P1 Region Research Articles

Antisera-Neutralizing Capacity of a Highly Evolved Type 2 Vaccine-Derived Poliovirus from an Immunodeficient Patient

Background: The serotype 2 oral poliovirus vaccine (OPV2) can revert to regain wild-type neurovirulence and spread, causing the emergence of vaccine-derived poliovirus (VDPV2) and immunodeficiency-related vaccine-derived polioviruses (iVDPVs). In the United States, testing carried out by the CDC of type II iVDPV (iVDPV2) with human immune serum from the vaccine has shown that the presence of the virus poses a threat to eradication efforts. Methods: We analyzed the major neutralization sites of VP1, VP2, and VP3 of the iVDPV using bioinformatics techniques and homology modeling (SWISS-MODEL). The three amino acid residues 679, 680, and 141 of the P1 region changed, which had an impact on the spatial conformation of the viral-neutralizing site. We tested polio-vaccinated human sera and rabbit anti-Sabin II polyantibodies against a panel of iVDPV pseudoviruses. Results: The results demonstrated that the serum’s capacity to neutralize mutant pseudoviruses diminished when amino acid substitutions were introduced into the P1 encapsidated protein, particularly when 141 and 679 were mutated together. This study emphasizes the significance of continually monitoring individuals who are known to be immunocompromised and maintaining high vaccination rates in OPV-using communities.

Novel Intertypic Recombinant Coxsackievirus A2 Containing Specific Amino Acid Mutations in the RNA-Dependent RNA Polymerase Potentially Associated With Its Emergence.

Coxsackievirus A2 (CVA2), a member of enterovirus A species (EV-A), is associated with diverse human diseases and occasionally causes acute gastroenteritis (AGE). In Thailand, CVA2 emerged as the predominant genotype in 2019. The increasing incidence of CVA2, coupled with the limited availability of full-length genomes, highlights the need for more complete genome sequence analysis to facilitate molecular epidemiology study. This study aimed to investigate the molecular epidemiology, evolutionary dynamics, and recombination characteristics of CVA2 associated with AGE in Thailand from 2013 to 2022. A total of 19 full-genome sequences of CVA2 isolated from stool samples of AGE patients in Thailand were characterized and analyzed together with the reference sequences available in the GenBank database. A novel lineage of CVA2 (subgenotype C5) was detected with the potential recombination with CVA10 within the P2 and P3 regions. Specific consensus amino acid mutations, A61S in the VP3 gene and R136K in the 3D (RdRp) gene, were identified in all CVA2 recombinant strains. Additionally, the S45G mutation in the RdRp gene was found to be potentially associated with the emergence of CVA2 infection in 2019. In conclusion, this study reveals potential intertypic recombinant events and specific mutations in CVA2 strains isolated from AGE patients and provides a broader understanding of its evolutionary epidemiology.

Molecular Analysis of Coxsackievirus B2 Associated With Severe Symptoms of the Central Nervous System.

Coxsackievirus B2 (CVB2) is a member of the enterovirus group known to induce a spectrum of illnesses, from mild to severe. In the summer of 2022, an unusual outbreak of enteroviral central nervous system (CNS) infections occurred that was attributed to CVB2. Cerebrospinal fluid (CSF) samples collected from patients in 2015-2022 were tested for enterovirus via RT-PCR, followed by Sanger sequencing for positive cases. CVB2 samples were further sequenced in the P1 region using NGS. A total of 30 CSF samples were identified as CVB2, with 60% of these cases occurring between June and August 2022. The 2022 CVB2 variants were associated with severe clinical symptoms, including encephalitis (50%) and ataxia (27.8%). Samples from 2015 to 2020 were also included due to the absence of these symptoms. Phylogenetic analysis revealed that CVB2 strains from 2019 to 2020 were also distinct from those obtained in 2022. Amino acid analysis of the capsid proteins VP1, VP2, and VP3 identified three unique substitutions with potential antigenic significance in the 2022 variant: S67A in VP2, and T93A and E274D in VP1. These substitutions were not present in earlier strains or reported in the literature, suggesting they may influence the virus's virulence. The clinical observations from this study highlight new patterns of CVB2 infection in the CNS that had not been previously observed. Additionally, it identifies unique genetic changes in the 2022 CVB2 variant that may account for the increased virulence seen in the 2022 outbreak. However, further analysis is required to validate this assumption.

Whole genome sequencing and genome characterization of Aichivirus isolated from Korean adults.

The whole-genome sequence (WGS) analysis of Aichivirus (AiV) identified in Korea was performed in this study. Using Sanger and Nanopore sequencing, the 8228-nucleotide-long genomic sequence of AiV (OQ121963) was determined and confirmed to belong to genotype A. The full-length genome of OQ121963 consisted of a 7296 nt open reading frame (ORF) that encodes a single polyprotein, and 5' UTR (676 nt) and 3' UTR (256 nt) at 5' and 3' ends, respectively. The ORF consisted of leader protein (L), structural protein P1 (VP0, VP1, and VP3), and nonstructural protein P2 (2A, 2B, and 2C) and P3 (3A, 3B, 3C, and 3D). The secondary structure analysis of the 5' UTR identified only stem-loop C (SL-C) and not SL-A and SL-B. The variable region of the AiV genome was analyzed by MegAlign Pro and reconfirmed by SimPlot analysis using 16 AiV whole genomes known to date. Among the entire regions, structural protein region P1 showed the lowest amino acid identity (96.07%) with reference sequence AB040749 (originated in Japan; genotype A), while the highest amino acid identity (98.26%) was confirmed in the 3D region among nonstructural protein region P2 and P3. Moreover, phylogenetic analysis of the WGS of OQ121963 showed the highest homology (96.96%) with JX564249 (originated in Taiwan; genotype A) and lowest homology (90.14%) with DQ028632 (originated in Brazil; genotype B). Therefore, the complete genome characterization of OQ121963 and phylogenetic analysis of the AiV conducted in this study provide useful information allowing to improve diagnostic tools and epidemiological studies of AiVs.

Ultrafast dynamics and internal processing mechanism of silica glass under double-pulse femtosecond laser irradiation

Femtosecond laser-induced plasma filaments have potential for various applications including attosecond physics, spectroscopy, and microprocessing. However, the use of plasma filaments to generate high-aspect-ratio internal modifications remains low-efficiency. Here, we experimentally demonstrated high-efficiency internal processing using plasma filaments induced by a double-pulse femtosecond laser. The processing mechanism was revealed through an investigation of the ultrafast dynamics of plasma filaments in experiments and simulations. We found that the excitation region of the first pulse (P1) exerted a temporal effect on the propagation and absorption of the second pulse (P2) due to the evolution of excited electrons, thus resulting in different processing characterizations. At a smaller inter-pulse delay (IPD), electrons and self-trapped excitons induced by P1 improved the absorption of P2 in the shallow region. Consequently, the main excitation regions of P1 and P2 were separated, resulting in a lower density of energy deposition and weak modifications. Whereas, at a larger IPD, P2 penetrated a deeper region with the relaxation of electrons and excitons induced by P1, leading to a better overlap of excitation regions between P2 and P1, thus improving the density of energy deposition and achieving efficient microprocessing. Besides, at an infinite IPD, P2 behaved like P1, but no modification was obtained owing to the complete energy diffusion of P1. Therefore, controlling the electron dynamic and energy diffusion contributes to the improvement of modification efficiency. Furthermore, the distribution of electron densities on the cross section was estimated to precisely analyze the microprocessing. These results are expected to aid in a better understanding of the interaction mechanism between dielectrics and intense ultrafast lasers and be useful for microprocessing applications.

Residues 2 to 7 of α-synuclein regulate amyloid formation via lipid-dependent and lipid-independent pathways

Amyloid formation by α-synuclein (αSyn) occurs in Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. Deciphering the residues that regulate αSyn amyloid fibril formation will not only provide mechanistic insight but may also reveal targets to prevent and treat disease. Previous investigations have identified several regions of αSyn to be important in the regulation of amyloid formation, including the non-amyloid-β component (NAC), P1 region (residues 36 to 42), and residues in the C-terminal domain. Recent studies have also indicated the importance of the N-terminal region of αSyn for both its physiological and pathological roles. Here, the role of residues 2 to 7 in the N-terminal region of αSyn is investigated in terms of their ability to regulate amyloid fibril formation in vitro and in vivo. Deletion of these residues (αSynΔN7) slows the rate of fibril formation in vitro and reduces the capacity of the protein to be recruited by wild-type (αSynWT) fibril seeds, despite cryo-EM showing a fibril structure consistent with those of full-length αSyn. Strikingly, fibril formation of αSynΔN7 is not induced by liposomes, despite the protein binding to liposomes with similar affinity to αSynWT. A Caenorhabditis elegans model also showed that αSynΔN7::YFP forms few puncta and lacks motility and lifespan defects typified by expression of αSynWT::YFP. Together, the results demonstrate the involvement of residues 2 to 7 of αSyn in amyloid formation, revealing a target for the design of amyloid inhibitors that may leave the functional role of the protein in membrane binding unperturbed.

A Potent Sybody Selectively Inhibits α-Synuclein Amyloid Formation by Binding to the P1 Region.

Increasing research efforts focus on exploiting antibodies to inhibit the amyloid formation of neurodegenerative proteins. Nevertheless, it is challenging to discover antibodies that inhibit this process in a specific manner. Using ribosome display, we screened for synthetic single-domain antibodies, i.e., sybodies, of the P1 region of α-synuclein (residues 36-42), a protein that forms amyloid in Parkinson's disease and multiple-system atrophy. Hits were assessed for direct binding to a P1 peptide and the inhibition of amyloid formation. We discovered a sybody, named αSP1, that inhibits amyloid formation of α-synuclein at substoichiometric concentrations in a specific manner, even within highly crowded heterogeneous mixtures. Fluorescence resonance energy transfer-based binding assays and seeding experiments with and without αSP1 further demonstrate the importance of the P1 region for both primary and secondary nucleation mechanisms of amyloid assembly.

Identifying SNP threshold from P2 sequences for investigating norovirus transmission

Noroviruses are a group of non-enveloped single-stranded positive-sense RNA virus belonging to Caliciviridae family. They can be transmitted by the fecal-oral route from contaminated food and water and cause mainly acute gastroenteritis. Outbreaks of norovirus infections could be difficult to detect and investigate. In this study, we developed a simple threshold detection approach based on variations of the P2 domain of the capsid protein. We obtained sequences from the norovirus hypervariable P2 region using Sanger sequencing, including 582 pairs of epidemiologically-related strains from 35 norovirus outbreaks and 6402 pairs of epidemiologically-unrelated strains during the four epidemic seasons. Genetic distances were calculated and a threshold was performed by adopting ROC (Receiver Operating Characteristic) curve which identified transmission clusters in all tested outbreaks with 80 % sensitivity. In average, nucleotide diversity between outbreaks was 67.5 times greater than the diversity within outbreaks. Simple and accurate thresholds for detecting norovirus transmissions of three genotypes obtained here streamlines molecular investigation of norovirus outbreaks, thus enabling rapid and efficient responses for the control of norovirus.

LUMiC Endoprosthetic Reconstruction of Periacetabular Tumor Defects: A Multicenter Follow-up Study.

This article was updated on July 17, 2024 because of a previous error, which was discovered after the preliminary version of the article was posted online. The byline that had read "Richard E. Evenhuis, MD 1 , Michiel A.J. van de Sande, MD, PhD 1,2 , Marta Fiocco, PhD 2,3,4 , Demien Broekhuis, MD 1 , Michaël P.A. Bus, MD, PhD 1 , and the LUMiC® Study Group*" now reads "Richard E. Evenhuis, MD 1 , Michiel A.J. van de Sande, MD, PhD 1,2 , Marta Fiocco, PhD 2,3,4 , Edwin F. Dierselhuis, MD, PhD 5 , Demien Broekhuis, MD 1 , Michaël P.A. Bus, MD, PhD 1 , and the LUMiC® Study Group*". The Department of Orthopaedic Surgery, Radboudumc, Nijmegen, The Netherlands, has been added as the affiliation for Edwin F. Dierselhuis, MD, PhD. We previously reported promising early results for periacetabular tumor reconstructions using the LUMiC prosthesis. The current study evaluates mid-term complications, revision rates, cumulative incidence of implant revision, and risk factors for complications in a multicenter cohort. We assessed patients in whom a tumor defect after type P1b+2, P2, P2+3, or P1b+2+3 internal hemipelvectomy was reconstructed with a LUMiC prosthesis during the period of 2008 to 2022. Complications were reported according to the Henderson classification. Competing risks models were used to estimate the cumulative incidence of implant revision for mechanical and nonmechanical reasons, and reoperations for any complication. Cox models were used to study the effect of risk factors on dislocation and infection. One hundred and sixty-six patients (median follow-up, 4.2 years [interquartile range, 2.6 to 7.6 years]) were included. A total of 114 (69%) were treated for a primary malignant tumor, 46 (28%) for metastatic carcinoma, 5 (3%) for a benign aggressive lesion, and 1 (1%) for another reason. One hundred and sixty-five reoperations were performed in 82 (49%) of the patients; 104 (63%) of the reoperations were within 6 months. Thirty-two (19%) of 166 implants were revised: 13 (8%) for mechanical reasons, mainly dislocation (n = 5, 3%), and 19 (11%) for nonmechanical reasons, mainly periprosthetic joint infection (PJI) (n = 15, 9%). The cumulative incidences of revision for mechanical reasons and PJI (Henderson 1 to 4) at 2, 5, and 10 years were 11% (95% confidence interval [CI], 7% to 17%), 18% (12% to 25%), and 24% (16% to 33%), respectively. Previous surgery at the same site was associated with an increased dislocation risk (cause-specific hazard ratio [HR CS ], 3.0 [95% CI, 1.5 to 6.4]; p < 0.01), and resections involving the P3 region were associated with an increased infection risk (HR CS , 2.5 [95% CI, 1.4 to 4.7]; p < 0.01). Despite a substantial reoperation risk, the LUMiC prosthesis demonstrated its durability in the mid-term, with a low mechanical revision rate and most patients retaining their primary implant. Most complications occur in the first postoperative months. Patients with previous surgery at the same site had an increased dislocation risk and might benefit from more conservative rehabilitation and aftercare. Measures should be aimed at reducing the PJI risk, especially in resections involving the P3 region. Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Molecular characterization of emerging Echovirus 11 (E11) shed light on the recombinant origin of a variant associated with severe hepatitis in neonates.

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. Due to the limited data available, the World Health Organization (WHO) considers public health risk to the general population to be low. The present study investigated the genetic variation and molecular evolution of E11 genomes collected from May to December 2023. Whole genome sequencing (WGS) was performed for 16 E11 strains. Phylogenetic analysis on WG showed how all Italian strains belonged to genogroup D5, similarly to other E11 strains recently reported in France and Germany all together aggregated into separate clusters. A cluster-specific recombination pattern was also identified using phylogenetic analysis of different genome regions. Echovirus 6 was identified as the major recombinant virus in 3Cpro and 3Dpol regions. The molecular clock analysis revealed that the recombination event probably occurred in June 2018 (95% HPD interval: Jan 2016-Jan 2020). Shannon entropy analyses, within P1 region, showed how 11 amino acids exhibited relatively high entropy. Five of them were exposed on the canyon region which is responsible for receptor binding with the neonatal Fc receptor. The present study showed the recombinant origin of a new lineage of E11 associated with severe neonatal infections.

The effect of changing vertical irradiation angle of periapical radiography bisecting technique on the length dimension of mandibular teeth

Objectives: This research is aimed to determine the effect of changing the vertical irradiation angle with a change in angle of +10°, +5°, -5°, -10° in bisecting technique periapical radiography on the length dimension of mandibular teeth. Materials and Methods: This study used a laboratory experimental method with a post test only control group design. The samples used in this study were teeth I1, I2, C, P1, P2, M1, and M2 region 4. All teeth were treated by changing the angle from the standard angle recommended by White and Pharoah with changes of +10°, +5°, -5°, and -10° in each tooth using a Morita Veraview iX 70 Kv, 7mA dental X-ray unit. Results: The results showed that the angle change of -10°, -5° causes foreshortening and +10°, +5° causes elongation. Based on the results of the Saphiro-Wilk and Kruskal-Wallis test, it is known that there are significant differences in the dimensions of tooth length at +10°, +5°, -5°, -10° against changes in the angle 0° or angulation form White and Pharoah (p &lt; 0.05) . Conclusion: There is a significant effect on the change of vertical irradiation angle with angle changes of +10°, +5°, -5°, -10° in bisecting technique periapical radiography on the length dimension of mandibular teeth.

TEE-Guided Cardiac Surgery in a Child with Mitral Valve Prolapse, Hyperthyroidism and Myasthenia Gravis: A Case Report

Intraoperative transesophageal echocardiography is used to more accurately assess a patient&amp;apos;s cardiac condition and is important for the guidance of cardiac surgery. This case reports a pediatric cardiac surgery performed under TEE guidance in a patient with multiple complications. A 5-year-old child presented with diarrhea as the first symptom. At the age of 2 years, she was admitted to the hospital with ptosis of the right upper eyelid, morning lightness and evening heaviness, hand tremor, and the presence of a murmur in the mid to late stages of cardiac systole on auscultation. She was diagnosed with mitral valve prolapse and myasthenia gravis, which resolved with treatment. Subsequently, she was diagnosed with hyperthyroidism due to obvious protrusion of the eyeballs, and was admitted to the hospital for heart valve surgery after her thyroid function was controlled. Intraoperative TEE suggested mitral valve prolapse combined with embolization of the P2 region. In the complex case of this child, the suture points during mitral valvuloplasty and the scar tissue caused by the mitral valvuloplasty annulus may limit the growth of the annulus as well as the leaflet motion. Therefore, it was recommended that the surgeon perform mitral valve extension to maximize the prognosis. TEE herein guided the cardiac surgical decision making to maximize the prognosis of the child.

Laser Scribing for Perovskite Solar Modules of Long‐Term Stability

Although the efficiency of hybrid lead‐halide perovskite solar cells has been significantly improved, the efficiency gap between small‐area cells and large modules continues to be a considerable challenge. Laser scribing is essential for realizing high‐quality monolithic connections; however, the laser‐induced material changes and their correlation with device performance have not been yet well understood, in particular for the perovskite material systems. In this study, the effect of P3 laser processing conditions on device performance and stability is explained. The most interesting finding is an improvement in open‐circuit voltage (VOC) after aging and long‐term stability under low‐laser‐overlap conditions that avoid direct laser exposure to perovskite material system as a source of material degradation. It is found that a high‐laser‐overlap during P3 results in a lower fill factor after aging and accelerated degradation due to larger portion of perovskite directly exposed to laser during the scribing process. The increased VOC under low‐overlap conditions is attributed to the increased PbI2 formation in the P3 region. Moreover, a minimal pulse overlap is favorable for preserving long‐term device stability. Finally, a perovskite minimodule with an efficiency of 20.24% is successfully developed as a result of these findings.

Abstract 4912: Unsupervised detection of stromal phenotypes with distinct fibrogenic and inflamed properties in NSCLC

Abstract Background: Understanding the composition of cancer-associated stroma (CAS) is vital, as the number and location of immune cells and fibroblasts, as well as the degree of extracellular matrix deposition, have implications for cancer progression and response to treatment, including in non-small cell lung cancer (NSCLC). Manual analysis of CAS does not fully describe the stromal milieu, especially from a spatial perspective, and is highly subjective. To this end, we have developed an unsupervised machine learning (ML) model to characterize the CAS in NSCLC from hematoxylin and eosin (H&amp;E) stained whole slide images (WSI) at scale. Methods: PathExploreTM models were deployed to predict stromal tissue and cell types, while another ML model was used to detect collagen fibers from H&amp;E stained WSIs from the TCGA LUAD (N=536) and LUSC (N=464) datasets. Stroma was divided into small regions (median = 0.02 mm2), and 88 features characterizing cell distribution, tissue composition and fiber density were extracted from each region. Graphs were generated connecting neighboring regions (nodes), and an unsupervised variational graph auto-encoder (VGAE) model was trained to learn 8 latent features through dimensionality reduction. Stromal phenotypes were then derived from the latent features using k-means clustering. The fraction of each phenotype in the stroma was correlated against immune- and stroma-related gene expression signatures (GES) and overall survival (OS). Results: Deployment of VGAE on LUAD and LUSC WSIs revealed three distinct stromal phenotypes - P0, P1 and P2. Fibroblast density was elevated in P0 and P1 regions (p&amp;lt;0.001), immune cell density was elevated in P2 regions (p&amp;lt;0.001), and collagen fiber intensity was highest in P1 regions (p&amp;lt;0.001). P2 enrichment was correlated with elevated expression of the T cell-inflamed gene expression profile (TGEP; Spearman ρ = 0.43 in LUAD; ρ = 0.27 in LUSC) and with improved OS (HR = 0.696; 95% CIs: 0.571-0.847 in LUSC). Conversely, P1 enrichment was positively associated with a transforming growth factor-β-induced cancer associated fibroblast GES (TGFβ-CAF: ρ = 0.19 in LUAD and ρ = 0.12 in LUSC) and poor OS (HR = 1.358; 95% CIs: 1.149-1.603 in LUSC). These phenotypes are consistent with fibroblast-enriched, collagen-depleted stroma (P0), collagen-rich, fibroblast-enriched tumor-promoting stroma (P1), and immune cell-enriched, tumor-suppressive stroma (P2). Conclusions: We describe an unsupervised, data-driven method of predicting stromal regions with discrete patterns of cell composition and collagen deposition in NSCLC. This approach identified three phenotypes of NSCLC stroma. These results highlight the ability of ML models to characterize and find meaningful patterns within the cell, tissue, and matrix components of a tumor. This work provides further evidence of the potential of ML to discover novel precision medicine biomarkers in NSCLC. Citation Format: Neel Patel, Nhat Le, Tan Nguyen, Fedaa Najdawi, Sandhya Srinivasan, Adam Stanford-Moore, Deeksha Kartik, Jun Zhang, Jacqueline Brosnan-Cashman, Robert Egger, Justin Lee, Matthew Bronnimann. Unsupervised detection of stromal phenotypes with distinct fibrogenic and inflamed properties in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4912.

Genome Sequencing of Historical Encephalomyocarditis Viruses from South Africa Links the Historical 1993/4 Savanna Elephant (Loxodonta africana) Outbreak to Cryptic Mastomys Rodents.

From 1993 to 1994, 64 free-ranging elephants (Loxodonta africana) succumbed to encephalomyocarditis in the Kruger National Park, South Africa, of which 83% were adult bulls. Mastomys rodents were implicated as the reservoir host of the Encephalomyocarditis virus (EMCV) based on serology and RT-PCR. However, in the absence of sequence-confirmation of both the virus and the rodent host, definitive links between the elephant outbreak strains and rodent reservoir could not be established. In this study, we generate the first reference genome sequences for three historical EMCVs isolated from two Mastomys rodents and one Mastomys-associated mite, Laelaps muricola, in Gauteng Province, South Africa, in 1961. In addition, near-complete genome sequences were generated for two elephant outbreak virus strains, for which data were previously limited to the P1 and 3D genome regions. The consensus sequence of each virus was determined using a PCR-Sanger sequencing approach. Phylogenetic analysis confirmed the three near-identical (99.95-99.97%) Mastomys-associated viruses to be sister to the two near-identical (99.85%) elephant outbreak strains, differing from each other at 6.4% of sites across the ~7400-nucleotide region characterised. This study demonstrates a link between Mastomys-associated viruses and the historical elephant outbreak strains and implicates Mastomys as reservoirs of EMCV in South Africa.

Genetic characterization and molecular epidemiological analysis of enterovirus C99 in China.

Enterovirus C99 (EV-C99) is a newly identified EV serotype within the species Enterovirus C. Few studies on EV-C99 have been conducted globally. More information and research on EV-C99 are needed to assess its genetic characteristics, phylogenetic relationships, and associations with enteroviral diseases. Here, the phylogenetic characteristics of 11 Chinese EV-C99 strains have been reported. The full-length genomic sequences of these 11 strains show 79.4-80.5% nucleotide identity and 91.7-94.3% amino acid (aa) identity with the prototype EV-C99. A maximum likelihood phylogenetic tree constructed based on the entire VP1 coding region identified 13 genotypes (A-M), revealing a high degree of variation among the EV-C99 strains. Phylogeographic analysis showed that the Xinjiang Uygur Autonomous Region is an important source of EV-C99 epidemics in various regions of China. Recombination analysis revealed inter-serotype recombination events of 16 Chinese EV-C99 strains in 5' untranslated regions and 3D regions, resulting in the formation of a single recombination form. Additionally, the Chinese strain of genotype J showed rich aa diversity in the P1 region, indicating that the genotype J of EV-C99 is still going through variable dynamic changes. This study contributes to the global understanding of the EV-C99 genome sequence and holds substantial implications for the surveillance of EV-C99.

Hybrid computational model depicts the contribution of non-significant lobes of human brain during the perception of emotional stimuli

Emotions are synchronizing responses of human brain while executing cognitive tasks. Earlier studies had revealed strong correlation between specific lobes of the brain to different types of emotional valence. In the current study, a comprehensive three-dimensional mapping of human brain for executing emotion specific tasks had been formulated. A hybrid computational machine learning model customized from Custom Weight Allocation Model (CWAM) and defined as Custom Rank Allocation Model (CRAM). This regression-based hybrid computational model computes the allocated tasks to different lobes of the brain during their respective executive stage. Event Related Potentials (ERP) were obtained with significant effect at P1, P2, P3, N170, N2, and N4. These ERPs were configured at Pz, Cz, F3, and T8 regions of the brain with maximal responses; while regions like Cz, C4 and F4 were also found to make effective contributions to elevate the responses of the brain, and thus these regions were configured as augmented source regions of the brain. In another circumstance of frequent –deviant - equal (FDE) presentation of the emotional stimuli, it was observed that the brain channels C3, C4, P3, P4, O1, O2, and Oz were contributing their emotional quotient to the overall response of the brain regions; whereas, the interaction effect was found presentable at O2, Oz, P3, P4, T8 and C3 regions of brain. The proposed computational model had identified the potential neural pathways during the execution of emotional task.

Novel intertypic recombination of Echovirus 11 in the Enterovirus species B.

Enteroviruses (EVs), single-stranded, positive-sense RNA viruses, can be classified into four species (A-D), which have previously been linked to a diverse range of disease manifestations and infections affecting the central nervous system. In the Enterovirus species B (EV-B), Echovirus type 11 (E11) has been observed to occasionally circulate in Taiwan, which was responsible for an epidemic of enterovirus infections in 2018. Here, 48 clinical specimens isolated in 2003, 2004, 2009, and 2018 were collected for the high-throughput sequencing. Notably, we identified 2018 Taiwanese strains having potential recombinations in the 3D gene, as well as one 2003 strain having a double recombination with E6 and Coxsackievirus B5 in the P2 and P3 regions, respectively. Additionally, one amino acid signature mutated from the Histidine (H) in throat swab specimens to the Tyrosine (Y) in cerebral spinal fluid specimens was detected at position 1496 (or 57) of the genomic coordinate (or 3A gene) to further demonstrate intra-host evolution in different organs. In conclusion, this study identifies potential intertypic recombination events and an intra-host signature mutation in E11 strains, isolated during a 2018 neurological disease outbreak in Taiwan, contributing to our understanding of its evolution and pathogenesis.

Y chromosome haplogroup N in a Japanese population is classified into three subclades, and two DYS385 loci, a duplicated Y-STR, are duplicated again in subclade N-M1819

DYS385 is one of the major Y chromosome short tandem repeats (Y-STRs) in forensic genetics and exists as 2 copies in the human Y chromosome palindrome P4 region. In this study, we found that some samples were estimated to have ≥ 4 copies of DYS385 in Y chromosome haplogroup N in a Japanese population. Y chromosome haplogroup N is distributed widely in eastern/central Asia, Siberia, and eastern/northern Europe, and is also observed in Japan; however, little is known about haplogroup N subclades in the Japanese population. To reveal the link between increased DYS385 copy number and haplogroup N subclades, we sequenced single nucleotide polymorphisms to classify the subclades. As a result, the Japanese Y chromosomes of haplogroup N were classified into three subclades, and an increased DYS385 copy number was specific to subclade N-M1819* (N1b2*). These results are of use in forensic DNA analysis because Y-STR copy number is important for the interpretation of Y-STR typing results of male DNA mixtures and kinship analysis. We also found that DYS458.1 microvariants (DYS458 intermediate alleles with single-nucleotide insertion) were observed only in subclade N-CTS962 (N1b1b∼) samples. Given that previous studies reported that DYS458.1 microvariants are observed in Y chromosomes of haplogroup N in other populations, DYS458.1 might be used to infer haplogroup N subclades without limitation to the Japanese population. The results of this study will be beneficial not only to forensic genetics but also to anthropological studies.

Seismic simulation and attribute analysis of Jurassic fluvial reservoirs in the P6 region, Xinjiang

Fluvial reservoirs are crucial for oil and gas exploration. In the Jurassic formations of Chepaizi anticline, ancient channels can be identified based on seismic facies similar to incised valleys. This study focuses on three key issues. Firstly, it aims to demonstrate the capability of spectral decomposition interpretation in distinguishing ancient channels. Secondly, it aims to prove that the incised valleys in the Jurassic formations of Chepaizi are ancient channels. Thirdly, given that the Jurassic is a new layer for oil and gas exploration in the region, it aims to identify the distribution of ancient channel and conglomerate. To address these issues, we conducted a seismic wave forward simulation study on channels and used spectral decomposition to interpret seismic data. The results show that: (1) Spectral decomposition can differentiate channels of different thicknesses, where low-frequency components correspond to thick channels and high-frequency components correspond to thin channels. (2) Using multi-attribute and multi-parameter fusion method can identify the fluvial sand body boundary. (3) The width of the channel in P6 area ranges from 400 to 1700 m, with an area of 78 km2. The fluvial sand bodies are generally distributed along the slopes. Few sandstones and conglomerates are distributed at the bottom of the channel. We conclude that further exploration should focus on the fluvial channel delta in the southeast of the study area.