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: The gene(s) encoding for endomorphin precursor(s) is/are still unknown. We have raised the possibility of and did find some evidence for a potential de novo biosynthetic route starting from Tyr-Pro precursor. To pursue further this possibility we measured the generation of immunoreactive endomorphin-2 (E2-IR) in adult rat isolated L4,5 dorsal root ganglia.\Question: Is immunoreactive endomorphin 2 generated extracellularly in rat isolated L4,5 dorsal root ganglia by DPP-IV?

SOLUTION: In rat isolated dorsal root ganglia the combination of presumed biosynthetic precursor of endomorphin 2 (E2), Tyr-Pro with the dipeptidyl peptidase IV (DPP-IV) inhibitor Ile-Pro-Ile generated 1.60+/-0.37 pg/mg Wet Tissue Weight_30 min E2-IR in the bathing fluid (n=4) with an 8-fold increase upon depolarization whereas the tissue content was low (0.50+/-0.08 pg/mg_WTW). Substance P, as determined by ELISA in the pilot experiments, was found almost exclusively within the tissues. It is concluded that E2-IR was generated extracellularly by a membrane-bound DPP-IV, which was switched to "synthase" mode by the hydrolase inhibitor Ile-Pro-Ile. DPP-IV was depolarization-sensitive in "synthase" functional mode.

PROBLEM: Context: In HIV patients, disorders in glucose metabolism seem to be side effects of highly active antiretroviral therapy (HAART) which may be favoured by obesity, abdominal fat accumulation and familial disposition for diabetes mellitus (DM). The aim of our study was to identify patients at high risk for abnormalities in glucose metabolism taking into account HAART, familial disposition for DM and anthropometric parameters.', 'Plasma glucose, insulin, c-peptide and insulin resistance (homeostasis model assessment, HOMA) were determined in 44 HIV patients [16 without HAART, 19 with protease inhibitors (PI), 9 without PI (non-PI)] and in 11 healthy subjects. Glucose tolerance was determined by standard procedures. Body mass index (BMI), triceps skin fold thickness and waist circumference were measured and the waist-to-hip-ratio was calculated. Familial disposition for DM was assessed by questionnaire.', 'Impaired fasting glucose was observed in 28% of HAART-treated patients (21% with PI, 7% non-PI), in 13% of HAART-naive but none in healthy controls. 58% of PI, 44% of non-PI, 38% of HAART-naive and none of healthy controls had a HOMA-index > 2.5 which indicates insulin resistance. HAART-treated patients had significantly higher fasting glucose levels (PI: 97 +/- 11 mg/dL, p = 0.048; non-PI: 109 +/- 58 mg/dL, p = 0.009) compared to healthy controls (72 +/- 8 mg/dL). HOMA-Index was higher in PI treated patients (3.74 +/- 3.08) than in HIV negative controls (0.95 +/- 0.28, p = 0.018). The duration of HAART (p = 0.045), overweight and familial disposition for DM (p = 0.017) significantly affected fasting glucose among PI users. Waist circumference affected c-peptide (p = 0.046) concentration in these patients.\Question: Are overweight HIV patients with abdominal fat distribution treated with protease inhibitors at high risk for abnormalities in glucose metabolism - a reason for glycemic control?

SOLUTION: HIV patients on long-term PI therapy with overweight and familial disposition for DM are at high risk to develop abnormalities of glucose metabolism. Thus, measurements of HOMA-Index, BMI and waist circumference should be routinely done especially in PI medicated patients.

PROBLEM: Context: Ionizing-radiation-resistant bacteria (IRRB) show a surprising capacity for adaptation to ionizing radiation and desiccation. Positive Darwinian selection is expected to play an important role in this trait, but no data are currently available regarding the role of positive adaptive selection in resistance to ionizing-radiation and tolerance of desiccation. We analyzed the four known genome sequences of IRRB (Deinococcus geothermalis, Deinococcus radiodurans, Kineococcus radiotolerans, and Rubrobacter xylanophilus) to determine the role of positive Darwinian selection in the evolution of resistance to ionizing radiation and tolerance of desiccation.', 'We used the programs MultiParanoid and DnaSP to deduce the sets of orthologs that potentially evolved due to positive Darwinian selection in IRRB. We find that positive selection targets 689 ortholog sets of IRRB. Among these, 58 ortholog sets are absent in ionizing-radiation-sensitive bacteria (IRSB: Escherichia coli and Thermus thermophilus). The most striking finding is that all basal DNA repair genes in IRRB, unlike many of their orthologs in IRSB, are subject to positive selection.\Question: Is basal DNA repair machinery subject to positive selection in ionizing-radiation-resistant bacteria?

SOLUTION:
Our results provide the first in silico prediction of positively selected genes with potential roles in the molecular basis of resistance to gamma-radiation and tolerance of desiccation in IRRB. Identification of these genes provides a basis for future experimental work aimed at understanding the metabolic networks in which they participate.