TASK DEFINITION: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: The role of Kdr (VEGFR-2/Flk-1) in vascular formation has been well described, but the role of Flt1 (VEGFR-1) is not well studied and is generally considered as a decoy receptor for trapping VEGF.', 'The effects of VEGFR1/2 kinase inhibitor (VRI) and calycosin on Flt1 tyrosine kinase (TK) activity were evaluated by molecular docking, enzymatic inhibition assay, protein co-immunoprecipitation and siRNA gene knock-down analysis in HUVECs. Toxicities of the chemicals were examined using HUVECs viability. Their effects on angiogenesis and vessel formation were furthered studied in HUVECs in vitro and Tg(fli-1:EGFP) zebrafish in vivo. The gene and protein expression of VEGF and VEGF receptors were investigated by quantitative RT-PCR and Western blot.', 'VRI strongly inhibited physiological functions of both VEGF receptors and suppressed endothelial cell survival. This resulted in blood vessel loss in zebrafish embryos. Interestingly, calycosin co-treatment impeded VRI-induced blood vessel loss. Docking and kinase inhibition assay revealed that calycosin competed with VRI for the tyrosine kinase domain of Flt1 without affecting ATP binding. On the contrary, calycosin did not affect the interaction between VRI and Kdr-TK. Consistent with these results, calycosin counteracted the inhibition of Flt1-TK and PI3K phosphorylation induced by VRI in HUVECs. Further studies in vitro and in vivo showed that the minimizing effect of calycosin on VRI-mediated endothelial cytotoxicity was blocked by wortmannin (a PI3K inhibitor). The impeding effect of calycosin on VRI-induced blood vessel loss was absent in zebrafish embryos injected with Flt1 MO.

SOLUTION: Is basal Flt1 tyrosine kinase activity a positive regulator of endothelial survival and vascularization during zebrafish embryogenesis?

PROBLEM: Recently we have shown that the imunoglobulins G from blood serum of some multiple sclerosis patients are capable of cleaving histone H1.', 'To check whether histone H1-hydrolyzing abzymes could be detected not only in blood plasma of autoimmune patients, but also during cancer development, particularly during the onset of multiple myeloma.', "Immunoglobulines were isolated from blood serum of multiple myeloma patients (n = 11) by precipitation with 50% ammonium sulfate and tested for proteolytic activity toward linker and core calf thymus histones. Antibody preparations able to cleaved histone H1 were subjected to affinity chromatography on histone H1-Sepharose with following analysis of chromatographic fractions' protease activity. To prove that antibody molecules are responsible for hydrolysis of histone H1, gel filtration at acidic pH with subsequent examination of protease activity of chromatographic fractions (pH-shock analysis) was used.", 'It was found that 3 of 11 antibody preparations are capable of hydrolyzing calf thymus histone H1 but not core histones. It was shown that histone H1-hydrolysing activity of 2 proteolytically active antibody preparations is associated with IgGs that possess affinity towards histone H1. pH-shock analysis proved that protease activity towards histone H1 is intrinsic property of IgG molecules.

SOLUTION: Are blood serum immunoglobulins of patients with multiple myeloma capable of hydrolysing histone H1?

PROBLEM: Prolonged re-exposure to a fear-eliciting cue in the absence of an aversive event extinguishes the fear response to the cue, and has been clinically used as an exposure therapy. Arc (also known as Arg3.1) is implicated in synaptic and experience-dependent plasticity. Arc is regulated by the transcription factor cAMP response element binding protein, which is upregulated with and necessary for fear extinction. Because Arc expression is also activated with fear extinction, we hypothesized that Arc expression is required for fear extinction.', 'Extinction training increased the proportion of Arc-labeled cells in the basolateral amygdala (BLA). Arc was transcribed during latter part of extinction training, which is possibly associated with fear extinction, as well as former part of extinction training. Intra-BLA infusions of Arc antisense oligodeoxynucleotide (ODN) before extinction training impaired long-term but not short-term extinction memory. Intra-BLA infusions of Arc antisense ODN 3\xa0h after extinction training had no effect on fear extinction.

SOLUTION:
Does fear extinction require Arc/Arg3.1 expression in the basolateral amygdala?