Evidence For Linkage Research Articles

Assessing dynamic co-movement of news based uncertainty indices and distance-to -default of global FinTech firms

Contemporary literature does not offer evidence on the causal relationship of default risk and investor sentiments for FinTech sector. We bridge this gap by assessing the dynamic co-movement between Distance-to-Default of leading global FinTech firms and three uncertainty indices namely Twitter Market Uncertainty Index-ENG, Twitter Economic Uncertainty Index-ENG, and US daily news-based Economic Policy. The sample period is from 07 April 2016–30 June 2021. The estimations are performed using Wavelet based analytical framework. The results reveal high dynamic co-movement of Twitter based uncertainty indices with Distance-to-Default of FinTech firms. However, there is very little co-movement between economic policy uncertainty and FinTech firms’ stability. The novelty of this work lies in the utilization of National University of Singapore’s Distance-to-Default measure, which is available in daily frequency and capable of performing dynamic data analysis. Our results offer maiden evidence of linkage of default risk and news based uncertainty indices.

Novel Loci (EIF4A2, ADIPOQ, TPRG1) for Triglyceride / High-density Lipoprotein Cholesterol Ratio Longitudinal Change (ΔTHR) among Subjects without Type 2 Diabetes: Evidence from the Long Life Family Study (LLFS) and the Framingham Heart Study (FHS) Offspring Cohort (OS).

Triglyceride (TG) /High density lipoprotein cholesterol (HDL-C) ratio (THR) represents a single surrogate predictor of hyperinsulinemia or insulin resistance that is associated with premature aging processes, risk of diabetes and increased mortality. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among subjects of European ancestry who had complete data from two exams collected about seven years apart from the Long Life Family Study (LLFS, n=1384), a study with familial clustering of exceptional longevity in the US and Denmark. Subjects with diabetes or using medications for dyslipidemia were excluded from this analysis. ΔTHR was derived using growth curve modeling, and adjusted for age, sex, field centers, and principal components (PCs). GWAS was conducted using a linear mixed model accounted for familial relatedness. Our linkage scan was built on haplotype-based IBD estimation with 0.5 cM average spacing. Heritability of ΔTHR was moderate (46%). Our GWAS identified a significant locus at the LPL (p=1.58e-9) for ΔTHR; this gene locus has been reported before influencing baseline THR levels. Our GWLS found evidence for a significant linkage with a logarithm of the odds (LODs) exceeding 3 on 3q28 (LODs=4.1). Using a subset of 25 linkage enriched families (pedigree-specific LODs>0.1), we assessed sequence elements under 3q28 and identified two novel variants (EIF4A2/ADIPOQ-rs114108468, p=5e-6, MAF=1.8%; TPRG1-rs16864075, p=3e-6, MAF=8%; accounted for ~28% and ~29% of the linkage, respectively, and 57% jointly). While the former variant was associated with EIF4A2 (p=7e-5) / ADIPOQ (p=3.49e-2) RNA transcriptional levels, the latter variant was not associated with TPRG1 (p=0.23) RNA transcriptional levels. Replication in FHS OS observed modest effect of these loci on ΔTHR. Of 188 metabolites from 13 compound classes assayed in LLFS, we observed multiple metabolites (e.g., DG.38.5, PE.36.4, TG.58.3) that were significantly associated with the variants (p<3e-4). our linkage-guided sequence analysis approach permitted our discovery of two novel gene variants EIF4A2/ADIPOQ-rs114108468 and TPRG1-rs16864075 on 3q28 for ΔTHR among subjects without diabetes selected for exceptional survival and healthy aging.

Low-level viremia episodes appear to affect the provirus composition of the circulating cellular HIV reservoir during antiretroviral therapy.

Low-level viremia (LLV) ranging from 50 to 1,000 copies/ml is common in most HIV-1-infected patients receiving antiretroviral therapy (ART). However, the source of LLV and the impact of LLV on the HIV-1 reservoir during ART remain uncertain. We hypothesized that LLV may arise from the HIV reservoir and its occurrence affect the composition of the reservoir after LLV episodes. Accordingly, we investigated the genetic linkage of sequences obtained from plasma at LLV and pre-ART time points and from peripheral blood mononuclear cells (PBMCs) at pre-ART, pre-LLV, LLV, and post-LLV time points. We found that LLV sequences were populated with a predominant viral quasispecies that accounted for 67.29%∼100% of all sequences. Two episodes of LLV in subject 1, spaced 6 months apart, appeared to have originated from the stochastic reactivation of latently HIV-1-infected cells. Moreover, 3.77% of pre-ART plasma sequences were identical to 67.29% of LLV-3 plasma sequences in subject 1, suggesting that LLV may have arisen from a subset of cells that were infected before ART was initiated. No direct evidence of sequence linkage was found between LLV viruses and circulating cellular reservoirs in all subjects. The reservoir size, diversity, and divergence of the PBMC DNA did not differ significantly between the pre- and post-LLV sampling points (P > 0.05), but the composition of viral reservoir quasispecies shifted markedly before and after LLV episodes. Indeed, subjects with LLV had a higher total PBMC DNA level, greater viral diversity, a lower proportion of variants with identical sequences detected at two or more time points, and a shorter variant duration during ART compared with subjects without LLV. Overall, our findings suggested that LLV viruses may stem from an unidentified source other than circulating cellular reservoirs. LLV episodes may introduce great complexity into the HIV reservoir, which brings challenges to the development of treatment strategies.

Re-examining the quality management and firm performance relationships: meta-analytical investigation on moderating effects of national culture differences

PurposeIn the last 3 decades, organization-wide programs and practices based on the Total Quality Management (TQM) philosophy have become central to continuous improvement (CI) strategy in both public and private enterprises. However, there is paradoxical evidence of TQM-firm performance linkage in non-Japanese contexts. This study presents a meta-analysis of empirical research on TQM-firm performance linkage and investigates the moderating influence of national cultural (NC) values on this relationship.Design/methodology/approachMeta-analytical procedures are adopted to analyse 364 effects accumulated from 135 independent samples across 31 nations, for 30,015 firm observations. Additionally, weighted least square (WLS) meta-regression is used to test the moderation effects of four NC dimensions based on the Global Leadership and Organizational Behavior Effectiveness (GLOBE) model.FindingsThe meta-analysis results reveal that the strengths of the association varied across five soft and hard TQM dimensions and three firm performance dimensions Meta-regression indicate that the effectiveness of the TQM program is high in cultures which reward collectivist behaviours, equity of power distribution and avoidance of ambiguity in rules/structures.Originality/valueThe study contributes to international operational management theory on cultural influences on the effectiveness of operations strategies and decisions.

Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia.

Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs. We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG). In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16). The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence.

Joint Linkage and Association Analysis Using GENEHUNTER-MODSCORE with an Application to Familial Pancreatic Cancer

Introduction: Joint linkage and association (JLA) analysis combines two disease gene mapping strategies: linkage information contained in families and association information contained in populations. Such a JLA analysis can increase mapping power, especially when the evidence for both linkage and association is low to moderate. Similarly, an association analysis based on haplotypes instead of single markers can increase mapping power when the association pattern is complex. Methods: In this paper, we present an extension to the GENEHUNTER-MODSCORE software package that enables a JLA analysis based on haplotypes and uses information from arbitrary pedigree types and unrelated individuals. Our new JLA method is an extension of the MOD score approach for linkage analysis, which allows the estimation of trait-model and linkage disequilibrium (LD) parameters, i.e., penetrance, disease-allele frequency, and haplotype frequencies. LD is modeled between alleles at a single diallelic disease locus and up to three diallelic test markers. Linkage information is contributed by additional multi-allelic flanking markers. We investigated the statistical properties of our JLA implementation using extensive simulations, and we compared our approach to another commonly used single-marker JLA test. To demonstrate the applicability of our new method in practice, we analyzed pedigree data from the German National Case Collection for Familial Pancreatic Cancer (FaPaCa). Results: Based on the simulated data, we demonstrated the validity of our JLA-MOD score analysis implementation and identified scenarios in which haplotype-based tests outperformed the single-marker test. The estimated trait-model and LD parameters were in good accordance with the simulated values. Our method outperformed another commonly used JLA single-marker test when the LD pattern was complex. The exploratory analysis of the FaPaCa families led to the identification of a promising genetic region on chromosome 22q13.33, which can serve as a starting point for future mutation analysis and molecular research in pancreatic cancer. Conclusion: Our newly proposed JLA-MOD score method proves to be a valuable gene mapping and characterization tool, especially when either linkage or association information alone provide insufficient power to identify the disease-causing genetic variants.

Metabolic syndrome and depression: evidence from a cross-sectional study of real-world data in Japan.

Both metabolic syndrome (MetS) and depression are high priority health problems, especially for working age. Numerous studies have explored the link between metabolic syndrome and depression; however, not all of them have consistently demonstrated an association. The objective of this study was to determine whether there is an association between MetS and depression by analyzing extensive real-world data (RWD). Our data was drawn from insurance claims and health checkups of local government officials across all prefectures in Japan except for Tokyo in the 2019 fiscal year. According to the number of months with diagnosis of depression and prescription of antidepressants, the study participants were classified into the following categories: Certainly not Depression (CN), Possibly not Depression (PN), Possible Depression (PD), and Certain Depression (CD). Associations between MetS and its components-visceral obesity, hypertension, hyperlipidemia, and diabetes- and these categories of depression were analyzed by logistic regression. The depression categories of the 130,059 participants were as follows: CN 85.2%; PN 6.9%; PD 3.9%; and CD 4.1%. For men, the adjusted odds ratio (AOR) for MetS were PN 0.94 (95% CI: 0.86-1.02), PD 1.31 (1.19-1.43), and CD 1.63 (1.50-1.76), with reference to CN. For women, AOR of MetS were PN 1.10 (0.91-1.32), PD 1.54 (1.24-1.91), and CD 2.24 (1.81-2.78). Among the MetS components, visceral obesity, hyperlipidemia, and diabetes were significantly associated with depression categories. In this study, we found a significant association between MetS and depression, this association being similar to that previously reported. Our findings provide robust evidence for linkage between MetS and depression, suggesting that analysis of RWD is useful for providing concrete evidence.

LINKAGE ANALYSIS OF PERCEIVED PHYSICAL FATIGABILITY IN THE LONG LIFE FAMILY STUDY

Abstract Fatigability, whole-body fatigue anchored to specific tasks, is a highly prevalent characteristic in older adults, but the biological mechanisms underlying perceived physical fatigability are unclear. Genetic studies may identify potential biological pathways contributing to physical fatigability. The family study design of the LLFS provides a unique opportunity to explore variants associated with fatigability using whole-genome linkage analysis. Whole genome sequencing (WGS) was available for N=2462, 496 families (age 73.6±10.5 years, 54.8% women, 99% white. Perceived physical fatigability was measured with the Pittsburgh Fatigability Scale (PFS, 0-50, lower=less severe). Prevalence of lower PFS scores (&amp;lt;15) was 57.9%. Multipoint linkage analysis employing likelihood-based variance components analyses were performed to identify families and genetic loci showing strong evidence for linkage. Based on linkage analysis results, a series of association analyses were performed in the subsets of linked families for PFS Physical scores. Association analyses were conducted using linear mixed models adjusted for age, field center, principal components and familial relatedness. For all families the LOD was 2.13 at chr17:79,549,108. The HLOD of the top 27 families (n=225) was 8.97. There were 8 single nucleotide polymorphisms (SNPs) identified under the linkage peak on chromosome 17. These variants were mapped to 8 different genes involved in regulation of transcription and metabolism, cellular proliferation, signal transduction, protein trafficking, and membrane structure; all important in maintenance of cellular health. Results suggest fatigability in older adults may have multiple molecular etiologies and identified variants may allude to molecular mechanisms to target in future interventions to promote healthy aging.

Enabling Population Biology Studies of Stemphylium vesicarium from Onion with Microsatellites.

Stemphylium leaf blight (SLB), caused by the fungus Stemphylium vesicarium, is dominant within the foliar disease complex affecting onion production in New York (NY). The disease causes premature defoliation and significant reductions in bulb weight and quality. Foliar diseases of onion are usually managed by an intensive fungicide program, but SLB management is complicated by resistance to multiple single-site modes of action. The design of integrated disease management strategies is limited by incomplete knowledge surrounding the dominant sources of S. vesicarium inoculum. To facilitate genomic-based studies of S. vesicarium populations, nine microsatellite markers were developed. The markers were multiplexed into two PCR assays containing four and five fluorescently labeled microsatellite markers. Initial testing of the S. vesicarium isolates found the markers were highly polymorphic and reproducible with an average of 8.2 alleles per locus. The markers were used to characterize 54 S. vesicarium isolates from major NY onion production regions in 2016 (n = 27) and 2018 (n = 27). Fifty-two multilocus genotypes (MLGs) were identified between these populations. Genotypic and allelic diversities were high in both the 2016 and 2018 populations. A greater degree of genetic variation was observed within populations than between years. No distinct pattern of MLGs according to population was identified and some MLGs were closely related between 2016 and 2018. The lack of evidence for linkage among loci also was strongly suggestive of clonal populations with only minor differences between the two populations. These microsatellite markers will be a foundational resource for the testing of hypotheses surrounding the population biology of S. vesicarium and therefore informing disease management.

Association of Common Mental Disorders with Diabetes Mellitus - Evidence from Community-based Matched Case-Control Study in North India.

Diabetes mellitus (DM) and depression are major public health problems globally. Evidence of linkage of common mental disorders (CMDs) including depression and anxiety disorders with DM is sparsely reported from community-based settings. The present study aimed to study the association between CMDs and DM among adult population (>30 years) residing in a rural area of North India. A community-based case-control study was conducted in 28 villages of Ballabgarh block of Faridabad district of Haryana. Cases (diabetes) were recruited from the community with at least 1 year of diabetes. Age- and sex-matched two neighborhood controls were selected from the same community. Diabetic status was confirmed using glycated hemoglobin. CMDs such as depression and anxiety disorders were screened using PRIME-MD Hindi version. Conditional logistic regression was used to study the relationship between diabetes and CMDs. Total 211 cases (diabetic) and 273 controls (nondiabetic) were approached for the study, of which 173 cases and 175 controls were analyzed. Cases and controls were comparable with respect to age, sex, and socioeconomic status. CMDs were found more among cases as compared to controls (67.5% vs. 37.5%) (P < 0.001). On conditional logistic regression analysis, CMDs were significantly higher among diabetes cases (adjusted odds ratio - 3.2, 95% confidence interval: 1.9-5.2). Strong evidence of coexistence of CMDs and DM from this population-based study necessitates the need of incorporation of management of CMDs into diabetes control program in India.

Urbanization is associated with non-coding polymorphisms in candidate behavioural genes in the Eurasian coot.

Extensive transformation of natural land cover into urbanized areas enhances accumulation of phenotypic differences between animals from urban and nonurban populations, but there is little information on whether these changes, especially in terms of animal behaviour and circadian rhythm, have a genetic basis. The aim of this study was to investigate genetic background of behavioural differences between four pairs of urban and nonurban populations of a common waterbird, the Eurasian coot Fulica atra. For this purpose, we quantified polymorphisms in personality-related candidate genes, previously reported to be associated with avian circadian rhythms and behavioural traits that may be crucial for urban life. We found general associations between landscape urbanization level and polymorphisms in 3'UTR region of CREB1 gene encoding transcriptional factor, which participates in development of cognitive functions and regulation of circadian rhythm. We also found significant differentiation between urban and nonurban populations in the intronic region of CKIɛ gene responsible for regulation of circadian clock. Although we lacked evidence for linkage of this intronic variation with coding polymorphisms, genetic differentiation between urban populations was significantly stronger at CKIɛ intron compared with neutral microsatellite markers, suggesting possible local adaptations of CKIɛ expression regulation to specific urban sites. Our results indicate that behavioural differentiation between urban and nonurban coot populations may be the effect of habitat-specific selective pressure resulting in genetic adaptations to urban environment and supporting the microevolutionary scenario. These adaptations, however, prevailed in non-coding regulatory rather than coding gene regions and showed either general or local patterns, revealing high complexity of associations between behaviour and landscape urbanization in birds.

Towards an integrative hope-dysfunctional beliefs perspective to personal recovery in schizophrenia: a path analysis

BackgroundEvidence shows that negative symptoms of schizophrenia and underlying dysfunctional cognition are related to persistently low functioning and quality of life. However, despite the abundance of existing recovery programs for people with schizophrenia, few have examined whether and how the widely-adopted hope-motivation recovery pathway and the deficit-oriented cognitive pathway might converge to influence functioning and quality of life.MethodsA cross-sectional, quantative survey recruited a convenient sample of adult outpatients with DSM-5 schizophrenia spectrum disorders and low social functioning (n = 124). Self-reported measurements included personal recovery (30-item Mental Health Recovery Measure), social functioning (8-item Social Functioning Questionnaire), hope (12-item Hope Scale), quality of life (28-item World Health Organization Quality of Life Scale-Abbreviated Version-Hong Kong), defeatist beliefs (15-item extracted from Dysfunctional Attitude Scale), and asocial beliefs (15-item extracted from Revised Social Anhedonia Scale). Correlation analysis and structural equation modelling was applied to investigate how the two pathways intertwined to predict social functioning and quality of life.ResultsAsocial beliefs and hope separately mediated two partial mediation pathways from defeatist beliefs to recovery outcomes (social functioning and personal recovery). Meanwhile, defeatist beliefs, social functioning, and personal recovery further predicted quality of life.ConclusionsThis is one of the very few studies that provides empirical evidence of a deficit-strength linkage in the recovery from schizophrenia. Remediation of dysfunctional beliefs and the injection of hope and successful experiences should be undertaken concurrently in recovery as they are associated with differential effects on enhancing social functioning and personal recovery, which then converge and contribute to a better quality of life.

Individual differences in second-order false-belief understanding and executive abilities: A meta-analytic review of evidence from school-age children and adults

Theory of Mind (ToM) and Executive Functioning (EF) are two pillars of human social cognition often studied in conjunction, but rarely considered together beyond childhood. Adults routinely undertake ToM activities of higher levels, such as those that require reasoning recursively through other individuals’ presumed reasoning about others (e.g., she believes that he believes that this is difficult to grasp). Yet, the possibility of links between EF and these special kinds of representations, termed second-order ToM, has been much less studied empirically. The objective of the current pre-registered report is to provide a meta-analytic review of the extant literature linking second-order ToM and EF in school-age children and adults. Studies reporting on the relation between EF and second-order ToM were located through systematic search of published and non-published research databases. A final set of 32 studies were meta-analyzed, providing 83 effect sizes and a pooled N of over 2584 child and adult participants. The developmental literature provided evidence of moderate second-order ToM-EF linkage in children (r = .25), which resisted statistical adjustment for age, and did not differ on the basis of children’s cultural background. In contrast, the adult findings were weaker (r = .09), and only accounted for a very small percentage of the meta-analyzed literature. Important methodological gaps were identified, highlighting the need for more research on the links between second-order ToM and EF.

Trustworthy brand signals, price fairness and organic food restaurant brand loyalty

PurposeThis research aims to examine the influence of brand signals (transparency, innovativeness and reputation) on brand trust and price fairness toward organic food restaurant brand.Design/methodology/approachThe empirical data were gathered with the survey instrument from respondents who had previously visited organic food restaurant. The formulated hypotheses were analyzed with structural equation modeling.FindingsThe collected data demonstrated the positive effect of brand signals on brand trust and price fairness. Trust in organic food restaurant brand was found to positively impact both price fairness and brand loyalty. Additionally, the results provided evidence of the positive linkage between price fairness and brand loyalty. Among brand signals, brand transparency exerted the greatest impact on brand trust and price fairness. The findings also indicated the significant indirect linkage of brand signals on restaurant brand loyalty through brand trust and price fairness.Originality/valueThrough the lens of signaling theory and equity theory, this study provides novel insights into how brand signals contribute to brand trust, price fairness and organic food restaurant brand loyalty. The managerial implications for implementing brand strategies for organic food restaurants were discussed.

Genetic evidence for the causal linkage between telomere length and aortic aneurysm risk: A Mendelian randomisation study.

Evidence of a clear causal relationship between telomere length and aortic aneurysms is limited by the potential for confounding or reverse causation effects. In this study, we used a Mendelian randomisation (MR) approach to investigate this putative causal association. In total, 118 telomere length-associated single-nucleotide polymorphisms, identified in 472,174 individuals of European ancestry, were used as the instrumental variables. Summary statistics for genome-wide association studies of aortic aneurysms were obtained from the FinnGen consortium. For the primary MR analyses, the inverse-variance weighted random-effects method was used and was supplemented with multivariable MR, weighted median and MR-Egger approaches. The MR-Egger intercept test, Cochran's Q test and 'leave-one-out' sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneity and stability of the genetic variants. Forward and reverse MR analyses were performed. All forward univariable MR analyses showed that longer telomere lengths decreased aortic aneurysm risks (total aortic aneurysms: OR = 0.80, 95% CI 0.67-0.96, p = .015; thoracic aortic aneurysms: OR = 0.82, 95% CI 0.68-0.98, p = .026; abdominal aortic aneurysms: OR = 0.525, 95% CI 0.398-0.69, p < .001), whereas all reverse MR analyses suggested the absence of aortic aneurysm liability on telomere length. The sensitivity analysis results were robust, and no evidence of horizontal pleiotropy was observed. Our results support a possible causal association between telomere length and aortic aneurysms, providing new insights into the involvement of telomere biology in this condition and offering a potential avenue for targeted therapeutic interventions.

Soil microbiomes of hardwood‐ versus pine‐dominated stands: Linkage with overstory species

AbstractBiodiversity in forest ecosystems is paradoxical. Whereas their most apparent component—the woody overstory—is the least diverse with respect to numbers of species, the least apparent component is the biotic community of highest diversity—the soil microbiome. Numerous factors influence the composition and diversity of soil microbial communities, which in turn exert a profound impact on plant species occupying the soil and the biogeochemistry of essential plant nutrients. Of interest in forest ecosystems is how the soil microbiome interacts with the overstory, a phenomenon referred to as linkage. This study compared the soil microbiome of two adjacent stand types—hardwood‐ and longleaf pine (Pinus palustris)‐dominated—and addressed the following questions: (1) How does soil microbiome vary with stand type? (2) Do the forest overstory community and soil microbiome exhibit linkage? Twelve 0.04‐ha circular plots were established in each stand type to assess tree community composition and structure and to sample mineral soil for three separate analyses: assessment of soil fertility, measurement of total carbon and nitrogen (N), and extraction of genomic DNA for assessment of microbiome communities. All live stems ≥2.5 cm dbh in each plot were identified to species and measured for dbh to the nearest 0.1 cm. Mineral soil was taken from a depth of 5 cm and oven‐dried at 38°C prior to analyses. Hardwood stands were dominated by flowering magnolia (Magnolia grandiflora) and southern evergreen oaks, whereas pine stands were dominated by longleaf pine and live oak (Quercus virginiana). Although soils of both stand types were highly acidic, the hardwood stands were generally higher in fertility, especially for total and available N. The overstory and soil microbial communities exhibited evidence of linkage among all sample plots combined. When assessed separately by stand type, only hardwood‐dominated stands displayed evidence of overstory/microbial linkage. These results have broader implications for future scenarios given the sensitivity of soil microbes to climate change.

A rare FGF5 candidate variant (rs112475347) for predisposition to nonsquamous, nonsmall-cell lung cancer.

A unique approach with rare resources was used to identify candidate variants predisposing to familial nonsquamous nonsmall-cell lung cancers (NSNSCLC). We analyzed sequence data from NSNSCLC-affected cousin pairs belonging to high-risk lung cancer pedigrees identified in a genealogy of Utah linked to statewide cancer records to identify rare, shared candidate predisposition variants. Variants were tested for association with lung cancer risk in UK Biobank. Evidence for linkage with lung cancer was also reviewed in families from the Genetic Epidemiology of Lung Cancer Consortium. Protein prediction modeling compared the mutation with reference. We sequenced NSNSCLC-affected cousin pairs from eight high-risk lung cancer pedigrees and identified 66 rare candidate variants shared in the cousin pairs. One variant in the FGF5 gene also showed significant association with lung cancer in UKBiobank. This variant was observed in 3/163 additional sampled Utah lung cancer cases, 2 of whom were related in another independent pedigree. Modeling of the predicted protein predicted a second binding site for SO4 that may indicate binding differences. This unique study identified multiple candidate predisposition variants for NSNSCLC, including a rare variant in FGF5 that was significantly associated with lung cancer risk and that segregated with lung cancer in the two pedigrees in which it was observed. FGF5 is an oncogenic factor in several human cancers, and the mutation found here (W81C) changes the binding ability of heparan sulfate to FGF5, which might lead to its deregulation. These results support FGF5 as a potential NSNSCLC predisposition gene and present additional candidate predisposition variants.

Microgroove Cues Guiding Fibrogenesis of Stem Cells via Intracellular Force

Groove patterns are widely used in material surface modifications. However, the independent role of ditches/ridges in regulating fibrosis of soft tissues is not well-understood, especially the lack of linkage evidence in vitro and in vivo. Herein, two kinds of combinational microgroove chips with the gradient ditch/ridge width were fabricated by photolithography technology, termed R and G groups, respectively. In group R, the ridge width was 1, 5, 10, and 30 μm, with a ditch width of 30 μm; in group G, the groove width was 5, 10, 20, and 30 μm, and the ridge width was 5 μm. The effect of microgrooves on the morphology, proliferation, and expression of fibrous markers of stem cells was systematically investigated in vitro. Moreover, thicknesses of fibrous capsules were evaluated after chips were implanted into the muscular pouches of rats for 5 months. The results show that microgrooves have almost no effect on cell proliferation but significantly modulate the morphology of cells and focal adhesions (FAs) in vitro, as well as fibrosis differentiation. In particular, the differentiation of stem cells is attenuated after the intracellular force caused by stress fibers and FAs is interfered by drugs, such as rotenone and blebbistatin. Histological analysis shows that patterns of high intracellular force can apparently stimulate soft tissue fibrosis in vivo. This study not only reveals the specific rules and mechanisms of ditch/ridge regulating stem cell behaviors but also offers insight into tailoring implant surface patterns to induce controlled soft tissue fibrosis.

Dialogue between VE-Cadherin and Sphingosine 1 Phosphate Receptor1 (S1PR1) for Protecting Endothelial Functions.

The endothelial cells (EC) of established blood vessels in adults remain extraordinarily quiescent in the sense that they are not actively proliferating, but they fulfill the necessary role to control the permeability of their monolayer that lines the interior of blood vessels. The cell-cell junctions between ECs in the endothelium comprise tight junctions and adherens homotypic junctions, which are ubiquitous along the vascular tree. Adherens junctions are adhesive intercellular contacts that are crucial for the organization of the EC monolayer and its maintenance and regulation of normal microvascular function. The molecular components and underlying signaling pathways that control the association of adherens junctions have been described in the last few years. In contrast, the role that dysfunction of these adherens junctions has in contributing to human vascular disease remains an important open issue. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid mediator found at high concentrations in blood which has important roles in the control of the vascular permeability, cell recruitment, and clotting that follow inflammatory processes. This role of S1P is achieved through a signaling pathway mediated through a family of G protein-coupled receptors designated as S1PR1. This review highlights novel evidence for a direct linkage between S1PR1 signaling and the mediation of EC cohesive properties that are controlled by VE-cadherin.

Genomic-based microsatellite development for Ternstroemia (Pentaphylacaceae) and transferability to other Ericales

BackgroundThe genus Ternstroemia is associated with the vulnerable tropical montane cloud forest in Mexico and with other relevant vegetation types worldwide. It contains threatened and pharmacologically important species and has taxonomic issues regarding its species limits. This study describes 38 microsatellite markers generated using a genomic-based approach.Methods and resultsWe tested 23 of these markers in a natural population of Ternstroemia lineata. These markers are highly polymorphic (all loci polymorphic with 3–14 alleles per locus and expected heterozygosity between 0.202 and 0.908), most of them (19 out of 23) are in Hardy-Weinberg Equilibrium and free of null alleles (18 out of 23). Also we found no evidence of linkage among them. Finally, we tested the transferability to six other American species of Ternstroemia, two other Pentaphylacaceae species, and four species from different families within the order Ericales.ConclusionsThese molecular resources are promising tools to investigate genetic diversity loss and as barcodes for ethnopharmacological applications and species delimitation in the family Pentaphylacaceae and some Ericales, among other applications.