Methods and apparatus for constructing and implementing a universal extension module for processing objects in a database

Methods and apparatus for providing a multi-tier object-relational database architecture are disclosed. In one illustrative embodiment of the present invention, a multi-tier database architecture comprises an object-relational database engine as a top tier, one or more domain-specific extension modules as a bottom tier, and one or more universal extension modules as a middle tier. The individual extension modules of the bottom tier operationally connect with the one or more universal extension modules which, themselves, operationally connect with the database engine. The domain-specific extension modules preferably provide such functions as search, index, and retrieval services of images, video, audio, time series, web pages, text, XML, spatial data, etc. The domain-specific extension modules may include one or more IBM DB2 extenders, Oracle data cartridges and/or Informix datablades, although other domain-specific extension modules may be used

A metaphyseal fracture rat model for mechanistic studies of osteoporotic bone healing

Most osteoporotic fractures occur at metaphyseal regions of long bones. The present study proposed a clinically relevant animal model that satisfied: i) induction of osteoporosis, ii) unilateral complete osteotomy at metaphysis, iii) internal fixation. 6 months old female Sprague-Dawley rats (n = 64) were randomly divided into the ovariectomised-metaphyseal osteotomy (OVX, n = 32) and metaphyseal osteotomy (SHAM, n = 32) groups. The metaphyseal-osteotomy model was created with a plate-fixation of the osteotomy and assessed by X-ray, micro-computed tomography, histomorphometry and mechanical testing at weeks 1, 3 and 6. X-ray results showed complete healing of metaphyseal osteotomy at week 6. Histology showed 3 stages of metaphyseal healing. Stage 1 was characterised by fibrous tissue, consisting of disorganised orientation of collagen fibres, and infiltration of immune cells. At stage 2, a transitional zone consisting of maturing fibrous tissue and differentiating mesenchymal cells with early trabecular bone formation and disorganised woven bone were observed. During stage 3, cortical bone ends unified and woven bone underwent transformation to lamellar bone. OVX group healing was significantly delayed when compared to SHAM samples. The study demonstrated that healing of osteoporotic osteotomy at the metaphyseal region was delayed in terms of radiography, histomorphometry and mechanical strength. These quantitative evaluations, along with histological features, may provide key references for future studies. The animal model may provide additional clinical relevance as most osteoporotic fracture in humans occurs at metaphyseal regions

Small RNA analysis in Sindbis virus infected human HEK293 cells

In contrast to the defence mechanism of RNA interference (RNAi) in plants and invertebrates, its role in the innate response to virus infection of mammals is a matter of debate. Since RNAi has a well-established role in controlling infection of the alphavirus Sindbis virus (SINV) in insects, we have used this virus to investigate the role of RNAi in SINV infection of human cells

Bio-anthropological Studies on Human Skeletons from the 6th Century Tomb of Ancient Silla Kingdom in South Korea

In November and December 2013, unidentified human skeletal remains buried in a mokgwakmyo (a traditional wooden coffin) were unearthed while conducting an archaeological investigation near Gyeongju, which was the capital of the Silla Kingdom (57 BCE– 660 CE) of ancient Korea. The human skeletal remains were preserved in relatively intact condition. In an attempt to obtain biological information on the skeleton, physical anthropological, mitochondrial DNA, stable isotope and craniofacial analyses were carried out. The results indicated that the individual was a female from the Silla period, of 155 ± 5 cm height, who died in her late thirties. The maternal lineage belonged to the haplogroup F1b1a, typical for East Asia, and the diet had been more C3- (wheat, rice and potatoes) than C4-based (maize, millet and other tropical grains). Finally, the face of the individual was reconstructed utilizing the skull (restored from osseous fragments) and three-dimensional computerized modelling system. This study, applying multi-dimensional approaches within an overall bio-anthropological analysis, was the first attempt to collect holistic biological information on human skeletal remains dating to the Silla Kingdom period of ancient Korea

Evaluation of 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole as a Novel Anti-Inflammatory Drug Candidate

BACKGROUND: 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole (DIC) is a five-membered heterocyclic compound containing a N-O bond. The anti-inflammatory effects of this compound were studied both in vitro and in vivo. PRINCIPAL FINDINGS: DIC effectively decreased TNF-α and IL-6 release from LPS-stimulated macrophages in a dose dependent manner. DIC diminished the levels of COX-2 with subsequent inhibition of PGE(2) production. DIC also compromised HMGB1 translocation from the nucleus to the cytoplasm. Moreover, DIC prevented the nuclear translocation of NF-κB and inhibited the MAPK pathway. In vivo, DIC inhibited migration of neutrophils to the peritoneal cavity of mice. CONCLUSIONS: This study presents the potential utilization of a synthetic compound, as a lead for the development of novel anti-inflammatory drugs

Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.

Epstein-Barr virus (EBV), aetiologically linked to nasopharyngeal carcinoma (NPC), is the first human virus found to encode many miRNAs. However, how these viral miRNAs precisely regulate the tumour metastasis in NPC remains obscure. Here we report that EBV-miR-BART1 is highly expressed in NPC and closely associated with pathological and advanced clinical stages of NPC. Alteration of EBV-miR-BART1 expression results in an increase in migration and invasion of NPC cells in vitro and causes tumour metastasis in vivo. Mechanistically, EBV-miR-BART1 directly targets the cellular tumour suppressor PTEN. Reduction of PTEN dosage by EBV-miR-BART1 activates PTEN-dependent pathways including PI3K-Akt, FAK-p130(Cas) and Shc-MAPK/ERK1/2 signalling, drives EMT, and consequently increases migration, invasion and metastasis of NPC cells. Reconstitution of PTEN rescues all phenotypes generated by EBV-miR-BART1, highlighting the role of PTEN in EBV-miR-BART-driven metastasis in NPC. Our findings provide new insights into the metastasis of NPC regulated by EBV and advocate for developing clinical intervention strategies against NPC

Big Domains Are Novel Ca2+-Binding Modules: Evidences from Big Domains of Leptospira Immunoglobulin-Like (Lig) Proteins

binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. with dissociation constants of 2–4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm), probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. binding

Identification of a Novel Marine Fish Virus, Singapore Grouper Iridovirus-Encoded MicroRNAs Expressed in Grouper Cells by Solexa Sequencing

BACKGROUND: MicroRNAs (miRNAs) are ubiquitous non-coding RNAs that regulate gene expression at the post-transcriptional level. An increasing number of studies has revealed that viruses can also encode miRNAs, which are proposed to be involved in viral replication and persistence, cell-mediated antiviral immune response, angiogenesis, and cell cycle regulation. Singapore grouper iridovirus (SGIV) is a pathogenic iridovirus that has severely affected grouper aquaculture in China and Southeast Asia. Comprehensive knowledge about the related miRNAs during SGIV infection is helpful for understanding the infection and the pathogenic mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether SGIV encoded miRNAs during infection, a small RNA library derived from SGIV-infected grouper (GP) cells was constructed and sequenced by Illumina/Solexa deep-sequencing technology. We recovered 6,802,977 usable reads, of which 34,400 represented small RNA sequences encoded by SGIV. Sixteen novel SGIV-encoded miRNAs were identified by a computational pipeline, including a miRNA that shared a similar sequence to herpesvirus miRNA HSV2-miR-H4-5p, which suggests miRNAs are conserved in far related viruses. Generally, these 16 miRNAs are dispersed throughout the SGIV genome, whereas three are located within the ORF057L region. Some SGIV-encoded miRNAs showed marked sequence and length heterogeneity at their 3' and/or 5' end that could modulate their functions. Expression levels and potential biological activities of these viral miRNAs were examined by stem-loop quantitative RT-PCR and luciferase reporter assay, respectively, and 11 of these viral miRNAs were present and functional in SGIV-infected GP cells. CONCLUSIONS: Our study provided a genome-wide view of miRNA production for iridoviruses and identified 16 novel viral miRNAs. To the best of our knowledge, this is the first experimental demonstration of miRNAs encoded by aquatic animal viruses. The results provide a useful resource for further in-depth studies on SGIV infection and iridovirus pathogenesis

Cytokine Levels Correlate with Immune Cell Infiltration after Anti-VEGF Therapy in Preclinical Mouse Models of Breast Cancer

The effect of blocking VEGF activity in solid tumors extends beyond inhibition of angiogenesis. However, no studies have compared the effectiveness of mechanistically different anti-VEGF inhibitors with respect to changes in tumor growth and alterations in the tumor microenvironment. In this study we use three distinct breast cancer models, a MDA-MB-231 xenograft model, a 4T1 syngenic model, and a transgenic model using MMTV-PyMT mice, to explore the effects of various anti-VEGF therapies on tumor vasculature, immune cell infiltration, and cytokine levels. Tumor vasculature and immune cell infiltration were evaluated using immunohistochemistry. Cytokine levels were evaluated using ELISA and electrochemiluminescence. We found that blocking the activation of VEGF receptor resulted in changes in intra-tumoral cytokine levels, specifically IL-1β, IL-6 and CXCL1. Modulation of the level these cytokines is important for controlling immune cell infiltration and ultimately tumor growth. Furthermore, we demonstrate that selective inhibition of VEGF binding to VEGFR2 with r84 is more effective at controlling tumor growth and inhibiting the infiltration of suppressive immune cells (MDSC, Treg, macrophages) while increasing the mature dendritic cell fraction than other anti-VEGF strategies. In addition, we found that changes in serum IL-1β and IL-6 levels correlated with response to therapy, identifying two possible biomarkers for assessing the effectiveness of anti-VEGF therapy in breast cancer patients

Characterization of Epstein-Barr Virus miRNAome in Nasopharyngeal Carcinoma by Deep Sequencing

Virus-encoded microRNAs (miRNAs) have been shown to regulate a variety of biological processes involved in viral infection and viral-associated pathogenesis. Epstein-Barr virus (EBV) is a herpesvirus implicated in nasopharyngeal carcinoma (NPC) and other human malignancies. EBV-encoded miRNAs were among the first group of viral miRNAs identified. To understand the roles of EBV miRNAs in the pathogenesis of NPC, we utilized deep sequencing technology to characterize the EBV miRNA transcriptome in clinical NPC tissues. We obtained more than 110,000 sequence reads in NPC samples and identified 44 EBV BART miRNAs, including four new mature miRNAs derived from previously identified BART miRNA precursor hairpins. Further analysis revealed extensive sequence variations (isomiRs) of EBV miRNAs, including terminal isomiRs at both the 5′ and 3′ ends and nucleotide variants. Analysis of EBV genomic sequences indicated that the majority of EBV miRNA nucleotide variants resulted from post-transcriptional modifications. Read counts of individual EBV miRNA in NPC tissue spanned from a few reads to approximately 18,000 reads, confirming the wide expression range of EBV miRNAs. Several EBV miRNAs were expressed at levels similar to highly abundant human miRNAs. Sequence analysis revealed that most of the highly abundant EBV miRNAs share their seed sequences (nucleotides 2–7) with human miRNAs, suggesting that seed sequence content may be an important factor underlying the differential accumulation of BART miRNAs. Interestingly, many of these human miRNAs have been found to be dysregulated in human malignancies, including NPC. These observations not only provide a potential linkage between EBV miRNAs and human malignancy but also suggest a highly coordinated mechanism through which EBV miRNAs may mimic or compete with human miRNAs to affect cellular functions