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Carboxypeptidase E precursor (EC (CPE) (Carboxypeptidase H) (CPH) (Enkephalin convertase) (Prohormone-processing carboxypeptidase)


Cross-Sectional and Cumulative Longitudinal Central Nervous System Penetration Effectiveness Scores Are Not Associated With Neurocognitive Impairment in a Well Treated Aging Human Immunodeficiency Virus-Positive Population in Switzerland.

Neurocognitive impairment (NCI) in people with human immunodeficiency virus (PWH) remains a concern despite potent antiretroviral therapy (ART). Higher central nervous system (CNS) penetration effectiveness (CPE) scores have been associated with better CNS human immunodeficiency virus (HIV) replication control, but the association between CPE and NCI remains controversial. The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a subgroup of the Swiss HIV Cohort Study (SHCS) that invited patients aged ≥45 years enrolled in the SHCS and followed-up at NAMACO-affiliated centers in Switzerland to participate between May 2013 and November 2016. In total, 981 patients were enrolled, all of whom underwent standardized neurocognitive assessment. Neurocognitive impairment, if present, was characterized using Frascati criteria. The CPE scores of NAMACO study participants with undetectable plasma HIV-ribonucleic acid at enrollment (909 patients) were analyzed. Cross-sectional CPE scores (at neurocognitive assessment) were examined as potential predictors of NCI in multivariate logistic regression models. The analysis was then repeated taking CPE as a cumulative score (summarizing CPE scores from ART initiation to the time of neurocognitive assessment). Most patients were male (80%) and Caucasian (92%). Neurocognitive impairment was present in 40%: 27% with HIV-associated NCI (mostly asymptomatic neurocognitive impairment), and 13% with NCI related to other factors. None of the CPE scores, neither cross-sectional nor cumulative, was statistically significantly associated with NCI. In this large cohort of aviremic PWH, we observed no association between NCI, whether HIV-associated or related to other factors, and CPE score, whether cross-sectional or cumulative.


  • CPE score
  • HIV
  • aging
  • cognitive disorders
  • neurocognitive impairment

COCOA (Theobroma cacao) Polyphenol-Rich Extract Increases the Chronological Lifespan of Saccharomyces cerevisiae.

BACKGROUND: Saccharomyces cerevisiae is a model organism with conserved aging pathways. Yeast chronological lifespan experiments mimic the processes involved in human non-dividing tissues, such as the nervous system or skeletal muscle, and can speed up the search for biomolecules with potential anti-aging effects before proceeding to animal studies. OBJECTIVE: To test the effectiveness of a cocoa polyphenol-rich extract (CPE) in expanding the S. cerevisiae chronological lifespan in two conditions: in the stationary phase reached after glucose depletion and under severe caloric restriction. MEASUREMENTS: Using a high-throughput method, wild-type S. cerevisiae and its mitochondrial manganese-dependent superoxide dismutase null mutant (sod2Δ) were cultured in synthetic complete dextrose medium. After 2 days, 0, 5 and 20 mg/ml of CPE were added, and viability was measured throughout the stationary phase. The effects of the major components of CPE were also evaluated. To determine yeast lifespan under severe caloric restriction conditions, cultures were washed with water 24 h after the addition of 0 and 20 mg/ml of CPE, and viability was followed over time. RESULTS : CPE increased the chronological lifespan of S. cerevisiae during the stationary phase in a dose-dependent manner. A similar increase was also observed in (sod2Δ). None of the major CPE components (theobromine, caffeine, maltodextrin, (-)-epicatechin, ( )-catechin and procyanidin B2) was able to increase the yeast lifespan. CPE further increased the yeast lifespan under severe caloric restriction. CONCLUSION: CPE increases the chronological lifespan of S. cerevisiae through a SOD2-independent mechanism. The extract also extends yeast lifespan under severe caloric restriction conditions. The high-throughput assay used makes it possible to simply and rapidly test the efficacy of a large number of compounds on yeast aging, requiring only small amounts, and is thus a convenient screening assay to accelerate the search for biomolecules with potential anti-aging effects.

MeSH Terms

  • Cacao
  • Caloric Restriction
  • Longevity
  • Plant Extracts
  • Polyphenols
  • Saccharomyces cerevisiae
  • Superoxide Dismutase

The choroid plexus-cerebrospinal fluid interface in Alzheimer's disease: more than just a barrier.

The choroid plexus is a complex structure which hangs inside the ventricles of the brain and consists mainly of choroid plexus epithelial (CPE) cells surrounding fenestrated capillaries. These CPE cells not only form an anatomical barrier, called the blood-cerebrospinal fluid barrier (BCSFB), but also present an active interface between blood and cerebrospinal fluid (CSF). CPE cells perform indispensable functions for the development, maintenance and functioning of the brain. Indeed, the primary role of the choroid plexus in the brain is to maintain homeostasis by secreting CSF which contains different molecules, such as nutrients, neurotrophins, and growth factors, as well as by clearing toxic and undesirable molecules from CSF. The choroid plexus also acts as a selective entry gate for leukocytes into the brain. Recent findings have revealed distinct changes in CPE cells that are associated with aging and Alzheimer's disease. In this review, we review some recent findings that highlight the importance of the CPE-CSF system in Alzheimer's disease and we summarize the recent advances in the regeneration of brain tissue through use of CPE cells as a new therapeutic strategy.


  • Alzheimer's disease
  • aging
  • blood-CSF barrier
  • brain barrier
  • choroid plexus
  • neurodegenerative diseases

Characterization of Clostridium perfringens in the feces of adult horses and foals with acute enterocolitis.

Up to 60% of cases of equine colitis have no known cause. To improve understanding of the causes of acute colitis in horses, we hypothesized that Clostridium perfringens producing enterotoxin (CPE) and/or beta2 toxin (CPB2) are common and important causes of severe colitis in horses and/or that C. perfringens producing an as-yet-undescribed cytotoxin may also cause colitis in horses. Fecal samples from 55 horses (43 adults, 12 foals) with clinical evidence of colitis were evaluated by culture for the presence of Clostridium difficile, C. perfringens, and Salmonella. Feces were also examined by enzyme-linked immunosorbent assay (ELISA) for C. difficile A/B toxins and C. perfringens alpha toxin (CPA), beta2 toxin (CPB2), and enterotoxin (CPE). Five C. perfringens isolates per sample were genotyped for the following genes: cpa, cpb, cpb2 consensus, cpb2 atypical, cpe (enterotoxin), etx (epsilon toxin), itx (iota toxin), netB (necrotic enteritis toxin B), and tpeL (large C. perfringens cytotoxin). The supernatants of these isolates were also evaluated for toxicity for an equine cell line. All fecal samples were negative for Salmonella. Clostridium perfringens and C. difficile were isolated from 40% and 5.4% of samples, respectively. All fecal samples were negative for CPE. Clostridium perfringens CPA and CPB2 toxins were detected in 14.5% and 7.2% of fecal samples, respectively, all of which were culture-positive for C. perfringens. No isolates were cpe, etx, netB, or tpeL gene-positive. Atypical cpb2 and consensus cpb2 genes were identified in 15 (13.6%) and 4 (3.6%) of 110 isolates, respectively. All equine C. perfringens isolates showed far milder cytotoxicity effects than a CPB-producing positive control, although cpb2-positive isolates were slightly but significantly more cytotoxic than negative isolates. Based on this studied population, we were unable to confirm our hypothesis that CPE and CPB2-producing C. perfringens are common in horses with colitis in Ontario and we failed to identify cytotoxic activity in vitro in the type A isolates recovered.

MeSH Terms

  • Acute Disease
  • Aging
  • Animals
  • Clostridium Infections
  • Clostridium perfringens
  • Enterocolitis
  • Feces
  • Horse Diseases
  • Horses

Expression of 25 high egg production related transcripts that identified from hypothalamus and pituitary gland in red-feather Taiwan country chickens.

Expression levels of 33 high egg production candidate transcripts in Red-feather Taiwan country chickens (TCCs) were examined by quantitative reverse-transcription (RT) polymerase chain reactions (PCR) in this study. Candidate transcripts were previously identified from a L2-B (L2-subtract-B) hypothalamus/pituitary gland subtractive cDNA library. In this subtractive cDNA library, two divergently selected strains of TCCs, B and L2 were used. These two strains were originated from one single population and were further subjected (since 1982) to the selections of body weight/comb size (B) and eggs to 40wk of age (L2), respectively. Hypothalamuses and pituitary glands that sampled from Red-feather TCCs were previously grouped into high (Red-high; n=20) and low (Red-low; n=20) egg productions based on the rate of lay after 1st egg (hen-day laying rate; %). Rates of lay after 1st egg (mean /-S.E.) in the Red-high and the Red-low subpopulations were 72.2 /-0.6 and 23.0 /-3.5, respectively (P<0.01). Quantitative RT-PCR validated that 25 candidate transcripts were significantly higher expressed in the Red-high than in the Red-low hens. These transcripts were ANP32A, BDH, CDC42, CNTN1, COMT, CPE, CTNNB1, DIO2, EIF4E, GARNL1, HSPCA, LAPTM4B, MBP, NAP1L4, NCAM1, PARK7, PCDHA@, PGDS, PLAG1, PRL, RAD21, SAR1A, SCG2, STMN1 and UFM1. Among these transcripts, 15 (79.0%), 13 (68.4%), and 12 (63.2%) genes were annotated to involve in cellular physiological process (GO:0050875), metabolism (GO:0008152) and cell communication (GO:0007154). Identified transcripts that related to high egg production are most active in focal adhesion, adherens junction, MAPK signaling, tight junction and cell adhesion pathways.

MeSH Terms

  • Aging
  • Animals
  • Chickens
  • Color
  • Feathers
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hypothalamus
  • Oviposition
  • Pituitary Gland
  • Taiwan
  • Transcription, Genetic

[Host and exacerbation factors related to influenza susceptibility].

The host factor of susceptibility to influenza are divided with two ones. First is HI titer (more than 40 or not) in each host according to the age groups to the prevalent influenza virus type. Second is the host conditions which mean high risk factors in influenza patients, especially CPE, lung fibrosis, the decreased lung-function patients and heart failure. I divided those patients with 5 groups from normal persons to high risk patients, and described the vaccine policy and the treatment procedures.

MeSH Terms

  • Aging
  • Brain Diseases
  • Diabetes Complications
  • Disease Susceptibility
  • Heart Diseases
  • Hemagglutinins, Viral
  • Humans
  • Immunologic Deficiency Syndromes
  • Influenza A virus
  • Influenza, Human
  • Liver Diseases
  • Lung Diseases
  • Neuraminidase
  • Risk Factors

Maturational differences in chlorpyrifos-oxonase activity may contribute to age-related sensitivity to chlorpyrifos.

Chlorpyrifos (CPF), a commonly used cholinesterase-inhibiting insecticide, is lethal at much lower doses to young animals than adults. To explain this higher sensitivity in younger animals, we hypothesized that young rats have less chlorpyrifos-oxonase (CPFOase) activity than adults. To test this hypothesis, CPFOase activity was measured in the brain, plasma, and liver of male, postnatal day 4 (PND4) and adult (PND90) Long-Evans rats. CPFOase is biochemically defined as a Ca(2 )-dependent A-esterase that hydrolyzes chlorpyrifos-oxon (CPFO), the active metabolite of CPE. No brain CPFOase activity was detected at either age. Plasma and liver CPFOase activities were markedly lower at PND4 compared to adult: PND4 plasma and liver CPFOase activities were 1/11 and 1/2 the adult plasma and liver activities, respectively. Because the Km of CPFOase activity was high (i.e., 210-380 microM), it was important to determine if this CPFOase activity could hydrolyze physiologically relevant concentrations (i.e., nM to low microM) of CPFO. This was accomplished by comparing the shifts in the tissue acetylcholinesterase (AChE) IC50 for CPFO in the presence or absence of CPFOase activity. One would expect an increase in the "apparent" IC50 if CPFOase hydrolyzes substantial amounts of CPFO during the 30 minutes the tissue is preincubated with the CPFO. In the adult, both plasma and liver AChE apparent IC50 values were higher in the presence of CPFOase activity, suggesting that the CPFOase in those tissues was capable of hydrolyzing physiologically relevant concentrations of CPFO within 30 minutes. In young animals, however, there was less of a shift in the IC50 curves compared to the adult, confirming that the young animal has less capacity than the adult to detoxify physiologically relevant concentrations of CPFO via CPFOase.

MeSH Terms

  • Acetylcholinesterase
  • Aging
  • Animals
  • Animals, Newborn
  • Brain
  • Chlorpyrifos
  • Esterases
  • Female
  • Insecticides
  • Kinetics
  • Liver
  • Male
  • Pregnancy
  • Rats
  • Rats, Inbred Strains

[Activity of basic arginine- and lysine-residue cleaving carboxypeptidase in rats of various ages].

Activities of basic carboxypeptidases (CP) in rat brain regions and peripheral tissues were determined on postnatal days 0-90. The highest phenylmethylsulfonyl fluoride-inhibited activity was detected immediately after birth; activity decreases on day 10 with subsequent increase on day 20 and decrease on day 90. The CPE activity was the lowest immediately after birth, increased on day 30, and decreased on day 90. The lysosomal CPB activity was highest at birth and on day 90 and was the lowest on day 20. The activity of CPN slowly increases till day 20 and then it decreases. The relationship between dynamics of basic CP activity in ontogenesis and functional role of these enzymes is discussed.

MeSH Terms

  • Aging
  • Animals
  • Arginine
  • Brain
  • Carboxypeptidases
  • Hydrolysis
  • Lysine
  • Male
  • Rats

[The biological range and characteristics of the importance of adenosine receptors for the resistance of the brain to total ischemia].

In the total brain ischemia the cerebroprotective effect (CPE) of adenosine was pronounced in the following order: mouse > rat approximately guinea pig (males > females). The sensitizing effect (SE) of theophylline is the same in different species but is more pronounced in females compared to males. Newborn rats are much more tolerant to the total brain ischemia. The adenosine CPE increases and the theophylline SE decreases with age. The adenosine receptor component, evidently, contributes greatly to the natural tolerance of newborn animals to the total brain ischemia.

MeSH Terms

  • Adenosine
  • Aging
  • Animals
  • Animals, Newborn
  • Brain
  • Brain Ischemia
  • Female
  • Guinea Pigs
  • Immunity, Innate
  • Male
  • Mice
  • Rats
  • Receptors, Purinergic P1
  • Sex Characteristics
  • Species Specificity
  • Theophylline
  • Vasodilator Agents

Polyadenylation of Na( )-K( )-ATPase beta 1-subunit during early development of Xenopus laevis.

In fully grown Xenopus oocytes, the synthesis of beta-subunits is limiting for the formation of functional Na( )-K( )-adenosinetriphosphatase alpha/beta-complexes (Geering, K. FEBS Lett. 285: 189-193, 1991). In the present study, we show that during oocyte growth (from stage I to stage VI) alpha 1-, but not beta 1- or beta 3-isoform, mRNAs accumulate. In addition, beta-mRNAs are apparently sequestered in an untranslated pool in fully grown oocytes (stage VI). From fertilization to morulation, the total pools of alpha 1-, beta 1-, or beta 3-mRNAs vary little. Whereas polyadenylated [poly(A) ] alpha 1- and beta 3-isoform mRNAs did not change significantly, poly(A) beta 1-mRNA abundance increased three- to fourfold at morulation, accompanied by a parallel increase in beta 1-protein synthesis. After midblastula transition (i.e., at early gastrula) and during neurulation, poly(A) alpha 1- and beta 3-mRNAs accumulated rapidly, whereas poly(A) beta 1-mRNA accumulation was delayed by approximately 2 h, beginning only at early neurula. Our results indicate that 1) the abundance of poly(A) beta 1-mRNA is rate limiting during embryonic development for the assembly of alpha 1/beta 1-heterodimers, shown to be involved in the vectorial transport of sodium in kidney cells, and 2) the polyadenylation of beta 1-mRNA is a rate-limiting factor during morulation for the synthesis and assembly of new sodium pumps at the time of blastocoel fluid formation. The 3'-untranslated region of beta 1-mRNA (but not of alpha 1-mRNA) expresses cytoplasmic polyadenylation elements (CPEs) with the consensus sequence AXX-AUUUU(A/U)(A/U)(A/U). A role of CPE in the differential polyadenylation of alpha 1- and beta 1-mRNA is proposed.

MeSH Terms

  • Aging
  • Amino Acid Sequence
  • Animals
  • Brain
  • Embryo, Nonmammalian
  • Embryonic and Fetal Development
  • Female
  • Male
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Oocytes
  • Poly A
  • Protein Biosynthesis
  • RNA, Messenger
  • Ribonuclease H
  • Sodium-Potassium-Exchanging ATPase
  • Xenopus laevis