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.

Input: Consider Input: Context: Pandemic strains of HIV-1 (group M) encode a total of nine structural (gag, pol, env), regulatory (rev, tat) and accessory (vif, vpr, vpu, nef) genes. However, some subtype A and C viruses exhibit an unusual gene arrangement in which the first exon of rev (rev1) and the vpu gene are placed in the same open reading frame. Although this rev1-vpu gene fusion is present in a considerable fraction of HIV-1 strains, its functional significance is unknown.', 'Examining infectious molecular clones (IMCs) of HIV-1 that encode the rev1-vpu polymorphism, we show that a fusion protein is expressed in infected cells. Due to the splicing pattern of viral mRNA, however, these same IMCs also express a regular Vpu protein, which is produced at much higher levels. To investigate the function of the fusion gene, we characterized isogenic IMC pairs differing only in their ability to express a Rev1-Vpu protein. Analysis in transfected HEK293T and infected CD4+ T cells showed that all of these viruses were equally active in known Vpu functions, such as down-modulation of CD4 or counteraction of tetherin. Furthermore, the polymorphism did not affect Vpu-mediated inhibition of NF-кB activation or Rev-dependent nuclear export of incompletely spliced viral mRNAs. There was also no evidence for enhanced replication of Rev1-Vpu expressing viruses in primary PBMCs or ex vivo infected human lymphoid tissues. Finally, the frequency of HIV-1 quasispecies members that encoded a rev1-vpu fusion gene did not change in HIV-1 infected individuals over time.
Answer: Expression of a rev1-vpu fusion gene does not affect regular Rev and Vpu functions or alter HIV-1 replication in primary target cells. Since there is no evidence for increased replication fitness of rev1-vpu encoding viruses, this polymorphism likely emerged in the context of other mutations within and/or outside the rev1-vpu intergenic region, and may have a neutral phenotype.

Output: Does a Naturally Occurring rev1-vpu Fusion Gene Confer a Fitness Advantage to HIV-1?


Input: Consider Input: Context: Downstream effects of muscarinic receptor stimulation in intestinal smooth muscle include contraction and intestinal transit. We thought to determine whether classic transient receptor potential (TRPC) channels integrate the intracellular signaling cascades evoked by the stimulated receptors and thereby contribute to the control of the membrane potential, Ca-influx, and cell responses.', 'We created trpc4-, trpc6-, and trpc4/trpc6-gene-deficient mice and analyzed them for intestinal smooth muscle function in vitro and in vivo.', 'In intestinal smooth muscle cells TRPC4 forms a 55 pS cation channel and underlies more than 80% of the muscarinic receptor-induced cation current (mI(CAT)). The residual mI(CAT) depends on the expression of TRPC6, indicating that TRPC6 and TRPC4 determine mI(CAT) channel activity independent of other channel subunits. In TRPC4-deficient ileal myocytes the carbachol-induced membrane depolarizations are diminished greatly and the atropine-sensitive contraction elicited by acetylcholine release from excitatory motor neurons is reduced greatly. Additional deletion of TRPC6 aggravates these effects. Intestinal transit is slowed down in mice lacking TRPC4 and TRPC6.
Answer: In intestinal smooth muscle cells TRPC4 and TRPC6 channels are gated by muscarinic receptors and are responsible for mI(CAT). They couple muscarinic receptors to depolarization of intestinal smooth muscle cells and voltage-activated Ca(2+)-influx and contraction, and thereby accelerate small intestinal motility in vivo.

Output: Does deletion of TRPC4 and TRPC6 in mice impair smooth muscle contraction and intestinal motility in vivo?


Input: Consider Input: Context: Uncontrolled intra-abdominal bleeding is a common cause of death in trauma patients in the prehospital and perioperative settings. The detrimental effects of abdominal hypertension are well studied, but the potential therapeutic use of abdominal insufflation for hemostasis has not been fully explored. We measured the effect of abdominal insufflation on blood loss and physiologic outcomes in a swine model of blunt liver injury.', 'Twenty-one anticoagulated swine (32 +/- 3 kg) were anesthesized; laparotomy was performed to localize liver anatomy and to place loose tourniquettes isolating the porta hepatis and supra/infrahepatic vena cava. A captive bolt gun was used to create a grade V hepatic laceration, producing massive parenchymal injury as well as complex tears of the middle and right hepatic veins. Animals were randomized into either control (n = 10) or abdominal insufflation at 20 cm H(2)O pressure (n = 11) groups. Crystalloid was used to maintain a mean arterial pressure of 30 mm Hg. Arterial pressure and other physiologic variables were recorded for 20 minutes. Animals were then sacrificed and blood loss measured.', 'Blood loss was 69% lower in insufflated animals compared with controls (384 +/- 51 versus 1252 +/- 88 cc, p < 0.001). After 20 minutes, insufflated animals had significantly higher mean arterial blood pressure (32.2 +/- 4.2 versus 21.2 +/- 4.0 mm Hg) and lower total resuscitation volume (195 +/- 83 versus 1356 +/- 95 cc). Three pigs died in the control group (30%), whereas no insufflated animals died (p < 0.05).
Answer: In a swine model of catastrophic blunt hepatic injury, abdominal insufflation significantly decreased blood loss and mortality.


Output: Does abdominal insufflation decrease blood loss and mortality after porcine liver injury?