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.

Context: To increase the Zn level in shoots, AtHMA4 was ectopically expressed in tomato under the constitutive CaMV 35S promoter. However, the Zn concentration in the shoots of transgenic plants failed to increase at all tested Zn levels in the medium. Modification of Zn root/shoot distribution in tomato expressing 35S::AtHMA4 depended on the concentration of Zn in the medium, thus indicating involvement of unknown endogenous metal-homeostasis mechanisms. To determine these mechanisms, those metal-homeostasis genes that were expressed differently in transgenic and wild-type plants were identified by microarray and RT-qPCR analysis using laser-assisted microdissected RNA isolated from two root sectors: (epidermis\u2009+\u2009cortex and stele), and leaf sectors (upper epidermis\u2009+\u2009palisade parenchyma and lower epidermis\u2009+\u2009spongy parenchyma).', 'Zn-supply-dependent modification of Zn root/shoot distribution in AtHMA4-tomato (increase at 5\xa0μM Zn, no change at 0.5\xa0μM Zn) involved tissue-specific, distinct from that in the wild type, expression of tomato endogenous genes. First, it is suggested that an ethylene-dependent pathway underlies the detected changes in Zn root/shoot partitioning, as it was induced in transgenic plants in a distinct way depending on Zn exposure. Upon exposure to 5 or 0.5\xa0μM Zn, in the epidermis\u2009+\u2009cortex of the transgenics\' roots the expression of the Strategy I Fe-uptake system (ethylene-dependent LeIRT1 and LeFER) was respectively lower or higher than in the wild type and was accompanied by respectively lower or higher expression of the identified ethylene genes (LeNR, LeACO4, LeACO5) and of LeChln. Second, the contribution of LeNRAMP2 expression in the stele is shown to be distinct for wild-type and transgenic plants at both Zn exposures. Ethylene was also suggested as an important factor in a pathway induced in the leaves of transgenic plants by high Zn in the apoplast, which results in the initiation of loading of the excess Zn into the mesophyll of "Zn accumulating cells".
Answer: In transgenic tomato plants, the export activity of ectopically expressed AtHMA4 changes the cellular Zn status, which induces coordinated tissue-specific responses of endogenous ethylene-related genes and metal transporters. These changes constitute an important mechanism involved in the generation of the metal-related phenotype of transgenic tomato expressing AtHMA4.
Does engineering high Zn in tomato shoot through expression of AtHMA4 involves tissue-specific modification of endogenous genes?

Context: Pineal function has been considered particularly as a neuroendocrine modulator in hormone responsive tumors, like the hormone-dependent mammary tumors. The complexity of the gland function, moreover, is denoted by the presence of a local renin-angiotensin-system (RAS) that regulates melatonin biosynthesis. Classically, angiotensin II (Ang II) has been considered as the effector peptide of the RAS, but Ang II is not the only active peptide. Several of its degradation products, including angiotensin III (Ang III) and angiotensin IV (Ang IV) also possess biological functions. These peptides are formed via the activity of several aminopeptidases. Our aim is to know their role in the regulation of pineal RAS and breast cancer.', 'Aminopeptidase N (APN), aminopeptidase B (APB) and aminopeptidase A (aspartyl- and glutamyl-aminopeptidase, APA) activities are measured in the pineal gland of rats with breast cancer induced by N-methyl nitrosourea (NMU).', 'Aminopeptidase activities were measured fluorimetrically using their corresponding aminoacyl-beta-naphthylamides as substrates.', 'Specific APN and APB activities in pineal gland of controls and NMU-treated rats were not modified. Aspartyl aminopeptidase activity significantly decreased in NMU-treated rats when compared with control group. On the contrary, glutamyl aminopeptidase activity did not show significant differences between groups.
Answer: We propose that the local RAS in pineal gland is modified in rats with breast cancer induced by NMU through the inhibition of AspAP activity, which may lead to increased levels of Ang II. Ang II could be responsible of the overproduction of melatonin, supporting a mechanism to restrain the promotion and/or progression of breast cancer.
Are renin-angiotensin system-regulating aminopeptidase activities modified in the pineal gland of rats with breast cancer induced by N-methyl-nitrosourea?

Context: To study bcl-2 expression in ductular proliferation cholangiocytes and hepatic stellate cell activation in liver biopsies from patients with autoimmune cholangitis and primary biliary cirrhosis.', 'Twenty-four primary biliary cirrhosis patients and 11 autoimmune cholangitis patients were included. Thirty-four females, average age: 52.5+/-12.6 years. We studied the presence of ductular proliferation, cholestasis, florid ductal lesion, granulomata, ductopenia and histologic stage. Patients were classified in primary biliary cirrhosis or autoimmune cholangitis according to antimitochondrial antibodies, antinuclear antibodies, smooth muscle antibody, antiGP210 and antiSP100 autoantibodies. We studied the presence of bcl-2 by monoclonal antibcl-2 antibody (clon 100, BioGenex). The presence of activated (specific antialpha-actin antibodies) and independent lobular, periportal and portal hepatic stellate cell was assessed using a semiquantitative scale.', "Interlobular ducts bcl-2 was seen in 18 (51.4%) patients. Activated periportal hepatic stellate cell correlated with Ludwig's stage (r=0.43; n=35; p=0.01). Ten out of 15 (66.6%) patients with ductular proliferation showed positive interlobular ducts bcl-2 while bcl-2 was negative in 8 out of 20 (40%) patients without ductular proliferation; p<0.05. Bcl-2 positive patients in ductular proliferation showed a more advanced Ludwig's stage (2.33+/-0.77 versus 1.26+/-1.05; p<0.05) and a higher periportal hepatic stellate cell activation index (0.83+/-0.78 versus 0.23+/-0.43; p=0.009). No relationship was found among periportal hepatic stellate cell activation and the presence of florid ductal lesion, cholestasis, granulomata or biliary erosive necrosis. Hepatic stellate cell activation was similar in patients with either autoimmune cholangitis or primary biliary cirrhosis.
Answer: Periportal hepatic stellate cell activation seems to play a main role in fibrosis progression in patients with autoimmune cholestasis. Bcl-2 expression in ductular proliferation may promote hepatic stellate cell activation and fibrosis.

Is expression of bcl-2 in ductular proliferation related to periportal hepatic stellate cell activation and fibrosis progression in patients with autoimmune cholestasis?