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: Reg IV, a secreted protein and member of the Reg multigene family, is up-regulated in malignancies of the human gastrointestinal tract, including colorectal carcinoma (CRC). However, in vitro signal transduction pathway(s) utilized by Reg IV are not yet known.', 'To determine the signaling pathway(s) responsive to Reg IV, we examined the effects of purified recombinant human Reg IV (rhR4) on HCT116 and HT29 colon adenocarcinoma cells.', 'Addition of rhR4 to cultures led to a dose-dependent increase in cell number similar to that observed after treatment with epidermal growth factor (EGF). In addition, rhR4 treatment resulted in rapid phosphorylation of EGF receptor at Tyr992 and Tyr1068 and Akt at Thr308 and Ser473. Using luciferase reporter gene assays, we demonstrated that Reg IV signaling through EGF receptor and Akt results in increased activator protein-1 (AP-1) transcription factor activity. Real-time reverse-transcription polymerase chain reaction and Western blot analyses revealed quantitative increases in c-Jun, JunB, JunD, and FosB expression associated with increased AP-1 activity. Electrophoretic mobility shift assay further revealed significant increases in AP-1 binding activity in rhR4-treated cells, with increased supershift in the presence of antibodies to JunB, JunD, and FosB. Furthermore, rhR4 treatments led to the increased expression of Bcl-2, Bcl-XL, survivin, and matrilysin, genes associated with a poor prognosis in advanced CRC.\Question: Does reg IV activate the epidermal growth factor receptor/Akt/AP-1 signaling pathway in colon adenocarcinomas?

SOLUTION: Reg IV is a potent activator of the EGF receptor/Akt/AP-1 signaling pathway in CRC. Disruption of Reg signaling may have utility as a therapeutic intervention for human gastrointestinal adenocarcinomas.

PROBLEM: Context: This study investigated whether anxiety, fear of pain, or pain catastrophizing were predictive of pain-related outcomes after induced delayed onset muscle soreness (DOMS) at the shoulder.', 'Healthy participants (19 males and 23 females) were eligible for participation if they had (a) no history of neck or shoulder pain, (b) no sensory or motor impairments of the upper-extremity, (c) not regularly participating in upper-extremity weight training, (d) not currently or regularly taking pain medication, and (e) no history of upper-extremity surgery. Participants completed self-report measures for fear of pain, pain catastrophizing, and anxiety. Then, participants underwent a standard fatigue protocol to induce DOMS in the shoulder external rotator muscles. Participants were reassessed 24 hours after DOMS induction on clinical and evoked pressure pain reports, muscle force production, self-report of upper-extremity disability, and kinesiophobia. Stepwise regression models considered sex, anxiety, pain intensity, fear of pain, and pain catastrophizing as outcome predictors.', 'Fear of pain alone explained 16% (P=0.008) of the variance in clinical pain and 10% (P=0.047) evoked pressure pain intensity. Clinical pain intensity alone explained 11% (P<0.031) of the variance in muscle force production. Clinical pain intensity and fear of pain explained 50% (P<0.001) of the variance in upper-extremity disability, whereas fear of pain and sex accounted for 26% (P=0.005) of the variance in kinesiophobia.\Question: Does fear of pain influence outcomes after exercise-induced delayed onset muscle soreness at the shoulder?

SOLUTION: With the exception of muscle force production, fear of pain had a consistent influence on shoulder DOMS outcomes, even after controlling for pain intensity. This study suggests fear of pain may be a relevant psychologic factor to consider in clinical studies investigating the development and treatment of chronic shoulder pain.

PROBLEM: Context: Vessel formation is a crucial event in tissue repair after injury. Thus, one assumption of innovative therapeutic approaches is the understanding of its molecular mechanisms. Notwithstanding our knowledge of the role of Protein Kinase C epsilon (PKCε) in cardio-protection and vascular restenosis, its role in vessel progenitor differentiation remains elusive.', 'Given the availability of PKCε pharmacological modulators already tested in clinical trials, the specific aim of this study is to unravel the role of PKCε in vessel progenitor differentiation, with implications in vascular pathology and vasculogenesis.', 'Mouse Peri-Vascular Adipose Tissue (PVAT) was used as source of mesenchymal vessel progenitors. VEGF-induced differentiation of PVAT cells down-regulates both PKCε and p-PAK1 protein expression levels. PKCε overexpression and activation: i) reduced the expression levels of SMA and PECAM in endothelial differentiation of PVAT cells; ii) completely abrogated tubules formation in collagen gel assays; iii) increased the expression of p-PAK1.\Question: Is pKCε a negative regulator of PVAT-derived vessel formation?

SOLUTION:
PKCε negatively interferes with vessel progenitor differentiation via interaction with PAK-1.

