Absence of annexin I expression in B-cell non-Hodgkin's lymphomas and cell lines

BACKGROUND: Annexin I, one of the 20 members of the annexin family of calcium and phospholipid-binding proteins, has been implicated in diverse biological processes including signal transduction, mediation of apoptosis and immunosuppression. Previous studies have shown increased annexin I expression in pancreatic and breast cancers, while it is absent in prostate and esophageal cancers. RESULTS: Data presented here show that annexin I mRNA and protein are undetectable in 10 out of 12 B-cell lymphoma cell lines examined. Southern blot analysis indicates that the annexin I gene is intact in B-cell lymphoma cell lines. Aberrant methylation was examined as a cause for lack of annexin I expression by treating cells 5-Aza-2-deoxycytidine. Reexpression of annexin I was observed after prolonged treatment with the demethylating agent indicating methylation may be one of the mechanisms of annexin I silencing. Treatment of Raji and OMA-BL-1 cells with lipopolysaccharide, an inflammation inducer, and with hydrogen peroxide, a promoter of oxidative stress, also failed to induce annexin I expression. Annexin I expression was examined in primary lymphoma tissues by immunohistochemistry and presence of annexin I in a subset of normal B-cells and absence of annexin I expression in the lymphoma tissues were observed. These results show that annexin I is expressed in normal B-cells, and its expression is lost in all primary B-cell lymphomas and 10 of 12 B-cell lymphoma cell lines. CONCLUSIONS: Our results suggest that, similar to prostate and esophageal cancers, annexin I may be an endogenous suppressor of cancer development, and loss of annexin I may contribute to B-cell lymphoma development

The influence of long-term treadmill exercise on bone mass and articular cartilage in ovariectomized rats

<p>Abstract</p> <p>Background</p> <p>Loss of bone quality and deterioration of articular cartilage are commonly seen after menopause. While exercise may protect against tissue degeneration, a clear link has yet to be established. The aim of the present study is to investigate the influence of long-term treadmill exercise on changes in bone mass and articular cartilage in ovariectomized rats.</p> <p>Methods</p> <p>Sixty female Sprague-Dawley rats were randomly assigned to 4 groups: ovariectomized (OVX), ovariectomized plus treadmill exercise (OVX-RUN), treadmill exercise alone (RUN), and control (CON) groups. After 36 weeks, the following variables were compared among the 4 groups. Bone mass was evaluated by trabecular bone volume and bone mineral density (BMD). Articular cartilage in the knee joints was evaluated by histology analysis and a modified Mankin score.</p> <p>Results</p> <p>Rats in the ovariectomized groups (OVX and OVX-RUN) had significantly lower BMD and bone mass than the non-ovariectomized rats (CON and RUN), indicating that exercise did little to preserve bone mass. However, the sedentary OVX group had a significantly worse modified Mankin score (7.7 ± 1.4) than the OVX-RUN group (4.8 ± 1.0), whose scores did not differ significantly from the other 2 non-operated groups. The articular cartilage in the sedentary OVX rats was relatively thinner, hypocellular, and had more clefts than in the other 3 groups.</p> <p>Conclusion</p> <p>This study suggests that long-term exercise protects articular cartilage in OVX rats but does not retard the loss of bone mass seen in after menopause.</p

New Physics in Bs -> J/psi phi: a General Analysis

Recently, the CDF and D0 collaborations measured indirect CP violation in Bs -> J/psi phi and found a hint of a signal. If taken at face value, this can be interpreted as a nonzero phase of Bs-Bsbar mixing (beta_s), in disagreement with the standard model, which predicts that beta_s ~= 0. In this paper, we argue that this analysis may be incomplete. In particular, there can be new physics (NP) in the bbar -> sbar c cbar decay. If so, the value of beta_s is different than for the case in which NP is assumed to be present only in the mixing. We have examined several models of NP and found that, indeed, there can be significant contributions to the decay. These effects are consistent with measurements in B -> J/psi K* and Bd -> J/psi Ks. Due to the NP in the decay, polarization-dependent indirect CP asymmetries and triple-product asymmetries are predicted in Bs -> J/psi phi.Comment: 28 pages, JHEP, no figures. Considerable changes made. Abstract and main text of paper modified to alter presentation. Appendix added. References added. Conclusions unchanged

Hospitalization for Heart Failure in the United States, UK, Taiwan, and Japan: An International Comparison of Administrative Health Records on 413,385 Individual Patients

BACKGROUND: Registries show international variations in the characteristics and outcome of patients with heart failure (HF) but national samples are rarely large, and case-selection may be biased due to enrolment in academic centres. National administrative datasets provide large samples with a low risk of bias. In this study, we compared the characteristics, healthcare resource utilization (HRU) and outcomes of patients with primary HF hospitalizations (HFH) using electronic health records (EHR) from four high-income countries (USA, UK, Taiwan, Japan) on three continents. METHODS AND RESULTS: We used EHR to identify unplanned HFH between 2012-2014. We identified 231,512, 10,991, 36,900 and 133,982 patients with a primary HFH from USA, UK, Taiwan and Japan, respectively. HFH per 100,000 population was highest in USA and lowest in Taiwan. Patients in Taiwan and Japan were older but fewer were obese or had chronic kidney disease. LOHS was shortest in USA (median 4 days) and longer in UK, Taiwan and Japan (medians 7, 9 and 17 days, respectively). HRU during hospitalization was highest in Japan and lowest in UK. Crude and direct standardized in-hospital mortality was lowest in USA (direct standardized rates: 1.8 [95%CI:1.7-1.9]%)and progressively higher in Taiwan (direct standardized rates: 3.9 [95%CI:3.8-4.1]%), UK (direct standardized rates: 6.4 [95%CI:6.1-6.7]%) and Japan (direct standardized rates: 6.7 [95%CI:6.6-6.8]%). 30-day all-cause (25.8%) and HF (7.2%) readmissions were highest in USA and lowest in Japan (11.9% and 5.1% respectively). CONCLUSION: Marked international variations in patient characteristics, HRU and clinical outcome exist; understanding them might inform health care policy and international trial design

Secondary contact and admixture between independently invading populations of the Western corn rootworm, diabrotica virgifera virgifera in Europe

The western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), is one of the most destructive pests of corn in North America and is currently invading Europe. The two major invasive outbreaks of rootworm in Europe have occurred, in North-West Italy and in Central and South-Eastern Europe. These two outbreaks originated from independent introductions from North America. Secondary contact probably occurred in North Italy between these two outbreaks, in 2008. We used 13 microsatellite markers to conduct a population genetics study, to demonstrate that this geographic contact resulted in a zone of admixture in the Italian region of Veneto. We show that i) genetic variation is greater in the contact zone than in the parental outbreaks; ii) several signs of admixture were detected in some Venetian samples, in a Bayesian analysis of the population structure and in an approximate Bayesian computation analysis of historical scenarios and, finally, iii) allelic frequency clines were observed at microsatellite loci. The contact between the invasive outbreaks in North-West Italy and Central and South-Eastern Europe resulted in a zone of admixture, with particular characteristics. The evolutionary implications of the existence of a zone of admixture in Northern Italy and their possible impact on the invasion success of the western corn rootworm are discussed

Neutral Gauge Boson Contributions to the Dimuon Charge Asymmetry in B Decays

Recently, the D0 Collaboration measured the CP-violating like-sign dimuon charge asymmetry in neutral B decays, finding a 3.2sigma difference from the standard-model (SM) prediction. A non-SM charge asymmetry a_sl^s suggests a new-physics (NP) contribution to Bs-Bsbar mixing. In this case, in order to explain the measured value of a_sl^s within its 1sigma range, NP must be present in Gamma_12^s, the absorptive part of the mixing. In this paper, we examine whether such an explanation is possible in models with flavor-changing Z (ZFCNC) or Z' (Z'FCNC) gauge bosons. The models must also reproduce the measured values of the indirect CP asymmetry S_psi-phi in Bs -> J/psi phi, and Delta Gamma_s, the Bs-Bsbar width difference. We find that the ZFCNC model cannot reproduce the present measured values of S_psi-phi and a_sl^s within their 1sigma ranges. On the other hand, in the Z'FCNC model, the values of all three observables can be simultaneously reproduced.Comment: 18 pages, 7 figures, JHEP format. Some ZFCNC equations corrected, ZFCNC analysis redone, references added, conclusions unchange

Disease-Associated Mutations Prevent GPR56-Collagen III Interaction

GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Mutations in GPR56 cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Using the N-terminal fragment of GPR56 (GPR56N) as a probe, we have recently demonstrated that collagen III is the ligand of GPR56 in the developing brain. In this report, we discover a new functional domain in GPR56N, the ligand binding domain. This domain contains four disease-associated mutations and two N-glycosylation sites. Our study reveals that although glycosylation is not required for ligand binding, each of the four disease-associated mutations completely abolish the ligand binding ability of GPR56. Our data indicates that these four single missense mutations cause BFPP mostly by abolishing the ability of GPR56 to bind to its ligand, collagen III, in addition to affecting GPR56 protein surface expression as previously shown

A Triple Protostar System Formed via Fragmentation of a Gravitationally Unstable Disk

Binary and multiple star systems are a frequent outcome of the star formation process, and as a result, almost half of all sun-like stars have at least one companion star. Theoretical studies indicate that there are two main pathways that can operate concurrently to form binary/multiple star systems: large scale fragmentation of turbulent gas cores and filaments or smaller scale fragmentation of a massive protostellar disk due to gravitational instability. Observational evidence for turbulent fragmentation on scales of $>$1000~AU has recently emerged. Previous evidence for disk fragmentation was limited to inferences based on the separations of more-evolved pre-main sequence and protostellar multiple systems. The triple protostar system L1448 IRS3B is an ideal candidate to search for evidence of disk fragmentation. L1448 IRS3B is in an early phase of the star formation process, likely less than 150,000 years in age, and all protostars in the system are separated by $<$200~AU. Here we report observations of dust and molecular gas emission that reveal a disk with spiral structure surrounding the three protostars. Two protostars near the center of the disk are separated by 61 AU, and a tertiary protostar is coincident with a spiral arm in the outer disk at a 183 AU separation. The inferred mass of the central pair of protostellar objects is $\sim$1 M$_{sun}$, while the disk surrounding the three protostars has a total mass of $\sim$0.30 M_{\sun}. The tertiary protostar itself has a minimum mass of $\sim$0.085 M$_{sun}$. We demonstrate that the disk around L1448 IRS3B appears susceptible to disk fragmentation at radii between 150~AU and 320~AU, overlapping with the location of the tertiary protostar. This is consistent with models for a protostellar disk that has recently undergone gravitational instability, spawning one or two companion stars.Comment: Published in Nature on Oct. 27th. 24 pages, 8 figure

GLAST: Understanding the High Energy Gamma-Ray Sky

We discuss the ability of the GLAST Large Area Telescope (LAT) to identify, resolve, and study the high energy gamma-ray sky. Compared to previous instruments the telescope will have greatly improved sensitivity and ability to localize gamma-ray point sources. The ability to resolve the location and identity of EGRET unidentified sources is described. We summarize the current knowledge of the high energy gamma-ray sky and discuss the astrophysics of known and some prospective classes of gamma-ray emitters. In addition, we also describe the potential of GLAST to resolve old puzzles and to discover new classes of sources.Comment: To appear in Cosmic Gamma Ray Sources, Kluwer ASSL Series, Edited by K.S. Cheng and G.E. Romer

Association between Frequency Domain Heart Rate Variability and Unplanned Readmission to Hospital in Geriatric Patients

<p>Abstract</p> <p>Background</p> <p>An accurate prediction of unplanned readmission (UR) after discharge from hospital can facilitate physician's decision making processes for providing better quality of care in geriatric patients. The objective of this study was to explore the association of cardiac autonomic functions as measured by frequency domain heart rate variability (HRV) and 14-day UR in geriatric patients.</p> <p>Methods</p> <p>Patients admitted to the geriatric ward of a regional hospital in Chiayi county in Taiwan were followed prospectively from July 2006 to June 2007. Those with invasive tubes and those who were heavy smokers, heavy alcohol drinkers, on medications that might influence HRV, or previously admitted to the hospital within 30 days were excluded. Cardiac autonomic functions were evaluated by frequency domain indices of HRV. Multiple logistic regression was used to assess the association between UR and HRV indices adjusted for age and length of hospitalization.</p> <p>Results</p> <p>A total of 78 patients met the inclusion criteria and 15 of them were readmitted within 14 days after discharge. The risk of UR was significantly higher in patients with lower levels of total power (OR = 1.39; 95% CI = 1.04-2.00), low frequency power (LF) (OR = 1.22; 95% CI = 1.03-1.49), high frequency power (HF) (OR = 1.27; 95% CI = 1.02-1.64), and lower ratios of low frequency power to high frequency power (LF/HF ratio) (OR = 1.96; 95% CI = 1.07-3.84).</p> <p>Conclusion</p> <p>This is the first study to evaluate the association between frequency domain heart rate variability and the risk of UR in geriatric patients. Frequency domain heart rate variability indices measured on admission were significantly associated with increased risk of UR in geriatric patients. Additional studies are required to confirm the value and feasibility of using HRV indices on admission as a non-invasive tool to assist the prediction of UR in geriatric patients.</p