TASK DEFINITION: Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
PROBLEM: To evaluate the role of apoptosis in the pathogenesis of brain lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary microangiopathy leading to cognitive decline and dementia, caused by mutations in the NOTCH3 gene. Detection of apoptotic nuclei in temporal lobe, brain stem, medulla oblongata, hippocampus and basal ganglia from one young CADASIL patient was performed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL). Our results showed a great involvement of glial cells in apoptotic cell death in the majority of the brain regions examined; neuronal apoptosis was significantly present only in the brain stem region. We hypothesized that in the early stages of the disease neuronal involvement of apoptosis is limited to the cells of the brain stem, sparing the cortical area which is involved in neuronal apoptosis and cognitive decline later.

SOLUTION: Which gene is involved in CADASIL?

PROBLEM: With an ageing population and improving cancer therapies, the two most common benign and malignant bone diseases, osteoporosis and bone metastases, will continue to affect an increasing number of patients. Our expanding knowledge of the molecular processes underlying these conditions has resulted in novel bone targets that are currently being explored in clinical trials. Clearly, the approval of denosumab, a monoclonal antibody directed against RANKL, has just marked the beginning of a new era for bone therapy with several additional new therapies lining up for clinical approval in the coming years. Potential agents targeting the osteoclast include cathepsin K, currently in phase 3 trials, and src inhibitors. Amongst anabolic agents, inhibitors of the Wnt-inhibitor sclerostin and dickkopf-1 are promising in clinical trials. Here, we will provide a comprehensive overview of the most promising agents currently explored for the treatment of bone diseases.

SOLUTION: To the ligand of which receptors does Denosumab (Prolia) bind?

PROBLEM: Parkinson's disease is the most common neurodegenerative movement disorder. -Synuclein is a small synaptic protein that has been linked to familial Parkinson's disease (PD) and is also the primary component of Lewy bodies, the hallmark neuropathology found in the brain of sporadic and familial PD patients. The function of -synuclein is currently unknown, although it has been implicated in the regulation of synaptic vesicle localization or fusion. Recently, overexpression of -synuclein was shown to cause cytoplasmic vesicle accumulation in a yeast model of -synuclein toxicity, but the exact role -synuclein played in mediating this vesicle aggregation is unclear. Here, we show that -synuclein induces aggregation of many yeast Rab GTPase proteins, that -synuclein aggregation is enhanced in yeast mutants that produce high levels of acidic phospholipids, and that -synuclein colocalizes with yeast membranes that are enriched for phosphatidic acid. Significantly, we demonstrate that -synuclein expression induces vulnerability to perturbations of Ypt6 and other proteins involved in retrograde endosome-Golgi transport, linking a specific trafficking defect to -synuclein phospholipid binding. These data suggest new pathogenic mechanisms for -synuclein neurotoxicity.

SOLUTION:
Which is the primary protein component of Lewy bodies?