TASK DEFINITION: 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.
PROBLEM: Context: Apicomplexan parasites actively release transmembrane (TM) adhesive proteins involved in host cell attachment and invasion. Rhomboids, a family of intramembrane serine proteases, cleave these secreted adhesive proteins within their TM domains as an essential step in completing the invasion process. In Cryptosporidium parvum, the activity of rhomboids in cleaving microneme proteins (MICs) has not been reported. In the present study, the interaction between C. parvum rhomboids (CpROM1 and CpROM4) and C. parvum microneme proteins (CpGP900 and CpTRAP-C1) was investigated using yeast two-hybrid assay and co-immunoprecipitation assays.', 'Our study demonstrated that CpROM1 protein could interact with CpGP900 protein in co-transformed AH109 yeasts. Analysis of these proteins in co-transfected mammalian cells showed that the cleavage product of the CpGP900 protein was detected in the co-transfected cells. As control, CpGP900 only was transfected into cells and no cleavage was observed. The results suggested that CpGP900 protein was the substrate of CpROM1. Moreover, CpROM1 and CpROM4 could not cleave CpTRAP-C1 protein, which is the substrate of T. gondii rhomboid 2.\Question: Does cryptosporidium parvum rhomboid1 have an activity in microneme protein CpGP900 cleavage?

SOLUTION: Our results showed that CpROM1 is an active protease that is involved in microneme protein CpGP900 cleavage, which lay the foundation for further research on the mechanisms of C. parvum invasion.

PROBLEM: Context: Infection of human immunodeficiency virus (HIV) has been associated with several chronic diseases, including pulmonary artery hypertension and atherosclerosis. However, the underlying mechanisms of these vascular complications are largely unknown. The objective of this study was to test a novel hypothesis that HIV Nef, an accessory HIV protein, may directly affect endothelial functions and gene expression in pulmonary arteries.', 'Fresh porcine pulmonary artery rings and human pulmonary artery endothelial cells (HPAECs) were treated with HIV Nef for 24 h. With a myograph device, vasomotor function was determined with thromboxane A2 analog, U46619, for contraction, bradykinin, and sodium nitroprusside for relaxation. The expression of endothelial nitric oxide synthase (eNOS) was determined with real-time PCR and immunohistochemistry. Nitric oxide (NO) production was determined by Calorimetric Nitric Oxide Assay kit. Superoxide anion levels were detected with lucigenin-enhanced chemiluminescence assay and dihydroethidium (DHE) staining.', 'The endothelium-dependent vasorelaxation in response to bradykinin was significantly reduced in HIV Nef-treated porcine pulmonary artery rings in a concentration-dependent manner. In response to bradykinin (10(-8) mol/L), HIV Nef (10 ng/mL) significantly reduced vasorelaxation by 32% compared with untreated controls (P < 0.05). In addition, HIV Nef significantly decreased eNOS expression in the vessels and HPAECs. HIV Nef at 10 ng/mL significantly decreased NO production in HPAECs by 21% compared with controls (P < 0.05). Furthermore, HIV Nef significantly increased superoxide anion production in porcine pulmonary arteries and HPAECs compared with controls (P < 0.05). Consequently, Mn (III) tetrakis porphyrin, a superoxide dismutase mimic, effectively blocked HIV Nef-induced vasomotor dysfunction and superoxide anion production. The specificity of HIV Nef action was confirmed by anti-Nef antibody blocking and Nef heat inactivation.\Question: Does hIV Nef protein cause endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells?

SOLUTION: HIV Nef protein significantly decreases endothelium-dependent vasorelaxation in porcine pulmonary arteries. It also reduces eNOS expression and induces oxidative stress in both porcine pulmonary arteries and HPAECs. This study demonstrates a new mechanism of HIV Nef, which causes endothelial dysfunction and may contribute to the human pulmonary artery disease in HIV-infected patients.

PROBLEM: Context: Overexpression of the human c-MYC (MYC) oncogene is one of the most frequently implicated events in the pathogenesis of hepatocellular carcinoma (HCC). Previously, we have shown in a conditional transgenic mouse model that MYC overexpression is restrained from inducing mitotic cellular division and tumorigenesis in the adult liver; whereas, in marked contrast, MYC induces robust proliferation associated with the very rapid onset of tumorigenesis in embryonic and neonatal mice.', 'Here, we show that non-genotoxic hepatotoxins induce changes in the liver cellular context associated with increased cellular proliferation and enhanced tumorigenesis. Both 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride (CCl(4)) cooperate with MYC to greatly accelerate the onset of liver cancer in an adult host to less than 7 days versus a mean latency of onset of over 35 weeks for MYC alone. These hepatotoxin-enhanced liver tumors grossly and histologically resemble embryonic and neonatal liver tumors. Importantly, we found that MYC overexpression is only capable of inducing expression of the mitotic Cyclin B1 in embryonic/neonatal hosts or adult hosts that were treated with either carcinogen.\Question: Do hepatotoxin-induced changes in the adult murine liver promote MYC-induced tumorigenesis?

SOLUTION:
Our results suggest a model whereby oncogenes can remain latently activated, but exposure of the adult liver to hepatotoxins that promote hepatocyte proliferation can rapidly uncover their malignant potential.