Single-pixel neural network object classification of sub-Nyquist ghost imaging.

A single-pixel neural network object classification scenario in the sub-Nyquist ghost imaging system is proposed. Based on the neural network, objects are classified directly by bucket measurements without reconstructing images. Classification accuracy can still be maintained at 94.23% even with only 16 measurements (less than the Nyquist limit of 1.56%). A parallel computing scheme is applied in data processing to reduce the object acquisition time significantly. Random patterns are used as illumination patterns to illuminate objects. The proposed method performs much better than existing methods for both binary and grayscale images in the sub-Nyquist condition, which is also robust to environment noise turbulence. Benefiting from advantages of ghost imaging, it may find applications for target recognition in the fields of remote sensing, military defense, and so on.

Characterization of the complete chloroplast genome of Hedysarum polybotrys var. alaschanicum (Fabaceae) and its phylogeny.

Hedysarum polybotrys var. alaschanicum is an important medicinal plant and is widely used in traditional Chinese medicine. The complete chloroplast genome of H. polybotrys var. alaschanicum was assembled from Illumina pair-end sequence reads. The whole chloroplast genome is 122,933 bp in length and encodes a total of 110 genes, including 76 protein-coding genes, 30 tRNA genes and 4 rRNA genes. The overall GC content of the cp genome is 35.3%. A maximum likelihood (ML) phylogenetic analysis revealed that H. polybotrys var. alaschanicum was close to Hedysarum semenovii.

MicroRNA-206 Downregulates Connexin43 in Cardiomyocytes to Induce Cardiac Arrhythmias in a Transgenic Mouse Model.

BACKGROUND: MicroRNAs (miRNAs) are critical modulators of various physiological and pathological processes, but their role in cardiac arrhythmias remains yet to be completely understood. Connexin43 (Cx43) is an important cardiac gap junction protein and a potential target of miR-206, and downregulation of Cx43 induces ventricular tachyarrhythmias. METHODS: We investigated the effects of miR-206 overexpression on the adult mouse heart and in cardiac arrhythmias. Luciferase activity assay was employed to validate Cx43 as a direct target of miR-206. Expression of Cx43 was measured in cardiac muscle cell line HL-1 securely expressing miR-206. An inducible miR-206 overexpression mouse model was established to evaluate the in vivo effect of miR-206 on Cx43 expression and cardiac rhythm. RESULTS: MiR-206 directly recognised 3'-untranslated region of Cx43 mRNA to inhibit its expression in HL-1 cells. Induction of miR-206 in the adult mouse heart suppressed Cx43 expression, particularly in the atria and ventricle. Importantly, miR-206 overexpression also induced abnormal heart-rate and PR interval, and shortened life-span in the experimental mice. CONCLUSIONS: In cardiomyocytes, miR-206 is a upstream regulator of Cx43, and its overexpression downregulates Cx43 to induce abnormal heart-rate and PR interval.

Luteolin decreases atherosclerosis in LDL receptor-deficient mice via a mechanism including decreasing AMPK-SIRT1 signaling in macrophages.

Lipid metabolism dysfunction and inflammatory infiltration into arterial walls are associated with the initiation and progression of atherosclerosis. Luteolin has been reported to possess anti-inflammatory actions and protect against tumor necrosis factor-α (TNF-α)-induced vascular inflammation, monocyte adhesion to endothelial cells and the formation of lipid-laden macrophages in vitro. However, the role of luteolin in atherosclerosis and the associated vascular inflammatory remains to be elucidated. The aim of the present study was to investigate the effects of luteolin on plaque development, lipid accumulation and macrophage inflammation low-density lipoprotein receptor-deficient (LDLR-/-) mice with atherosclerosis, as well as the underlying mechanisms in ox-induced THP-1-derived macrophages. Firstly, 9-week-old male C57BL/6 mice were fed a standard chow diet, western diet or western diet supplemented with 100 mg/kg luteolin for 14 weeks. The results of histological staining revealed that 100 mg/kg dietary luteolin ameliorated western diet-induced atherosclerotic plaque development and lipid accumulation in the abdominal aorta. Furthermore, total cholesterol, triglyceride and LDL-cholesterol levels were decreased in the plasma of western diet + luteolin mice compared with those fed with a western diet alone. Quantitative polymerase chain reaction analysis revealed that dietary luteolin inhibited the expression of cluster of differentiation 68, macrophage chemoattractant protein 2 and inflammatory cytokines, including interleukin-6 (IL-6) and TNF-α. Mechanistically, luteolin decreased the total cholesterol level as well as macrophage chemokine and inflammatory cytokine expression in THP-1-derived macrophages via AMP-activated protein kinase (AMPK)-Sirtuin (SIRT)1 signaling following induction with oxidized low-density lipoprotein. The results of the present study suggest that luteolin prevents plaque development and lipid accumulation in the abdominal aorta by decreasing macrophage inflammation during atherosclerosis, which is mediated by mechanisms including AMPK-SIRT1 signaling.

High serum YKL-40 level positively correlates with coronary artery disease.

AIM: We investigated the predictive value of chitinase-like protein YKL-40 in coronary artery disease (CAD). PATIENTS: Serum YKL-40 levels in 116 CAD patients and 82 healthy controls were analyzed. Severity of CAD was evaluated using Gensini scores. Spearman's correlation was used to evaluate the correlation between Gensini scores and YKL-40 levels. The predictive value of YKL-40 was determined by receivers operating characteristic curve analysis. RESULTS: Serum YKL-40 levels were significantly elevated in CAD group as compared with control group. A positive correlation was found between the serum YKL-40 level and Gensini score. The optimum cut-off value of YKL-40 concentration was 127.7 ng/ml for distinguishing CAD patients from healthy controls with a 75.9% sensitivity and 57.3% specificity. CONCLUSION: A positive correlation exists between YKL-40 levels and CAD, and YKL-40 might be a useful adjunct in the diagnosis of CAD.

PDGF upregulates CLEC-2 to induce T regulatory cells.

The effect of platelet derived growth factor (PDGF) on immune cells is not elucidated. Here, we demonstrate PDGF inhibited the maturation of human DCs and induced IL-10 secretion. Culture of PDGF-DCs with T cells induced the polarization of T cells towards FoxP3 expressing T regulatory cells that secreted IL-10. Gene expression studies revealed that PDGF induced the expression of C-type lectin like receptor member 2, (CLEC-2) receptor on DCs. Furthermore, DCs transfected with CLEC-2 induced T regulatory cells in DC-T cell co-culture. CLEC-2 is naturally expressed on platelets. Therefore, to confirm whether CLEC-2 is responsible for inducing the T regulatory cells, T cells were cultured with either CLEC-2 expressing platelets or soluble CLEC-2. Both conditions resulted in the induction of regulatory T cells. The generation of T regulatory cells was probably due to the binding of CLEC-2 with its ligand podoplanin on T cells, since crosslinking of podoplanin on the T cells also resulted in the induction of T regulatory cells. These data demonstrate that PDGF upregulates the expression of CLEC-2 on cells to induce T regulatory cells.

MiR-214 regulates the pathogenesis of patients with coronary artery disease by targeting VEGF.

Circulating microRNAs (miRNAs) in patient body fluids have recently been considered to hold the potential of being novel disease biomarkers and drug targets. We aimed to investigate the correlation between the levels of circulating miR-214 and the expression of vascular endothelial growth factor (VEGF) in the pathogenesis of coronary heart disease patients to further explore the mechanism involved in the vasculogenesis. Three different cohorts, including 13 acute myocardial infarction patients, 176 angina pectoris patients, and 127 control subjects, were enrolled to investigate the expression levels of circulating miR-214 in patients with myocardial ischemia and also the relationship between plasma miR-214 and severity of coronary stenosis. Plasma miR-214 levels of participants were examined by real-time quantitative PCR. Simultaneously, plasma cardiac troponin I concentrations were measured by ELISA assays. We further detected the correlation of miR-214 and VEGF by molecular and animal assays. MiR-214 was enriched in not only diseased endothelial progenitor cells (EPCs) but also the plasma of coronary artery disease (CAD) patients. Besides, we found out miR-214 was able to suppress VEGF expression and EPC activities. Reporter assays confirmed the direct binding and repression of miR-214 to the 39-UTR of VEGF mRNA. Knockdown of miR-214 not only restored VEGF levels and angiogenic activities of diseased EPCs in vitro, but also further promoted blood flow recovery in ischemic limbs of mice. Circulating miR-214 may be a new biomarker for CAD and as a potential diagnostic tool. And increased miR-214 level may be used to predict the presence and severity of coronary lesions in CAD patients.

Alterations in gene array patterns in dendritic cells from aged humans.

Dendritic cells (DCs) are major antigen-presenting cells that play a key role in initiating and regulating innate and adaptive immune responses. DCs are critical mediators of tolerance and immunity. The functional properties of DCs decline with age. The purpose of this study was to define the age-associated molecular changes in DCs by gene array analysis using Affymatrix GeneChips. The expression levels of a total of 260 genes (1.8%) were significantly different (144 down-regulated and 116 upregulated) in monocyte-derived DCs (MoDCs) from aged compared to young human donors. Of the 260 differentially expressed genes, 24% were down-regulated by more than 3-fold, suggesting that a large reduction in expression occurred for a notable number of genes in the aged. Our results suggest that the genes involved in immune response to pathogens, cell migration and T cell priming display significant age-related changes. Furthermore, downregulated genes involved in cell cycle arrest and DNA replication may play a critical role in aging-associated genetic instability. These changes in gene expression provide molecular based evidence for age-associated functional abnormalities in human DCs that may be responsible for the defects in adaptive immunity observed in the elderly.

Impaired secretion of interferons by dendritic cells from aged subjects to influenza : role of histone modifications.

Increased susceptibility to respiratory infections such as influenza is the hallmark of advancing age. The mechanisms underlying the impaired immune response to influenza are not well understood. In the present study, we have investigated the effect of advancing age on dendritic cell (DC) function because they are critical in generating robust antiviral responses. Our results indicate that monocyte derived DCs from the aged are impaired in their capacity to secrete interferon (IFN)-I in response to influenza virus. Additionally, we observed a severe reduction in the production of IFN-III, which plays an important role in defense against viral infections at respiratory mucosal surfaces. This reduction in IFN-I and IFN-III were a result of age-associated modifications in the chromatin structure. Investigations using chromatin immunoprecipitation with H3K4me3 and H3K9me3 antibodies revealed that there is increased association of IFN-I and IFN-III promoters with the repressor histone, H3K9me3 in non-stimulated aged DCs compared to young DCs. This was accompanied by decreased association of these promoters with activator histone, H3K4me3 in aged DCs after activation with influenza. In contrast to interferons, the association of TNF-alpha promoter with both these histones was comparable between aged and young subjects. Investigations at 48 h suggested that these changes are not stable and change with time. In summary, our study demonstrates that myeloid DCs from aged subjects are impaired in their capacity to produce IFNs in response to influenza virus and that age-associated altered histone expression patterns are responsible for the decrease in IFN production.

Mitogen-activated protein/extracellular signal-regulated kinase kinase 1act/tubulin interaction is an important determinant of mitotic stability in cultured HT1080 human fibrosarcoma cells.

Activation of the mitogen-activated protein kinase (MAPK) pathway plays a major role in neoplastic cell transformation. Using a proteomics approach, we identified alpha tubulin and beta tubulin as proteins that interact with activated MAP/extracellular signal-regulated kinase kinase 1 (MEK1), a central MAPK regulatory kinase. Confocal analysis revealed spatiotemporal control of MEK1-tubulin colocalization that was most prominent in the mitotic spindle apparatus in variant HT1080 human fibrosarcoma cells. Peptide arrays identified the critical role of positively charged amino acids R108, R113, R160, and K157 on the surface of MEK1 for tubulin interaction. Overexpression of activated MEK1 caused defects in spindle arrangement, chromosome segregation, and ploidy. In contrast, chromosome polyploidy was reduced in the presence of an activated MEK1 mutant (R108A, R113A) that disrupted interactions with tubulin. Our findings indicate the importance of signaling by activated MEK1-tubulin in spindle organization and chromosomal instability.

Age-related alterations of gene expression patterns in human CD8+ T cells.

Aging is associated with progressive T-cell deficiency and increased incidence of infections, cancer and autoimmunity. In this comprehensive study, we have compared the gene expression profiles in CD8+ T cells from aged and young healthy subjects using Affymetrix microarray Human Genome U133A-2 GeneChips. A total of 5.2% (754) of the genes analyzed had known functions and displayed statistically significant age-associated expression changes. These genes were involved in a broad array of complex biological processes, mainly in nucleic acid and protein metabolism. Functional groups, in which downregulated genes were overrepresented, were the following: RNA transcription regulation, RNA and DNA metabolism, intracellular (Golgi, endoplasmic reticulum and nuclear) transportation, signaling transduction pathways (T-cell receptor, Ras/MAPK, JNK/Stat, PI3/AKT, Wnt, TGFbeta, insulin-like growth factor and insulin), and the ubiquitin cycle. In contrast, the following functional groups contained more up-regulated genes than expected: response to oxidative stress and cytokines, apoptosis, and the MAPKK signaling cascade. These age-associated gene expression changes may be responsible for impaired DNA replication, RNA transcription, and signal transduction, possibly resulting in instability of cellular and genomic integrity, and alterations of growth, differentiation, apoptosis and anergy in human aged CD8+ T cells.

Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway.

Aging represents a state of paradox where chronic inflammation is associated with declining immune responses. Dendritic cells (DCs) are the major APCs responsible for initiating an immune response. However, DC functions in aging have not been studied in detail. In this study, we have compared the innate immune functions of monocyte-derived myeloid DCs from elderly subjects with DCs from young individuals. We show that although phenotypically comparable, DCs from the aging are functionally different from DCs from the young. In contrast to DCs from the young, DCs from elderly individuals display 1) significantly reduced capacity to phagocytose Ags via macropinocytosis and endocytosis as determined by flow cytometry; 2) impaired capacity to migrate in vitro in response to the chemokines MIP-3beta and stromal cell-derived factor-1; and 3) significantly increased LPS and ssRNA-induced secretion of TNF-alpha and IL-6, as determined by ELISA. Investigations of intracellular signaling revealed reduced phosphorylation of AKT in DCs from the aging, indirectly suggesting decreased activation of the PI3K pathway. Because the PI3K-signaling pathway plays a positive regulatory role in phagocytosis and migration, and also functions as a negative regulator of TLR signaling by inducing activation of p38 MAPK, this may explain the aberrant innate immune functioning of DCs from elderly subjects. Results from real-time PCR and protein expression by flow cytometry demonstrated an increased expression of phosphatase and tensin homolog, a negative regulator of the PI3K-signaling pathway, in DCs from the aging. Increased phosphatase and tensin homolog may thus be responsible for the defect in AKT phosphorylation and, therefore, the altered innate immune response of DCs from elderly humans.