraction was performed in the Microbiology and Immunology Laboratory of the Federal University of Amapá (UNIFAP). The Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) method was used for HPV detection. The analysis to investigate the relationship between the presence of HPV and cancer was the extension of Fisher's exact test and the alpha significance level equal to 5% was applied. RESULTS: 157 patients, 95 (60.5%) with PCa, 55 (35.0%) without cancer, and 7 (4.5%) as inconclusive (ASAP). The presence of HPV was 7/95 =(7.4%) in patients with cancer, and 2/55 =(3.6%) in those without evidence of cancer or inconclusive diagnosis ASAP. The inferential results revealed that the presence of HPV was not related to the diagnosis of cancer when the ASAP diagnosis was considered in the analysis (p=0.663) and, also when the ASAP diagnosis was not included (p=0.487). CONCLUSIONS: There was no L1 gene expression and significant levels of HPV L1 in prostate tissue. These findings suggest no oncogenic activity of HPV in PCa. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e192 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nalisson Pereira More articles by this author Emerson Martins More articles by this author Mateus Quintela More articles by this author Arthur Cunha More articles by this author Jaques Waisberg More articles by this author Expand All Advertisement PDF downloadLoading ...

Phylogeny and amino acid analysis in single and mixed bovine papillomavirus infections in Southern Brazil, 2016-2020.

Bovine papillomaviruses (BPVs) exhibit a high degree of genetic variability, and several viral types have been identified based on analysis of the L1 gene. The L1 is the main capsid protein and the main target for neutralizing antibodies. We performed a retrospective study onBPVscirculating in Rio Grande do Sul state, Southern Brazil, in 2016-2020. DNA from 43 bovine papilloma samples were amplified using two degenerate primer sets - FAP59/64 and MY09/11 - targeting the L1 region, and analyzed for phylogeny, mixed BPV infections(coinfections) and amino acid (aa) sequences. We also performed an in silico analysis with 114 BPV L1 sequences from the GenBank database to assess the agreement between the phylogeny obtained based on complete L1 sequences versus that based on the region amplified using the FAP59/64 and MY09/11 primer sets. Considering single and coinfections, we identified 31 BPV-1 (31/43; 72.1%), 27 BPV-2 (27/43; 62.8%) and 4 BPV-6 (4/43; 9.3%). Coinfections with BPV-1 and BPV-2 were observed in 61.3% of the samples. Our results are supported by in silico analyses that demonstrate that the classification usingFAP59/64 or MY09/11 matches the complete L1 results, except for BPV-17 and -18, which may be mistakenly classified depending on the primers used. Furthermore, we found unique or rare amino acids in at least one L1 sequence of each BPV type identified in our study, some of which have been identified previously in papillomavirus epitopes, suggesting immune-mediated selection. Finally,our study provides an overview of BPVscirculatingin Southern Brazil over the last five years and point to the combined use of primers FAP59/64 and MY09/11 for analysis of BPV coinfections and putative epitopes.

Prevalence of human papillomavirus genotypes and related cervical morphological results in southern Hunan Province of China, 2018-2020: Baseline measures at a tertiary institution prior to mass human papillomavirus vaccination.

Human papillomavirus (HPV) infection is closely correlated with cervical lesions. However, the HPV prevalence varies among different districts. This retrospective study investigated the HPV genotype distribution and its relationship with cervical lesions in southern Hunan Province. The database at our Pathology Department was searched for HPV and morphological results during 2018-2020 were reviewed. A total of 49,955 gynaecological inpatients and outpatients, each of whom underwent HPV testing based on the amplification of L1 sequence and reverse dot blot hybridization, were included in this study. Available cytology and relevant histological examination results were reviewed. Enrolled cases were categorized into seven groups based on their age. Household registry and educational level were evaluated. Seven thousand two hundred eighty-six females were positive for HPV and the overall HPV positivity rate was 14.59%. The top five most prevalent HPV genotypes were HPV52, 16, 58, 53 and 51 (22.98%, 17.54%, 14.29%, 7.47%, and 5.70%, respectively). The HPV prevalence curve specific to the seven age groups showed a bimodal distribution. High school education or blow and rural residence served as risk factors for HPV infection. Single infection was the main type of HPV infection, and multiple infections occurred in 21.92% of the infected women. Of 3,148 cases had cytological results, 1,149 (36.50%) had abnormal cytological abnormalities. Among 2,833 participants with histological examination, 2000 (70.60%) had cervical abnormalities. Cytological and pathological abnormalities were mainly associated with infection with HPV16, 52 and 58. Further analysis found that HPV16, 58, 52 and 33 were the main genotypes associated with high-grade squamous lesions (HSIL) and that HPV16, 31, 33 and 58 were independent risk factors for HSIL (odd ratio [OR] = 1.70, 1.99, 2.59, 2.29; 95% CI = 1.41-2.03, 1.17-3.41, 1.88-3.59, 1.85-2.82; all p < 0.05). HPV16, 58, 52, 18 and 33 were the most frequent genotypes detected in squamous cell carcinoma (SCC) patients, and HPV16 and 18 were independent risk factors for cervical carcinomas (OR = 6.72;95% CI = 5.48-8.25; p < 0.001; OR = 1.67, 95% CI = 1.22-2.30; p = 0.001). This retrospective study demonstrated the prevalence and the distribution characteristics of HPV infection and its correlation with cervical lesions in southern Hunan Province. The comprehensive results of this survey can guide HPV vaccine research to protect against some common genotypes in China.

Discovery of novel papillomaviruses in the critically endangered Malayan and Chinese pangolins.

Pangolins are scaly and toothless mammals which are distributed across Africa and Asia. Currently, the Malayan, Chinese and Philippine pangolins are designated as critically endangered species. Although few pangolin viruses have been described, their viromes have received more attention following the discovery that they harbour sarbecoviruses related to SARS-CoV-2. Using large-scale genome mining, we discovered novel lineages of papillomaviruses infecting the Malayan and Chinese pangolins. We were able to assemble three complete circular papillomavirus genomes with an intact coding capacity and five additional L1 genes encoding the major capsid protein. Phylogenetic analysis revealed that seven out of eight L1 sequences formed a monophyletic group which is the sister lineage to the Tupaia belangeri papillomavirus 1, isolated from Yunnan province in China. Additionally, a single L1 sequence assembled from a Chinese pangolin was placed in a clade closer to Alphapapillomavirus and Omegapapillomavirus. Examination of the SRA data from 95 re-sequenced genomes revealed that 49.3% of Malayan pangolins and 50% of Chinese pangolins were positive for papillomavirus reads. Our results indicate that pangolins in South-East Asia are the hosts of diverse and highly prevalent papillomaviruses, and highlight the value of in silico mining of host sequencing data for the discovery of novel viruses.

Replicative Senescence-Associated LINE1 Methylation and LINE1-Alu Expression Levels in Human Endothelial Cells

One of the main challenges of current research on aging is to identify the complex epigenetic mechanisms involved in the acquisition of the cellular senescent phenotype. Despite some evidence suggested that epigenetic changes of DNA repetitive elements, including transposable elements (TE) sequences, are associated with replicative senescence of fibroblasts, data on different types of cells are scarce. We previously analysed genome-wide DNA methylation of young and replicative senescent human endothelial cells (HUVECs), highlighting increased levels of demethylated sequences in senescent cells. Here, we aligned the most significantly demethylated single CpG sites to the reference genome and annotated their localization inside TE sequences and found a significant hypomethylation of sequences belonging to the Long-Interspersed Element-1 (LINE-1 or L1) subfamilies L1M, L1P, and L1HS. To verify the hypothesis that L1 demethylation could be associated with increased transcription/activation of L1s and/or Alu elements (non-autonomous retroelements that usually depend on L1 sequences for reverse transcription and retrotransposition), we quantified the RNA expression levels of both L1 (generic L1 elements or site-specific L1PA2 on chromosome 14) and Alu elements in young and senescent HUVECs and human dermal fibroblasts (NHDFs). The RNA expression of Alu and L1 sequences was significantly increased in both senescent HUVECs and NHDFs, whereas the RNA transcript of L1PA2 on chromosome 14 was not significantly modulated in senescent cells. Moreover, we found an increased amount of TE DNA copies in the cytoplasm of senescent HUVECs and NHDFs. Our results support the hypothesis that TE, which are significantly increased in senescent cells, could be retrotranscribed to DNA sequences.

A note on the Schur and Phillips lemmas

It is well-known that every weakly convergent sequence in ℓ1 is convergent in the norm topology (Schur's lemma). Phillips' lemma asserts even more strongly that if a sequence (μn)n∈N in ℓ∞′ converges pointwise on {0,1}N to 0, then its ℓ1-projection converges in norm to 0. In this note we show how the second category version of Schur's lemma, for which a short proof is included, can be used to replace in Phillips' lemma {0,1}N by any of its subsets which contains all finite sets and having some kind of interpolation property for finite sets.

Sequence stratigraphy of the ca 1640 Ma Barney Creek Formation, McArthur Basin, Australia

The ca 1640 Ma Barney Creek Formation is a mostly fine-grained silicicastic unit of the McArthur Group in the southern McArthur Basin of northern Australia. It is one of the most prospective units for clastic-dominated (CD-type) Zn–Pb deposits in the world, hosting the giant McArthur River Zn–Pb–Ag and the Teena Zn–Pb deposits. The Barney Creek Formation records deposition of dominantly dolomitic siltstone turbidite facies at or below storm wave base. These strata were deposited in a series of sub-basins and on submerged paleohighs that formed in response to roughly north–south extension during early Barney Creek times. A detailed, regional-scale sequence stratigraphic analysis based on 20 wells indicates that the middle McArthur Group (Emmerugga Dolostone to Lynott Formation) comprises six third-order depositional sequences, of which the Barney Creek Formation includes two (named B1 and B2). These two sequences and the overlying sequence L1 (Reward Dolostone and lower Lynott Formation) record significant lateral facies and thickness changes across the southern McArthur Basin. These variations can be explained by a geographical shift in the depocentre during structural re-organisation of the basin. The depocentre migrated from the south, where accommodation was mostly created during deposition of sequence B1, towards the north during deposition of sequence B2. KEY POINTS Sequence stratigraphic analysis of the Barney Creek Formation on a regional scale based on 20 wells. Barney Creek Formation includes two third-order depositional sequences (named B1 and B2), which record significant lateral thickness and facies shifts. Thickness and facies shifts can be explained by geographical shift of depocentre from the present-day south to north.

Full-length L1 Sequences are Over-Represented on the Heterochromatic Short Arms of Human Acrocentric Chromosomes

Full-length L1 Sequences are Over-Represented on the Heterochromatic Short Arms of Human Acrocentric Chromosomes

Human Papillomavirus Type 16 L2 Gene Sequence Variation Analysis in Indonesian Cervical Cancer Specimens.

Background: Human papillomavirus type 16 (HPV16) is the most prevalent etiology of cervical cancer in Indonesian women. The L2 minor capsid protein has considerable potential as a broad-protective antigen target of the cervical cancer vaccine strategies, yet the data on L2 gene variation is still minimal. In this research, we determined the variations of the HPV16 L2 gene sequences in Indonesian cervical cancer specimens. Methods:We cross-sectionally observed 23 DNA isolates of HPV16 positive cervical cancer specimens stored in the laboratory of the Center for Diagnostic and Research on Infectious Diseases (PDRPI Lab), Faculty of Medicine, Universitas Andalas, Padang, Indonesia. We detected and amplified the HPV16 L2 gene sequences in the samples, followed by sequencing, DNA alignment, single nucleotide polymorphisms (SNPs) analysis, and phylogenetic tree reconstruction. Results:As many as 35 SNPs were found, consist of 18 synonymous SNPs (sSNPs) and 17 non-synonymous SNPs (nsSNPs). Amino acid variations were mostly detected at S269P (100%) and L330F (43.48%) with no variation in the immuno-protective region near L2 N-terminus. A total of 5 HPV16 phylogenetic sub-lineages were found closely related to A1 (n=5), A2 (n=12), A3 (n=2), A4 (n=3), and C (n=1). Conclusion:The variations of HPV16 L2 gene sequences are mainly located in the central region of the L2 sequences, and the cross-protective region near the L2 N-terminus is remarkably conserved. This study should enhance the information about HPV16 L2 gene variation in Indonesia.

Reconstruction of full-length LINE-1 progenitors from ancestral genomes.

Sequences derived from the Long INterspersed Element-1 (L1) family of retrotransposons occupy at least 17% of the human genome, with 67 distinct subfamilies representing successive waves of expansion and extinction in mammalian lineages. L1s contribute extensively to gene regulation, but their molecular history is difficult to trace, because most are present only as truncated and highly mutated fossils. Consequently, L1 entries in current databases of repeat sequences are composed mainly of short diagnostic subsequences, rather than full functional progenitor sequences for each subfamily. Here, we have coupled 2 levels of sequence reconstruction (at the level of whole genomes and L1 subfamilies) to reconstruct progenitor sequences for all human L1 subfamilies that are more functionally and phylogenetically plausible than existing models. Most of the reconstructed sequences are at or near the canonical length of L1s and encode uninterrupted ORFs with expected protein domains. We also show that the presence or absence of binding sites for KRAB-C2H2 Zinc Finger Proteins, even in ancient-reconstructed progenitor L1s, mirrors binding observed in human ChIP-exo experiments, thus extending the arms race and domestication model. RepeatMasker searches of the modern human genome suggest that the new models may be able to assign subfamily resolution identities to previously ambiguous L1 instances. The reconstructed L1 sequences will be useful for genome annotation and functional study of both L1 evolution and L1 contributions to host regulatory networks.

Impedimetric sensing platform for human papillomavirus and p53 tumor suppressor gene in cervical samples

The oncogenic human papillomavirus (HPV) is an excellent biomarker for cervical cancer screening. The present research reports the construction of an integrated sensor platform (biosensor MY11 and biosensor p53 ) for the impedimetric detection of the HPV L1 sequence and p53 tumor suppressor gene. The nanostructured biosensor is composed of electrosynthesized polypyrrole (PPy) and gold nanoparticles (AuNPs). Methodological strategies based on cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) were used. The exposure of the genetic biosensors to molecular targets triggered changes in the analytical signals. Calibration plots for the biosensor MY11 showed a linear range between 0.001 to 100 pg μL −1 for all analyzed genotypes (HPV6, 11, 16, 18, 45, 53, 54, and 58). The detection limits were measured between 0.11 to 0.61 pg μL −1 and limits of quantification between 0.33 to 1.86 pg μL −1 . The sensors exhibited reproducibility with a relative standard deviation of 4.21% and high repeatability (less than 2.5%). Two electrochemical profiles were obtained for high and low-risk HPV groups, suggesting the differential diagnosis using a degenerate oligonucleotide probe. Our results allow correlating the p53 gene expression in clinical samples infected with papillomavirus. The proposed biosensor represents an innovative device for the integrated monitoring of biomarkers related to cervical cancer with ultra-sensitive analytical performance. • A nanointegrated system was designed for the differential diagnosis of papillomavirus. • Polypyrrole conjugated to gold particles acted as an ultrasensitive signal transducer. • High and low-risk HPV groups were identified using a degenerate oligonucleotide probe. • Molecular screening for oncogenic HPV and p53 gene was performed in clinical samples. • The biosensor showed high specificity with a linear range from 0.001 to 100 pg μL −1 .

Genetic variation of E6, E7, and L1 genes of human papillomavirus 51 from central China.

The incidence of cervical cancer is closely related to high-risk human papillomavirus (HR-HPV). Women in Jingzhou had relatively high susceptibility to HPV-51, whose ratio was 9.61% (456/4743) among HR-HPV-positive samples and ranked fifth in all analyzed HR-HPV types. In this study, variations and phylogenetic trees of HPV-51 E6-E7 and L1 sequences were analyzed by MEGA-X. The selective pressure was estimated using PAML. The B-cell epitope of L1 amino acid sequences and T-cell epitope of E6 and E7 amino acid sequences were further predicted by ABCpred server and IEDB website, respectively. In the E6-E7 sequences 14 single nucleotide variants occurred, among which 4 were nonsynonymous variants and 10 were synonymous variants. A total of 41 single nucleotide variants were identified in the L1 sequences, including 10 nonsynonymous variants and 31 synonymous variants. All the isolates of both E6-E7 and L1 were classified into the A variant lineage. In HPV-51E6-E7 and L1 sequences, no positively selected site was found. Two nonconservative substitutions, H119Y and N176S in L1, affected multiple hypothetical B-cell epitopes. Three nonconservative substitutions, T86P, S100L in E6, and F29L in E7, affected multiple hypothetical T-cell epitopes. Elucidation of the HR-HPV prevalence characteristics and genetic variations of HPV-51 in central China may contribute to future investigations of diagnostic probes, therapeutic or preventative vaccines with wider coverage.

Investigation of the Role of Hydrophobic Amino Acids on the Structure-Activity Relationship in the Antimicrobial Venom Peptide Ponericin L1.

Venom mixtures from insects, reptiles, and mollusks have long been a source of bioactive peptides which often have alternative uses as therapeutics. While these molecules act in numerous capacities, there have been many venom components that act on the target cells through membrane disruptive mechanisms. These peptides have long been of interest as potential antimicrobial peptide platforms, but the inherent cytotoxicity of venom peptides often results in poor therapeutic potential. Despite this, efforts are ongoing to identify and characterize venom peptide which exhibit high antimicrobial activity with low cytotoxicity and modify these to further enhance the efficacy while reducing toxicity. One example is ponericin L1 from Neoponera goeldii which has been demonstrated to have good antimicrobial activity and low in vitro cytotoxicity. The L1 sequence was modified by uniformly replacing the native hydrophobic residues with either Leu, Ile, Phe, Ala, or Val. Spectroscopic and microbiological approaches were employed to investigate how the amino acid sequence changes impacted membrane interaction, secondary structure, and antimicrobial efficacy. The L1 derivatives showed varying degrees of bilayer interaction, in some cases driven by bilayer composition. Several of the variants exhibited enhanced antimicrobial activity compared to the parent strain, while others lost all activity. Interestingly, the variant containing Val lost all antimicrobial activity and ability to interact with bilayers. Taken together the results indicate that peptide secondary structure, amino acid composition, and hydrophobicity all play a role in peptide activity, although this is a delicate balance that can result in non-specific binding or complete loss of activity if specific amino acids are incorporated.