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1.
Besides vobtusine and vobtusine-lactone, deoxyvobtusine was isolated from the leaves of Voacanga grandifolia (Miq. Rolfe. Spectral and chemical evi 相似文献
2.
Joanne K. Gardner Cyril D. S. Mamotte Priya Patel Teong Ling Yeoh Connie Jackaman Delia J. Nelson 《PloS one》2015,10(4)
Dendritic cells (DCs) play an important role in the generation of anti-cancer immune responses, however there is evidence that DCs in cancer patients are dysfunctional. Lipid accumulation driven by tumor-derived factors has recently been shown to contribute to DC dysfunction in several human cancers, but has not yet been examined in mesothelioma. This study investigated if mesothelioma tumor cells and/or their secreted factors promote increases in DC lipid content and modulate DC function. Human monocyte-derived DCs (MoDCs) were exposed to human mesothelioma tumor cells and tumor-derived factors in the presence or absence of lipoproteins. The data showed that immature MoDCs exposed to mesothelioma cells or factors contained increased lipid levels relative to control DCs. Lipid accumulation was associated with reduced antigen processing ability (measured using a DQ OVA assay), upregulation of the co-stimulatory molecule, CD86, and production of the tolerogenic cytokine, IL-10. Increases in DC lipid content were further enhanced by co-exposure to mesothelioma-derived factors and triglyceride-rich lipoproteins, but not low-density lipoproteins. In vivo studies using a murine mesothelioma model showed that the lipid content of tumor-infiltrating CD4+CD8α- DCs, CD4-CD8α- DCs DCs and plasmacytoid DCs increased with tumor progression. Moreover, increasing tumor burden was associated with reduced proliferation of tumor-antigen-specific CD8+ T cells in tumor-draining lymph nodes. This study shows that mesothelioma promotes DC lipid acquisition, which is associated with altered activation status and reduced capacity to process and present antigens, which may impair the ability of DCs to generate effective anti mesothelioma T cell responses. 相似文献
3.
Summary Measurements of foliage quality, physiological, and phenological condition of sample trees were used as independent variables in multiple correlation analyses to determine their effect on female and male spruce budworm larval dry weights. Female budworm from trees high in foliar concentrations of beta-pinene, myrcene and total nitrogen weighed less than those from trees lacking these characteristics. Male budworm from trees high in foliar concentrations of alpha-pinene, myrcene, terpinolene, citronellyl acetate, and bornyl acetate weighted less than those from trees lacking these characteristics. Additionally, relatively vigorous and productive trees tended to be less susceptible (as evidenced by reduced larval weight) to budworm of either sex. 相似文献
4.
5.
C?George Priya DossEmail author N?Nagasundaram Chiranjib?Chakraborty Luonan?Chen Hailong?ZhuEmail author 《Human genomics》2013,7(1):10
Background
Recent reports suggest the role of nonsynonymous single nucleotide polymorphisms (nsSNPs) in cyclin-dependent kinase 7 (CDK7) gene associated with defect in the DNA repair mechanism that may contribute to cancer risk. Among the various inhibitors developed so far, flavopiridol proved to be a potential antitumor drug in the phase-III clinical trial for chronic lymphocytic leukemia. Here, we described a theoretical assessment for the discovery of new drugs or drug targets in CDK7 protein owing to the changes caused by deleterious nsSNPs.Methods
Three nsSNPs (I63R, H135R, and T285M) were predicted to have functional impact on protein function by SIFT, PolyPhen2, I-Mutant3, PANTHER, SNPs&GO, PhD-SNP, and screening for non-acceptable polymorphisms (SNAP). Furthermore, we analyzed the native and proposed mutant models in atomic level 10 ns simulation using the molecular dynamics (MD) approach. Finally, with the aid of Autodock 4.0 and PatchDock, we analyzed the binding efficacy of flavopiridol with CDK7 protein with respect to the deleterious mutations.Results
By comparing the results of all seven prediction tools, three nsSNPs (I63R, H135R, and T285M) were predicted to have functional impact on the protein function. The results of protein stability analysis inferred that I63R and H135R exhibited less deviation in root mean square deviation in comparison with the native and T285M protein. The flexibility of all the three mutant models of CDK7 protein is diverse in comparison with the native protein. Following to that, docking study revealed the change in the active site residues and decrease in the binding affinity of flavopiridol with mutant proteins.Conclusion
This theoretical approach is entirely based on computational methods, which has the ability to identify the disease-related SNPs in complex disorders by contrasting their costs and capabilities with those of the experimental methods. The identification of disease related SNPs by computational methods has the potential to create personalized tools for the diagnosis, prognosis, and treatment of diseases.Lay abstract
Cell cycle regulatory protein, CDK7, is linked with DNA repair mechanism which can contribute to cancer risk. The main aim of this study is to extrapolate the relationship between the nsSNPs and their effects in drug-binding capability. In this work, we propose a new methodology which (1) efficiently identified the deleterious nsSNPs that tend to have functional effect on protein function upon mutation by computational tools, (2) analyze d the native protein and proposed mutant models in atomic level using MD approach, and (3) investigated the protein-ligand interactions to analyze the binding ability by docking analysis. This theoretical approach is entirely based on computational methods, which has the ability to identify the disease-related SNPs in complex disorders by contrasting their costs and capabilities with those of the experimental methods. Overall, this approach has the potential to create personalized tools for the diagnosis, prognosis, and treatment of diseases.6.
7.
Priya Padmanabhan Mukund R. Shukla J. Alan Sullivan Praveen K. Saxena 《Plant Cell, Tissue and Organ Culture》2017,128(1):145-160
C4 plants can efficiently accumulate CO2 in leaves and thus reduce wasteful oxygen fixation by the RuBisCO enzyme. Three C4 enzymes, namely carbonic anhydrase (CA), phosphoenol pyruvate (PEPC) and pyruvate orthophosphate dikinase (PPDK), were over expressed in Oryza sativa L. ssp. indica var. Khitish under the control of green tissue specific promoters PD54o, PEPC and PPDK, respectively. Integration of these genes was confirmed by Southern hybridization. The relative expression of PEPC, CA and PPDK were, respectively, 6.75, 6.57 and 3.6-fold higher in transgenic plants compared to wild type plants (control). Photosynthetic efficiency of the transgenic plants increased significantly along with a 12?% increase in grain yield compared to wild type plants. Compared to control plants, transgenic plants also showed phenotypic changes such as increased leaf blade size, root biomass, and plant height and anatomical changes such as greater leaf vein number, bundle sheath cells, and bulliform cells. Our findings indicate that the combined over expression of these three enzymes is an efficient strategy for incorporating beneficial physiological and anatomical features that will enable subsequent yield enhancement in C3 rice plants. 相似文献
8.
Ruby Priya Damandeep Kaur Komal Attri Sandeep Kaur Deepinder Sharda Diptiman Choudhury O. P. Pandey 《Luminescence》2024,39(2):e4652
In this article, we have reported the effect of varying concentration of europium (Eu) in (50 − x)% P2O5–25% Na2O–24% CaO–% Eu2O3, where x = 1, 3, 5. The glass samples were synthesised via conventional melt-quench method. The impact of europium ion (Eu3+) on the structural, optical and luminescent properties of phosphate soda lime glasses has been studied using X-ray diffraction (XRD), Fourier-transformed infrared (FTIR) spectroscopy, ultraviolet-visible spectroscopy, scanning electron microscopy coupled with energy-dispersive spectroscopy and photoluminescent techniques. The amorphous nature of glass samples was confirmed by XRD patterns. FTIR confirmed the presence of various functional groups. The emission spectra of synthesised samples exhibited intense emission peaks corresponding to Eu3+ under excitation at 393 nm. Among all the peaks, the maximum intensity was observed for 5D0 → 7F2 transition. Judd–Ofelt (J–O) parameters (Ω2, Ω4) and other radiative parameters such as band width, radiative transition probabilities, stimulated emission cross-sections and branching ratio were determined from emission spectra. The other photometric parameters such as CIE coordinates and colour purity were also determined. Furthermore, cytotoxic studies were carried out on normal cell line human embryonic kidney cells (HEK-293) using MTT assay. Results showed that the prepared samples significantly enhanced growth in glass sample-treated cells as compared to control cells. These findings suggest that synthesised glass samples are biocompatible in nature and have potential for applications in display devices and biomedical research area. 相似文献
9.
Lana Sargent Mike Nalls Andrew Singleton Priya Palta Anna Kucharska-Newton Jim Pankow Hunter Young Weihong Tang Pamela Lutsey Amy Olex Jered M. Wendte Danni Li Alvaro Alonso Michael Griswold B. Gwen Windham Stefania Baninelli Luigi Ferrucci 《Aging cell》2024,23(2):e14030
Aging adults experience increased health vulnerability and compromised abilities to cope with stressors, which are the clinical manifestations of frailty. Frailty is complex, and efforts to identify biomarkers to detect frailty and pre-frailty in the clinical setting are rarely reproduced across cohorts. We developed a predictive model incorporating biological and clinical frailty measures to identify robust biomarkers across data sets. Data were from two large cohorts of older adults: “Invecchiare in Chianti (Aging in Chianti, InCHIANTI Study”) (n = 1453) from two small towns in Tuscany, Italy, and replicated in the Atherosclerosis Risk in Communities Study (ARIC) (n = 6508) from four U.S. communities. A complex systems approach to biomarker selection with a tree-boosting machine learning (ML) technique for supervised learning analysis was used to examine biomarker population differences across both datasets. Our approach compared predictors with robust, pre-frail, and frail participants and examined the ability to detect frailty status by race. Unique biomarker features identified in the InCHIANTI study allowed us to predict frailty with a model accuracy of 0.72 (95% confidence interval (CI) 0.66–0.80). Replication models in ARIC maintained a model accuracy of 0.64 (95% CI 0.66–0.72). Frail and pre-frail Black participant models maintained a lower model accuracy. The predictive panel of biomarkers identified in this study may improve the ability to detect frailty as a complex aging syndrome in the clinical setting. We propose several concrete next steps to keep research moving toward detecting frailty with biomarker-based detection methods. 相似文献
10.
Lukas Frank Anne Rademacher Norbert Mücke Stephan M Tirier Emma Koeleman Caroline Knotz Sabrina Schumacher Sabine
A Stainczyk Frank Westermann Stefan Frhling Priya Chudasama Karsten Rippe 《Nucleic acids research》2022,50(11):e61
Alternative lengthening of telomeres (ALT) occurs in ∼10% of cancer entities. However, little is known about the heterogeneity of ALT activity since robust ALT detection assays with high-throughput in situ readouts are lacking. Here, we introduce ALT-FISH, a method to quantitate ALT activity in single cells from the accumulation of single-stranded telomeric DNA and RNA. It involves a one-step fluorescent in situ hybridization approach followed by fluorescence microscopy imaging. Our method reliably identified ALT in cancer cell lines from different tumor entities and was validated in three established models of ALT induction and suppression. Furthermore, we successfully applied ALT-FISH to spatially resolve ALT activity in primary tissue sections from leiomyosarcoma and neuroblastoma tumors. Thus, our assay provides insights into the heterogeneity of ALT tumors and is suited for high-throughput applications, which will facilitate screening for ALT-specific drugs. 相似文献