Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.
--------
Question: We demonstrated previously that striatal adenosine modulates ethanol-induced motor incoordination (EIMI) via adenosine A1 receptors coupled to pertussis toxin (PT)-sensitive G protein and adenylyl cyclase-cyclic adenosine monophosphate (cAMP). Additionally, intrastriatal (IST) PT antagonizes EIMI and its potentiation by the adenosine A1 agonist N-cyclohexyladenosine; it also inhibits cAMP concentration.', 'Guide cannulas were stereotaxically implanted for IST pretreatment with PT followed 5 days later by IST of N-cyclohexyladenosine and intraperitoneal ethanol. The adenosine diphosphate (ADP) ribosylation reaction involved PT-catalyzed [P]nicotinamide adenine dinucleotide (NAD) labeling of rat striatal membranes. Antagonism of EIMI (Rotorod method) after IST microinfusion of PT was investigated to determine whether it was due to a decrease in the functional activity of G proteins due to ADP ribosylation of the Gialpha subunit caused it.', 'Striatal membranes from IST PT (0.5 microg)-treated animals exhibited significantly attenuated (up to 90%) in vitro ADP ribosylation with [P]NAD. Striatal membranes from animals injected with ethanol (1.5 g/kg intraperitoneally) exhibited statistically significant increase (11%) in in vitro ADP ribosylation. Similarly, ethanol (50 mM) added to striatal membranes from untreated animals produced significant stimulation of in vitro ADP ribosylation. The decrease in the functional activity of G proteins due to ADP ribosylation of the Gialpha subunit after IST PT was functionally correlated with marked attenuation in EIMI, as observed previously. This finding suggests a blockade of functional activity of PT-sensitive striatal Gi/Go proteins (i.e., fewer available sites for labeled NAD incorporation). The in vivo ethanol results indicate that it must have caused an increase in the ribosylation capacity of Gialpha in vivo (i.e., increased Gi activity). Increased ADP ribosylation by in vitro ethanol increases Gi/Go activity, consistent with EIMI, as previously reported.

Answer: 0


Question: Trans-activation Response DNA-binding Protein-43 (TDP-43) lesions are observed in Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Lobar Degeneration with ubiquitin inclusions (FTLD-TDP) and 25-50% of Alzheimer's Disease (AD) cases. These abnormal protein inclusions are composed of either amorphous TDP-43 aggregates or highly ordered filaments. The filamentous TDP-43 accumulations typically contain clean 10-12 nm filaments though wider 18-20 nm coated filaments may be observed. The TDP-43 present within these lesions is phosphorylated, truncated and ubiquitinated, and these modifications appear to be abnormal as they are linked to both a cellular heat shock response and microglial activation. The mechanisms associated with this abnormal TDP-43 accumulation are believed to result in a loss of TDP-43 function, perhaps due to the post-translational modifications or resulting from physical sequestration of the TDP-43. The formation of TDP-43 inclusions involves cellular translocation and conversion of TDP-43 into fibrillogenic forms, but the ability of these accumulations to sequester normal TDP-43 and propagate this behavior between neurons pathologically is mostly inferred. The lack of methodology to produce soluble full length TDP-43 and recapitulate this polymerization into filaments as observed in disease has limited our understanding of these pathogenic cascades.", 'The protocols described here generate soluble, full-length and untagged TDP-43 allowing for a direct assessment of the impact of various posttranslational modifications on TDP-43 function. We demonstrate that Casein Kinase II (CKII) promotes the polymerization of this soluble TDP-43 into 10 nm diameter filaments that resemble the most common TDP-43 structures observed in disease. Furthermore, these filaments are recognized as abnormal by Heat Shock Proteins (HSPs) which can inhibit TDP-43 polymerization or directly promote TDP-43 filament depolymerization.

Answer: 0


Question: Most patients with Fusarium infection present with affection of the tegumentary system, with the presence of necrotic and/or inflammatory lesions associated with pain.', 'To evaluate the effect of the intradermal application of a metabolic extract of Fusarium oxysporum in the skin of Wistar rats.', 'The extract was obtained from fungal cultivation in Czapek-Dox medium. It was sterilized by filtration through a Millipore membrane, and injected (0.5 mg/mL) intradermally into the skin of rats, which were killed 3, 6, 12, and 24 h after inoculation. Skin specimens were placed in paraffin and stained using hematoxylin and eosin, and toluidine blue, for the evaluation of the inflammatory response, and Sirius red for the quantification of collagen. Terminal deoxynucleotidyl transferase-mediated UTP nick end labelling (TUNEL) was used for the identification of apoptosis. Tissue reactions were graded and compared over time and compartment.', 'The inflammatory reaction reached a peak at 12 h for both the dermis and subcutaneous region, being graded as moderate and moderate to severe, respectively. There was an influx of granulocytes, lymphocytes, and macrophages. A significant increase in the number of mast cells, as well as the presence of hyperemic vessels and apoptotic bodies, was observed. There was TUNEL staining in keratinocytes, fibroblasts, endothelial cells, muscles, and in the cells of the inflammatory infiltrate. There was a significant decrease in the area occupied by collagen after 12 h.

Answer:
1