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.

[Q]: Corticotropin-releasing factor (CRF) is the primary physiologic regulator of the hypothalamic-pituitary-adrenal (HPA) axis and serves to globally coordinate the mammalian stress response. Hyperactivity of central nervous system CRF neurotransmission, acting primarily via the CRF(1) receptor, has been strongly implicated in the pathophysiology of depression and anxiety. Furthermore, there is evidence of enhanced CRF transcription, release, and neuronal activity after the administration of and withdrawal from several drugs of abuse, including cannabis, cocaine, ethanol, and morphine. Treatment with CRF antagonists has been demonstrated to reduce the severity of certain drug withdrawal symptoms, implicating a specific role for activation of CRF neurons in mediating the anxiogenic and stress-like reactions observed after abrupt drug discontinuation.', 'To extend these findings, we investigated whether pretreatment with the selective CRF(1) receptor antagonist R121919 decreases the behavioral and neuroendocrine activation observed after the precipitation of benzodiazepine (BZ) withdrawal in BZ-dependent rats.', 'Pretreatment with R121919 attenuated the subsequent HPA axis activation, behavioral measures of anxiety, and expression of the CRF gene in the paraventricular nucleus of the hypothalamus, as measured by CRF heteronuclear RNA, which occurs after flumazenil-precipitation of withdrawal from the BZ, lorazepam.
[A]: Does the CRF1 receptor antagonist R121919 attenuate the neuroendocrine and behavioral effects of precipitated lorazepam withdrawal?


[Q]: Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that plays a role in angiogenesis and microvascular permeability. This study was conducted to determine whether common sequence variation in the VEGFA gene plays a role in the development of diabetic retinopathy (DR).', 'Five hundred fifty-four subjects with diabetes mellitus (DM) including 190 type 1 DM (T1DM) and 364 type 2 DM (T2DM) were recruited. The study group consisted of 235 participants without DR, 158 with nonproliferative DR (NPDR), 132 with proliferative DR (PDR), and 93 with clinically significant macular edema (CSME). Blinding DR was defined as severe NPDR, PDR, or CSME. Fifteen VEGFA tag single-nucleotide polymorphisms (SNPs) were genotyped in all subjects and tested for association with blinding DR.', 'Multiple tag SNPs in the VEGFA gene were associated with blinding DR. After controlling for sex, HbA1c, and duration of disease, in T1DM, the AA genotype of rs699946 (P = 0.007, odds ratio [OR], 4.1; 95% confidence interval [CI], 1.5-11.4) and the GG genotype of rs833068 (P = 0.017, OR, 3.1; 95% CI, 1.3-7.2) were most significantly associated. In T2DM, the C allele of rs3025021 (P = 0.002; OR, 3.8; 95% CI, 1.5-10.0) and the G allele of rs10434 (P = 0.002; OR, 2.6; 95% CI, 1.3-5.3) were most significantly associated with blinding DR. Haplotype analyses suggested an important role for the haplotype TCCGCG in blinding DR (P = 0.0004).
[A]: Does common sequence variation in the VEGFA gene predict risk of diabetic retinopathy?


[Q]: Dopamine and corticotrophin-releasing hormone (CRH; also known as corticotrophin-releasing factor) are key neurotransmitters in the interaction between stress and addiction. Repeated treatment with cocaine potentiates glutamatergic transmission in the rat basolateral amygdala/cortex pathway through a synergistic action of D1 -like dopamine receptors and CRH type-2α receptors (CRF2 α receptors). We hypothesized that this observed synergism could be instrumented by heteromers containing the dopamine D1 receptor and CRF2 α receptor.', 'D1 /CRF2 α receptor heteromerization was demonstrated in HEK293T cells using co-immunoprecipitation, BRET and FRET assays, and by using the heteromer mobilization strategy. The ability of D1 receptors to signal through calcium, when singly expressed or co-expressed with CRF2 α receptors, was evaluated by the calcium mobilization assay.', 'D1 /CRF2 α receptor heteromers were observed in HEK293T cells. When singly expressed, D1 receptors were mostly located at the cell surface whereas CRF2 α receptors accumulated intracellularly. Interestingly, co-expression of both receptors promoted D1 receptor intracellular and CRF2 α receptor cell surface targeting. The heteromerization of D1 /CRF2 α receptors maintained the signalling through cAMP of both receptors but switched D1 receptor signalling properties, as the heteromeric D1 receptor was able to mobilize intracellular calcium upon stimulation with a D1 receptor agonist.
[A]:
Do dopamine D1 and corticotrophin-releasing hormone type-2α receptors assemble into functionally interacting complexes in living cells?