For more than a decade, pan-genome analysis has been applied as an effective method for explaining the genetic contents variation of prokaryotic species. However, genomic characteristics and detailed ...structures of gene pools have not been fully clarified, because most studies have used a small number of genomes. Here, we constructed pan-genomes of seven species in order to elucidate variations in the genetic contents of >27,000 genomes belonging to
,
subsp.
,
subsp.
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and
spp.,
complex,
, and
This work showed the pan-genomes of all seven species has open property. Additionally, systematic evaluation of the characteristics of their pan-genome revealed that phylogenetic distance provided valuable information for estimating the parameters for pan-genome size among several models including Heaps' law. Our results provide a better understanding of the species and a solution to minimize sampling biases associated with genome-sequencing preferences for pathogenic strains.
Some polypeptide N-acetyl-galactosaminyltransferases (GALNTs) are associated with cancer, but their function in organ-specific metastasis remains unclear. Here, we report that GALNT14 promotes breast ...cancer metastasis to the lung by enhancing the initiation of metastatic colonies as well as their subsequent growth into overt metastases. Our results suggest that GALNT14 augments the self-renewal properties of breast cancer cells (BCCs). Furthermore, GALNT14 overcomes the inhibitory effect of lung-derived bone morphogenetic proteins (BMPs) on self-renewal and therefore facilitates metastasis initiation within the lung microenvironment. In addition, GALNT14 supports continuous growth of BCCs in the lung by not only inducing macrophage infiltration but also exploiting macrophage-derived fibroblast growth factors (FGFs). Finally, we identify KRAS-PI3K-c-JUN signalling as an upstream pathway that accounts for the elevated expression of GALNT14 in lung-metastatic BCCs. Collectively, our findings uncover an unprecedented role for GALNT14 in the pulmonary metastasis of breast cancer and elucidate the underlying molecular mechanisms.
The development of biofunctional and bioactive hybrid polymeric scaffolds seek to mitigate the current challenges in the emerging field of tissue engineering. In this paper, we report the fabrication ...of a biomimetic and biocompatible nanofibrous scaffolds of polyamide-6,6 (PA-6,6) blended with biopolymer chitosan via one step co-electrospinning technique. Different weight percentage of chitosan 10wt%, 15wt%, and 20wt% were blended with PA-6,6, respectively. The nanocomposite electrospun scaffolds mats enabled to provide the osteophilic environment for cells growth and biomineralization. The morphological and physiochemical properties of the resulted scaffolds were studied using field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and Fourier transform-infrared (FT-IR) spectroscopy. The improvement in hydrophilicity and mechanical strength of the bio-nanocomposite mesh with 20wt% chitosan embedded, was the desired avenue for adhesion, proliferation and maturation of osteoblast cells as compared to other sample groups and pure PA-6,6 fibrous mat. The biomineralization of the nanocomposite electrospun mats also showed higher ability to nucleate bioactive calcium phosphate (Ca/P) nanoparticles comparing to pristine PA-6,6. Furthermore, the biomimetic nature of scaffolds exhibited the cells viability and regeneration of pre-osteoblast (MC3T3-E1) cells which were assessed via in vitro cell culture test. Collectively, the results suggested that the optimized 20wt% of chitosan supplemented hybrid electrospun fibrous scaffold has significant effect in biomedical field to create osteogenic capabilities for tissue engineering.
Objective
Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using ...clinical and serological manifestations in SLE patients.
Methods
We genotyped a total of 1,655 Korean patients with SLE (n = 1,243 as a discovery set and n = 412 as a replication set) using a customized genome‐wide single‐nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well‐validated non‐HLA SNPs and HLA haplotypes of SLE‐risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration.
Results
Childhood‐onset SLE (<16 years) conferred the highest genetic risk compared with adult‐onset (16–50 years) or late‐onset (>50 years) SLE (P = 6.8 × 10−6). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (β = 0.143, P = 1.8 × 10−6). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio HR 1.74, P = 2.2 × 10−8) and anti–Sm antibody production (HR 1.85, P = 2.8 × 10−5). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10−5) and class V (HR 2.79, P = 1.0 × 10−3), but especially lupus nephritis class V in anti–Sm‐positive SLE (area under the curve 0.68, P = 1.8 × 10−4).
Conclusion
Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti–Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients.
Bone tissue engineering is an interdisciplinary field where the principles of engineering are applied on bone-related biochemical reactions. Scaffolds, cells, growth factors, and their interrelation ...in microenvironment are the major concerns in bone tissue engineering. Among many alternatives, electrospinning is a promising and versatile technique that is used to fabricate polymer fibrous scaffolds for bone tissue engineering applications. Copolymerization and polymer blending is a promising strategic way in purpose of getting synergistic and additive effect achieved from either polymer. In this review, we summarize the basic chemistry of bone, principle of electrospinning, and polymers that are used in bone tissue engineering. Particular attention will be given on biomechanical properties and biological activities of these electrospun fibers. This review will cover the fundamental basis of cell adhesion, differentiation, and proliferation of the electrospun fibers in bone tissue scaffolds. In the last section, we offer the current development and future perspectives on the use of electrospun mats in bone tissue engineering.
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•Gas foaming technique is applied to prepare a 3-D nanofibrous scaffold.•Sodium borohydride solution is introduced as gas foaming reagent.•Novel mechanism for in situ gas foaming is ...demonstrated.•Nature of the polymers affects the fabrication process.
In the past decade, considerable efforts have been made to fabricate the biomimetic scaffolds from electrospun nanofibers for tissue engineering applications. However, one of the major concerns with electrospun nanofibrous scaffolds is the densely packed fibers in two-dimensional (2-D) array which impedes their applicability in tissue regeneration. To overcome this problem, a simple and facile post-electrospinning procedure was developed to modify a densely packed 2-D electrospun membrane into low density three-dimensional (3-D) scaffolds. In this strategy, an electrospun nanofibrous mat was immersed in a sodium borohydride (SB) solution. The interconnected pores of a mat are filled with the SB solution driven by capillary forces where it undergoes hydrolysis to produce hydrogen gas. The in situ generated gas molecules form clusters to minimize the free energy resulting in pore nucleation that reorganizes the nanofibers to form a low density, macroporous, spongy and multi-layered 3-D scaffold. Electrospun mats of various polar and non-polar polymers were subjected to post-electrospinning process to monitor the fabrication process. It has been found that the solvent for sodium borohydride (either water or methanol) played a crucial role in post-electrospinning process. Only the electrospun mat of polar polymers were amended into 3-D architecture using aqueous SB solution while methanol solution was found equally effective for both polar and non-polar polymers. Moreover, the fabrication process was fast in methanol solution compared to an aqueous solution due to the rapid liberation of hydrogen gas from the methanolysis reaction compared to the hydrolysis reaction. This process will reveal a new approach for the fabrication of a three-dimensional, low-density, nanofibrous materials for biomedical and industrial applications using a wide variety of polymers.
Genome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. ...As a continuous effort, we conducted GWAS in a large Korean RA case-control population.
We newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations.
We identified six new RA-risk loci (
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and
) with p
<5×10
and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases.
This study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.
Herein, we engineered a self-electrical stimulated double-layered nerve guidance conduit (NGC) assembled from electrospun mats with an aligned oriented inward layer covered with a random oriented ...outer layer. The biomimetic NGC can be achieved from chitosan grafted polyurethane with well-dispersed functionalized multiwall carbon nanotubes (fMWCNTs) nanofibrous mats after a uniform coating of polypyrrole (PPy). The structural framework of interconnected NGC exhibited cellular biomaterial interface and improved the physicochemical properties, including electrical conductivity, mechanical strength, and cytocompatibility, serving as natural hosting substrate to natural extracellular matrices (ECM) for vital roles in nerve tissue engineering. The regrowth, proliferation, and migration, of Schwann cells (S42) and the differentiation of rat pheochromocytoma cells (PC12) were greatly accelerated on the aligned oriented mats as compared to the randomly oriented mats during in vitro cell cultures. The morphology of the spontaneous outgrowth and phenotype of neurite bundles were preferentially guided along the axis of the aligned oriented nanofibers, which maintains a strong adaptability in axonal regeneration. In addition, the differentiation of PC12 cells cultured on as-fabricated NGCs were evaluated from cDNA gene expression. It is hoped that the results will contribute to the efficient application of designed NGCs and can be used in therapeutic strategies for treating injured sites and stimulate recovery from substantial damage to nerve cells.
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Herein, we demonstrate the exfoliation of bulk graphitic carbon nitrides (g-C3N4) into ultra-thin (~3.4nm) two-dimensional (2D) nanosheets and their functionalization with proton (g-C3N4H+). The ...layered semiconductor g-C3N4H+ nanosheets were doped with cylindrical spongy shaped polypyrrole (CSPPy-g-C3N4H+) using chemical polymerization method. The as-prepared nanohybrid composite was utilized to fabricate cholesterol biosensors after immobilization of cholesterol oxidase (ChOx) at physiological pH. Large specific surface area and positive charge nature of CSPPy-g-C3N4H+ composite has tendency to generate strong electrostatic attraction with negatively charged ChOx, and as a result they formed stable bionanohybrid composite with high enzyme loading. A detailed electrochemical characterization of as-fabricated biosensor electrode (ChOx-CSPPy-g-C3N4H+/GCE) exhibited high-sensitivity (645.7 µAmM−1 cm−2) in wide-linear range of 0.02–5.0mM, low detection limit (8.0μM), fast response time (~3s), long-term stability, and good selectivity during cholesterol detection. To the best of our knowledge, this novel nanocomposite was utilized for the first time for cholesterol biosensor fabrication that resulted in high sensing performance. Hence, this approach opens a new prospective to utilize CSPPy-g-C3N4H+ composite as cost-effective, biocompatible, eco-friendly, and superior electrocatalytic as well as electroconductive having great application potentials that could pave the ways to explore many other new sensors fabrication and biomedical applications.
•Preparation of ultrathin 2D nanosheets of graphite carbon nitride and their protonation.•Doping of engineered g-C3N4H+ nanosheets with cylindrical spongy shaped polypyrrole.•ChOx immobilization on CSPPy-g-C3N4H+ nanohybrid composite to fabricate cholesterol biosensor.•The biosensor is highly sensitive and reproducible for cholesterol detection.•The biosensor was applied for the cholesterol detection in human serum samples successfully.
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