TASK DEFINITION: Given a passage with a context and an answer, 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: Context: Cerebral deposition of phospho-tau in Alzheimer's disease (AD) occurs with varying patterns within hippocampus. Lamina-specific tau changes in AD may reflect trans-synaptic propagation of phospho-tau along neuroanatomical pathways.", 'To study patterns of tau deposition within inner (IML) and outer (OML) molecular layers of dentate gyrus and their clinical and neuropathological correlates.', '98 consecutive autopsied brains from the Columbia University Brain Bank were stained for phospho-tau using AT-8. Staining density was rated as High versus Low within IML and OML. Four patterns were observed among the 98 brains: High IML&OML, n = 44; High OML Only (n = 35); High IML Only (n = 5); and Low IML&OML (n = 14). Demographic, clinical, and neuropathological characteristics of these four groups were compared.', 'High IML&OML subjects, versus High OML Only, were more likely to fulfill CERAD criteria for Definite AD (93% versus 66%, p < 0.01) and to have higher median Braak stage (6 versus 5, p < 0.01) and earlier mean age of onset (65.9 versus 73.7 y, p = 0.02), with similar symptom duration. Using logistic regression, the association between High IML&OML and AD remained significant after adjustment for demographics but not symptom duration. In the 70 subjects with Definite AD, High IML&OML was associated with younger age of onset (mean difference 3.7 years, 95%CI -6.7 to -0.7, p < 0.01), after adjustment for demographics and symptom duration.
Answer: Phospho-tau pathology, when prominent within both IML and OML, is associated with CERAD diagnosis of Definite AD and earlier age of onset in AD. Laminar patterns of tau deposition reflect regional involvements during disease course.

SOLUTION: Does hippocampal laminar distribution of tau relate to Alzheimer 's disease and age of onset?

PROBLEM: Context: Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Deletions and duplications of the Williams-syndrome region have also been associated with autism, and with schizophrenia, two disorders centrally involving social cognition. Several lines of evidence have linked the gene GTF2I (General Transcription Factor IIi) with the social phenotypes of Williams syndrome, but a role for this gene in sociality within healthy populations has yet to be investigated.', 'We genotyped a large set of healthy individuals for two single-nucleotide polymorphisms in the GTF2I gene that have recently been significantly associated with autism, and thus apparently exhibit functional effects on autism-related social phenotypes. GTF2I genotypes for these SNPs showed highly significant association with low social anxiety combined with reduced social-communication abilities, which represents a metric of the Williams-syndrome cognitive profile as described from previous studies.
Answer: These findings implicate the GTF2I gene in the neurogenetic basis of social communication and social anxiety, both in Williams syndrome and among individuals in healthy populations.

SOLUTION: Are cognitive-behavioral phenotypes of Williams syndrome associated with genetic variation in the GTF2I gene , in a healthy population?

PROBLEM: Context: Phosphatidylinositol 3-OH kinase (PI3K) has a long-recognized role in beta-cell mass regulation and gene transcription and is implicated in the modulation of insulin secretion. The role of nontyrosine kinase receptor-activated PI3K isoforms is largely unexplored. We therefore investigated the role of the G-protein-coupled PI3Kgamma and its catalytic subunit p110gamma in the regulation of insulin granule recruitment and exocytosis.', 'The expression of p110gamma was knocked down by small-interfering RNA, and p110gamma activity was selectively inhibited with AS605240 (40 nmol/l). Exocytosis and granule recruitment was monitored by islet perifusion, whole-cell capacitance, total internal reflection fluorescence microscopy, and electron microscopy in INS-1 and human beta-cells. Cortical F-actin was examined in INS-1 cells and human islets and in mouse beta-cells lacking the phosphatase and tensin homolog (PTEN).', 'Knockdown or inhibition of p110gamma markedly blunted depolarization-induced insulin secretion and exocytosis and ablated the exocytotic response to direct Ca(2+) infusion. This resulted from reduced granule localization to the plasma membrane and was associated with increased cortical F-actin. Inhibition of p110gamma had no effect on F-actin in beta-cells lacking PTEN. Finally, the effect of p110gamma inhibition on granule localization and exocytosis could be rapidly reversed by agents that promote actin depolymerization.
Answer: The G-protein-coupled PI3Kgamma is an important determinant of secretory granule trafficking to the plasma membrane, at least in part through the negative regulation of cortical F-actin. Thus, p110gamma activity plays an important role in maintaining a membrane-docked, readily releasable pool of secretory granules in insulinoma and human beta-cells.

SOLUTION:
Is insulin granule recruitment and exocytosis dependent on p110gamma in insulinoma and human beta-cells?