| 1. |
- Deng, Min, et al.
(författare)
-
Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
-
Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
|
|
| 2. |
- Yang, Fan, et al.
(författare)
-
Uncovering a Distinct Gene Signature in Endothelial Cells Associated With Contrast Enhancement in Glioblastoma
- 2021
-
Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Glioblastoma (GBM) is the most aggressive and lethal type of brain tumors. Magnetic resonance imaging (MRI) has been commonly used for GBM diagnosis. Contrast enhancement (CE) on T1-weighted sequences are presented in nearly all GBM as a result of high vascular permeability in glioblastomas. Although several radiomics studies indicated that CE is associated with distinct molecular signatures in tumors, the effects of vascular endothelial cells, the key component of blood brain barrier (BBB) controlling vascular permeability, on CE have not been thoroughly analyzed. Methods Endothelial cell enriched genes have been identified using transcriptome data from 128 patients by a systematic method based on correlation analysis. Distinct endothelial cell enriched genes associated with CE were identified by analyzing difference of correlation score between CE-high and CE-low GBM cases. Immunohistochemical staining was performed on in-house patient cohort to validate the selected genes associated with CE. Moreover, a survival analysis was conducted to uncover the relation between CE and patient survival. Results We illustrated that CE is associated with distinct vascular molecular imprints characterized by up-regulation of pro-inflammatory genes and deregulation of BBB related genes. Among them, PLVAP is up-regulated, whereas TJP1 and ABCG2 are down-regulated in the vasculature of GBM with high CE. In addition, we found that the high CE is associated with poor prognosis and GBM mesenchymal subtype. Conclusion We provide an additional insight to reveal the molecular trait for CE in MRI images with special focus on vascular endothelial cells, linking CE with BBB disruption in the molecular level. This study provides a potential new direction that may be applied for the treatment optimization based on MRI features.
|
|
| 3. |
- Lawrenson, Kate, et al.
(författare)
-
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
|
|
| 4. |
- Xie, Yuan, et al.
(författare)
-
Key molecular alterations in endothelial cells in human glioblastoma uncovered through single-cell RNA sequencing
- 2021
-
Ingår i: JCI Insight. - : American Society For Clinical Investigation. - 2379-3708. ; 6:15
-
Tidskriftsartikel (refereegranskat)abstract
- Passage of systemically delivered pharmacological agents into the brain is largely blocked by the blood-brain-barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). Tumor vessels in glioblastoma (GBM), the most common malignant brain tumor in humans, are abnormally permeable, but this phenotype is heterogeneous and may differ between the tumor's center and invasive front. Here, through single-cell RNA sequencing (scRNA-seq) of freshly isolated ECs from human glioblastoma and paired tumor peripheral tissues, we have constructed a molecular atlas of human brain ECs providing unprecedented molecular insight into the heterogeneity of the human BBB and its molecular alteration in glioblastoma. We identified 5 distinct EC phenotypes representing different states of EC activation and BBB impairment, and associated with different anatomical locations within and around the tumor. This unique data resource provides key information for designing rational therapeutic regimens and optimizing drug delivery.
|
|
| 5. |
- Gao, Xiang, et al.
(författare)
-
Planting Age Identification and Yield Prediction of Apple Orchard Using Time-Series Spectral Endmember and Logistic Growth Model
- 2023
-
Ingår i: Remote Sensing. - : MDPI AG. - 2072-4292. ; 15:3, s. 642-642
-
Tidskriftsartikel (refereegranskat)abstract
- In response to significant shifts in dietary and lifestyle preferences, the global demand for fruits has increased dramatically, especially for apples, which are consumed worldwide. Growing apple orchards of more productive and higher quality with limited land resources is the way forward. Precise planting age identification and yield prediction are indispensable for the apple market in terms of sustainable supply, price regulation, and planting management. The planting age of apple trees significantly determines productivity, quality, and yield. Therefore, we integrated the time-series spectral endmember and logistic growth model (LGM) to accurately identify the planting age of apple orchard, and we conducted planting age-driven yield prediction using a neural network model. Firstly, we fitted the time-series spectral endmember of green photosynthetic vegetation (GV) with the LGM. By using the four-points method, the environmental carrying capacity (ECC) in the LGM was available, which serves as a crucial parameter to determine the planting age. Secondly, we combined annual planting age with historical apple yield to train the back propagation (BP) neural network model and obtained the predicted apple yields for 12 counties. The results show that the LGM method can accurately estimate the orchard planting age, with Mean Absolute Error (MAE) being 1.76 and the Root Mean Square Error (RMSE) being 2.24. The strong correlation between orchard planting age and apple yield was proved. The results of planting age-driven yield prediction have high accuracy, with the MAE up to 2.95% and the RMSE up to 3.71%. This study provides a novel method to accurately estimate apple orchard planting age and yields, which can support policy formulation and orchard planning in the future.
|
|
| 6. |
- Gu, Enyao, et al.
(författare)
-
A real-time Raman spectroscopy study of the dynamics of laser-thinning of MoS2 flakes to monolayers
- 2017
-
Ingår i: AIP Advances. - : AIP Publishing. - 2158-3226. ; 7:12
-
Tidskriftsartikel (refereegranskat)abstract
- Transition metal dichalcogenides (TMDCs) in monolayer form have attracted a great deal of attention for electronic and optical applications. Compared to mechanical exfoliation and chemical synthesis, laser thinning is a novel and unique “on-demand” approach to fabricate monolayers or pattern desired shapes with high controllability and reproducibility. Its successful demonstration motivates a further exploration of the dynamic behaviour of this local thinning process. Here, we present an in-situ study of void formation by laser irradiation with the assistance of temporal Raman evolution. In the analysis of time-dependent Raman intensity, an empirical formula relating void size to laser power and exposure time is established. Void in thinner MoS2 flakes grows faster than in thicker ones as a result of reduced sublimation temperature in the two-dimensional (2D) materials. Our study provides useful insights into the laser-thinning dynamics of 2D TMDCs and guidelines for an effective control over the void formation.
|
|
| 7. |
- Wang, Jianhao, et al.
(författare)
-
An Integrated Transcriptome Analysis Reveals IGFBP7 Upregulation in Vasculature in Traumatic Brain Injury
- 2021
-
Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Vasculature plays critical roles in the pathogenesis and neurological repair of traumatic brain injury (TBI). However, how vascular endothelial cells respond to TBI at the molecular level has not been systematically reviewed. Here, by integrating three transcriptome datasets including whole cortex of mouse brain, FACS-sorted mouse brain endothelial cells, and single cell sequencing of mouse brain hippocampus, we revealed the key molecular alteration of endothelial cells characterized by increased Myc targets and Epithelial-Mesenchymal Transition signatures. In addition, immunofluorescence staining of patients' samples confirmed that IGFBP7 was up-regulated in vasculature in response to TBI. TGF beta 1, mainly derived from microglia and endothelial cells, sufficiently induces IGFBP7 expression in cultured endothelial cells, and is significantly upregulated in response to TBI. Our results identified IGFBP7 as a potential biomarker of vasculature in response to TBI, and indicate that TGF beta signaling may contribute to the upregulation of IGFBP7 in the vasculature.
|
|
| 8. |
- Zhang, Yanyu, et al.
(författare)
-
1p/19q co-deletion status is associated with distinct tumor-associated macrophage infiltration in IDH mutated lower-grade gliomas
- 2021
-
Ingår i: Cellular Oncology. - : Springer. - 2211-3428 .- 2211-3436. ; 44:1, s. 193-204
-
Tidskriftsartikel (refereegranskat)abstract
- Background Tumor-associated macrophages (TAM)s are critical regulators of glioma progression. As yet, however, TAMs in isocitrate dehydrogenase (IDH) mutated lower-grade gliomas (LGGs) have not been thoroughly investigated. The aim of this study was to determine whether 1p/19q co-deletion status affects the TAM phenotype or its prevalence in IDH mutated LGGs. Methods TAMs in IDH mutated LGGs were analyzed using transcriptome data from 230 samples in the TCGA database in combination with transcriptome data from single-cell RNA sequencing of IDH-mutated LGGs. Proteins potentially involved in TAM regulation were examined by immuno-staining in primary LGG samples harboring IDH mutations. Essential signaling pathways regulating TAM phenotypes were investigated in a glioma mouse model using small molecule inhibitors. Results Most of the TAMs in IDH-mutated LGGs expressed the M1 activation markers CD86 and TNF, whereas a subset of individual TAMs co-expressed both M1 and M2-related markers. Bioinformatics analysis in combination with immuno-staining of IDH-mutated patient samples revealed higher amounts of TAMs expressing M2-related markers in 1p/19q non-codeletion IDH-mutated LGGs compared to 1p/19q codeletion LGGs. The levels of transforming growth factor beta 1 (TGF beta 1) and macrophage colony-stimulating factor (M-CSF) were significantly higher in 1p/19q non-codeletion LGGs than in 1p/19q codeletion LGGs. M-CSF and TGF beta 1 signal inhibition decreased tumor growth and modulated the TAM phenotype in a glioma mouse model. Conclusions Our data indicate that 1p/19q co-deletion status relates to distinct TAM infiltration in gliomas, which is likely mediated by M-CSF and TGF beta 1 signaling. M-CSF and TGF beta 1 signaling may play a pivotal role in regulating the TAM phenotype in glioma.
|
|
| 9. |
- Zhang, Youwei, et al.
(författare)
-
Competing Mechanisms for Photocurrent Induced at the Monolayer-Multilayer Graphene Junction
- 2018
-
Ingår i: Small. - : WILEY-V C H VERLAG GMBH. - 1613-6810 .- 1613-6829. ; 14:24
-
Tidskriftsartikel (refereegranskat)abstract
- Graphene is characterized by demonstrated unique properties for potential novel applications in photodetection operated in the frequency range from ultraviolet to terahertz. To date, detailed work on identifying the origin of photoresponse in graphene is still ongoing. Here, scanning photocurrent microscopy to explore the nature of photocurrent generated at the monolayer-multilayer graphene junction is employed. It is found that the contributing photocurrent mechanism relies on the mismatch of the Dirac points between the monolayer and multilayer graphene. For overlapping Dirac points, only photothermoelectric effect (PTE) is observed at the junction. When they do not coincide, a different photocurrent due to photovoltaic effect (PVE) appears and becomes more pronounced with larger separation of the Dirac points. While only PTE is reported for a monolayer-bilayer graphene junction in the literature, this work confirms the coexistence of PTE and PVE, thereby extending the understanding of photocurrent in graphene-based heterojunctions.
|
|
| 10. |
- Zhao, Wenhao, et al.
(författare)
-
Comparison and application of SOFM, fuzzy c-means and k-means clustering algorithms for natural soil environment regionalization in China
- 2023
-
Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 216
-
Tidskriftsartikel (refereegranskat)abstract
- Soil attributes and their environmental drivers exhibit different patterns in different geographical directions, along with distinct regional characteristics, which may have important effects on substance migration and transformation such as organic matter and soil elements or the environmental impacts of pollutants. Therefore, regional soil characteristics should be considered in the process of regionalization for environmental management. However, no comprehensive evaluation or systematic classification of the natural soil environment has been established for China. Here, we established an index system for natural soil environmental regionalization (NSER) by combining literature data obtained based on bibliometrics with the analytic hierarchy process (AHP). Based on the index system, we collected spatial distribution data for 14 indexes at the national scale. In addition, three clustering algorithms—self-organizing feature mapping (SOFM), fuzzy c-means (FCM) and k-means (KM)—were used to classify and define the natural soil environment. We imported four cluster validity indexes (CVI) to evaluate different models: Davies-Bouldin index (DB), Silhouette index (Sil) and Calinski-Harabasz index (CH) for FCM and KM, clustering quality index (CQI) for SOFM. Analysis and comparison of the results showed that when the number of clusters was 13, the FCM clustering algorithm achieved the optimal clustering results (DB = 1.16, Sil = 0.78, CH = 6.77 × 106), allowing the natural soil environment of China to be divided into 12 regions with distinct characteristics. Our study provides a set of comprehensive scientific research methods for regionalization research based on spatial data, it has important reference value for improving soil environmental management based on local conditions in China.
|
|
