ABSTRACT
Among the four fundamental forces, only gravity does not couple to particle spins according to the general theory of relativity. We test this principle by searching for an anomalous scalar coupling between the neutron spin and the Earth's gravity on the ground. We develop an atomic gas comagnetometer to measure the ratio of nuclear spin-precession frequencies between ^{129}Xe and ^{131}Xe, and search for a change of this ratio to the precision of 10^{-9} as the sensor is flipped in Earth's gravitational field. The null results of this search set an upper limit on the coupling energy between the neutron spin and the gravity on the ground at 5.3×10^{-22} eV (95% confidence level), resulting in a 17-fold improvement over the previous limit. The results can also be used to constrain several other anomalous interactions. In particular, the limit on the coupling strength of axion-mediated monopole-dipole interactions at the range of Earth's radius is improved by a factor of 17.
ABSTRACT
Purpose Glioblastoma multiforme (GBM) represents the most common and the most malignant type of brain tumor. Cell division cycle 6 (CDC6), a gene associated with DNA replication initiation, has been proven to be associated with the prognosis of multiple tumors. In this study, we aim to explore the association between CDC6 expression and GBM carcinogenesis and prognosis. Methods CDC6 expression in normal cells and GBM cells was explored by analyzing TCGA dataset, as well as by RT-PCR and western blot methods. Survival analysis was performed by the KaplanMeier method. Multivariate Cox-regression analysis was adopted to estimate the independence of CDC6 as a GBM prognostic factor. Results and conclusions Elevated CDC6 levels in GBM tumor tissues compared with those in normal brain tissues were illustrated by analyzing the gene expression profiles from TCGA dataset, and confirmed by RT-PCR and western blot assays in GBM tumor and normal human astrocyte cell lines. KaplanMeier analysis indicated the negative influence of high CDC6 expression on GBM overall survival (OS) probability and days to progression (D2P) after initial treatment, but not on days to recurrence (D2R) after initial treatment. Multivariate Cox regression analysis showed CDC6 as an independent signature marker gene for GBM prognosis. In addition, the combination of CDC6 mRNA expression and CpG island methylator phenotype (CIMP) could sensitively predict 3-year OS and D2P. In conclusion, our study uncovered the role of CDC6 in GBM carcinogenesis and prognosis for the first time, which could shed new light on GBM diagnosis and treatment (AU)
Subject(s)
Humans , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Glioblastoma/genetics , Glioblastoma/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Gene Expression Regulation, Neoplastic , Brain Neoplasms/mortality , Glioblastoma/mortality , Up-Regulation , Survival Rate , PrognosisABSTRACT
PURPOSE: Glioblastoma multiforme (GBM) represents the most common and the most malignant type of brain tumor. Cell division cycle 6 (CDC6), a gene associated with DNA replication initiation, has been proven to be associated with the prognosis of multiple tumors. In this study, we aim to explore the association between CDC6 expression and GBM carcinogenesis and prognosis. METHODS: CDC6 expression in normal cells and GBM cells was explored by analyzing TCGA dataset, as well as by RT-PCR and western blot methods. Survival analysis was performed by the Kaplan-Meier method. Multivariate Cox-regression analysis was adopted to estimate the independence of CDC6 as a GBM prognostic factor. RESULTS AND CONCLUSIONS: Elevated CDC6 levels in GBM tumor tissues compared with those in normal brain tissues were illustrated by analyzing the gene expression profiles from TCGA dataset, and confirmed by RT-PCR and western blot assays in GBM tumor and normal human astrocyte cell lines. Kaplan-Meier analysis indicated the negative influence of high CDC6 expression on GBM overall survival (OS) probability and days to progression (D2P) after initial treatment, but not on days to recurrence (D2R) after initial treatment. Multivariate Cox regression analysis showed CDC6 as an independent signature marker gene for GBM prognosis. In addition, the combination of CDC6 mRNA expression and CpG island methylator phenotype (CIMP) could sensitively predict 3-year OS and D2P. In conclusion, our study uncovered the role of CDC6 in GBM carcinogenesis and prognosis for the first time, which could shed new light on GBM diagnosis and treatment.
Subject(s)
Brain Neoplasms/genetics , Cell Cycle Proteins/genetics , Glioblastoma/genetics , Nuclear Proteins/genetics , Blotting, Western , Brain/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/mortality , Cell Cycle Proteins/metabolism , Cell Line, Tumor , CpG Islands/genetics , Databases, Genetic , Female , Gene Expression , Glioblastoma/metabolism , Glioblastoma/mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Nuclear Proteins/metabolism , Prognosis , Proportional Hazards Models , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Survival Analysis , Transcriptome , Up-RegulationABSTRACT
The present study aimed to investigate the potential role of microRNA-141-3p (miR-141-3p) in chronic inflammatory pain (CIP) by targeting the high-mobility group box1 (HMGB1) gene. In the in vitro study, BV2 microglial cells were selected and assigned into blank, lipopolysaccharide (LPS), miR-141-3p mimics, mimics control, miR-141-3p inhibitor, inhibitor control, miR-141-3p mimics+LPS, mimics control+ LPS, miR-141-3p inhibitor+LPS and inhibitor control+LPS groups. Ninety-six rats were randomly divided into 8 groups (12 rats in each group): blank control, model control, negative control (NC), miR-141-3p mimics+ complete Freund's adjuvant (CFA), mimics control+CFA, HMGB1 short hairpin RNA (shRNA)+CFA, HMGB1 NC+CFA and miR-141-3p mimics+HMGB1 shRNA+CFA groups. The quantitative real-time PCR, western blotting, enzyme-linked immunosorbent assay and pain behavioral test were used to measure the miR-141-3p and HMGB1 mRNA expressions, HMGB1 protein expression, inflammatory cytokines levels, and thermal and mechanical pain thresholds, respectively. Compared with the blank, mimics control, inhibitor control and miR-141-3p mimics+LPS groups, the miR-141-3p mimics group had increased miR-141-3p expression and interleukin (IL)-10 levels, and had decreased mRNA and protein expressions of HMGB1 and the levels of IL-1ß, tumor necrosis factor-α (TNF-α) and IL-6, whereas the opposite trend were found in the LPS, miR-141-3p inhibitor, mimics control+LPS and inhibitor control+LPS groups. Compared with the LPS, miR-141-3p inhibitor, mimics control+LPS and inhibitor control+LPS groups, the miR141-3p+LPS group had an obviously decreased expression of miR-141-3p and IL-10, increased mRNA and protein expressions of HMGB1 and the levels of IL-1ß, TNF-α and IL-6. Compared with the rats in the blank control group, the miR-141-3p expression, IL-10 level, and thermal and mechanical pain thresholds decreased significantly, whereas the mRNA and protein expressions of HMGB1, IL-1ß, TNF-α and IL-6 increased significantly in rats in the NC, mimics control+CFA and HMGB1 NC+ CFA groups. The miR-141-3p expression was increased in rats in the miR-141-3p mimics+HMGB1 shRNA+CFA group. Our study demonstrated that miR-141-3p can alleviate the CIP by downregulating the downstream target gene HMGB1.
Subject(s)
Chronic Pain/therapy , Down-Regulation , Genetic Therapy/methods , HMGB1 Protein/genetics , MicroRNAs/genetics , Neuralgia/therapy , Animals , Cell Line , Cytokines/blood , HMGB1 Protein/metabolism , Mice , Pain Threshold , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Behçet's disease (BD) is known to be associated with human leucocyte antigen (HLA)-B*51 in many ethnic groups. However, the association of HLA class II gene with BD has been described to be different according to different countries and regions. OBJECTIVE: This study aims to investigate the association between polymorphism of HLA-DRB1 alleles and BD. METHODS: Forty patients with BD and 100 healthy controls were typed for HLA-DRB1 alleles by the LABType SSO method. RESULTS: The frequency of HLA-DRB1*14 was significantly higher in BD patients than in controls (P < 0.05), while the frequency of HLA-DRB1*15 was markedly lower in BD patients (P < 0.05). Regarding clinical manifestations, the frequency of HLA-DRB1*15 was significantly decreased in BD patients with genital ulcerations compared with controls (P < 0.05); the frequency of HLA-DRB1*14 was significantly increased in BD patients with erythema nodosum-like lesions and in BD patients with folliculitis-like lesions when compared to controls (P < 0.05, respectively). Moreover, the frequency of HLA-DRB1*14 was significantly increased in BD patients under 20 years of age at the onset of disease (P < 0.01), while the frequency of HLA-DRB1*15 was significantly decreased in them (P < 0.05), compared with controls. CONCLUSION: The results suggested that HLA-DRB1 alleles might play an important role in the onset and clinical manifestations of BD.
Subject(s)
Alleles , Behcet Syndrome/genetics , HLA-DR Antigens/genetics , Polymorphism, Genetic , Behcet Syndrome/immunology , Case-Control Studies , HLA-DRB1 Chains , HumansABSTRACT
Bullous pemphigoid (BP) is an autoimmune disease mediated by autoantibodies against hemidesmosome components. This study used PCR-sequence-specific primers to genotype polymorphisms in HLA-DR and DQ in 25 BP patients and 57 normal controls from northern China. We found lower frequencies of DRB1*08 (DR8) and DRB1*08/DQB1*06 (DR8/DQ6) haplotypes in BP patients than in controls (4.08% vs. 15.19% and 1.54% vs. 13.82%, respectively; P < 0.05), suggesting a protective role for DR8 and DR8/DQ6 haplotypes in BP patients from northern China; there were no statistical differences among other alleles tested. This result is strikingly different from previous reports that DQB1*0301 is associated with BP in Caucasian patients and DRB1*1101, DQB1*0302, DRB1*04/DQA1*0301/DQB1*0302 and DRB1*1101/ DQA1*0505/DQB1*0302 with Japanese BP patients. Ethnic differences in the polymorphic composition of the HLA-DR and DQ genes may influence genetic susceptibility to BP.
Subject(s)
HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Pemphigoid, Bullous/genetics , Polymorphism, Genetic , Case-Control Studies , China , Gene Frequency , Humans , Polymerase Chain Reaction/methodsABSTRACT
OBJECTIVE: To establish a PCR-SSP method for discriminating as many HLA-A*02 alleles, which could easily be introduced into a routine laboratory. METHODS: In this study we typed HLA-A*02 polymorphisms by a sequence-specific primer (SSP) method, which involved round 1 and round 2 PCR reactions to detect 17 HLA-A*02 alleles (they are HLA-A*0201-0217 alleles) covering exon 2 and exon 3. RESULTS: We have found that DNA sample concentration and purity were the most important variable in determining the quality of the result. For identifying correct band size, the size marker used was important. We noticed that different PCR machines performed differently. By this method, we detected 20 HLA-A*02 positive genomic DNA samples and found 4 kinds of HLA-A*02 alleles. They were HLA-A*0201, 0203, 0206 and 0210. CONCLUSION: The HLA-A*02 PCR-SSP method was proven to be a reliable and easily applicable typing method. Our results suggest that the SSP described here provides an optimal HLA-A*02 typing technique that may be useful in selecting donor-recipient pairs in bone marrow transplantation between unrelated individuals.
Subject(s)
DNA/genetics , HLA-A2 Antigen/genetics , Histocompatibility Testing/methods , Alleles , Bone Marrow/chemistry , DNA/isolation & purification , DNA Primers , HLA-A2 Antigen/classification , Humans , Polymerase Chain Reaction/methodsSubject(s)
HLA-DR Antigens/genetics , Psoriasis/genetics , Adolescent , Adult , Aged , Female , Gene Frequency , Genetic Predisposition to Disease , HLA-DRB1 Chains , Humans , Male , Middle AgedABSTRACT
"In a country such as the United States, the contribution of net international migration to overall population change overshadows the contribution of natural increase.... Some analysts have assumed that if the same number of people leave and enter the country each year, then the effect of net international migration will be zero. This article examines that assumption and shows that it is fallacious. Examining the direct, indirect, total, and negative demographic impacts of zero net international migration through simulations with demographic data, we demonstrate that zero net international migration is not the same and therefore does not have the same demographic results and implications as zero international migration. We conclude that zero net international migration should not be confused with zero international migration."
Subject(s)
Demography , Emigration and Immigration , Population Dynamics , Population Growth , Statistics as Topic , Terminology as Topic , Americas , Developed Countries , North America , Population , Research , United StatesABSTRACT
"The idea of ¿zero net migration' is gaining increasing currency. It has been assumed that if there is balance between the number of immigrants and emigrants, migration will have no impact on a country's population size. However, this article demonstrates that zero net migration is not necessarily the same as zero migration, and can result in a higher population than would have occurred without any migration at all." The examples of Germany and the United States are presented.
Subject(s)
Emigration and Immigration , Population Density , Public Policy , Americas , Demography , Developed Countries , Europe , Germany , North America , Population , Population Dynamics , United StatesABSTRACT
To confirm a relationship between the central nervous system and the acupuncture, the response was examined in the rat brain using radioautography with tritiated 2-deoxyglucose, after stimulation of some acupoints. Eight groups, of a total of 27 rats were submitted to acupuncture at 6 different acupoints (Zusanli, Renzhong, Tianshu, Shenmen, Neiguan, Yongquan) and control, with or without electric pulses or with anesthesia respectively, prior to the injection with isotopic deoxyglucose. A hundred twenty cryosections were cut from a freshly frozen brain and exposed on single-coated X-ray films. The results showed that the acupuncture on the four acupoints of Zusanli, Tianshu, Shenmen and Neiguan enhanced the activity of the neocortex, the limbic cortex and the thalamic nuclei in comparison with the control group. The acupoints on Renzhong and Yongquan depressed the activity on the thalamic nuclei and the midbrain. The anesthesia with pentobarbital concealed the most activity on the whole area of the brain, which hardly responded to any stimulation of acupuncture. These results lead to the suggestion that the brain may reflect the signals by the stimulation of acupuncture and change the activity depending upon each acupoint.
Subject(s)
Acupuncture Therapy , Brain/physiology , Deoxyglucose/pharmacokinetics , Acupuncture Therapy/methods , Anesthesia , Animals , Autoradiography , Brain/metabolism , Brain Mapping , Electroacupuncture , Energy Metabolism , Male , Rats , Rats, Wistar , Specific Pathogen-Free OrganismsABSTRACT
Occluding unilateral middle cerebral artery (MCAo) of rat, the compensatory blood vessels (CBV) within ischemic area in cerebral surface shown by cerebral perfusion and effect of acupuncture were observed dynamically. Perfusing immediately after MCAo, there was no any blood vessel in the ischemic area. In acupuncture group, the CBV had extended a lot from anastomotic network of cerebral pia mater (ACA-MCA, PCA-MCA) located in marginal zone of ischemic area 3 hs after MCAo. 6.24 and 48 hs after MCAo, the CBV increased much more than control group (non-acupuncture) P < 0.01. The experiment pointed out that there existed a serious vasospasm in the MCA system in initial stage of MCAo, which led up to decompensation in the ischemic area. The acupuncture can remit the vasospasm, and reverse the deteriorated process in early.
Subject(s)
Acupuncture Therapy , Cerebral Infarction/pathology , Pia Mater/blood supply , Animals , Cerebral Infarction/therapy , Cerebrovascular Circulation , Collateral Circulation , Female , Male , Random Allocation , Rats , Rats, WistarABSTRACT
Occluding unilateral middle cerebral artery (MCAO) of rat, the ischemic volume within cerebrum shown by nitroblue tetrazolium (N-BT) histochemistry method and effect of acupuncture were observed dynamically. 18 hs after MCAO, the ischemic area began to extend from cerebral cortex into subcortical area. 36 hs after MCAO, there was a large ischemic area in cortical and subcortical area, whose volume occupied 20.7 percent of the whole. Whereas the ischemic area in the cortex disappeared in the acupuncture group, the ischemic volume reduced to 6.3 percent of the whole. The experiment pointed out that the acupuncture is an effective therapeutic procedure for cerebral infarction.
Subject(s)
Acupuncture Therapy , Brain/pathology , Cerebral Infarction/pathology , Animals , Cerebral Infarction/therapy , Female , Image Processing, Computer-Assisted , Male , Nitroblue Tetrazolium , Rats , Rats, WistarABSTRACT
It was aimed at observing the histochemical basis of physiological experiment about the effect of electroacupuncture (EA) on acute myocardial ischemia (AMI) in this paper. The capillaries of myocardium were reflected with both alkaline phosphatase (ALP) and Mg(2+)-ATPase. Thirty min after ligating the left ventricular branch (LVB), the capillaries stained by ALP were much decreased in the ischemic group without EA, while in EA group they were increased distinctly. The number and the total length of the capillaries in a 220 x 320 microns ischemic area of the posterior wall (section 10 microns) were measured and compared. In ischemic group the number was 17.2 +/- 1.65, the length was 634.62 +/- 66.24 microns, in EA group 22.5 +/- 1.44, 1187.57 +/- 103.69 microns, respectively. Both counts were significant differences (P < 0.05, P < 0.001). It reflected that EA could improve the microcirculation and metabolic function of AMI. Mg(2+)-ATPase was shown on the plasma membrane of endothelial cell of microvasculature and analysed quantitatively with a Univar scanning microspectrophotometer. After occluding LVB for 30 min its optic density of AMI was decreased to 106.83 +/- 14.06, while it was increased to 210.83 +/- 24.88 in EA group, P < 0.05. The activity of Mg(2+)-ATPase could increase in transporting Na+, k+ ions through the membrane of the endothelial cells of ischemic myocardium. The result was consistent with the physiological experiment, because EA could regulate the changes of mean repolarization rate induced by AMI and adjust the ion concentration of transmembrane. The catecholamine (CA) in myocardium was located at sympathetic adrenergic terminals with varicosities containing norepinephrine (NE).(ABSTRACT TRUNCATED AT 250 WORDS)