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.

Ex Input:
Context: The proportion of dendritic cell subpopulations in the skin is important for the severity of atopic dermatitis because topical treatment with tacrolimus leads to rapid depletion of inflammatory dendritic epidermal cells, whereas Langerhans cells (LCs) predominate in cured sites.', 'The effects of tacrolimus and TGF-beta1 on LC differentiation and the idea of tacrolimus skewing the differentiation of epidermal precursors to LCs were evaluated.', 'The presence of LC markers, MHC, and costimulatory molecules and stimulatory capacity toward T cells of monocyte-derived LCs were analyzed. Skin samples of patients with atopic dermatitis were assessed by means of immunofluorescence microscopy before and after tacrolimus treatment. TGF-beta production of skin cells was analyzed.', 'Tacrolimus and TGF-beta1 act synergistically on the generation of LCs and the expression of CD40, CD80, CD86, CD83, and MHC II; stabilize TGF-beta receptor II expression; and decrease the stimulatory capacity of LCs toward T cells. In vivo the number of epidermal LCs in tacrolimus-treated skin increased.
Answer: The synergism between TGF-beta1 and tacrolimus leads to the generation of LCs, reduced expression of costimulatory and MHC II molecules, and reduced stimulatory activity. Shifting the balance of the dendritic cell population to LCs might be of major importance for the therapeutic effect of tacrolimus.

Ex Output:
Do tacrolimus and TGF-beta act synergistically on the generation of Langerhans cells?


Ex Input:
Context: In streptozotocin-injected rats (STZ-rats), we previously demonstrated a role for angiotensin II (AT-II) in cardiac remodelling and insulin resistance partially counteracted by in vivo treatment with losartan, an AT-II receptor antagonist.We now aimed to investigate the effect of treating diabetic STZ-rats with losartan on diabetes vascular response to vasoconstrictors.', 'Male Wistar rats were randomly divided in four groups, two of them were assigned to receive losartan in the drinking water (20 mg/kg/day) until the experiment ending (3 weeks afterward). After 1 week, two groups, one of which receiving losartan, were injected in the tail vein with citrate buffer (normoglycemic, N and normoglycemic, losartan-treated, NL). The remaining received a single injection of streptozotocin (50 mg/kg in citrate i.v.) thus becoming diabetic (D) and diabetic losartan-treated (DL). Plasma glycaemia and blood pressure were measured in all animals before the sacrifice (15 days after diabetes induction).In aortic strips isolated from N, NL, D and DL rats we evaluated i) the isometric concentration-dependent contractile response to phenylephrine (Phe) and to AT-II; ii) the RhoA-kinase (ROCK1) activity and expression by enzyme-immunoassay and Western blot respectively.', 'The concentration-dependent contractile effect of Phe was similar in aortas from all groups, whereas at all concentrations tested, AT-II contraction efficacy was 2 and half and 1 and half times higher in D and DL respectively in comparison with N and NL. AT-II contracture was similarly reduced in all groups by AT-II receptor antagonists, irbesartan or irbesartan plus PD123319. HA-1077 (10 microM), an inhibitor of ROCK1 activity, reduced AT-II efficacy (Deltamg/mg tissue w.w.) by -3.5 +/- 1.0, -4.6 +/- 1.9, -22.1 +/- 2.2 and -11.4 +/- 1.3 in N, NL, D and DL respectively). ROCK1 activity and expression were higher in D than in N/NL and DL aortas.
Answer: Aortas isolated from STZ-rats present hyper-contracture to AT-II mainly dependent on the up-regulation of ROCK1 expression/activity. In vivo losartan treatment partially corrects AT-II hyper-contracture, limiting the increase in ROCK1 expression/activity. These data offer a new molecular mechanism supporting the rationale for using losartan in the prevention of diabetic vascular complications.

Ex Output:
Does losartan counteract the hyper-reactivity to angiotensin II and ROCK1 over-activation in aortas isolated from streptozotocin-injected diabetic rats?


Ex Input:
Context: Osteoarthritis (OA) is associated with a gradual reduction in the interstitial osmotic pressure within articular cartilage. The aim of this study was to compare the effects of sudden and gradual hypo-osmotic challenge on chondrocyte morphology and biomechanics.', 'Bovine articular chondrocytes were exposed to a reduction in extracellular osmolality from 327 to 153 mOsmol/kg applied either suddenly (<5 s) or gradually (over 180 min). Temporal changes in cell diameter and the existence of regulatory volume decrease (RVD) were quantified along with changes in cortical actin and chromatin condensation. The cellular viscoelastic mechanical properties were determined by micropipette aspiration.', 'In response to a sudden hypo-osmotic stress, 66% of chondrocytes exhibited an increase in diameter followed by RVD, whilst 25% showed no RVD. By contrast, cells exposed to gradual hypo-osmotic stress exhibited reduced cell swelling without subsequent RVD. There was an increase in the equilibrium modulus for cells exposed to sudden hypo-osmotic stress. However, gradual hypo-osmotic challenge had no effect on cell mechanical properties. This cell stiffening response to sudden hypo-osmotic challenge was abolished when actin organization was disrupted with cytochalasin D or RVD inhibited with REV5901. Both sudden and gradual hypo-osmotic challenge reduced cortical F-actin distribution and caused chromatin decondensation.
Answer: Sudden hypo-osmotic challenge increases chondrocyte mechanics by activation of RVD and interaction with the actin cytoskeleton. Moreover, the rate of hypo-osmotic challenge is shown to have a profound effect on chondrocyte morphology and biomechanics. This important phenomenon needs to be considered when studying the response of chondrocytes to pathological hypo-osmotic stress.

Ex Output:

Does the rate of hypo-osmotic challenge influence regulatory volume decrease ( RVD ) and mechanical properties of articular chondrocytes?