Designing B-ISDN network topologies using the genetic algorithm

In this paper, the topology design of B-ISDN networks is addressed. We model the topological planning as a non-linear mixed-integer programming problem. The genetic algorithm, an effective optimization method, is applied to this problem. Since the randomness of the genetic algorithm cannot guarantee the biconnectivity requirement in the topologies generated by the genetic algorithm, we propose an algorithm to make all topologies at least biconnected while increasing the overall cost of the topologies the least. The result for a 20-node test case is presented in the paper and it is shown that the algorithm we propose has a very good convergence property.published_or_final_versio

Simultaneous profiling of transcriptome and DNA methylome from a single cell.

BackgroundSingle-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.ResultsHere, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.ConclusionsOur method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation

Ghrelin contributes to protection of hepatocellular injury induced by ischaemia/reperfusion

Background & Aims Ghrelin, a gut hormone with pleiotropic effects, may act as a protective signal in parenchymal cells. We investigated the protective effects of ghrelin on hepatocytes after ischaemia/reperfusion (I/R). Methods Hepatic injury was assessed by measurement of plasma alanine aminotransferase ( ALT ) and lactate dehydrogenase ( LDH ), histological analysis, and TUNEL assay. Effects of exogenous ghrelin and ghrelin receptor gene deletion on I/R induced injury of liver were evaluated. Results Ischaemia/reperfusion induced a profound injury to hepatocytes. This was accompanied by elevations in plasma ALT and LDH . Pretreatment with ghrelin significantly reduced elevations in plasma ALT and LDH , and attenuated tissue damage induced by hepatic I/R in mice. Hepatic injury induced by I/R was more pronounced in ghrelin receptor gene null mice. Ghrelin administration blocked the up‐regulation of AMP ‐activated protein kinase ( AMPK ) activity induced by hepatic I/R. Conclusions This study demonstrates that ghrelin contributes to the cytoprotection during hepatic I/R.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106759/1/liv12286.pd

Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's Sarcoma-associated herpesvirus by herpes simplex virus type 1

<p>Abstract</p> <p>Background</p> <p>Kaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to several acquired immunodeficiency syndrome-related malignancies, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and a subset of multicentric Castleman's disease. Regulation of viral lytic replication is critical to the initiation and progression of KS. Recently, we reported that herpes simplex virus type 1 (HSV-1) was an important cofactor that activated lytic cycle replication of KSHV. Here, we further investigated the possible signal pathways involved in HSV-1-induced reactivation of KSHV.</p> <p>Results</p> <p>By transfecting a series of dominant negative mutants and protein expressing constructs and using pharmacologic inhibitors, we found that either Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) or JAK1/STAT6 signaling failed to regulate HSV-1-induced KSHV replication. However, HSV-1 infection of BCBL-1 cells activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB, also called AKT) pathway and inactivated phosphatase and tensin homologue deleted on chromosome ten (PTEN) and glycogen synthase kinase-3β (GSK-3β). PTEN/PI3K/AKT/GSK-3β pathway was found to be involved in HSV-1-induced KSHV reactivation. Additionally, extracellular signal-regulated protein kinase (ERK) mitogen-activated protein kinase (MAPK) pathway also partially contributed to HSV-1-induced KSHV replication.</p> <p>Conclusions</p> <p>HSV-1 infection stimulated PI3K/AKT and ERK MAPK signaling pathways that in turn contributed to KSHV reactivation, which provided further insights into the molecular mechanism controlling KSHV lytic replication, particularly in the context of HSV-1 and KSHV co-infection.</p

Cardiac-derived CTRP9 protects against myocardial ischemia/reperfusion injury via calreticulin-dependent inhibition of apoptosis.

Cardiokines play an essential role in maintaining normal cardiac functions and responding to acute myocardial injury. Studies have demonstrated the heart itself is a significant source of C1q/TNF-related protein 9 (CTRP9). However, the biological role of cardiac-derived CTRP9 remains unclear. We hypothesize cardiac-derived CTRP9 responds to acute myocardial ischemia/reperfusion (MI/R) injury as a cardiokine. We explored the role of cardiac-derived CTRP9 in MI/R injury via genetic manipulation and a CTRP9-knockout (CTRP9-KO) animal model. Inhibition of cardiac CTRP9 exacerbated, whereas its overexpression ameliorated, left ventricular dysfunction and myocardial apoptosis. Endothelial CTRP9 expression was unchanged while cardiomyocyte CTRP9 levels decreased after simulated ischemia/`reperfusion (SI/R) in vitro. Cardiomyocyte CTRP9 overexpression inhibited SI/R-induced apoptosis, an effect abrogated by CTRP9 antibody. Mechanistically, cardiac-derived CTRP9 activated anti-apoptotic signaling pathways and inhibited endoplasmic reticulum (ER) stress-related apoptosis in MI/R injury. Notably, CTRP9 interacted with the ER molecular chaperone calreticulin (CRT) located on the cell surface and in the cytoplasm of cardiomyocytes. The CTRP9-CRT interaction activated the protein kinase A-cAMP response element binding protein (PKA-CREB) signaling pathway, blocked by functional neutralization of the autocrine CTRP9. Inhibition of either CRT or PKA blunted cardiac-derived CTRP9\u27s anti-apoptotic actions against MI/R injury. We further confirmed these findings in CTRP9-KO rats. Together, these results demonstrate that autocrine CTRP9 of cardiomyocyte origin protects against MI/R injury via CRT association, activation of the PKA-CREB pathway, ultimately inhibiting cardiomyocyte apoptosis

Mechanistic examination of causes for narrow distribution in an endangered shrub: a comparison of its responses to drought stress with a widespread congeneric species

Although deep rooting is usually considered a drought-tolerant trait, we found that Syringapinnatifolia, a deep rooting and hydrotropic shrub, has a limited distribution in arid areas. To elucidate the mechanisms for its narrow distribution, we conducted two experiments to examine the physiological and morphological responses to water availability and heterogeneity in S. pinnatifolia and a widespread congeneric species, S. oblata. We measured gas exchange, water use efficiency, and plasticity index in plants of these two species grown at different levels of soil water regimes and in containers with patched water distribution. Our results showed that high photosynthetic capacity in the narrowly distributed S. pinnatifolia was an important factor enabling its survival in the harsh sub-alpine environment. High photosynthetic capacity in S. pinnatifolia, however, was obtained at the expense of high transpiratory water loss, resulting in lower integrative water use efficiency. Biomass allocation to roots in S. pinnatifolia increased by 73 % when soil water increased from 75 to 95 % field capacity, suggesting that S. pinnatifolia could be less competitive for above-ground resources under favorable water regimes. The horizontal root hydrotropism and vertical root hydrotropism of S. pinnatifolia in soil with patched water patterns were likely related to compensation for leaf water loss at low soil water level, indicating a limited capacity for homeostasis within the plant for water conservation and lower level of inherent drought-tolerance. In summary, greater degree of morphological plasticity but lower degree of physiological adjustment may be the main causes for the hydrotropism and narrow distribution of S. pinnatifolia in the sub-alpine habitats