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1.
Phys Rev Lett ; 130(10): 101001, 2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36962014

ABSTRACT

Dark matter elastic scattering off nuclei can result in the excitation and ionization of the recoiling atom through the so-called Migdal effect. The energy deposition from the ionization electron adds to the energy deposited by the recoiling nuclear system and allows for the detection of interactions of sub-GeV/c^{2} mass dark matter. We present new constraints for sub-GeV/c^{2} dark matter using the dual-phase liquid argon time projection chamber of the DarkSide-50 experiment with an exposure of (12 306±184) kg d. The analysis is based on the ionization signal alone and significantly enhances the sensitivity of DarkSide-50, enabling sensitivity to dark matter with masses down to 40 MeV/c^{2}. Furthermore, it sets the most stringent upper limit on the spin independent dark matter nucleon cross section for masses below 3.6 GeV/c^{2}.

2.
Phys Rev Lett ; 130(10): 101002, 2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36962032

ABSTRACT

We present a search for dark matter particles with sub-GeV/c^{2} masses whose interactions have final state electrons using the DarkSide-50 experiment's (12 306±184) kg d low-radioactivity liquid argon exposure. By analyzing the ionization signals, we exclude new parameter space for the dark matter-electron cross section σ[over ¯]_{e}, the axioelectric coupling constant g_{Ae}, and the dark photon kinetic mixing parameter κ. We also set the first dark matter direct-detection constraints on the mixing angle |U_{e4}|^{2} for keV/c^{2} sterile neutrinos.

3.
Phys Rev Lett ; 128(9): 091803, 2022 Mar 04.
Article in English | MEDLINE | ID: mdl-35302807

ABSTRACT

We report the measurement of sub-MeV solar neutrinos through the use of their associated Cherenkov radiation, performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The measurement is achieved using a novel technique that correlates individual photon hits of events to the known position of the Sun. In an energy window between 0.54 to 0.74 MeV, selected using the dominant scintillation light, we have measured 10 887_{-2103}^{+2386}(stat)±947(syst) (68% confidence interval) solar neutrinos out of 19 904 total events. This corresponds to a ^{7}Be neutrino interaction rate of 51.6_{-12.5}^{+13.9} counts/(day·100 ton), which is in agreement with the standard solar model predictions and the previous spectroscopic results of Borexino. The no-neutrino hypothesis can be excluded with >5σ confidence level. For the first time, we have demonstrated the possibility of utilizing the directional Cherenkov information for sub-MeV solar neutrinos, in a large-scale, high light yield liquid scintillator detector. This measurement provides an experimental proof of principle for future hybrid event reconstruction using both Cherenkov and scintillation signatures simultaneously.

4.
Phys Rev Lett ; 129(25): 252701, 2022 Dec 16.
Article in English | MEDLINE | ID: mdl-36608219

ABSTRACT

We present an improved measurement of the carbon-nitrogen-oxygen (CNO) solar neutrino interaction rate at Earth obtained with the complete Borexino Phase-III dataset. The measured rate, R_{CNO}=6.7_{-0.8}^{+2.0} counts/(day×100 tonnes), allows us to exclude the absence of the CNO signal with about 7σ C.L. The correspondent CNO neutrino flux is 6.6_{-0.9}^{+2.0}×10^{8} cm^{-2} s^{-1}, taking into account the neutrino flavor conversion. We use the new CNO measurement to evaluate the C and N abundances in the Sun with respect to the H abundance for the first time with solar neutrinos. Our result of N_{CN}=(5.78_{-1.00}^{+1.86})×10^{-4} displays a ∼2σ tension with the "low-metallicity" spectroscopic photospheric measurements. Furthermore, our result used together with the ^{7}Be and ^{8}B solar neutrino fluxes, also measured by Borexino, permits us to disfavor at 3.1σ C.L. the "low-metallicity" standard solar model B16-AGSS09met as an alternative to the "high-metallicity" standard solar model B16-GS98.

5.
Phys Rev Lett ; 121(11): 111303, 2018 Sep 14.
Article in English | MEDLINE | ID: mdl-30265123

ABSTRACT

We present new constraints on sub-GeV dark-matter particles scattering off electrons based on 6780.0 kg d of data collected with the DarkSide-50 dual-phase argon time projection chamber. This analysis uses electroluminescence signals due to ionized electrons extracted from the liquid argon target. The detector has a very high trigger probability for these signals, allowing for an analysis threshold of three extracted electrons, or approximately 0.05 keVee. We calculate the expected recoil spectra for dark matter-electron scattering in argon and, under the assumption of momentum-independent scattering, improve upon existing limits from XENON10 for dark-matter particles with masses between 30 and 100 MeV/c^{2}.

6.
Phys Rev Lett ; 121(8): 081307, 2018 Aug 24.
Article in English | MEDLINE | ID: mdl-30192596

ABSTRACT

We present the results of a search for dark matter weakly interacting massive particles (WIMPs) in the mass range below 20 GeV/c^{2} using a target of low-radioactivity argon with a 6786.0 kg d exposure. The data were obtained using the DarkSide-50 apparatus at Laboratori Nazionali del Gran Sasso. The analysis is based on the ionization signal, for which the DarkSide-50 time projection chamber is fully efficient at 0.1 keVee. The observed rate in the detector at 0.5 keVee is about 1.5 event/keVee/kg/d and is almost entirely accounted for by known background sources. We obtain a 90% C.L. exclusion limit above 1.8 GeV/c^{2} for the spin-independent cross section of dark matter WIMPs on nucleons, extending the exclusion region for dark matter below previous limits in the range 1.8-6 GeV/c^{2}.

7.
Braz J Med Biol Res ; 51(10): e7423, 2018 Jul 26.
Article in English | MEDLINE | ID: mdl-30066727

ABSTRACT

Epithelial cell migration is an essential response to enteric pathogens such as enteropathogenic Escherichia coli (EPEC). This study aimed to investigate the effects of EPEC infection on intestinal epithelial cell migration in vitro, as well as the involvement of type III secretion system (T3SS) and Rho GTPases. Crypt intestinal epithelial cells (IEC-6) were infected with EPEC strains (E2348/69, ΔescF, and the LDI001 strain isolated from a malnourished Brazilian child) and commensal E. coli HS. Wound migration and cell death assays were performed at different time-points. Transcription and expression of Rho GTPases were evaluated using real-time PCR and western blotting. Overall, EPEC E2348/69 reduced migration and increased apoptosis and necrosis levels compared to EPEC LDI001 and E. coli HS strains. Moreover, EPEC LDI001 impaired cell migration at a higher level than E. coli HS and increased necrosis after 24 hours compared to the control group. The different profiles of virulence genes between the two wild-type EPEC strains, characterized by the absence of espL and nleE genes in the LDI001, might explain the phenotypic results, playing significant roles on cell migration impairment and cell death-related events. Moreover, the type III secretion system is determinant for the inhibition of intestinal epithelial cell migration by EPEC 2348/69, as its deletion prevented the effect. Active Rac1 concentrations were increased in E2348/69 and LDI001-infected cells, while the T3SS-deficient strain did not demonstrate this activation. This study contributes with valuable insight to characterize the mechanisms involved in the impairment of intestinal cell migration induced by EPEC.


Subject(s)
Cell Movement/physiology , Enteropathogenic Escherichia coli/pathogenicity , Epithelial Cells/microbiology , Type III Secretion Systems/physiology , Virulence Factors/genetics , rho GTP-Binding Proteins/physiology , Apoptosis , Blotting, Western , Flow Cytometry , Humans , Real-Time Polymerase Chain Reaction , Virulence Factors/physiology
8.
Sports Med Open ; 4(1): 7, 2018 01 31.
Article in English | MEDLINE | ID: mdl-29388074

ABSTRACT

ERRATUM: The original article [1] mistakenly omits a grant acknowledgement; thus, the authors would like to acknowledge that the original article was supported by FAPESP 2015/20082-7.

9.
J Helminthol ; 92(1): 109-115, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28274281

ABSTRACT

A new nematode species, Philometroides acreanensis n. sp. (Philometridae), is described from female specimens recovered from the stomach wall of the freshwater catfish Pimelodus blochii Valenciennes (Pimelodidae) collected in the Acre River (Amazon River basin), Acre State, Brazil. Based on examination by light and scanning electron microscopy, the new species differs from the two other South American congeneric species mainly in the body length of the gravid female (240-280 mm), the length of the oesophagus (1.25 mm in holotype) representing 0.5% of the entire body length, the range of cuticular embossment, as well as the location in the host (stomach), order of the fish host (Siluriformes) and the geographical distribution (Amazon River drainage system). This is the third known species of Philometroides Yamaguti, 1935 reported from South America. A key to species of Philometroides occurring in the fish of America is provided.


Subject(s)
Catfishes/parasitology , Dracunculoidea/isolation & purification , Fish Diseases/parasitology , Animals , Brazil/epidemiology , Female , Fish Diseases/epidemiology , Microscopy, Electron, Scanning
10.
Braz. j. med. biol. res ; 51(10): e7423, 2018. tab, graf
Article in English | LILACS | ID: biblio-951708

ABSTRACT

Epithelial cell migration is an essential response to enteric pathogens such as enteropathogenic Escherichia coli (EPEC). This study aimed to investigate the effects of EPEC infection on intestinal epithelial cell migration in vitro, as well as the involvement of type III secretion system (T3SS) and Rho GTPases. Crypt intestinal epithelial cells (IEC-6) were infected with EPEC strains (E2348/69, ΔescF, and the LDI001 strain isolated from a malnourished Brazilian child) and commensal E. coli HS. Wound migration and cell death assays were performed at different time-points. Transcription and expression of Rho GTPases were evaluated using real-time PCR and western blotting. Overall, EPEC E2348/69 reduced migration and increased apoptosis and necrosis levels compared to EPEC LDI001 and E. coli HS strains. Moreover, EPEC LDI001 impaired cell migration at a higher level than E. coli HS and increased necrosis after 24 hours compared to the control group. The different profiles of virulence genes between the two wild-type EPEC strains, characterized by the absence of espL and nleE genes in the LDI001, might explain the phenotypic results, playing significant roles on cell migration impairment and cell death-related events. Moreover, the type III secretion system is determinant for the inhibition of intestinal epithelial cell migration by EPEC 2348/69, as its deletion prevented the effect. Active Rac1 concentrations were increased in E2348/69 and LDI001-infected cells, while the T3SS-deficient strain did not demonstrate this activation. This study contributes with valuable insight to characterize the mechanisms involved in the impairment of intestinal cell migration induced by EPEC.


Subject(s)
Humans , Cell Movement/physiology , rho GTP-Binding Proteins/physiology , Virulence Factors/genetics , Epithelial Cells/microbiology , Enteropathogenic Escherichia coli/pathogenicity , Type III Secretion Systems/physiology , Blotting, Western , Apoptosis , Virulence Factors/physiology , Real-Time Polymerase Chain Reaction , Flow Cytometry
11.
Braz J Med Biol Res ; 49(10): e5340, 2016 Oct 10.
Article in English | MEDLINE | ID: mdl-27737316

ABSTRACT

Undernutrition represents a major public health challenge for middle- and low-income countries. This study aimed to evaluate whether a multideficient Northeast Brazil regional basic diet (RBD) induces acute morphological and functional changes in the ileum of mice. Swiss mice (∼25 g) were allocated into two groups: i) control mice were fed a standard diet and II) undernourished mice were fed the RBD. After 7 days, mice were killed and the ileum collected for evaluation of electrophysiological parameters (Ussing chambers), transcription (RT-qPCR) and protein expression (western blotting) of intestinal transporters and tight junctions. Body weight gain was significantly decreased in the undernourished group, which also showed decreased crypt depth but no alterations in villus height. Electrophysiology measurements showed a reduced basal short circuit current (Isc) in the undernourished group, with no differences in transepithelial resistance. Specific substrate-evoked Isc related to affinity and efficacy (glutamine and alanyl-glutamine) were not different between groups, except for the maximum Isc (efficacy) induced by glucose. Transcription of Sglt1 and Pept1 was significantly higher in the undernourished group, while SN-2 transcription was decreased. No changes were found in transcription of CAT-1 and CFTR, while claudin-2 and occludin transcriptions were significantly increased in the undernourished group. Despite mRNA changes, SGLT-1, PEPT-1, claudin-2 and occludin protein expression showed no difference between groups. These results demonstrate early effects of the RBD on mice, which include reduced body weight and crypt depth in the absence of significant alterations to villus morphology, intestinal transporters and tight junction expression.


Subject(s)
Animal Nutritional Physiological Phenomena , Growth/physiology , Ileum/anatomy & histology , Ileum/metabolism , Malnutrition/metabolism , Malnutrition/physiopathology , Acute Disease , Animals , Body Weight , Disease Models, Animal , Energy Intake/physiology , Immunoblotting , Intestinal Absorption/physiology , Ion Transport/physiology , Male , Malnutrition/complications , Membrane Transport Proteins/analysis , Mice , RNA, Messenger , Reverse Transcriptase Polymerase Chain Reaction , Tight Junction Proteins/analysis , Tight Junction Proteins/metabolism , Time Factors
12.
Braz. j. med. biol. res ; 49(10): e5340, 2016. tab, graf
Article in English | LILACS | ID: biblio-951651

ABSTRACT

Undernutrition represents a major public health challenge for middle- and low-income countries. This study aimed to evaluate whether a multideficient Northeast Brazil regional basic diet (RBD) induces acute morphological and functional changes in the ileum of mice. Swiss mice (∼25 g) were allocated into two groups: i) control mice were fed a standard diet and II) undernourished mice were fed the RBD. After 7 days, mice were killed and the ileum collected for evaluation of electrophysiological parameters (Ussing chambers), transcription (RT-qPCR) and protein expression (western blotting) of intestinal transporters and tight junctions. Body weight gain was significantly decreased in the undernourished group, which also showed decreased crypt depth but no alterations in villus height. Electrophysiology measurements showed a reduced basal short circuit current (Isc) in the undernourished group, with no differences in transepithelial resistance. Specific substrate-evoked Isc related to affinity and efficacy (glutamine and alanyl-glutamine) were not different between groups, except for the maximum Isc (efficacy) induced by glucose. Transcription of Sglt1 and Pept1 was significantly higher in the undernourished group, while SN-2 transcription was decreased. No changes were found in transcription of CAT-1 and CFTR, while claudin-2 and occludin transcriptions were significantly increased in the undernourished group. Despite mRNA changes, SGLT-1, PEPT-1, claudin-2 and occludin protein expression showed no difference between groups. These results demonstrate early effects of the RBD on mice, which include reduced body weight and crypt depth in the absence of significant alterations to villus morphology, intestinal transporters and tight junction expression.


Subject(s)
Animals , Male , Rabbits , Malnutrition/physiopathology , Malnutrition/metabolism , Growth/physiology , Ileum/anatomy & histology , Ileum/metabolism , Animal Nutritional Physiological Phenomena , Time Factors , Body Weight , Energy Intake/physiology , RNA, Messenger , Immunoblotting , Acute Disease , Ion Transport/physiology , Malnutrition/complications , Disease Models, Animal , Intestinal Absorption/physiology
13.
Phys Rev Lett ; 115(23): 231802, 2015 Dec 04.
Article in English | MEDLINE | ID: mdl-26684111

ABSTRACT

Borexino is a liquid scintillation detector located deep underground at the Laboratori Nazionali del Gran Sasso (LNGS, Italy). Thanks to the unmatched radio purity of the scintillator, and to the well understood detector response at low energy, a new limit on the stability of the electron for decay into a neutrino and a single monoenergetic photon was obtained. This new bound, τ≥6.6×10^{28} yr at 90% C.L., is 2 orders of magnitude better than the previous limit.

14.
J Environ Radioact ; 138: 444-6, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24725806

ABSTRACT

The decays of (214)Po into (210)Pb and of (212)Po into (208)Pb tagged by the previous decays from (214)Bi and (212)Bi have been studied inserting quartz vials inside the Counting Test Facility (CTF) at the underground laboratory in Gran Sasso (LNGS). We find that the mean lifetime of (214)Po is (236.00 ± 0.42(stat) ± 0.15(syst)) µs and that of (212)Po is (425.1 ± 0.9(stat) ± 1.2(syst)) ns. Our results are compatible with previous measurements, have a much better signal to background ratio, and reduce the overall uncertainties.


Subject(s)
Lead Radioisotopes/analysis , Polonium/analysis , Radioactive Pollutants/analysis , Alpha Particles , Half-Life , Laboratories , Radiation Monitoring
15.
Phys Rev Lett ; 108(5): 051302, 2012 Feb 03.
Article in English | MEDLINE | ID: mdl-22400925

ABSTRACT

We observed, for the first time, solar neutrinos in the 1.0-1.5 MeV energy range. We determined the rate of pep solar neutrino interactions in Borexino to be 3.1±0.6{stat}±0.3{syst} counts/(day·100 ton). Assuming the pep neutrino flux predicted by the standard solar model, we obtained a constraint on the CNO solar neutrino interaction rate of <7.9 counts/(day·100 ton) (95% C.L.). The absence of the solar neutrino signal is disfavored at 99.97% C.L., while the absence of the pep signal is disfavored at 98% C.L. The necessary sensitivity was achieved by adopting data analysis techniques for the rejection of cosmogenic {11}C, the dominant background in the 1-2 MeV region. Assuming the Mikheyev-Smirnov-Wolfenstein large mixing angle solution to solar neutrino oscillations, these values correspond to solar neutrino fluxes of (1.6±0.3)×10{8} cm{-2} s^{-1} and <7.7×10{8} cm{-2} s{-1} (95% C.L.), respectively, in agreement with both the high and low metallicity standard solar models. These results represent the first direct evidence of the pep neutrino signal and the strongest constraint of the CNO solar neutrino flux to date.

16.
Article in English | MEDLINE | ID: mdl-23366321

ABSTRACT

This paper presents a medical remote monitoring application which aims at detecting falls. The detection system is based on three modalities: a wearable sensor, infrared sensors and a sound analysis module. The sound analysis is presented briefly. The multimodal fusion is made using the Dempster Schaffer theory through Evidential Network. A first evaluation of the use of data mining techniques in order to extract blindly data representatives is proposed. These representatives are used to continuously increase the system performances. The system is evaluated on a local recorded data base.


Subject(s)
Accidental Falls/prevention & control , Actigraphy/methods , Algorithms , Artificial Intelligence , Data Mining/methods , Monitoring, Ambulatory/methods , Telemedicine/methods , Accidental Falls/statistics & numerical data , Decision Support Systems, Clinical , Humans
17.
Phys Rev Lett ; 107(14): 141302, 2011 Sep 30.
Article in English | MEDLINE | ID: mdl-22107184

ABSTRACT

The rate of neutrino-electron elastic scattering interactions from 862 keV (7)Be solar neutrinos in Borexino is determined to be 46.0±1.5(stat)(-1.6)(+1.5)(syst) counts/(day·100 ton). This corresponds to a ν(e)-equivalent (7)Be solar neutrino flux of (3.10±0.15)×10(9) cm(-2) s(-1) and, under the assumption of ν(e) transition to other active neutrino flavours, yields an electron neutrino survival probability of 0.51±0.07 at 862 keV. The no flavor change hypothesis is ruled out at 5.0 σ. A global solar neutrino analysis with free fluxes determines Φ(pp)=6.06(-0.06)(+0.02)×10(10) cm(-2) s(-1) and Φ(CNO)<1.3×10(9) cm(-2) s(-1) (95% C.L.). These results significantly improve the precision with which the Mikheyev-Smirnov-Wolfenstein large mixing angle neutrino oscillation model is experimentally tested at low energy.

18.
Phytomedicine ; 18(7): 539-43, 2011 May 15.
Article in English | MEDLINE | ID: mdl-21112750

ABSTRACT

This study was undertaken to elucidate the effect of the essential oil from Alpinia speciosa (EOAs) on cardiac contractility and the underlying mechanisms. The essential oil was obtained from Alpinia speciosa leaves and flowers and the oil was analyzed by GC-MS method. Chemical analysis revealed the presence of at least 18 components. Terpinen-4-ol and 1,8-cineole corresponded to 38% and 18% of the crude oil, respectively. The experiments were conducted on spontaneously-beating right atria and on electrically stimulated left atria isolated from adult rats. The effect of EOAs on the isometric contractions and cardiac frequency in vitro was examined. EOAs decreased rat left atrial force of contraction with an EC50 of 292.2±75.7 µg/ml. Nifedipine, a well known L-type Ca²+ blocker, inhibited in a concentration-dependent manner left atrial force of contraction with an EC50 of 12.1±3.5 µg/ml. Sinus rhythm was diminished by EOAs with an EC50 of 595.4±56.2 µg/ml. Whole-cell L-type Ca²+ currents were recorded by using the patch-clamp technique. EOAs at 25 µg/ml decreased I(Ca,L) by 32.6±9.2% and at 250 µg/ml it decreased by 89.3±7.4%. Thus, inhibition of L-type Ca²+ channels is involved in the cardiodepressive effect elicited by the essential oil of Alpinia speciosa in rat heart.


Subject(s)
Alpinia/chemistry , Calcium Channel Blockers/pharmacology , Calcium Channels, L-Type/drug effects , Myocardial Contraction/drug effects , Oils, Volatile/pharmacology , Plant Extracts/chemistry , Animals , Calcium Channels, L-Type/metabolism , Depression, Chemical , Dose-Response Relationship, Drug , Female , Flowers/chemistry , Heart/drug effects , Male , Oils, Volatile/chemistry , Patch-Clamp Techniques , Plant Leaves/chemistry , Plant Oils/chemistry , Plant Oils/pharmacology , Plants, Medicinal/chemistry , Rats
19.
Neurology ; 74(14): 1118-26, 2010 Apr 06.
Article in English | MEDLINE | ID: mdl-20368632

ABSTRACT

BACKGROUND: Genetic and environmental factors are thought to contribute to the etiology of the autoimmune disease myasthenia gravis (MG). Viral involvement has long been suspected, but direct evidence of involvement has not been found. We recently reported that Toll-like receptor 4 (TLR4)-a key activator of innate immunity-was overexpressed in the thymus of some patients with MG, suggesting that thymic infection by pathogens might be involved in MG pathogenesis. We searched for evidence of intrathymic infection in patients with MG. METHODS: Twenty-seven MG thymuses (6 involuted, 7 hyperplastic, 5 thymitis, and 9 thymoma) previously tested for TLR4 expression, 18 nonpathologic control thymuses, and 10 pathologic control thymuses from patients without MG (8 thymoma and 2 hyperplastic) were analyzed for cytomegalovirus, varicella-zoster virus, herpes simplex virus types 1 and 2, eubacteria, respiratory syncytial virus, and enteroviruses using PCR techniques. Immunohistochemistry and double immunofluorescence were used to detect enterovirus capsid protein VP1 in thymic specimens and analyze TLR4 expression in VP1-positive cells. RESULTS: Poliovirus was detected in 4 MG thymuses (14.8%; 2 thymitis and 2 thymoma). No virus was detected in any control thymus. A linear correlation between plus and minus strand poliovirus RNA levels was observed in all 4 thymuses, suggesting persistent thymic infection. VP1 protein was detected in the cytoplasm of CD68-positive macrophages scattered through thymic medulla in all PV-positive thymuses. VP1 and TLR4 colocalized in infected cells. CONCLUSIONS: Poliovirus-infected macrophages are present in thymus of some patients with myasthenia gravis, suggesting a viral contribution to the intrathymic alterations leading to the disease.


Subject(s)
Macrophages/virology , Myasthenia Gravis/immunology , Myasthenia Gravis/virology , Poliomyelitis/complications , Poliovirus/immunology , Thymus Gland/virology , Antigens, CD/analysis , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/analysis , Antigens, Differentiation, Myelomonocytic/metabolism , Capsid Proteins/analysis , Capsid Proteins/metabolism , Fluorescent Antibody Technique , Immunohistochemistry , Macrophages/pathology , Myasthenia Gravis/physiopathology , Poliovirus/genetics , Predictive Value of Tests , RNA, Viral/genetics , Thymus Gland/cytology , Toll-Like Receptor 4/analysis , Toll-Like Receptor 4/metabolism
20.
Genomics ; 89(1): 143-50, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17059877

ABSTRACT

The human SIRT3 gene contains an intronic VNTR enhancer whose variability is correlated with life span. The SIRT3 5' flanking region encompasses the PSMD13 gene encoding the p40.5 regulator subunit of the 26S proteasome. Proteasome is a multicatalytic proteinase whose function declines with aging. SIRT3 and PSMD13 are linked in a head-to-head configuration (788-bp intergenic region). The molecular configuration of two genes that are both related to aging prompted us to search for shared regulatory mechanisms between them. Transfection experiments carried out in HeLa cells by deletion mutants of the PSMD13-SIRT3 intergenic region showed a complex pathway of coregulation acting in both directions. Furthermore, linkage disequilibrium (LD) analyses carried out in a sample of 710 subjects (18-108 years of age) screened for A21631G (marker of PSMD13), and for G477T and VNTR(intron5) (markers of SIRT3), revealed high LD, with significantly different PSMD13-SIRT3 haplotype pools between samples of centenarians and younger people.


Subject(s)
Aging/genetics , Mitochondrial Proteins/genetics , Promoter Regions, Genetic , Proteasome Endopeptidase Complex/genetics , Sirtuins/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Base Sequence , Chromosome Mapping , DNA/genetics , DNA, Intergenic , Female , Genes, Reporter , Genetics, Population , Haplotypes , HeLa Cells , Humans , Linkage Disequilibrium , Male , Middle Aged , Minisatellite Repeats , Molecular Sequence Data , Sequence Deletion , Sirtuin 3
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