Prolyl endopeptidase (EC 3.4.21.26) (PE) (Post-proline cleaving enzyme) [PEP]

PublicationsПравить

Genome-wide association study and annotating candidate gene networks affecting age at first calving in Nellore cattle.

We performed a genome-wide mapping for the age at first calving (AFC) with the goal of annotating candidate genes that regulate fertility in Nellore cattle. Phenotypic data from 762 cows and 777k SNP genotypes from 2,992 bulls and cows were used. Single nucleotide polymorphism (SNP) effects based on the single-step GBLUP methodology were blocked into adjacent windows of 1 Megabase (Mb) to explain the genetic variance. SNP windows explaining more than 0.40% of the AFC genetic variance were identified on chromosomes 2, 8, 9, 14, 16 and 17. From these windows, we identified 123 coding protein genes that were used to build gene networks. From the association study and derived gene networks, putative candidate genes (e.g., PAPPA, PREP, FER1L6, TPR, NMNAT1, ACAD10, PCMTD1, CRH, OPKR1, NPBWR1 and NCOA2) and transcription factors (TF) (STAT1, STAT3, RELA, E2F1 and EGR1) were strongly associated with female fertility (e.g., negative regulation of luteinizing hormone secretion, folliculogenesis and establishment of uterine receptivity). Evidence suggests that AFC inheritance is complex and controlled by multiple loci across the genome. As several windows explaining higher proportion of the genetic variance were identified on chromosome 14, further studies investigating the interaction across haplotypes to better understand the molecular architecture behind AFC in Nellore cattle should be undertaken.

MeSH Terms

  • Aging
  • Animals
  • Breeding
  • Cattle
  • Female
  • Fertility
  • Gene Regulatory Networks
  • Genome-Wide Association Study
  • Genotype
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci

Keywords

  • beef cattle
  • gene function
  • single-step


Mechanism of Action of Prolyl Oligopeptidase (PREP) in Degenerative Brain Diseases: Has Peptidase Activity Only a Modulatory Role on the Interactions of PREP with Proteins?

In the aging brain, the correct balance of neural transmission and its regulation is of particular significance, and neuropeptides have a significant role. Prolyl oligopeptidase (PREP) is a protein highly expressed in brain, and evidence indicates that it is related to aging and in neurodegenration. Although PREP is regarded as a peptidase, the physiological substrates in the brain have not been defined, and after intense research, the molecular mechanisms where this protein is involved have not been defined. We propose that PREP functions as a regulator of other proteins though peptide gated direct interaction. We speculate that, at least in some processes where PREP has shown to be relevant, the peptidase activity is only a consequence of the interactions, and not the main physiological activity.


Keywords

  • aging neuroscience
  • neurodegeneration
  • neuropeptides
  • prolyl oligopeptidase
  • proten-protein interactions


Improving Pain Relief in Elder Patients (I-PREP): An Emergency Department Education and Quality Intervention.

To assess the effectiveness of a novel combined education and quality improvement (QI) program for management of pain in older adults in the emergency department (ED). Controlled pre/postintervention examination. An academic urban ED seeing 60,000 adult visits annually. Individuals aged 65 and older experiencing moderate to severe pain. Linked standardized education and continuous QI for multidisciplinary staff in an urban, academic ED from January 2012 to January 2014. Pain intensity, percentage receiving and time to pain assessment and reassessment, percentage receiving and time to delivery of analgesic. The percentage of participants with final pain score of 4 or less (out of 10) increased 47.5% (95% confidence interval (CI) = 41.8-53.2%). Median decrease in pain intensity improved significantly, from 0.0 to 5.0 points (P < .001). Median final pain score decreased from 7.0 to 4.0 points (P < .001). The percentage of participants with any pain improvement increased 43.7% (95% CI = 37.1-50.3%, P < .001). Pain reassessments increased significantly (from 51.9% to 82.5%, P < .001). The percentage receiving analgesics increased significantly (from 64.1% to 84.8%, P < .001). After the intervention, participants had 3.1 (95% CI = 2.1-4.4, P < .001) greater odds of receiving analgesics and 4.7 (95% CI = 3.5-6.5, P < .001) greater odds of documented pain reassessment. The I-PREP intervention substantially improved pain management in older adults in the ED with moderate to severe musculoskeletal or abdominal pain. Significant reductions in pain intensity were achieved, the timing of pain assessments and reassessments was improved, and analgesics were delivered faster. Tightly linking education to targeted QI improved pain management of older adults in the ED.

MeSH Terms

  • Aged
  • Analgesics
  • Chicago
  • Emergency Service, Hospital
  • Female
  • Hospitals, Urban
  • Humans
  • Male
  • Pain Management
  • Pain Measurement
  • Quality Improvement

Keywords

  • emergency department
  • geriatrics
  • intervention
  • older adults
  • pain management
  • quality improvement


Age and muscle-dependent variations in corticospinal excitability during standing tasks.

In this study, we investigated how modulation in corticospinal excitability elicited in the context of standing tasks varies as a function of age and between muscles. Changes in motor evoked potentials (MEPs) recorded in tibialis anterior (TA) and gastrocnemius lateralis (GL) were monitored while participants (young, n = 10; seniors, n = 11) either quietly stood (QS) or performed a heel raise (HR) task. In the later condition, transcranial magnetic stimulation (TMS) pulses were delivered at three specific time points during the task: 1) 250 ms before the "go" cue (preparatory (PREP) phase), 2) 100 ms before the heel rise (anticipatory postural adjustment (APA) phase), and 3) 200 ms after heel rise (execution (EXEC) phase). In each task and each phase, variations in MEP characteristics were analysed for age and muscle-dependent effects. Variations in silent period (SP) duration were also examined for certain phases (APA and EXEC). Our analysis revealed no major difference during QS, as participants exhibited very similar patterns of modulation in both TA and GL, irrespective of their age group. During the HR task, young adults exhibited a differential modulation in the PREP phase with enhanced responses in TA relative to GL, which was not seen in seniors. Finally, besides differences in MEP latency, age had little influence on MEP modulation during the APA and EXEC phases, where amplitude was largely a function of background muscle activity associated with each phase (i.e., APA: TA; EXEC: GL). No age or muscle effects were detected for SP measurements. Overall, our results revealed no major differences between young adults and healthy seniors in the ability to modulate corticospinal facilitation destined to ankle muscles during standing tasks, with maybe the exception of the ability to prime muscle synergies in the preparatory phase of action.

MeSH Terms

  • Aged
  • Aging
  • Electromyography
  • Evoked Potentials, Motor
  • Female
  • Heel
  • Humans
  • Male
  • Muscle, Skeletal
  • Posture
  • Psychomotor Performance
  • Pyramidal Tracts
  • Task Performance and Analysis
  • Young Adult