Strong Linkage Research Articles

Assessment and predictive analysis of health professions students' proficiency in health economics and pharmacoeconomics in Southwest China: a cross-sectional study

ObjectivesThis study addresses the growing importance of health economics and pharmacoeconomics in preparing healthcare professionals for economic decision-making, particularly in China’s evolving healthcare system. Despite their significance, these subjects are inconsistently included in health education in Southwest China, making it crucial to assess students' proficiency and educational needs.MethodsA cross-sectional study was conducted from July to October 2023, involving medical and pharmaceutical programs across universities in Sichuan, Chongqing, Guizhou, and Yunnan. Data on students' knowledge, attitudes, and proficiency were captured using a structured questionnaire. Advanced statistical methods, including descriptive analysis, ANOVA, regression analysis, PCA, and Spearman correlation heatmaps, were employed for data analysis using IBM SPSS and Python. The sample consisted of 781 students, with the survey facilitated via the Questionnaire Star platform.ResultsThe survey revealed moderate comprehension of health economics and pharmacoeconomics among 781 health-related students, with an average knowledge score of 2.9. The majority were pharmacy students (45.58%) and aged 21–24 years (65.81%) with a significant female majority (64.92%). Academic year significantly influenced understanding, while gender differences were minimal. Spearman correlation indicated a strong linkage (0.78) between Supply and Demand and Cost Effectiveness, with minimal correlations between knowledge and attitudes towards the educational importance of health economics. Multiple regression analysis highlighted the impact of gender and academic progression on students' comprehension of Supply and Demand concepts, as well as the influence of knowledge levels on their attitudes towards the importance of health economics education. PCA indicated the complex structure of knowledge and attitudes.ConclusionsThe study found moderate knowledge levels in health economics among health professions students in Southwest China, with academic year affecting comprehension and minimal gender differences. Pharmacy students had higher proficiency in pharmaceutical-related areas, but gaps in complex topics like 'Economic Evaluation' highlight the need for targeted educational improvements to better prepare students for healthcare economic decision-making.

Enhancing preparedness by developing robust implementation

Abstract In EUVABECO, a goal is defined as a public health objective that motivates a vaccination practice. A vaccination practice encompasses specific methods or approaches used in vaccination efforts, while a tool refers to a tangible resource or software developed to support the implementation of these practices. EUVABECO is undertaking a series of structured activities from January 2024 until mid-2026. These include mapping innovative practices, deriving requirements for tools and validation plans, developing implementation plans, and facilitating their adoption by European MS. The project will also evaluate, validate, and verify these plans to ensure their efficacy and sustainability. EUVABECO’s methodology is informed by the Systems Development Lifecycle (SDLC) framework, utilizing the V-model to ensure a strong linkage between the development and testing phases, thereby guaranteeing a cohesive workflow. Each implementation plan developed will feature comprehensive policy recommendations and a workplan that covers the necessary organizational, technical, legal, and ethical aspects required for the tool’s deployment. Additionally, these plans will include tailored strategies to enhance the tool’s functionality during outbreaks, criteria for verifying implementation effectiveness, and financial considerations critical for supporting adoption. The implementation plans will undergo a rigorous validation process to assess their suitability, transferability, and sustainability across MS. The ultimate goal is to disseminate validated plans whilst ensuring a parallel multistakeholder engagement approach to ensure MS are actively involved in key project phases, thus, facilitating rapid uptake of said plans across EU MS and a transformation of the vaccination ecosystem across Europe.

Intronic Variants in the MSH2 (rs2303426 and rs10179950) and PMS2 (rs2286681 and rs62456178) Genes Are Not Associated with Colorectal Cancer in Mexican Patients

Background/Objectives: In the origin and development of colorectal cancer (CRC), a global public health problem, a dysfunction mismatch repair system appears to be a key factor. The objective was to determine the association of intronic variants in the MSH2 and PMS2 genes with CRC in Mexican patients. Methods: Blood samples of 143 CRC patients and 146 reference individuals were genotyped through TaqMan® Genotyping Assays. Genotypic and allelic frequencies were determined by direct counting. To compare genotypic and allelic distributions, the chi-square test was used. For the association analysis, the risks of alleles and genotypes were estimated by odds ratio with 95% confidence intervals. Haplogroups were inferred with a Bayesian algorithm. Linkage disequilibrium was measured using D’ and r2 with Arlequin v3.5.2. The in silico analysis was carried out using the SpliceAI, UCSC, JASPAR and TRRUST platforms. All statistical analyses were performed with SPSS v29.0.2.0. Results: In the CRC group, the mean age was 58.2 ± 14.7 years and 60.8% were men. No variant was associated with CRC or implicated in gene post-replicative processing. Linkage disequilibrium was observed for loci rs2303426 and rs10179950 in MSH2 and for loci rs2286681 and rs62456178 in PMS2. Conclusions: The genotypic and allelic frequencies of the four variants are reported for the first time in Mexican patients with CRC. No association was found between gene variants and risk for CRC but there was a strong linkage disequilibrium between the loci of both MSH2 and PMS2 genes. None of the variants showed a possible repercussion on splicing.

Socio-Emotional Disposition’s Mediation in Technical Skills and Graduate Employability in Tourism and Hospitality Industry—South-Western Uganda

Despite possessing technical skills, many hospitality graduates in Southwestern Uganda struggle to secure employment. This suggests a possible deficiency in their socio-emotional abilities. The study investigated the mediating effect of socio-emotional disposition in the relationship between technical skills and graduate employability. The research design employed in this study was the cross-sectional quantitative research method with a population of 640 graduates and a sample size of 400 was established for hospitality graduates based on Krejcie, & Morgan’s (1970) table and formula. The data was collected employing questionnaires and the data analysis was done by SPSS V. 23 and Smart PLS V 4. The results revealed that the technical skills and socio-emotional disposition of graduates have significant direct effects on the graduates’ employability, with path coefficients of (β = 0.348, p < 0.001) for technical skills and (β = 0.716, p< 0.001) for socio-emotional disposition. Sensitively, socio-emotional disposition was also reported to mediate the link between technical skill and employability (β = 0.438, p<0.001). Thus, socio-emotional disposition increases the level of readiness for employment. The study indicates technical competencies are mandatory prerequisites to getting a job in the hospitality industry; socio-emotional competencies enhance these results. The study recommended that carrying out tracer studies and skills audits, mentorship schemes, certification of future graduates, creating a strong linkage between higher educational institutions (HEIs) and the hospitality sector, and authorities should take into account the programs that encourage socio-emotional enhancement appropriate to the needs of the sector

Strong Linkage Between Observed Daily Precipitation Extremes and Anthropogenic Emissions Across the Contiguous United States

AbstractThe results of probabilistic event attribution studies depend on the choice of the extreme value statistics used in the analysis, particularly with the arbitrariness in the selection of appropriate thresholds to define extremes. We bypass this issue by using the Extended Generalized Pareto Distribution (ExtGPD), which jointly models low precipitation with a generalized Pareto distribution and extremes with a different Pareto tail, to conduct daily precipitation attribution across the contiguous United States (CONUS). We apply the ExtGPD to 12 general circulation models from the Coupled Model Intercomparison Project Phase 6 and compare counterfactual scenarios with and without anthropogenic emissions. Observed precipitation by the Climate Prediction Center is used for evaluating the GCMs. We find that greenhouse gases rather than natural variability can explain the observed magnitude of extreme daily precipitation, especially in the temperate regions. Our results highlight an unambiguous linkage of anthropogenic emissions to daily precipitation extremes across CONUS.

Interlinkages between public expenditures, non-tax government revenues and corruption in the transition economies

PurposeThis article examines potential impacts of increase in non-tax government revenues and public expenses on corruption for 11 transition economies in the Central and Eastern Europe.Design/methodology/approachThe empirical analysis uses yearly panel datasets and employs second-generation panel data models which take cross-sectional dependency and slope heterogeneity into account.FindingsThe empirical results reveal the fact that there is a strong linkage between public expenses and corruption and a weak linkage between non-tax revenue collection and corruption in the transition economies. We perform the same analysis by using data sets from G-7 countries but do not notice any linkages between those variables.Research limitations/implicationsThe research topic requires further discussion on constitutional political economy to digest the empirical findings. Thus, an extended version combined with political economic approach might be useful.Practical implicationsThrough economic transitions, there might be a linkage between public expenditures and corruption index. Thus, public spending might be controlled by using constitutional economics policies.Originality/valueThis paper is the first empirical work in the literature, which examines if there is a linkage between corruption and public expenditures and government tax income structure by using panel data sets. Moreover, it compares the results from transition countries with those of G-7 countries and provides certain policy suggestions in the context of constitutional economics.

ApaI Polymorphism in the Vitamin D Receptor Gene Decreases the Risk of Perianal Fistulas in Crohn’s Disease

Background: Vitamin D, through the activation of its receptor (VDR), plays an immunomodulatory role in the gastrointestinal tract. Single-nucleotide polymorphisms (SNPs) in the VDR gene have been associated with Crohn’s disease (CD) risk, and patients carrying the TaqI polymorphism in this gene run a higher risk of developing a penetrating behavior. Aims: We analyzed the association of BsmI, ApaI, TaqI, and FokI SNPs in the VDR gene with the clinical characteristics of CD. Methods: Four polymorphisms identified in the VDR gene (BsmI, FokI, ApaI, and TaqI) were genotyped in blood samples from CD patients (n = 115) by using PCR-RFLP. The disease’s location and behavior and the presence of perianal fistulas were collected from each patient. Intestinal fibroblasts from ileal resections of CD patients (n = 10) were genotyped, and the expression of fibrotic and inflammatory markers was analyzed by RT-PCR. Results: The data reveal no association between any of the polymorphisms and CD risk. A strong linkage disequilibrium was detected between TaqI and both ApaI and BsmI, which in turn were strongly associated. Homozygosis or heterozygosis for the a allele of the ApaI SNP or b allele of the BsmI SNP was significantly associated with a lower risk of a penetrating behavior, while the aa genotype was associated with a lower risk of perianal fistulas. Fibroblasts carrying the aa genotype expressed lower levels of fibrotic and inflammatory markers. Conclusion: The aa genotype of the ApaI SNP in the VDR gene is associated with a lower risk of perianal fistulas in CD and a reduced expression of fibrotic and inflammatory markers in intestinal fibroblasts.

Influenza A virus within-host evolution and positive selection in a densely sampled household cohort over three seasons.

While influenza A virus (IAV) antigenic drift has been documented globally, in experimental animal infections, and in immunocompromised hosts, positive selection has generally not been detected in acute infections. This is likely due to challenges in distinguishing selected rare mutations from sequencing error, a reliance on cross-sectional sampling, and/or the lack of formal tests of selection for individual sites. Here, we sequenced IAV populations from 346 serial, daily nasal swabs from 143 individuals collected over three influenza seasons in a household cohort. Viruses were sequenced in duplicate, and intrahost single nucleotide variants (iSNVs) were identified at a 0.5% frequency threshold. Within-host populations exhibited low diversity, with >75% mutations present at <2% frequency. Children (0-5 years) had marginally higher within-host evolutionary rates than adolescents (6-18 years) and adults (>18 years, 4.4 × 10-6 vs. 9.42 × 10-7 and 3.45 × 10-6, P < .001). Forty-five iSNVs had evidence of parallel evolution but were not over-represented in HA and NA. Several increased from minority to consensus level, with strong linkage among iSNVs across segments. A Wright-Fisher approximate Bayesian computational model identified positive selection at 23/256 loci (9%) in A(H3N2) specimens and 19/176 loci (11%) in A(H1N1)pdm09 specimens, and these were infrequently found in circulation. Overall, we found that within-host IAV populations were subject to genetic drift and purifying selection, with only subtle differences across seasons, subtypes, and age strata. Positive selection was rare and inconsistently detected.

Identification of candidate causal variants and target genes at 41 breast cancer risk loci through differential allelic expression analysis

Understanding breast cancer genetic risk relies on identifying causal variants and candidate target genes in risk loci identified by genome-wide association studies (GWAS), which remains challenging. Since most loci fall in active gene regulatory regions, we developed a novel approach facilitated by pinpointing the variants with greater regulatory potential in the disease’s tissue of origin. Through genome-wide differential allelic expression (DAE) analysis, using microarray data from 64 normal breast tissue samples, we mapped the variants associated with DAE (daeQTLs). Then, we intersected these with GWAS data to reveal candidate risk regulatory variants and analysed their cis-acting regulatory potential. Finally, we validated our approach by extensive functional analysis of the 5q14.1 breast cancer risk locus. We observed widespread gene expression regulation by cis-acting variants in breast tissue, with 65% of coding and noncoding expressed genes displaying DAE (daeGenes). We identified over 54 K daeQTLs for 6761 (26%) daeGenes, including 385 daeGenes harbouring variants previously associated with BC risk. We found 1431 daeQTLs mapped to 93 different loci in strong linkage disequilibrium with risk-associated variants (risk-daeQTLs), suggesting a link between risk-causing variants and cis-regulation. There were 122 risk-daeQTL with stronger cis-acting potential in active regulatory regions with protein binding evidence. These variants mapped to 41 risk loci, of which 29 had no previous report of target genes and were candidates for regulating the expression levels of 65 genes. As validation, we identified and functionally characterised five candidate causal variants at the 5q14.1 risk locus targeting the ATG10 and ATP6AP1L genes, likely acting via modulation of alternative transcription and transcription factor binding. Our study demonstrates the power of DAE analysis and daeQTL mapping to identify causal regulatory variants and target genes at breast cancer risk loci, including those with complex regulatory landscapes. It additionally provides a genome-wide resource of variants associated with DAE for future functional studies.

Target Gene-Based Association Study of High Mobility Group Box Protein 1 in Intracranial Aneurysms in Koreans.

Objective: We investigated the effect of high mobility group box 1 (HMGB1) on intracranial aneurysms (IAs) by analyzing single-nucleotide polymorphisms (SNPs) based on genome-wide association study (GWAS) data. HMGB1 mRNA and protein expression levels in plasma were also analyzed. Methods: This study was a comprehensive analysis of a GWAS dataset, including 250 patients with IAs and 294 controls. The HMGB1 gene region was targeted within SNP rs3742305 ± 10 kbp. Multivariate logistic regression analysis determined its association with IAs after adjusting for relevant clinical factors. HMGB1 mRNA expression was analyzed in the plasma of 24 patients selected from the GWAS dataset. The HMGB1 protein was analyzed by Western blotting. Results: A total of seven polymorphisms, including rs1360485, rs185382445, rs2039338, rs1045411, rs3742305, rs2249825, and rs189034241, were observed. Two SNPs, including rs1045411 (UTR-3) and rs3742305 (intron), showed strong linkage disequilibrium (r2 = 0.99). However, none of the seven SNPs associated with IAs had an adjusted p-value of < 0.0016 on multiple comparison analysis. HMGB1 mRNA levels (2-ΔCt) did not differ significantly between patients with IAs and the control subjects [1.07 (1.00-1.15) in patients with IAs vs. 1.05 (0.94-1.12) in controls; p = 0.67)]. Also, no significant difference in the degree of plasma HMGB1 protein expression was seen between the two groups (p = 0.82). Conclusions: The number of SNPs associated with HMGB1 and the degree of HMGB1 mRNA and protein expression were not significantly different between patients diagnosed with IAs and the controls.

Estrogen Receptor-α rs9340799 Polymorphism Influences Bone Mineral Density in Women Over 60 Years of Age and Women Who are Postmenopausal for More than 10 Years

Background: Osteoporosis is a multifactorial disorder where genetic and environmental factors contribute to changes in bone mineral density. Several genetic polymorphisms are associated with low bone mineral density and osteoporosis risk, including estrogen receptor-α rs2234693 and rs9340799 single nucleotide polymorphisms. Objective: To determine the allele frequencies of these polymorphisms among postmenopausal Jordanian women and to assess their association with low bone mineral density and osteoporosis among studied subjects. Methods: This cross-sectional study enrolled 450 postmenopausal Jordanian women having dual-energy X-ray absorptiometry scans at the National Center for Diabetes, Endocrinology, and Genetics. The study protocol was approved by this center "Institutional Review Board." The estrogen receptor-α gene sequence containing rs2234693 and rs9340799 polymorphisms was identified by polymerase chain reaction, followed by restriction fragment length polymorphism. Results: The wild-type allele frequencies of rs2234693 (T) and rs9340799 (A) were 54% and 59%, respectively. The rs9340799 GG genotype was significantly associated with lower femoral neck T-scores in women who were postmenopausal for more than 10 years (p = 0.023) and was significantly associated with lower lumbar spine (p = 0.033) and femoral neck (p = 0.002) T-scores in women older than 60 years of age. However, there was no association between rs2234693, rs9340799, or their haplotypes with osteoporosis or bone mineral density T-score values. The two polymorphisms were in Heidy-Weinberg equilibrium and exhibited strong but incomplete linkage disequilibrium. Conclusion: The data suggest that rs9340799 polymorphism may render some women more susceptible to osteoporosis than others.

Temporal-scale-dependent mechanisms of forest soil nitrous oxide emissions under nitrogen addition

Nitrous oxide (N₂O) emissions from forest soils are typically intensified under elevated anthropogenic nitrogen (N) deposition, likely due to increased N availability. However, the extent to which these emissions are linked to N availability across different timescales remains poorly understood. Here we investigated the temporal-scale-dependent mechanisms of N₂O emissions in a subalpine forest under N-addition, using hourly-resolved N₂O measurements. Our findings revealed that N-addition induced both pulse emissions and a long-lasting effect on soil N₂O emissions. The pulse emissions occurred immediately after each N-addition, indicating a strong linkage between the pulse events and elevated N availability. However, variations in annual N₂O emissions were not directly regulated by N availability but were instead explained by denitrifying microbial functional genes ratio. A global meta-analysis further confirmed the importance of microbial functional genes in regulating N2O emissions in natural terrestrial ecosystems. Our results suggest a crucial role of microbial functional genes in predicting annual N2O emissions from forest soils.

Linkage of alternative exon assembly in Drosophila TrpA1 transcripts

Drosophila TrpA1 (transient receptor potential ankyrin 1) transcripts are alternatively spliced at two distinct sites each with a choice of mutually exclusive exons. The first site determines exon1 encoding the amino terminus to produce either nucleophile-, electrophile- and noxious temperature-gated TRPA1(A) or electrophile- and innocuous warmth-gated TRPA1(B). The second site selects for exon10, resulting in TrpA1 variants with either exon10a or exon10b encoding a domain between the N-terminal ankyrin repeats and the transmembrane segments. Although unbiased assembly would generate TRPA1 with four different domain combinations, the functional impact of these alternative domains remains to be thoroughly examined. Here, we find that there is a relatively strong linkage in mRNA splicing between the two sites in case of TrpA1(B), but not TrpA1(A), transcripts. Our semi-quantitative assay, consisting of reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing, revealed that exon10b is little coupled with TrpA1(B) transcripts, suggesting that only three isoforms, TRPA1(A)-exon10a [denoted as TRPA1(A)], TRPA1(A)-exon10b [TRPA1(A)10b] and TRPA1(B)-exon10a [TRPA1(B)], are present at detectable levels using our method. Interestingly, heterologously expressed TRPA1(A)10b showed elevated sensitivity to low concentrations of N-methyl maleimide (NMM), a cysteine-modifying electrophile, compared with other isoforms. Equivalent isoforms in malaria-transmitting Anopheles gambiae displayed a similar pattern of isoform-dependent NMM dose dependences, suggesting that the chemosensory regulation by selective domain assembly is conserved in insect TRPA1s. Thus, alternative RNA splicing of exon10 is coordinated in conjunction with the first exons, regulating chemical sensitivity of insect TRPA1s.

Feeding ecology of the urchin symbiont Dactylopleustes yoshimurai (Amphipoda) revealed by DNA metabarcoding

The nature of symbiotic relationships between organisms can be difficult to assess and may range from commensalism, to mutualism, and parasitism. Trophic linkage and feeding ecology are essential to disentangle symbiont-host relationships/interactions. Amphipods of the genus Dactylopleustes are known as urchin symbionts. Though their ecology remains largely unknown, Dactylopleustes was recently reported to aggregate on diseased hosts, suggesting that Dactylopleustes feeds on diseased urchins’ tissues and uses urchins as both a habitat and prey. We investigated by DNA metabarcoding analyses, the feeding ecology of Dactylopleustes yoshimurai in relation to growth and disease status of the host (Strongylocentrotus intermedius). Contrary to our hypothesis, sequence reads from the gut contents were dominated by planktonic copepods regardless of body size or host disease status. These results suggest that they mainly feed on copepod fecal pellets deposited on sediments, and do not have a strong trophic linkage with their host. Large individuals on diseased urchins feed more on urchins than those on healthy urchins. However, their main prey still remains copepods, implying that host disease has a limited effect on the feeding behavior. In conclusion, our study indicates that this species is mainly commensal, but also may parasitize its host depending on the situation.

The rs3918188 and rs1799983 loci of eNOS gene are associated with susceptibility in patients with systemic lupus erythematosus in Northeast China

To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P < 0.05; C vs A: OR = 1.558, P < 0.001), and this locus increased the risk of SLE in the dominant model and the recessive model (AC + CC vs AA: OR = 1.542, P < 0.05; CC vs AA + AC: OR = 1.707, P < 0.001), while the risk of SLE was reduced in the overdominant model (AC vs AA + CC: OR = 0.628, P < 0.001). The GT genotype and T allele at locus rs1799983 may be a protective factor for SLE (GT vs GG: OR = 0.328, P < 0.001; T vs G: OR = 0.438, P < 0.001) and this locus reduced the risk of SLE in the overdominant model (GT vs GG + TT: OR = 0.385, P < 0.001). There is a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene. Among them, the formed haplotype AG increased the risk of SLE compared to GG. AT and GT decreased the risk of SLE compared to GG. In this study, the eNOS gene rs3918188 and rs1799983 loci were found to be associated with susceptibility to SLE. This helps to deeply explore the mechanism of eNOS gene and genetic susceptibility to SLE. It provides a certain research basis for the subsequent exploration of the molecular mechanism of these loci and SLE, as well as the early diagnosis, treatment and prognosis of SLE.

Self-Standing Covalent Organic Polymer Membrane with High Stability and Enhanced Ion-Sieving Effect for Flow Battery.

Fabrication of ion-conducting membranes with continuous sub-nanometer channels holds fundamental importance for flow batteries in achieving safe integration of renewable energy into grids. Self-standing covalent organic polymer (COP) membranes provide feasibility due to their rapid and selective ion transport. However, the development of a scale-up possible, mechanically robust and chemically stable membranes remains a significant challenge. Herein, using irreversible strong secondary amine linkage, we propose a self-standing COP membrane with sub-nanometer pores ranging from 4.5 to 6.4 Å, by a simple and efficient in-situ polymerization approach. This membrane exhibits enhanced selectivity for proton and vanadium ions, especially excellent electrochemical stability, delivering an energy efficiency of over 80% at the current density of 200 mA cm-2 over 1000 cycles for an all-vanadium redox flow battery (VFB). This study provides novel insights for COP-based ion-sieving membranes in sustainable energy fields.

Event classification, seismicity, and eruption forecasting at Great Sitkin Volcano, Alaska: 1999–2023

The frequency content of volcanogenic seismicity is often used to classify events and their spatial and temporal progression is then used to map subsurface volcanic processes. The progression of volcano-seismic events and associated source processes also plays a critical role in eruption forecasting. Here we develop and evaluate a computerized methodology for characterizing volcano-seismic event types using Frequency Index and Average Peak Frequency. We apply and test this technique at Great Sitkin Volcano, Alaska, classifying over 9000 hypocenters between 1999 and 2023. This 24-year time span covers periods of seismic quiescence, earthquake activity on nearby tectonic (bookshelf) faults, precursory unrest from 2016 to 2021, and the explosive onset in May 2021 of the ongoing effusive eruption. We use the spatial and temporal evolution of classified event types to map the active volcanic and tectonic processes, develop a conceptual model of the subsurface magmatic system, and perform a retrospective analysis of eruption forecasts at Great Sitkin Volcano between 2016 and the present. The classification and progression of hypocenters suggests the subsurface Great Sitkin Volcano magmatic system consists of a mid- to lower- crustal source zone between 10 and 40 km depth and an upper crustal magma storage area between −1 and 10 km depth (hypocenter depth is referenced to sea level and negative depths reflect height above sea level). The earliest precursors occurred in July 2016 and consisted of deep long-period and volcano-tectonic earthquakes at mid-crustal depths suggesting the subsequent unrest and eruption were triggered by a deeper intrusion of magma. This mid-crustal seismic activity was immediately followed by the onset upper-crustal long-period events and volcano-tectonic earthquakes VTs suggesting a strong linkage between the shallow and deeper portions of the magmatic system. The upper crustal area was likely capped by the 1974 lava dome until the magmatic explosion on May 26, 2021.

The pan-tandem repeat map highlights multiallelic variants underlying gene expression and agronomic traits in rice

Tandem repeats (TRs) are genomic regions that tandemly change in repeat number, which are often multiallelic. Their characteristics and contributions to gene expression and quantitative traits in rice are largely unknown. Here, we survey rice TR variations based on 231 genome assemblies and the rice pan-genome graph. We identify 227,391 multiallelic TR loci, including 54,416 TR variations that are absent from the Nipponbare reference genome. Only 1/3 TR variations show strong linkage with nearby bi-allelic variants (SNPs, Indels and PAVs). Using 193 panicle and 202 leaf transcriptomic data, we reveal 485 and 511 TRs act as QTLs independently of other bi-allelic variations to nearby gene expression, respectively. Using plant height and grain width as examples, we identify and validate TRs contributions to rice agronomic trait variations. These findings would enhance our understanding of the functions of multiallelic variants and facilitate rice molecular breeding.

Polygenic polymorphism is associated with NKG2A repertoire and influences lymphocyte phenotype and function

AbstractCD94/NKG2A is a heterodimeric receptor commonly found on natural killer (NK) and T cells, and its interaction with its ligand HLA-E on adjacent cells leads to inhibitory signaling and cell suppression. We have identified several killer cell lectin–like receptor (KLR)C1 (NKG2A) single nucleotide polymorphisms (SNPs) that are associated with NKG2A expression on NK cells, CD8+ T cells, and Vγ9/Vδ2+ T cells. Additionally, due to strong linkage disequilibrium, polymorphisms in KLRC2 (NKG2C) and KLRK1 (NKG2D) are also associated with NKG2A surface density and frequency. NKG2A surface expression correlates with single-cell NK responsiveness, and NKG2A+ NK cell frequency is associated with total NK repertoire response and inhibitability, making the identification of SNPs responsible for expression and frequency important for predicting the innate immune response. Because HLA-E expression is dependent on HLA class I signal peptides, we analyzed the relationship between peptide abundance and HLA-E expression levels. Our findings revealed a strong association between peptide availability and HLA-E expression. We identified the HLA-C killer immunoglobulin–like receptor ligand epitope as a predictive marker for HLA-ABC expression, with the HLA-C1 epitope associated with high HLA-E expression and the HLA-C2 epitope associated with low HLA-E expression. The relationship between HLA-C epitopes and HLA-E expression was independent of HLA-E allotypes and HLA-B leader peptides. Although HLA-E expression showed no significant influence on NKG2A-mediated NK education, it did affect NK cell inhibition. In summary, these findings underscore the importance of NKG2A SNPs and HLA-C epitopes as predictive markers of NK cell phenotype and function and should be evaluated as prognostic markers for diseases that express high levels of HLA-E.

Influenza A virus within-host evolution and positive selection in a densely sampled household cohort over three seasons.

While influenza A virus (IAV) antigenic drift has been documented globally, in experimental animal infections, and in immunocompromised hosts, positive selection has generally not been detected in acute infections. This is likely due to challenges in distinguishing selected rare mutations from sequencing error, a reliance on cross-sectional sampling, and/or the lack of formal tests of selection for individual sites. Here, we sequenced IAV populations from 346 serial, daily nasal swabs from 143 individuals collected over three influenza seasons in a household cohort. Viruses were sequenced in duplicate, and intrahost single nucleotide variants (iSNV) were identified at a 0.5% frequency threshold. Within-host populations were subject to purifying selection with >75% mutations present at <2% frequency. Children (0-5 years) had marginally higher within-host evolutionary rates than adolescents (6-18 years) and adults (>18 years, 4.4×10-6 vs. 9.42×10-7 and 3.45×10-6, p <0.001). Forty-five iSNV had evidence of parallel evolution, but were not overrepresented in HA and NA. Several increased from minority to consensus level, with strong linkage among iSNV across segments. A Wright Fisher Approximate Bayesian Computational model identified positive selection at 23/256 loci (9%) in A(H3N2) specimens and 19/176 loci (11%) in A(H1N1)pdm09 specimens, and these were infrequently found in circulation. Overall, we found that within-host IAV populations were subject to purifying selection and genetic drift, with only subtle differences across seasons, subtypes, and age strata. Positive selection was rare and inconsistently detected.