In this task, you are given an abstract of article. Your task is to generate title for this article. Preferred titles are under thirty words.

Ex Input:
Publisher Summary This chapter discusses the developmental roles of vascular endothelial growth factor (VEGF) in skeletal morphogenesis, speculates on the future directions of research in this area, and describes some of the challenges in the field. VEGF regulates osteoclastic differentiation, migration, and activity. VEGF is, therefore, a key coordinator of the entire process. VEGF is necessary for osteoclastic activity both at the stage when the primary ossification center is established and later during bone growth. A number of studies have led to the identification of VEGF as a critical factor for the survival of chondrocytes. Several factors with important roles in regulating bone formation also induce the expression of VEGF by osteoblasts. Prostaglandins E1 and E2, BMP-4, BMP-6, BMP-7, FGF-2, TGF-, endothelin-1, IGF-1, and vitamin D3 can all induce VEGF expression in osteoblasts by activating a variety of signaling pathways. Bone fractures can heal in two divergent ways, similar to the two ways of forming bone during embryonic development. Stabilized fractures heal by intramembranous ossification, and unstable fractures undergo endochondral ossification. The similarity between the embryonic bone development and repair of fractured bones, coupled with the finding that VEGF is expressed at sites of bone fracture, suggests that VEGF is involved in bone repair as it is in bone development.

Ex Output:
Multiple roles of vascular endothelial growth factor (VEGF) in skeletal development, growth, and repair.

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The prognosis of glioblastoma, the most malignant type of glioma, is still poor, with only a minority of patients showing long-term survival of more than three years after diagnosis. To elucidate the molecular aberrations in glioblastomas of long-term survivors, we performed genome- and/or transcriptome-wide molecular profiling of glioblastoma samples from 94 patients, including 28 long-term survivors with >36 months overall survival (OS), 20 short-term survivors with <12 months OS and 46 patients with intermediate OS. Integrative bioinformatic analyses were used to characterize molecular aberrations in the distinct survival groups considering established molecular markers such as isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations, and O(6) -methylguanine DNA methyltransferase (MGMT) promoter methylation. Patients with long-term survival were younger and more often had IDH1/2-mutant and MGMT-methylated tumors. Gene expression profiling revealed over-representation of a distinct (proneural-like) expression signature in long-term survivors that was linked to IDH1/2 mutation. However, IDH1/2-wildtype glioblastomas from long-term survivors did not show distinct gene expression profiles and included proneural, classical and mesenchymal glioblastoma subtypes. Genomic imbalances also differed between IDH1/2-mutant and IDH1/2-wildtype tumors, but not between survival groups of IDH1/2-wildtype patients. Thus, our data support an important role for MGMT promoter methylation and IDH1/2 mutation in glioblastoma long-term survival and corroborate the association of IDH1/2 mutation with distinct genomic and transcriptional profiles. Importantly, however, IDH1/2-wildtype glioblastomas in our cohort of long-term survivors lacked distinctive DNA copy number changes and gene expression signatures, indicating that other factors might have been responsible for long survival in this particular subgroup of patients.

Ex Output:
Molecular characterization of long-term survivors of glioblastoma using genome- and transcriptome-wide profiling.

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We have systematically made a set of precisely defined, singlegene deletions of all nonessential genes in Escherichia coli K12. Openreading frame coding regions were replaced with a kanamycin cassette flanked by FLP recognition target sites by using a onestep method for inactivation of chromosomal genes and primers designed to create inframe deletions upon excision of the resistance cassette. Of 4288 genes targeted, mutants were obtained for 3985. To alleviate problems encountered in highthroughput studies, two independent mutants were saved for every deleted gene. These mutantsthe 'Keio collection'provide a new resource not only for systematic analyses of unknown gene functions and gene regulatory networks but also for genomewide testing of mutational effects in a common strain background, E . coli K12 BW25113. We were unable to disrupt 303 genes, including 37 of unknown function, which are candidates for essential genes. Distribution is being handled via GenoBase (http://ecoli.aistnara.ac.jp/).

Ex Output:
Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection