TASK DEFINITION: Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
PROBLEM: Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by hypoproliferative anemia, associated physical malformations and a predisposition to cancer. DBA has been associated with mutations and deletions in the large and small ribosomal protein genes, and genetic aberrations have been detected in 50-60% of patients. In this study, nine Korean DBA patients were screened for mutations in eight known DBA genes (RPS19, RPS24, RPS17, RPS10, RPS26, RPL35A, RPL5 and RPL11) using the direct sequencing method. Mutations in RPS19, RPS26 and RPS17 were detected in four, two and one patient, respectively. Among the mutations detected in RPS19, two mutations were novel (c.26T>A, c.357-2A>G). For the mutation-negative cases, array-CGH analysis was performed to identify copy-number variations, and no deletions involving the known DBA gene regions were identified. The relative mRNA expression of RPS19 estimated using real-time quantitative PCR analysis revealed two- to fourfold reductions in RPS19 mRNA expression in three patients with RPS19 mutations, and p53 protein expression analysis by immunohistochemistry showed variable but significant nuclear staining in the DBA patients. In conclusion, heterozygous mutations in the known DBA genes RPS19, RPS26 and RPS17 were detected in seven out of nine Korean DBA patients. Among these patients, RPS19 was the most frequently mutated gene. In addition, decreased RPS19 mRNA expression and p53 overexpression were observed in the Korean DBA patients, which supports the hypothesis that haploinsufficiency and p53 hyperactivation represent a central pathway underlying the pathogenesis of DBA.

SOLUTION: In which syndrome is the RPS19 gene most frequently mutated?

PROBLEM: The Bacillus anthracis toxin genes, cya, lef, and pag, can be viewed as a regulon, in which transcription of all three genes is activated in trans by the same regulatory gene, atxA, in response to the same signal, CO2. In atxA+ strains, toxin gene expression is increased 5- to 20-fold in cells grown in 5% CO2 relative to cells grown in air. CO2-enhanced toxin gene transcription is not observed in atx4-null mutants. Here, we used two independent techniques to obtain evidence for additional CO2-induced atxA-regulated genes. First, total protein preparations from atxA4+ and atxA isolates grown in 5% CO2 and in air were examined by two-dimensional electrophoresis. Comparison of the resulting protein patterns indicated that synthesis of non-toxin proteins is influenced by growth in elevated CO2 and the toxin gene regulator, atxA. Second, we generated random transcriptional lacZ fusions in B. anthracis with transposon Tn917-LTV3. Transposon-insertion libraries were screened for mutants expressing CO2-enhanced atxA-dependent beta-galactosidase activity. DNA sequence analysis of transposon insertion sites in 17 mutants carrying CO2- and atxA-regulated fusions revealed 10 mutants carrying independent insertions on the 185-kb toxin plasmid pXO1 which did not map to the toxin genes. The tcr-lacZ fusion mutants (tcr for toxin coregulated) were Tox+, indicating that these genes may not be involved in anthrax toxin gene activation. Our data indicate a clear association of atxA with CO2-enhanced gene expression in B. anthracis and provide evidence that atxA regulates genes other than the structural genes for the anthrax toxin proteins.

SOLUTION: Which metabolite activates AtxA?

PROBLEM: Darma (Pierre Andre) is traumatised by the mysterious death of his fiancee, Rose (Intan Ladyana) who had killed herself. Unknown to him, Rose had been haunted by a malicious spirit which they had brought to her home after picking up a small jar found washed up at the beach. Apparently, the spirit had been imprisoned and was inadvertently released by the couple.At her home, after her death, before leaving Darma had taken the small jar with him, and with it, the malignant spirit.Not satisfied with why Rose had suddenly killed herself, Darma decides to investigate the case with the help of Rose's twin sister, Seri, (also played by Intan Ladyana). As they probe into the death, a series of strange occurrences start to unravel, leaving Darma in a disturbed state of mind that affects his life and career. When he is advised to take a week's break from work, he returns to his village to rest. Unknown to him, he is only getting closer to solving his fiancee's death and the truth behind the strange happenings.It was Darma's senile grandmother who could see the ghost and had unwittingly invited the spirit into the house. In Malay belief, certain spirits cannot enter the house unless invited in. This is similar to the vampire mythology in the West. The ghost in this movie is called Saka. Saka was a ghost that has been kept by the elder for some uncertified reason. Mostly, Saka starts to give problems when it's owner die and Saka needs to be feed. Mostly, Saka will haunt the next generation of the owner.

SOLUTION:
What is Darma advised to take from work?