Search Results (488)

Background/Objectives: Cardiovascular diseases are a global health issue with an increasing burden and are exacerbated by hypertension. High blood pressure is partly attributed to genetic variants that are generally not well understood or extensively studied in sub-Saharan African populations. Variants linked to blood pressure have been found through genome-wide association studies (GWASs), which were mostly conducted among European ancestry populations; however, limited research has been undertaken in Africa. The current study evaluated single-nucleotide polymorphisms (SNPs) of PCSK9, ABCA1, LPL, and PON1 in relation to blood pressure measurements of 1839 Ghanaian adults. Methods: Genotypes were extracted from data generated by the H3Africa SNP array. After adjusting for sex, age, smoking, and body mass index (BMI), inferential statistics were used to investigate the relationships between SNPs and blood pressure (BP) indices. Additionally, Bonferroni correction was used to adjust for multiple testing. Results: Diastolic blood pressure (DBP) and the minor allele T of the PCSK9 variant (rs17111557) were positively associated at p = 0.006 after covariate adjustments. Although this novel DBP-associated variant is located in the 3′ untranslated region (3′ UTR) of the PCSK9 gene, in silico functional prediction suggests it is an expression quantitative trait locus (eQTL) that may change the binding site of transcription factors, potentially altering the rate of transcription and impacting DBP in this Ghanaian population. Conclusions: Our findings highlight the role of genetics in hypertension risk and the potential of discovering new therapies targeting isolated diastolic blood pressure in this rural African population. Full article

Apolipoprotein E (APOE) allele 4 (APOE4), one of the robust genetic risk factors for AD, has also been associated with cognitive decline in terms of memory, executive function, language, and global cognitive function. APOE genotype-stratified analysis can help to identify additional genetic loci which might be masked due to a strong effect of APOE4. We conducted a genome-wide meta-analysis in APOE2 carriers, APOE4 carriers, and APOE 3/3 homozygote groups among 2969 non-Hispanic Whites aged ≥ 65 years using slopes of decline over time across five cognitive domains (attention, language, executive function, memory, and visuospatial function) and global cognitive function. We identified novel genome-wide significant associations for decline in global cognitive function in the intergenic region between RNU7-66P/RNA5SP208 at rs116379916 (p = 1.44 × 10⁻⁹) in the APOE 3/3 group and for decline in language in the intergenic region between LINC0221/DTWD2 at rs13187183 (p = 3.79 × 10⁻⁸) in APOE4 carriers. A previously reported locus for decline in attention near RASEF at rs6559700 (p = 9.95 × 10⁻⁹) was found to be confined to the APOE 3/3 group. We also found two sub-threshold significant associations in the APOE 2 group for decline in attention (IL1RL2/rs77127114; p = 8.64 × 10⁻⁸) and decline in language (YTHDC2/KCNN2, rs116191836; p = 5.66 × 10⁻⁸). Our study points to potential biological pathways pertaining to specific domains within each APOE genotype group, and the findings suggest that immune-related pathways, plasma levels of polysaturated fatty acids, and bitter taste receptors may play roles in cognitive decline. Our findings enhance the understanding of cognitive aging and provide a framework for future studies. Full article

The promotion of sustainability, especially with regard to social and urban sustainability (e.g., well-being and neighborhood revitalization), is mainly linked to human activities and behaviors. Notably, pro-environmental behaviors and actions that promote sustainability depend on the degree to which the individual attributes responsibility, namely, internal and external environmental locus of control (E-LOC). Moreover, from a collectivist perspective, the well-being of communities may also depend on their ability to take action to achieve sustainability goals. In keeping with this, we conducted two different studies to develop and validate (internally and externally) a new instrument that is able to assess internal and external E-LOC by also capturing a third dimension in respect of community E-LOC. In the first study, we performed exploratory factor analysis (EFA) by collecting data from 694 subjects (55.3% cis females; mean age = 30.1, sd = 12.6). In the second study, we conducted confirmatory factor analysis (CFA) on a sample of 1.852 subjects (57% cis females; mean age = 27.6, sd = 11.4), which demonstrated an adequate fit to the theorized model. The final form of the instrument comprises nine items subdivided into internal, external, and community NE-LOC factors. Moreover, the results pointed out significant correlations between the NE-LOC scale and engagement in pro-environmental behaviors and attitudes, pro-environmental self-identity, readiness to change for sustainability, and eco-anxiety. Therefore, the NE-LOC scale can be considered a suitable instrument for the assessment of internal and external NE-LOC, as well as to measure the attribution of collective environmental responsibility. Full article

For a highly beneficial mutation A at locus 1 spreading in a very large population, we have analyzed the scenario that at a closely linked locus 2 a second beneficial mutant B arises before A has fixed. Under the assumptions that the fitness of B is greater than that of A and that A- and B-carrying chromosomes can recombine at some rate $r$, recombinants AB may form and eventually fix. We present explicit formulas for the fixation time of AB under additive fitness of the mutants as a function of the frequency $X_2\left(0\right)$ of A at the time when B is introduced. Our analysis suggests that the effect of interference between the beneficial mutations is most pronounced for small values of $X_2\left(0\right)<0.1.$ Furthermore, we identify a threshold value for $r$, above which recombination speeds up fixation. Using published simulation data, we also describe the genomic footprint of competing beneficial mutations. At neutral sites between the two linked selected loci, an excess of intermediate-frequency variants may occur when interference is strong, i.e.,$X_2\left(0\right)$ small. Finally, we discuss under which circumstances this scenario may be encountered in real sequences from recombining genomic regions. Full article

In the baculovirus expression system, recombinant viruses generated via bacmids often exhibit reduced expression and genetic stability of target genes during serial passages. This instability is thought to arise from the proximity of non-essential exogenous genes to the target gene insertion site. This study investigated the impact of the target gene insertion locus on its expression and stability within the recombinant viral genome. In addition to the conventional polyhedrin (polh) locus, we evaluated four additional loci located distal to the non-essential exogenous genes. Among them, the ODV-e56 and ChiA/v-cath loci maintained target gene expression and genetic stability more effectively than the polh and p10 loci, even after ten consecutive undiluted viral passages. Notably, essential or functionally important viral genes were located near the ODV-e56 and ChiA/v-cath loci, whereas such genes were absent near the p10 locus. These findings suggest that enhanced stability and expression are associated with the proximity to essential viral genes. Therefore, the strategic selection of target gene insertion sites in close proximity to essential viral elements, rather than simply avoiding non-essential exogenous regions, represents a promising strategy to enhance recombinant protein production in baculovirus expression systems. Full article

Blue light (BL) plays a crucial role in regulating floral transition and can be precisely manipulated in controlled-environment agriculture (CEA). However, previous studies on BL-mediated flowering in CEA have produced conflicting results, likely due to species-specific responses and variations in experimental conditions (such as light spectrum and intensity) as summarized in our recent systematic review. This speculation still lacks a mechanistic explanation at the molecular level. By synthesizing recent advances in our understanding of the signaling mechanisms underlying floral transition, this review highlights how both internal signals (e.g., hormones, carbohydrates, and developmental stage) and external cues (e.g., light spectrum, temperature, nutrients, stress, and magnetic fields) are integrated into the flowering pathway mediated by BL. Key signal integration nodes have been identified, ranging from photoreceptors (e.g., cryptochromes) to downstream components such as transcription factors and central flowering regulator, FLOWERING LOCUS T (FT). This signal integration offers a potential mechanistic explanation for the previously inconsistent findings, which may arise from interspecies differences in photoreceptor composition and variation in the expression of downstream components influenced by hormonal crosstalk, environmental conditions, and developmental stage, depending on the specific context. This review provides novel molecular insights into how BL modulates floral transition through interactions with other signals. By systematically compiling and critically assessing recent research findings, we identify key research gaps and outline future directions, particularly the need for more studies in agriculturally important crops. Furthermore, this review proposes a conceptual framework for optimizing BL-based lighting strategies and exploring underexamined interaction factors in the regulation of flowering. Full article

Single-cell RNA sequencing (scRNA-seq) enables expression quantitative trait locus (eQTL) analysis at cellular resolution, offering new opportunities to uncover regulatory variants with cell-type-specific effects. However, existing tools are often limited in functionality, input compatibility, or scalability for sparse single-cell data. To address these challenges, we developed scQTLtools, a comprehensive R/Bioconductor package that facilitates end-to-end single-cell eQTL analysis, from preprocessing to visualization. The toolkit supports flexible input formats, including Seurat and SingleCellExperiment objects, handles both binary and three-class genotype encodings, and provides dedicated functions for gene expression normalization, SNP and gene filtering, eQTL mapping, and versatile result visualization. To accommodate diverse data characteristics, scQTLtools implements three statistical models—linear regression, Poisson regression, and zero-inflated negative binomial regression. We applied scQTLtools to scRNA-seq data from human acute myeloid leukemia and identified eQTLs with regulatory effects that varied across cell types. Visualization of SNP–gene pairs revealed both positive and negative associations between genotype and gene expression. These results demonstrate the ability of scQTLtools to uncover cell-type-specific regulatory variation that is often missed by bulk eQTL analyses. Currently, scQTLtools supports cis-eQTL mapping; future development will extend to include trans-eQTL detection. Overall, scQTLtools offers a robust, flexible, and user-friendly framework for dissecting genotype–expression relationships in heterogeneous cellular populations. Full article

The neurological basis of consciousness remains unknown despite innumerable theories proposed for over a century. The major obstacle is that empirical studies demonstrate that all sensory information is subdivided and parcellated as it is processed within the brain. A central region where such diverse information combines to form conscious expression has not been identified. A novel hypothesis was introduced over two decades ago that proposed astrocytes, with their ability to interconnect to form a global syncytium within the neocortex, are the locus of consciousness based on their ability to integrate synaptic signals. However, it was criticized because intercellular calcium waves, which are initiated by synaptic activity, are too slow to contribute to consciousness but ideal for memory formation. Although astrocytes are known to exhibit rapid electrical responses in active sensory pathways (e.g., vision), it was technically impossible to determine electrical activity within the astroglia syncytium because of the challenge of separating syncytial electrical responses from simultaneous neuronal electrical activity. Therefore, research on astroglia syncytial electrical activity lagged for over sixty years, until recently, when an ingenuous technique was developed to eliminate neuronal electrical interference. These technical advances have demonstrated that the astroglia syncytium, although massive and occupying the entire neocortex, is isoelectric with minimal impedance. Most importantly, the speed of electrical conductance within the syncytium is as rapid as that of neural networks. Therefore, the astroglia syncytium is theoretically capable of transmitting integrated local synaptic signaling globally throughout the entire neocortex to bind all functional areas of the brain in a timeframe required for consciousness. Full article

Background: Population differences in gut microbiota composition and related metabolites may influence their potential causal relationship with chronic kidney disease (CKD); however, this relationship remains poorly understood in the Chinese population. Materials and Methods: We conducted a two-sample Mendelian randomization (MR) study using summary statistics of 500 gut microbial features (9 phyla, 3 classes, 14 orders, 32 families, 95 genera, 248 species, and 99 gut metabolic modules (GMMs)) from the 4D-SZ (from Shenzhen, China) discovery cohort (n = 1539). CKD summary statistics were obtained from the China Kadoorie Biobank (CKB) (489 cases and 75,531 controls). Associations between gut microbiota and CKD were evaluated via inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO. To validate our findings, we replicated the analyses in two independent East Asian CKD GWAS datasets: the Biobank of Japan (BBJ) dataset (2117 cases and 174,345 controls) and the J-Kidney-Biobank (JKB) dataset (382 cases and 3471 controls). We further validated the results via a meta-GWAS of BUN and eGFR in Biobank Japan (BBJ) and the Taiwan Biobank (TWB). Additionally, we analyzed 304 serum proteins from the Guangzhou Nutrition and Health Study (GNHS) and conducted mediation MR analyses to explore potential mediators. Result: At the locus-wide significance threshold, we identified 18 gut microbiome features associated with CKD onset in the China Kadoorie Biobank (CKB). Genus Alistipes (OR 1.02, 95% CI 1.00–1.03, p = 0.03) was associated with incident CKD risk in the JKB cohort. Species Bifidobacterium catenulatum–Bifidobacterium pseudocatenulatum complex (OR 1.0074, 95% CI 1.0070–1.0142, p = 0.01) was associated with incident CKD risk in a meta-GWAS of BUN. Sensitivity analyses, including Cochran’s Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots, yielded consistent results. Mediation analysis revealed that 26.7% (95% CI: 0.006–0.6700, p = 0.04) of the effect of Alistipes on CKD risk was mediated through the serum protein FBLN1. Conclusions: Our study provides Mendelian randomization-based evidence supporting a potential causal relationship between gut microbiota and CKD, highlighting the potential mediating role of FBLN1 in the association between genus Alistipes and CKD. Further studies are needed to explore whether and how genus Alistipes and FBLN1 contribute to CKD development. Full article

Shiga-toxin-producing E. coli (STEC) is a leading causing of bacterial foodborne and zoonotic illnesses in the USA. Whole-genome sequencing (WGS) is a powerful tool used in public health and microbiology for the detection, surveillance, and outbreak investigation of STEC. In this study, we applied three WGS-based subtyping methods, high quality single-nucleotide polymorphism (hqSNP) analysis, whole genome multi-locus sequence typing using chromosome-associated loci [wgMLST (chrom)], and core genome multi-locus sequence typing (cgMLST), to isolate sequences from 11 STEC outbreaks. For each outbreak, we evaluated the concordance between subtyping methods using pairwise genomic differences (number of SNPs or alleles), linear regression models, and tanglegrams. Pairwise genomic differences were highly concordant between methods for all but one outbreak, which was associated with international travel. The slopes of the regressions for hqSNP vs. allele differences were 0.432 (cgMLST) and 0.966 wgMLST (chrom); the slope was 1.914 for cgMLST vs. wgMLST (chrom) differences. Tanglegrams comprised of outbreak and sporadic sequences showed moderate clustering concordance between methods, where Baker’s Gamma Indices (BGIs) ranged between 0.35 and 0.99 and Cophenetic Correlation Coefficients (CCCs) were ≥0.88 across all outbreaks. The K-means analysis using the Silhouette method showed the clear separation of outbreak groups with average silhouette widths ≥0.87 across all methods. This study validates the use of cgMLST for the national surveillance of STEC illness clusters using the PulseNet 2.0 system and demonstrates that hqSNP or wgMLST can be used for further resolution. Full article

Background/Objectives: The genus Vitis comprises approximately 70 species with high genetic diversity, among which Vitis vinifera is the most economically significant. Despite numerous studies on the genetic characterizations of V. vinifera, selecting optimal chloroplast DNA barcoding regions for intraspecific differentiation remains unresolved. Most studies have focused on nuclear markers (SSRs, SNPs) or widely used chloroplast loci (e.g., matk, rbcl), which have shown limited resolution at the subspecies level. In this study, the complete chloroplast genomes of 34 V. vinifera accessions from different varieties and hybrids (vinifera, sylvestris, caucasica, and labrusca) were analyzed to identify the key genomic regions for DNA barcoding. Methods: Using bioinformatics tools, we assessed the genome structure, nucleotide variability, microsatellites, codon usage bias, and phylogenetic relationships among the investigated varieties. Results: The chloroplast genomes displayed a quadripartite structure, with lengths ranging from 160,906 to 160,929 bp and a guanine–cytosine (GC) content of ~37.4%. Phylogenetic analysis revealed an unusual position for VV-5 vini and VVVL-3 lab, suggesting potential taxonomic misclassification or hybridization effects. A single locus showed low discrimination power, but the concatenation of five loci (ccsA-trnN-GUU, rpl16, rpl2-rps19, rpoC2, and trnM-CAU) exhibited significantly improved resolution (44.11% K2P), surpassing traditional markers. Conclusions: This study addresses the gap in the literature regarding the use of concatenated chloroplast loci for subspecies research; the results validate these markers across a broader range of Vitis accessions and integrate nuclear and mitochondrial data to achieve a more comprehensive understanding of the evolutionary history and genetic diversity of V. vinifera. Full article

Cryptosporidium spp. and Giardia intestinalis are important zoonotic protozoa that are closely related to diarrhea and cause considerable economic losses in the livestock breeding industry. Ganzi is one of the main production areas for yaks in China, but there have been few reports on the occurrence of Cryptosporidium spp. and G. intestinalis in yaks. This study used PCR-based sequencing techniques to survey the prevalence and species/genotypes of Cryptosporidium spp. and G. intestinalis in faecal samples from 223 yaks in Ganzi, Sichuan Province. The positive rate of Cryptosporidium spp. was 7.2% (16/223), with the highest positive rate of yaks found in Yajiang (37%, 10/27), which was significantly higher than that in Litang (3.1%, 4/130) and Seda (3%, 2/66). The positive rate of Cryptosporidium spp. in young animals aged <6 months (20.5%, 8/39) was significantly higher than that in older animals aged 12–23 months (0; 0/43) and >24 months (3.3%, 3/90). Three Cryptosporidium species were found by sequence analysis of 18S rRNA locus, namely C. andersoni, C. ryanae, and C. bovis. The total positive rate of G. intestinalis was 15.7% (35/223), with significant differences identified between Yajiang (40.7%, 11/27), Litang (17.7%, 23/130), and Seda (1.5%, 1/66). One genotype (assemblage E) was found by analyzing the sequence of gdh, bg, and tpi loci. Meanwhile, co-infection of Cryptosporidium spp. and Giardia intestinalis was identified in five samples. The present study explores the infection of Cryptosporidium spp. and G. intestinalis from yaks in Ganzi, aiming to enrich our understanding of the occurrence of these protozoa in livestock. Full article

Background: Hippocampal sclerosis (HS) is a hallmark of mesial temporal lobe epilepsy (MTLE). However, genetic studies on MTLE patients with HS (MTLE-HS) remain limited, especially in East Asian populations. This study aimed to identify genetic variants associated with MTLE-HS and elucidate their biological relevance through integrative genomic and transcriptomic analyses. Methods: We conducted a genome-wide association study (GWAS) on 157 Korean epilepsy patients, including 52 MTLE-HS subjects and 105 non-acquired focal epilepsy individuals without HS as controls. The splicing and expression quantitative trait locus (sQTL and eQTL, respectively) effects of significant variants were analyzed using GTEx datasets. Transcriptomic data from the hippocampi of MTLE-HS subjects and an epilepsy mouse model were examined to assess TMEM14A expression. Gene correlation enrichment analysis was performed to investigate potential associations with epilepsy-related phenotypes. Results: The GWAS identified rs6924849, located downstream of TMEM14A, as significantly associated with MTLE-HS. The sQTL analysis revealed that rs6924849 induces abnormal TMEM14A splicing in hippocampal tissue. Transcriptomic analyses showed reduced TMEM14A expression in MTLE-HS hippocampi, while mice with pilocarpine-induced epilepsy exhibited a transient increase in TMEM14A expression during the acute phase post-status epilepticus. Gene correlation enrichment analyses linked TMEM14A to seizure-related phenotypes in both humans and mice. Conclusions: This study identifies rs6924849 as a novel genetic variant associated with MTLE-HS in an East Asian population. The dysfunctional splicing and altered expression of TMEM14A may contribute to the neuronal loss characteristic of HS, as TMEM14A regulates apoptosis. These findings emphasize the potential role of TMEM14A in MTLE-HS pathogenesis from genomic and transcriptomic perspectives. Full article

Illusory health beliefs (IHBs) represent invalid ideations about health and potentially impact health behaviours and practices in meaningful ways. Examples include the uptake of methods with less conclusive evidence/support (e.g., complementary and alternative medicine, CAM) versus empirically validated approaches (e.g., recommended by health professionals). However, measurement obfuscation of IHB has hindered construct operationalisation. This study examined a newly developed measure (the Illusory Health Beliefs Scale) in the context of health outcomes. Specifically, we explored adherence to recommended health behaviours (e.g., lifestyle, vaccines) and trust in healthcare professionals versus CAM use. Assessments included theoretically linked constructs, comprising health locus of control, belief in science, and belief in CAM. Using a sample of 1507 (734 males, 768 females, 7 non-binary), a statistical model tested relationships across time points. Path analysis revealed that IHBs aligned with openness to unorthodox treatments alongside lower confidence in conventional treatment methods. Crucially, locus of control and belief in science mediated/weakened this relationship, predicting greater adherence to health recommendations and trust in health professionals. Belief in CAM strengthened the relationship between IHBs and CAM use. The findings provide initial evidence regarding the contribution of IHBs to health outcomes, and a basis for future research to further explore the IHB-health relationship. Full article

Overweight and obese individuals show lower mortality rates or better prognoses than those of normal weight in a variety of diseases, a phenomenon called the “obesity paradox”. An inverse association of adiposity with atherosclerosis has been observed in both humans and mice. To dissect phenotypic and genetic connections between the traits, 154 female and 145 male F2 mice were generated from an intercross between BALB/cJ and LP/J apolipoprotein E-deficient mice and fed a Western diet for 12 weeks. Atherosclerotic lesion size in the aortic root, body weight, plasma lipids, and glucose were measured, and genotyping was performed on miniMUGA SNP arrays. Quantitative trait locus (QTL) analyses on all F2 mice with sex as a covariate revealed four significant QTLs on chromosomes (Chr) 3, 6, 13, and 15 for atherosclerosis and three significant QTLs on Chr2, 7, and 15 for body weight. Chr15 QTL for atherosclerosis overlapped with one for body weight near 36 Mb. After adjusting for variation in body weight, Chr15 atherosclerosis QTL was downgraded from significant to suggestive linkage. Body weight was inversely correlated with atherosclerotic lesion sizes and accounted for more variance than a single other risk factor for atherosclerosis among F2 mice. Analysis of public data collected from two backcross cohorts revealed strong correlations between body weight and fat mass in adult mice (r ≥ 0.93; p ≤ 1.6 × 10⁻¹³⁶). Thus, the obesity paradox in atherosclerosis is partially attributable to shared genetic components that have an opposite effect on adiposity and atherosclerosis. Full article