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1.
Science ; 383(6681): 402-406, 2024 Jan 26.
Article En | MEDLINE | ID: mdl-38271522

SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.S.S.) and found an energy-dependent shift in the apparent position of the gamma-ray emission from the parsec-scale jets. These observations trace the energetic electron population and indicate that inverse Compton scattering is the emission mechanism of the gamma rays. Our modeling of the energy-dependent gamma-ray morphology constrains the location of particle acceleration and requires an abrupt deceleration of the jet flow. We infer the presence of shocks on either side of the binary system, at distances of 25 to 30 parsecs, and that self-collimation of the precessing jets forms the shocks, which then efficiently accelerate electrons.

2.
Phys Rev Lett ; 129(11): 111101, 2022 Sep 09.
Article En | MEDLINE | ID: mdl-36154418

The central region of the Milky Way is one of the foremost locations to look for dark matter (DM) signatures. We report the first results on a search for DM particle annihilation signals using new observations from an unprecedented γ-ray survey of the Galactic Center (GC) region, i.e., the Inner Galaxy Survey, at very high energies (≳100 GeV) performed with the H.E.S.S. array of five ground-based Cherenkov telescopes. No significant γ-ray excess is found in the search region of the 2014-2020 dataset and a profile likelihood ratio analysis is carried out to set exclusion limits on the annihilation cross section ⟨σv⟩. Assuming Einasto and Navarro-Frenk-White (NFW) DM density profiles at the GC, these constraints are the strongest obtained so far in the TeV DM mass range. For the Einasto profile, the constraints reach ⟨σv⟩ values of 3.7×10^{-26} cm^{3} s^{-1} for 1.5 TeV DM mass in the W^{+}W^{-} annihilation channel, and 1.2×10^{-26} cm^{3} s^{-1} for 0.7 TeV DM mass in the τ^{+}τ^{-} annihilation channel. With the H.E.S.S. Inner Galaxy Survey, ground-based γ-ray observations thus probe ⟨σv⟩ values expected from thermal-relic annihilating TeV DM particles.

3.
Science ; 376(6588): 77-80, 2022 04.
Article En | MEDLINE | ID: mdl-35271303

Recurrent novae are repeating thermonuclear explosions in the outer layers of white dwarfs, due to the accretion of fresh material from a binary companion. The shock generated when ejected material slams into the companion star's wind can accelerate particles. We report very-high-energy (VHE; [Formula: see text]) gamma rays from the recurrent nova RS Ophiuchi, up to 1 month after its 2021 outburst, observed using the High Energy Stereoscopic System (H.E.S.S.). The temporal profile of VHE emission is similar to that of lower-energy giga-electron volt emission, indicating a common origin, with a 2-day delay in peak flux. These observations constrain models of time-dependent particle energization, favoring a hadronic emission scenario over the leptonic alternative. Shocks in dense winds provide favorable environments for efficient acceleration of cosmic rays to very high energies.

4.
Science ; 372(6546): 1081-1085, 2021 06 04.
Article En | MEDLINE | ID: mdl-34083487

Gamma-ray bursts (GRBs), which are bright flashes of gamma rays from extragalactic sources followed by fading afterglow emission, are associated with stellar core collapse events. We report the detection of very-high-energy (VHE) gamma rays from the afterglow of GRB 190829A, between 4 and 56 hours after the trigger, using the High Energy Stereoscopic System (H.E.S.S.). The low luminosity and redshift of GRB 190829A reduce both internal and external absorption, allowing determination of its intrinsic energy spectrum. Between energies of 0.18 and 3.3 tera-electron volts, this spectrum is described by a power law with photon index of 2.07 ± 0.09, similar to the x-ray spectrum. The x-ray and VHE gamma-ray light curves also show similar decay profiles. These similar characteristics in the x-ray and gamma-ray bands challenge GRB afterglow emission scenarios.

5.
Article Zh | MEDLINE | ID: mdl-33036533

Objective: To investigate and understand the general situation and quality of life of migrant workers with pneumoconiosis, and analyze the influencing factors, so as to provide scientific basis for effective countermeasures to improve the quality of life of migrant workers with pneumoconiosis. Methods: In June 2019, 79 cases of migrant workers' pneumoconiosis diagnosed by Shandong Occupational Disease Hospital from March 2017 to August 2018 were selected as the study object by cluster random sampling method. Questionnaires and on-site visits were used to investigate the quality of life and its influencing factors. The questionnaire was administered by self-designed questionnaire and WHO quality of life questionnaire. Results: The farmer's pneumoconiosis patients are generally lower in culture. High school or above is only 6.33% (5/79) . Their economic income is low. The monthly income of less than 1000 RMB is 49.37% (39/79) . The disease was heavy and pneumoconiosis was 58.23% (46/79) . Pneumoconiosis patients without systematic treatment accounted for 69.62% (55/79) . Only 11.39% of rural workers with pneumoconiosis can timely increase or decrease clothing and wear masks to avoid respiratory irritation. Pneumoconiosis patients who smoked accounted for 77.22% (61/79) . The quality of life of the pneumoconiosis patients in the physiological, psychological, social and environmental fields were (10.40±2.31) , (11.40±2.82) , (11.46±3.03) and (8.38±3.37) respectively. The influencing factors of quality of life were pneumoconiosis stage, education level, economic income and smoking (P< 0.05) . Conclusion: The quality of life of migrant workers with pneumoconiosis is generally low. The main factors that affect the quality of life of patients are disease severity (pneumoconiosis stage) , education level, economic income and smoking.


Occupational Diseases , Pneumoconiosis , Transients and Migrants , China , Humans , Pneumoconiosis/epidemiology , Quality of Life , Surveys and Questionnaires
7.
Sci Rep ; 8(1): 15888, 2018 Oct 26.
Article En | MEDLINE | ID: mdl-30367090

Computed Tomography (CT) is a powerful method for non-destructive testing (NDT) and metrology awakes with expanding application fields. To improve the spatial resolution of high energy CT, a micro-spot gamma-ray source based on bremsstrahlung from a laser wakefield accelerator was developed. A high energy CT using the source was performed, which shows that the resolution of reconstruction can reach 100 µm at 10% contrast. Our proof-of-principle demonstration indicates that laser driven micro-spot gamma-ray sources provide a prospective way to increase the spatial resolution and toward to high energy micro CT. Due to the advantage in spatial resolution, laser based high energy CT represents a large potential for many NDT applications.

8.
Phys Rev Lett ; 120(19): 195001, 2018 May 11.
Article En | MEDLINE | ID: mdl-29799245

We present the first experimental evidence supported by simulations of kinetic effects launched in the interpenetration layer between the laser-driven hohlraum plasma bubbles and the corona plasma of the compressed pellet at the Shenguang-III prototype laser facility. Solid plastic capsules were coated with carbon-deuterium layers; as the implosion neutron yield is quenched, DD fusion yield from the corona plasma provides a direct measure of the kinetic effects inside the hohlraum. An anomalous large energy spread of the DD neutron signal (∼282 keV) and anomalous scaling of the neutron yield with the thickness of the carbon-deuterium layers cannot be explained by the hydrodynamic mechanisms. Instead, these results can be attributed to kinetic shocks that arise in the hohlraum-wall-ablator interpenetration region, which result in efficient acceleration of the deuterons (∼28.8 J, 0.45% of the total input laser energy). These studies provide novel insight into the interactions and dynamics of a vacuum hohlraum and near-vacuum hohlraum.

9.
J Environ Qual ; 45(1): 276-84, 2016 Jan.
Article En | MEDLINE | ID: mdl-26828183

Liming with Ca and Mg carbonates is commonly used to reduce soil and stream acidity and to improve vegetation growth and nutrition in forests. Ten years ago, dolomite lime was experimentally applied to a forest catchment on granite in the Vosges Mountains (northeast France), which is characterized by acid soils and drained by an acid stream. The average Mg isotope composition of the dolomite lime (-1.75‰) was low compared with that of tree foliage (-0.70‰), granite and deep soil layers (-0.40‰), and stream water (-0.80‰) in the control catchment. After liming, the exchangeable Mg concentrations in surface soil layers, which were initially very low, increased, and the Mg isotope composition decreased (up to -0.60‰). The decrease was smaller in deeper layers but not in proportion to the increase in exchangeable Mg content, suggesting contributions from mineralization of organic matter and/or displacement of exchangeable Mg from surface layers. Before application, Mg concentration in beech and fir leaves was low, and that of 1-yr-old fir needles was lower than that in current needles. Internal Mg translocation within fir needles also resulted in a lower δMg of older needles. Three years after dolomite application, the Mg isotope composition of plant leaves was lower than that in the control catchment; this decrease (up to -1.00‰) was attributed to direct uptake of Mg from dissolving dolomite. Liming doubled the concentration of Mg in the stream, whereas the Mg isotope composition decreased correspondingly from -0.80 to -1.20‰, indicating a fast transfer of dolomite Mg to the stream. Our findings indicate that monitoring of δMg may be a promising tool to study the fate of dolomitic inputs in terrestrial and aquatic ecosystems.


Ecosystem , Magnesium/analysis , Soil/chemistry , France , Isotopes
10.
Hum Exp Toxicol ; 35(11): 1183-1193, 2016 11 01.
Article En | MEDLINE | ID: mdl-26825964

Hepatorenal toxicities are an important side effect of anthracycline antibiotics. The objective of this study was to determine whether sesamin (Ses) protects against acute doxorubicin (DOX)-induced hepatorenal toxicities. Rats received daily treatment with either 0.5% carboxymethylcellulose (10 mL/kg) or Ses (10, 20 and 40 mg/kg) orally for 10 days, followed by an intravenous injection at day 8 of either saline (10 mL/kg) or DOX (20 mg/kg). Hepatorenal toxicity was assessed by measuring the levels of serum creatinine (Cre), blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). The protein expression of 4-hydroxynonenal (4-HNE) in hepatorenal tissues was evaluated using immunohistochemistry. The malondialdehyde (MDA) content and antioxidant activity in the kidney and liver tissues were also measured. The results suggest that pretreatment with Ses ameliorated DOX-induced liver and kidney injury by lowering the serum ALT, AST, ALP, Cre and BUN levels (p < 0.05 or p < 0.01), and the histological damage to the liver and kidney tissues induced by DOX compared to control were also significantly attenuated by Ses. Furthermore, Ses significantly decreased the DOX-induced increase of MDA and 4-HNE and increased the activity of CAT, SOD and GPX compared to the DOX-treated rats (p < 0.05 or p < 0.01), whereas the change of DOX + Ses (10 mg/kg) group is not significant compared to the DOX-treated group (p > 0.05). These findings indicate that Ses elicits a typical protective effect against DOX-induced acute hepatorenal toxicity via the suppression of oxidative stress.

11.
Eur Rev Med Pharmacol Sci ; 19(21): 4012-9, 2015 Nov.
Article En | MEDLINE | ID: mdl-26592822

OBJECTIVE: Ischemic stroke (IS) is a complex disease that resulting from the interaction of various environmental and genetic risk factors. As genetic factors exerting a direct contributory role in IS, it is one of the focus areas of identification the genetic factors of IS. This study aimed to screen bio-targets of ischemic stroke (IS), and to identify related drug molecules. MATERIALS AND METHODS: The gene expression profile GSE22255 was downloaded from Gene Expression Omnibus (GEO) database, including 20 whole blood samples from IS patients (IS group) and 20 samples from healthy controls (control group). Differentially expressed genes (DEGs) were screened out using limma package in R. Hierarchical clustering and differences between the groups analysis were conducted for confirming these DEGs. Database for Annotation, Visualization and Integrated Discovery (DAVID) and Kyoto Enrichment of Genes and Genomes (KEGG) were used to obtain the functional genes and pathways respectively. The DEGs were then entered into the WebGestalt database and related drug molecules were retrieved. RESULTS: Compared with the control group, 27 DEGs were identified from IS group including 25 up- and 2 down-regulated genes. Then functions and pathways enrichment analysis for DEGs were conducted and TNF, IL1B and TNFAIP3 were found to be both participate in apoptosis and NOD-like receptor signaling pathway. Finally, collagenase and other most-related drug molecules were identified from the DEGs. CONCLUSIONS: In addition to DEGs, several drug molecules were retrieved, which may be related with stroke. Our study provides some underlying bio-targets such as TNF, IL1B and TNFAIP3 for IS and potential drug molecules such as collagenase for the treatment of IS.


Gene Expression Profiling , Stroke/drug therapy , Stroke/genetics , Aged , Case-Control Studies , Cluster Analysis , DNA-Binding Proteins/genetics , Drug Discovery , Female , Humans , Interleukin-1beta/genetics , Intracellular Signaling Peptides and Proteins/genetics , Leukocytes, Mononuclear/metabolism , Male , Molecular Targeted Therapy , Nuclear Proteins/genetics , Oligonucleotide Array Sequence Analysis , Signal Transduction/genetics , Stroke/pathology , Transcriptome , Tumor Necrosis Factor alpha-Induced Protein 3 , Tumor Necrosis Factor-alpha/genetics
12.
Genet Mol Res ; 14(1): 2290-301, 2015 Mar 27.
Article En | MEDLINE | ID: mdl-25867375

Parathyroid hormone-related protein (PTHrP) is involved in the deposition of milk calcium in mammal lactation, but its role in buffalo is unclear. In this study, the full-length coding sequence of the water buffalo PTHrP gene was first isolated using reverse transcription-polymerase chain reaction. The protein was then subjected to molecular characterization using bioinformatic methods, and the tissue expression pattern was further assayed by semi-quantitative reverse-transcription polymerase chain reaction. The water buffalo PTHrP gene contains an open reading frame of 534 base pairs encoding a polypeptide of 177 amino acid residues, a theoretical molecular weight of 20.32 kDa, and an isoelectric point of 10.00. In addition, water buffalo PTHrP was predicted to contain a signal peptide, a typical hydrophobic region with no hydrophobic transmembrane regions, and to exert its function in the cell nucleus. A conserved domain of parathyroid superfamily from amino acids 34-114 was observed in the polypeptide. Sequence comparison and the phylogenetic analysis showed that the sequence of the water buffalo PTHrP protein shared high homology with that of other mammals, particularly cattle and goat. Among the 16 tissues examined, the PTHrP gene was only expressed in adipose tissue, placenta, uterine wall, hypophysis, and mammary gland tissue, but gene expression levels were higher in the uterus wall and adipose tissue. The results of this study suggest that the PTHrP gene plays an important role in the deposition of milk calcium of water buffalo.


Buffaloes/genetics , DNA, Complementary/genetics , Gene Expression Profiling , Parathyroid Hormone-Related Protein/genetics , Amino Acid Sequence , Animals , Base Sequence , Buffaloes/metabolism , Cloning, Molecular , DNA, Complementary/chemistry , Female , Molecular Sequence Data , Parathyroid Hormone-Related Protein/classification , Parathyroid Hormone-Related Protein/metabolism , Phylogeny , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Sequence Homology, Amino Acid
13.
Psychol Med ; 42(12): 2591-8, 2012 Dec.
Article En | MEDLINE | ID: mdl-22716960

BACKGROUND: The relationship between recurrent major depression (MD) in women and suicidality is complex. We investigated the extent to which patients who suffered with various forms of suicidal symptomatology can be distinguished from those subjects without such symptoms. METHOD: We examined the clinical features of the worst episode in 1970 Han Chinese women with recurrent DSM-IV MD between the ages of 30 and 60 years from across China. Student's t tests, and logistic and multiple logistic regression models were used to determine the association between suicidality and other clinical features of MD. RESULTS: Suicidal symptomatology is significantly associated with a more severe form of MD, as indexed by both the number of episodes and number of MD symptoms. Patients reporting suicidal thoughts, plans or attempts experienced a significantly greater number of stressful life events. The depressive symptom most strongly associated with lifetime suicide attempt was feelings of worthlessness (odds ratio 4.25, 95% confidence interval 2.9-6.3). Excessive guilt, diminished concentration and impaired decision-making were also significantly associated with a suicide attempt. CONCLUSIONS: This study contributes to the existing literature on risk factors for suicidal symptomatology in depressed women. Identifying specific depressive symptoms and co-morbid psychiatric disorders may help improve the clinical assessment of suicide risk in depressed patients. These findings could be helpful in identifying those who need more intense treatment strategies in order to prevent suicide.


Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/psychology , Suicidal Ideation , Suicide, Attempted/psychology , Adult , China , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Cognition Disorders/psychology , Cross-Sectional Studies , Depressive Disorder, Major/epidemiology , Female , Humans , Life Change Events , Middle Aged , Recurrence , Self Concept , Suicide, Attempted/statistics & numerical data
14.
Genet Mol Res ; 11(1): 606-16, 2012 Mar 14.
Article En | MEDLINE | ID: mdl-22535396

To identify amplified fragment length polymorphism (AFLP) markers associated with resistance or susceptibility of alfalfa to common leafspot (CLS) caused by the fungus Pseudopeziza medicaginis (Dermateaceae), bulked segregant analysis was conducted based on an F(1(M × M)) population of 93 plants and a BC(1)S population of 91 plants. Three AFLP markers, ACTCAA(R206), TAGCAC(R185), and GGACTA(S264), were found to be associated with CLS resistance or susceptibility. All three markers were found at significantly different frequencies (71.9, 80.3 and 91.8%) compared to resistant or susceptible plants in the original population. Subsequently, these three AFLP markers were converted into three SCAR markers, ACTCAA(R136), TAGCAC(R128) and GGACTA(S254), which are easier to employ in breeding programs. The three SCAR markers were used in a randomly selected population with 50% resistance; the probability of finding one resistant plant was increased to 67.3, 66.7 and 90.0% with markers ACTCAA(R136), TAGCAC(R128) and GGACTA(S254), independently. If two of the SCAR markers were used simultaneously, the probability would be higher than 89%. The three SCAR markers identified in this study would be applicable for selection for CLS resistance in alfalfa breeding programs. Moreover, the genetic analysis indicated that CLS resistance in alfalfa is conferred by a single dominant gene.


Amplified Fragment Length Polymorphism Analysis , Genes, Plant , Medicago sativa/genetics , Plant Diseases/genetics , Base Sequence , Genetic Markers , Genetic Predisposition to Disease , Medicago sativa/microbiology , Molecular Sequence Data , Plant Diseases/microbiology , Reproducibility of Results
15.
Eur Rev Med Pharmacol Sci ; 16(15): 2162-70, 2012 Dec.
Article En | MEDLINE | ID: mdl-23280035

BACKGROUND AND OBJECTIVES: The adverse reactions in combination of angiotensin-converting enzyme inhibitors (ACEIs) and Ang II receptor blockers (ARBs) were severer than that in monotherapy for patients with nephropathy. The effect of candesartan on pharmacokinetics of enalaprilat in nephrotic rats was investigated to make references for the clinical therapy in patients with nephropathy to avoid related adverse effects. MATERIALS AND METHODS: Nephrotic rats were prepared by adriamycin injection. Control group and one nephrotic group received enalapril alone, another nephrotic group received enalapril and candesartan simultaneously. Blood samples were drawn at time points after a single oral administration. The concentration of enalaprilat was determined using LC-MS/MS. RESULTS: Compared with control group and nephrotic group received enalapril alone respectively, Tmax of enalaprilat in nephrotic group received both enalapril and candesartan cilexetil prolonged about 21.43% and 6.224%, respectively; AUC(0-t) increased by 185.3% and 60.63%, respectively; Cmax increased by 219.4% and 56.64%, respectively; t1/2 increased by 163.7% and 30.05%, respectively; CL/F reduced by 65.12% and 40.78%, respectively. There were no significant differences of the V1/F of enalaprilat between three groups. The CL/F and t1/2 of enalaprilat showed significant correlations with serum creatinine (Scr) respectively (r = -0.7502; r = 0.5626). DISCUSSION: The combination with candesartan in nephrotic rats significantly changed the pharmacokinetics of enalaprilat, showing increased accumulation and decreased elimination. In view of these findings, we should lower dosage and prolong dosing interval for nephrotic patients in the combination of enalapril and candesartan.


Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacokinetics , Benzimidazoles/pharmacology , Enalaprilat/pharmacokinetics , Nephrosis/drug therapy , Tetrazoles/pharmacology , Animals , Biphenyl Compounds , Drug Interactions , Female , Male , Nephrosis/metabolism , Rats , Rats, Sprague-Dawley
16.
Plant Dis ; 94(11): 1379, 2010 Nov.
Article En | MEDLINE | ID: mdl-30743629

Southern blight caused by Sclerotium rolfsii Sacc. was observed on okra (Abelmoschus esculentus) cv. Clemson Spineless in January 2010 during a survey of vegetable fields in Rubbino, Côte d'Ivoire, which is one of the most important areas for vegetable production. Plants exhibited symptoms of a dark brown lesion on the stems near the soil line. Upper roots became light to dark brown, the lower leaves wilted, turned yellow, and a white mat of fungal mycelium developed on the stem lesion. Numerous, white, spherical sclerotia formed on the infected stem and on soil surfaces around the infected plants. Sclerotia (0.5 to 1.2 mm in diameter) later turned tan to dark brown and the entire plant wilted. Eleven fields, with a total of approximately 26 ha surveyed, were affected and disease incidence reached approximately 15% in the fields. Sclerotia were collected and the fungus cultured on acidified potato dextrose agar (PDA) plates. The fungus grew rapidly on PDA and the hyphae at the edge of the colonies were large straight cells with one or more clamp connections at each septum. Secondary and tertiary hyphae were slender and lacked clamp connections. Whitish sclerotia were observed on the mycelial mats 5 to 7 days after incubation, which later turned tan to brown when mature. The fungus was identified as S. rolfsii based on the characteristics of mycelia and sclerotia (1). Sclerotia produced on PDA were used to inoculate okra seedlings under greenhouse conditions at rates of 10, 20, and 30 sclerotia per plant. Sclerotia were placed just under the soil surface around the root of 4-week-old seedlings of okra cv. Clemson Spineless. Symptoms identical to those on field samples developed on all inoculated plants. S. rolfsii was reisolated from diseased plants and the identity was confirmed. S. rolfsii has previously been reported as causing disease in Côte d'Ivoire (2). To our knowledge, this is the first report of southern blight caused by S. rolfsii on okra in this country. Okra is an important vegetable crop in Côte d'Ivoire and therefore the occurrence of southern blight and susceptibility of okra cultivars to this disease needs to be taken into account in okra production. References: (1) Z. K. Punja and A. Damiani. Mycologia 88:694, 1996. (2) R. Resplandy et al. Ann. Epiphyt. 1:1, 1954.

17.
Int J Dent Hyg ; 4(4): 179-82, 2006 Nov.
Article En | MEDLINE | ID: mdl-17038055

This study was conducted to assess the usefulness of the gingival crevicular blood for estimating the glucose level during routine periodontal examination using Xitux Diagnostics Smart-X self-monitoring blood glucose device among Jordanian patients attending dental teaching clinics. A total of 34 type 2 diabetic patients (18 males and 16 females) and 26 non-diabetic patients (14 males and 12 females) participated in this study. Glucose level was measured in a sample of gingival crevicular blood and in another sample obtained by finger puncture using a self-monitoring device. Glucose measurements from gingival crevicular blood samples, ranged from 57 to 250 mg dl-1 with a mean of 125.4+/-60.7 mg dl-1 (+/-SD) and glucose measurements obtained by finger puncture, ranged from 62 to 263 mg dl-1 with a mean of 131.9+/-61.1 mg dl-1. Pearson's correlation coefficient was performed to assess the correlation between the glucose measurements in these two samples. Pearson's correlation coefficient showed an almost perfect positive correlation between the gingival readings and finger-puncture readings (r=0.997, P<0.0001). In conclusion, gingival crevicular blood can provide an acceptable source for measuring blood glucose level. However, the technique to obtain an acceptable blood sample from gingival crevices is not always feasible which would limit its application as a clinical practice. Additional studies that refine this technique and use larger sample size are recommended.


Blood Glucose Self-Monitoring/methods , Diabetes Mellitus, Type 2/blood , Gingiva/blood supply , Adult , Blood Glucose/analysis , Case-Control Studies , Diabetes Mellitus, Type 2/diagnosis , Female , Fingers/blood supply , Humans , Male , Mass Screening/methods , Middle Aged , Phlebotomy
18.
Immunology ; 104(1): 37-42, 2001 Sep.
Article En | MEDLINE | ID: mdl-11576218

The CD95 death receptor activates caspases that cleave a variety of intracellular substrates, including cell cycle control proteins. However, the significance of this cleavage for the induction of apoptosis is unclear. In this study, CD95-induced cleavage of the G1/S checkpoint regulator proteins, retinoblastoma protein (pRb) and murine-double-minute-2 (mdm-2), was associated with an increased protein concentration of a key transcription factor, E2F-1, which is regulated by both of them. Furthermore, DNA-binding activity to E2F sites is increased. In thymocytes, CD95-induced apoptosis was associated with increased E2F-1 DNA-binding activity, while thymocytes that lacked E2F-1 were less susceptible to CD95-induced apoptosis. We conclude that the G1/S checkpoint is an important target of CD95 signalling. CD95-activated caspases cleave regulator proteins to increase E2F-1 activity, and inappropriate activation of E2F-1 is part of the mechanism of CD95-induced apoptosis.


Cell Cycle Proteins/metabolism , Nuclear Proteins , T-Lymphocytes/immunology , Transcription Factors/metabolism , fas Receptor/immunology , Animals , Apoptosis/immunology , Blotting, Western , Cell Culture Techniques , Cell Cycle/immunology , Cell Cycle Proteins/genetics , DNA-Binding Proteins/metabolism , E2F Transcription Factors , E2F1 Transcription Factor , Mice , Mice, Inbred Strains , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-mdm2 , Retinoblastoma Protein/metabolism , Signal Transduction/immunology , Transcription Factors/genetics , fas Receptor/metabolism
19.
Proc Natl Acad Sci U S A ; 98(15): 8433-9, 2001 Jul 17.
Article En | MEDLINE | ID: mdl-11459986

Human Dmc1 protein, a meiosis-specific homolog of Escherichia coli RecA protein, has previously been shown to promote DNA homologous pairing and strand-exchange reactions that are qualitatively similar to those of RecA protein and Rad51. Human and yeast Rad51 proteins each form a nucleoprotein filament that is very similar to the filament formed by RecA protein. However, recent studies failed to find a similar filament made by Dmc1 but showed instead that this protein forms octameric rings and stacks of rings. These observations stimulated further efforts to elucidate the mechanism by which Dmc1 promotes the recognition of homology. Dmc1, purified to a state in which nuclease and helicase activities were undetectable, promoted homologous pairing and strand exchange as measured by fluorescence resonance energy transfer (FRET). Observations on the intermediates and products, which can be distinguished by FRET assays, provided direct evidence of a three-stranded synaptic intermediate. The effects of helix stability and mismatched base pairs on the recognition of homology revealed further that human Dmc1, like human Rad51, requires the preferential breathing of A small middle dotT base pairs for recognition of homology. We conclude that Dmc1, like human Rad51 and E. coli RecA protein, promotes homologous pairing and strand exchange by a "synaptic pathway" involving a three-stranded nucleoprotein intermediate, rather than by a "helicase pathway" involving the separation and reannealing of DNA strands.


Adenosine Triphosphatases/metabolism , Cell Cycle Proteins , DNA-Binding Proteins/metabolism , Meiosis/physiology , Recombination, Genetic , Adenosine Triphosphatases/genetics , DNA Helicases/metabolism , DNA-Binding Proteins/genetics , Deoxyribonucleases/metabolism , Humans , Male , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism
20.
Clin Exp Immunol ; 121(1): 106-11, 2000 Jul.
Article En | MEDLINE | ID: mdl-10886246

The human IgA Fc receptor (FcalphaR, CD89) plays an important role in host defence against invading pathogens. To study the properties of the receptor, 12 MoAbs, namely, MIP7c, MIP8a, MIP9a, MIP10c, MIP11c, MIP14b, MIP15b, MIP38c, MIP59c, MIP65c, MIP68b and MIP71a, were generated. The inhibitory effects of the antibodies on FcalphaR functions were tested. Three of the antibodies, MIP7c, MIP8a and MIP59c, were able to block up to 90% of soluble FcalphaR binding to IgA-coated beads and 70-80% of neutrophil phagocytosis of IgA immune complexes (IC). MIP8a could also inhibit IgA IC-induced neutrophil lactoferrin release, while cross-linking of FcalphaR with MIP8a and anti-mouse IgG could elicit neutrophil lactoferrin release. However, IgA IC-induced lactoferrin release required both extracellular calcium and magnesium, whereas MIP8a-induced release did not require extracellular magnesium and only partially required extracellular calcium. In addition, the time course of IgA IC-induced lactoferrin release was slow. Lactoferrin was not detectable if the incubation time was less than 0.5 h. In contrast, MIP8a-induced lactoferrin release was fast. Lactoferrin could be detected within 5 min of incubation. Therefore, neutrophil lactoferrin release induced by IgA IC differed from that induced by cross-linking of FcalphaR with MIP8a.


Antigen-Antibody Complex/metabolism , Antigens, CD/metabolism , Immunoglobulin A/metabolism , Lactoferrin/metabolism , Neutrophils/metabolism , Receptors, Fc/metabolism , Animals , Antibodies, Monoclonal/immunology , Antigens, CD/genetics , Antigens, CD/immunology , CHO Cells , Calcium/metabolism , Cations, Divalent , Cricetinae , Cross-Linking Reagents , Humans , Magnesium/metabolism , Mice , Rabbits , Receptors, Fc/genetics , Receptors, Fc/immunology , Time Factors
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