In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

Ex Input:
Context: Monocytes are cellular components of wound repair, arteriogenesis, and atherogenesis. Vascular endothelial growth factor (VEGF)-A and placental growth factor recruit monocytes to sites of arteriogenesis via stimulation of VEGF receptor-1 (VEGFR-1). The chemotactic response of monocytes to VEGF-A is attenuated in individuals with diabetes mellitus (DM). This VEGF resistance correlates with impaired collateral growth. The aim of this study is to elucidate the molecular basis of VEGF resistance and impaired monocyte response in DM.', 'Phosphorylation of Akt, p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) could be stimulated with either placental growth factor-1 or VEGF-A in monocytes from non-DM but not DM individuals. In contrast, formyl-methionyl-leucyl-phenylalanine caused a comparable activation of these molecules in both DM and non-DM monocytes. Baseline phosphorylation of Akt, p38, and ERK1/2 was significantly elevated in monocytes from DM compared with non-DM subjects. Of note, H(2)O(2) activated Akt, p38, and ERK1/2 in non-DM monocytes ex vivo. Protein tyrosine phosphatases had stronger oxidative modifications in monocytes from DM than from non-DM individuals, which reflects functional protein tyrosine phosphatase inhibition, similar to that seen after H(2)O(2) challenge. Overall, protein tyrosine phosphatase and protein tyrosine phosphatase-1B activity were reduced in DM monocytes. DM monocytes revealed higher expression of the receptor for advanced glycation end products. Stimulation with advanced glycation end products ligands resulted in activation of non-DM monocytes and inhibition of VEGFR-1-mediated chemotaxis. The elevated baseline phosphorylation/activation of Akt, p38, and ERK1/2 in DM monocytes likely causes the resistance to further stimulation with specific stimuli such as VEGF-A, revealing a molecular explanation of the DM-related signal transduction defect.\Question: Does diabetes mellitus activate signal transduction pathways resulting in vascular endothelial growth factor resistance of human monocytes?

Ex Output:
We propose that elevated advanced glycation end products expression and increased oxidative stress in diabetic monocytes lead to activation of VEGFR-1-related signaling pathways and to desensitization of VEGFR-1 responses. These data establish VEGF resistance as a novel molecular concept for DM-related cellular dysfunction.


Ex Input:
Context: Globally, heterosexual intercourse is the primary route of HIV-1 (HIV) transmission. It follows that mechanisms that protect against HIV infection are likely operative at the genital mucosa. In HIV-resistant Kenyan sex workers who are highly exposed to HIV infection yet remain uninfected, protection correlates with HIV-specific immune responses and genetic factors. However, these factors do not entirely explain this model of natural immunity to HIV. We hypothesized that protection may be mediated by innate immune proteins in the genital tract of HIV-resistant sex workers.', 'The genital proteome of mucosal secretions from HIV-resistant women was examined using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Cervical lavage samples were collected from 315 HIV-resistant, HIV-uninfected and HIV-infected commercial sex workers.', 'Univariate analysis identified a 6 kDa biomarker of HIV resistance in genital secretions from these women. This protein was identified by tandem mass spectrometry as elafin and was found to be overexpressed in HIV-resistant women compared with HIV-uninfected (P = 0.001) and infected (P = 0.002) women. The elevated levels of elafin/trappin-2 in HIV-resistant women were confirmed using ELISA. The prospective association of elevated cervicovaginal elafin/trappin-2 levels with protection from HIV acquisition was then confirmed in an independent cohort of high-risk female sex workers.\Question: Does elevated elafin/trappin-2 in the female genital tract is associate with protection against HIV acquisition?

Ex Output:
Using a unique proteomics approach in a large scale, cross-sectional cohort study, we identified elafin/trappin-2 as a novel innate immune factor, which is highly associated with resistance. This association was confirmed within an independent, prospective cohort study. Genital tract elafin/trappin-2 levels constitute a natural correlate of HIV protection in humans.


Ex Input:
Context: Chemokines play a critical role in the pathogenesis of asthma and facilitate the recruitment of inflammatory cells in the airways. Evidence now suggests that airway smooth muscle (ASM) may serve as a source of chemokines in inflamed airways. Although vitamin D has potent anti-inflammatory properties in vitro in some cell types, its effects on ASM cells remain unclear. Here, we investigated whether 1alpha, 25-dihydroxy vitamin D3 (calcitriol) modulated chemokine production in ASM.', 'Human ASM cell cultures were derived from tracheal samples taken during surgery. ASM cells were treated with tumour necrosis factor alpha (TNFalpha) and/or interferon gamma (IFNgamma) for 24 h in the presence of calcitriol and/or the glucocorticoid fluticasone added 2 h before. RANTES (regulated upon activation, normal T-cell expressed and secreted), interferon-inducible protein 10 (IP-10) and fractalkine (FKN) levels in cell supernatants were measured by ELISA.', 'In TNFalpha-treated cells, calcitriol inhibited RANTES and IP-10 secretion in a concentration-dependent manner. FKN levels were negligible. In TNFalpha/IFNgamma-treated cells, whereas fluticasone or calcitriol alone partially inhibited RANTES secretion (by 38 and 20%, respectively), the combination of both drugs additively inhibited RANTES secretion (by 60%). No effect was observed on IP-10 secretion. Whereas fluticasone enhanced FKN secretion (by 50%), calcitriol significantly decreased FKN levels (by 50%). Interestingly, calcitriol blocked the stimulatory effect of fluticasone on FKN secretion, which was inhibited by 60% with the combination of calcitriol and fluticasone.\Question: Do vitamin D and glucocorticoids differentially modulate chemokine expression in human airway smooth muscle cells?

Ex Output:

These findings suggest that vitamin D uniquely modulates human ASM expression of chemokines and may exert some beneficial effects in the treatment of steroid-resistant patients with asthma.