Multi-omics analysis of glioblastoma and glioblastoma cell line: Molecular insights into the functional role of GPR56 in mesenchymal transition

G protein-coupled receptor 56 (GPR56/ADGRG1) is an adhesion GPCR with an essential role in brain development and cancer. Elevated expression of GPR56 was observed in the clinical specimens of Glioblastoma (GBM), a highly invasive primary brain tumor. However, we found the expression to be variable across the specimens, presumably due to the intratumor heterogeneity of GBM. Therefore, we re-examined GPR56 expression in public domain spatial gene expression data and single-cell expression data for GBM, which revealed that GPR56 expression was high in cellular tumors, infiltrating tumor cells, and proliferating cells, low in microvascular proliferation and peri-necrotic areas of the tumor, especially in hypoxic mesenchymal-like cells. To gain a better understanding of the consequences of GPR56 downregulation in tumor cells and other molecular changes associated with it, we generated a sh-RNA-mediated GPR56 knockdown in the GBM cell line U373 and performed transcriptomics, proteomics, and phospho-proteomics analysis. Our analysis revealed enrichment of gene signatures, pathways, and phosphorylation of proteins potentially associated with mesenchymal (MES) transition in the tumor and concurrent increase in cell invasion and migration behavior of the GPR56 knockdown GBM cells. Interestingly, our analysis also showed elevated expression of Transglutaminase 2 (TG2) - a known interactor of GPR56, in the knockdown cells. The inverse expression of GPR56 and TG2 was also observed in intratumoral, spatial gene expression data for GBM and in GBM cell lines cultured in vitro under hypoxic conditions. Integrating all these observations, we infer a functional link between the inverse expression of the two proteins, the hypoxic niche, and the mesenchymal status in the tumor. Hypoxia-induced downregulation of GPR56 and activation of TG2 may result in a network of molecular events that contribute to the mesenchymal transition of GBM cells, and we propose a putative model to explain this functional and regulatory relationship of the two proteins

Multiphase phenomena in Diesel fuel injection systems

Fuel Injection Equipment (FIE) are an integral component of modern Internal Combustion Engines (ICE), since they play a crucial role in the fuel atomization process and in the formation of a fuel/air combustible mixture, consequently affecting efficiency and pollutant formation. Advancements and improvements of FIE systems are determined by the complexity of the physical mechanisms taking place; the spatial scales are in the order of millimetres, flow may become locally highly supersonic, leading to very small temporal scales of microseconds or less. The operation of these devices is highly unsteady, involving moving geometries such as needle valves. Additionally, extreme pressure changes imply that many assumptions of traditional fluid mechanics, such as incompressibility, are no longer valid. Furthermore, the description of the fuel properties becomes an issue, since fuel databases are scarce or limited to pure components, whereas actual fuels are commonly hydrocarbon mixtures. Last but not least, complicated phenomena such as phase change or transition from subcritical to transcritical/supercritical state of matter further pose complications in the understanding of the operation of these devices

Positional Cloning of “Lisch-like”, a Candidate Modifier of Susceptibility to Type 2 Diabetes in Mice

In 404 Lepob/ob F2 progeny of a C57BL/6J (B6) x DBA/2J (DBA) intercross, we mapped a DBA-related quantitative trait locus (QTL) to distal Chr1 at 169.6 Mb, centered about D1Mit110, for diabetes-related phenotypes that included blood glucose, HbA1c, and pancreatic islet histology. The interval was refined to 1.8 Mb in a series of B6.DBA congenic/subcongenic lines also segregating for Lepob. The phenotypes of B6.DBA congenic mice include reduced β-cell replication rates accompanied by reduced β-cell mass, reduced insulin/glucose ratio in blood, reduced glucose tolerance, and persistent mild hypoinsulinemic hyperglycemia. Nucleotide sequence and expression analysis of 14 genes in this interval identified a predicted gene that we have designated “Lisch-like” (Ll) as the most likely candidate. The gene spans 62.7 kb on Chr1qH2.3, encoding a 10-exon, 646–amino acid polypeptide, homologous to Lsr on Chr7qB1 and to Ildr1 on Chr16qB3. The largest isoform of Ll is predicted to be a transmembrane molecule with an immunoglobulin-like extracellular domain and a serine/threonine-rich intracellular domain that contains a 14-3-3 binding domain. Morpholino knockdown of the zebrafish paralog of Ll resulted in a generalized delay in endodermal development in the gut region and dispersion of insulin-positive cells. Mice segregating for an ENU-induced null allele of Ll have phenotypes comparable to the B.D congenic lines. The human ortholog, C1orf32, is in the middle of a 30-Mb region of Chr1q23-25 that has been repeatedly associated with type 2 diabetes

Structural and spectroscopic studies on HoCr1-xFexO3 (x = 0 and 0.5) compounds

We report on the structural and spectroscopic studies on HoCr1-xFexO3 (x = 0 and 0.5) compounds. X-ray diffraction studies confirmed the phase purity of the compounds. An increase in the lattice parameter as well as bond lengh are evident with the addition of Fe at Cr-site in HoCrO3 compound. The addition of Fe content to Cr-site in HoCrO3 compound led to shift the position of phonon mode in Raman spectra as well as position of vibrational bands in FTIR specta recorded at room temperature. Temperature dependent Raman studies on both the compounds indicate the absence of structural phase transition in the investigated temperature region

Structural and spectroscopic studies on HoCr1-xFexO3 (x = 0 and 0.5) compounds

We report on the structural and spectroscopic studies on HoCr1-xFexO3 (x = 0 and 0.5) compounds. X-ray diffraction studies confirmed the phase purity of the compounds. An increase in the lattice parameter as well as bond lengh are evident with the addition of Fe at Cr-site in HoCrO3 compound. The addition of Fe content to Cr-site in HoCrO3 compound led to shift the position of phonon mode in Raman spectra as well as position of vibrational bands in FTIR specta recorded at room temperature. Temperature dependent Raman studies on both the compounds indicate the absence of structural phase transition in the investigated temperature region

“RECYCLED COARSE AGGREGATES”

The amount of construction waste has been dramatically increased in the last decade, and social and environmental concerns on the recycling of the waste have consequently been increased. Waste concrete is particularly crucial among the construction wastes. Recent technology has also improved the recycling process. In this rapid industrialized world, recycling construction material plays an important role to preserve the natural resources. This study aims to evaluate physical properties of concrete using recycled coarse aggregate. In this research concrete waste is from demolished structure (Near Kamla Nehru Park, Bhandarkar Rd, Pune) has been collected and coarse aggregate of different % is used for preparing fresh concrete. The amount of recycled coarse aggregate used in this research is approximately 125 kg. Many researchers state that recycled aggregates are only suitable for non-structural concrete application. This research, however, shows that the recycled aggregates that are obtained from concrete specimen make good quality concrete. The compressive strength of recycled coarse aggregate (RCA) is found to be higher than the compressive strength of normal concrete when used upto a certain %. Recycled aggregate concrete is in close proximity to normal concrete in terms of split tensile strength. The slump of recycled aggregate concrete is more than the normal concrete. At the end it can be said that the RCA upto 50 % can be used for optaining good quality concrete

Complete reversal of stereoselectivity in cyclopropanation of 2-arylidene-1-tetralone tricarbonylchromium complexes

Cyclopropanation of 2-arylidene-1-tetralone tricarbonylchromium complexes with dimethylsulfoxonium methylide under phase-transfer catalysis condition provided cyclopropanes exclusively from the endo-face

Complete DNA Sequences of Two Oka Strain Varicella-Zoster Virus Genomes▿

Varicella-zoster virus (VZV) is a herpesvirus and is the causative agent of chicken pox (varicella) and shingles (herpes zoster). Active immunization against varicella became possible with the development of live attenuated varicella vaccine. The Oka vaccine strain was isolated in Japan from a child who had typical varicella, and it was then attenuated by serial passages in cell culture. Several manufacturers have obtained this attenuated Oka strain and, following additional passages, have developed their own vaccine strains. Notably, the vaccines Varilrix and Varivax are produced by GlaxoSmithKline Biologicals and Merck & Co., Inc., respectively. Both vaccines have been well studied in terms of safety and immunogenicity. In this study, we report the complete nucleotide sequence of the Varilrix (Oka-VGSK) and Varivax (Oka-VMerck) vaccine strain genomes. Their genomes are composed of 124,821 and 124,815 bp, respectively. Full genome annotations covering the features of Oka-derived vaccine genomes have been established for the first time. Sequence analysis indicates 36 nucleotide differences between the two vaccine strains throughout the entire genome, among which only 14 are involved in unique amino acid substitutions. These results demonstrate that, although Oka-VGSK and Oka-VMerck vaccine strains are not identical, they are very similar, which supports the clinical data showing that both vaccines are well tolerated and elicit strong immune responses against varicella