bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-124 and -137 cooperativity controls caspase-3 activity through BCL2L13 in hippocampal neural stem cells
Authors: Schouten Marijn , Fratantoni Silvina A. , Hubens Chantal J. , Piersma Sander R. , Pham Thang V. , Bielefeld Pascal , Voskuyl Rob A. , Lucassen Paul J. , Jimenez Connie R. , Fitzsimons Carlos P. 
Published: July 2015

AbstractAdult neurogenesis continuously contributes new neurons to hippocampal circuits and the programmed death of a subset of immature cells provides a primary mechanism controlling this contribution. Epileptic seizures induce strong structural changes in the hippocampus, including the induction of adult neurogenesis, changes in gene expression and mitochondrial dysfunction, which may all contribute to epileptogenesis. However, a possible interplay between this factors remains largely unexplored. Here, we investigated gene expression changes in the hippocampal dentate gyrus shortly after prolonged seizures induced by kainic acid, focusing on mitochondrial functions. Using comparative proteomics, we identified networks of proteins differentially expressed shortly after seizure induction, including members of the BCL2 family and other mitochondrial proteins. Within these networks, we report for the first time that the atypical BCL2 protein BCL2L13 controls caspase-3 activity and cytochrome C release in neural stem/progenitor cells. Furthermore, we identify BCL2L13 as a novel target of the cooperative action of microRNA-124 and microRNA-137, both upregulated shortly after seizure induction. This cooperative microRNA-mediated fine-tuning of BCL2L13 expression controls casp3 activity, favoring non-apoptotic caspase-3 functions in NSPC exposed to KA and thereby may contribute to the early neurogenic response to epileptic seizures in the dentate gyrus.
RE-IIBP Methylates H3K79 and Induces MEIS1-mediated Apoptosis via H2BK120 Ubiquitination by RNF20
Authors: Woo Park Jin , Kim Kee-Beom , Kim Ji-Young , Chae Yun-Cheol , Jeong Oh-Seok , Seo Sang-Beom 
Published: July 2015

AbstractHistone lysine methylation contributes to transcriptional regulation by serving as a platform for the recruitment of various cofactors. Intense studies have been conducted for elucidating the functional meaning of H3K79 methylation and to date, the only known HMTase responsible for the modification was DOT1L. In this study, we report that the MMSET isoform RE-IIBP has HMTase activity for H3K79. It was uncovered that RE-IIBP up-regulates MEIS1 transcription through H3K79 methylation via recruitment to the MEIS1 promoter. By means of proteomic and biochemical analysis, association of RE-IIBP with the E3 ubiquitin ligase RNF20 was demonstrated for synergistic activation of MEIS1 transcription via H3K79 HMTase activity. Furthermore, It was observed that RE-IIBP induces MEIS1-mediated apoptosis, which was dependent on H2BK120 ubiquitination by RNF20. These findings suggest RE-IIBP as another candidate for further studies to elucidate the mechanism of H3K79 methylation and its biological functions.
Hypoxia-inducible miR-182 enhances HIF1α signaling via targeting PHD2 and FIH1 in prostate cancer
Authors: Li Yan , Zhang Duo , Wang Xiaoyun , Yao Xuan , Ye Cheng , Zhang Shengjie , Wang Hui , Chang Cunjie , Xia Hongfeng , Wang Yu-cheng , Fang Jing , Yan Jun , Ying Hao 
Published: July 2015

AbstractActivation of hypoxia-inducible factor 1α (HIF1α) controls the transcription of genes governing angiogenesis under hypoxic condition during tumorigenesis. Here we show that hypoxia-responsive miR-182 is regulated by HIF1α at transcriptional level. Prolyl hydroxylase domain enzymes (PHD) and factor inhibiting HIF-1 (FIH1), negative regulators of HIF1 signaling, are direct targets of miR-182. Overexpression of miR-182 in prostate cancer cells led to a reduction of PHD2 and FIH1 expression and an increase in HIF1α level either under normoxic or hypoxic condition. Consistently, inhibition of miR-182 could increase PHD2 and FIH1 levels, thereby reducing the hypoxia-induced HIF1α expression. Matrigel plug assay showed that angiogenesis was increased by miR-182 overexpression and vice versa. miR-182 overexpression in PC-3 prostate cancer xenografts decreased PHD2 and FIH1 expression, elevated HIF1α protein levels and increased tumor size. Lastly, we revealed that the levels of both miR-182 and HIF1α were elevated, while the expression PHD2 and FIH1 was downregulated in a mouse model of prostate cancer. Together, our results suggest that the interplay between miR-182 and HIF1α could result in a sustained activation of HIF1α pathway, which might facilitate tumor cell adaption to hypoxic stress during prostate tumor progression.
Fluoxetine increases plasticity and modulates the proteomic profile in the adult mouse visual cortex
Authors: Ruiz-Perera L. , Muniz M. , Vierci G. , Bornia N. , Baroncelli L. , Sale A. , Rossi F.M. 
Published: July 2015

AbstractThe scarce functional recovery of the adult CNS following injuries or diseases is largely due to its reduced potential for plasticity, the ability to reorganize neural connections as a function of experience. Recently, some new strategies restoring high levels of plasticity in the adult brain have been identified, especially in the paradigmatic model of the visual system. A chronic treatment with the anti-depressant fluoxetine reinstates plasticity in the adult rat primary visual cortex, inducing recovery of vision in amblyopic animals. The molecular mechanisms underlying this effect remain largely unknown. Here, we explored fluoxetine effects on mouse visual cortical plasticity and exploited a proteomic approach to identify possible candidates mediating the outcome of the antidepressant treatment on adult cortical plasticity. We showed that fluoxetine restores ocular dominance plasticity in the adult mouse visual cortex and identified 31 differentially expressed protein spots in fluoxetine-treated animals vs. controls. MALDITOF/TOF mass spectrometry identification followed by bioinformatics analysis revealed that these proteins are involved in the control of cytoskeleton organization, endocytosis, molecular transport, intracellular signaling, redox cellular state, metabolism and protein degradation. Altogether, these results indicate a complex effect of fluoxetine on neuronal signaling mechanisms potentially involved in restoring plasticity in the adult brain.
Quantitative determination of target gene with electrical sensor
Authors: Zhang Xuzhi , Li Qiufen , Jin Xianshi , Jiang Cheng , Lu Yong , Tavallaie Roya , Gooding J. Justin 
Published: July 2015

AbstractIntegrating loop-mediated isothermal amplification (LAMP) with capacitively coupled contactless conductivity detection (C4D), we have developed an electrical sensor for the simultaneous amplification and detection of specific sequence DNA. Using the O26-wzygene as a model, the amount of initial target gene could be determined via thethreshold timeobtained by monitoring the progression of the LAMP reaction in real time. Using the optimal conditions, a detection limit of 12.5 copy/μL can be obtained within 30 min. Monitoring the LAMP reaction by C4D has not only all the advantages that existing electrochemical methods have, but also additional attractive features including being completely free of carryover contamination risk, high simplicity and extremely low cost. These benefits all arise from the fact that the electrodes are separated from the reaction solution, that is C4D is a contactless method. Hence in proof of principle, the new strategy promises a robust, simple, cost-effective and sensitive method for quantitative determination of a target gene, that is applicable either to specialized labs or at point-of-care.
Large-mode-area single-mode-output Neodymium-doped silicate glass all-solid photonic crystal fiber
Authors: Li Wentao , Chen Danping , Qinling Zhou , Hu Lili 
Published: July 2015

AbstractWe have demonstrated a 45 μm core diameter Neodymium-doped all-solid silicate glass photonic crystal fiber laser with a single mode laser output. The structure parameters and modes information of the fiber are both demonstrated by theoretical calculations using Finite Difference Time Domain (FDTD) method and experimental measurements. Maximum 0.8 W output power limited by launched pump power has been generated in 1064 nm with laser beam quality factor M2 1.18.
PARP is activated in human asthma and its inhibition by olaparib blocks house dust mite-induced disease in mice
Authors: Ghonim Mohamed A. , Pyakurel Kusma , Ibba Salome V. , Wang Jeffrey , Rodriguez Paulo , Al-Khami Amir A. , Lammi Matthew R. , Kim Hogyoung , Zea Arnold H. , Davis Christian , Okpechi Samuel , Wyczechowska Dorota , Al-Ghareeb Kamel , Mansy Moselhy S. , Ochoa Augusto , Naura Amarjit S. , Boulares A. Hamid 
Published: July 2015

Our laboratory established a role for poly(ADP-ribose)polymerase (PARP) in asthma. To increase the clinical significance of our studies, it is imperative to demonstrate that PARP is actually activated in human asthma, to examine whether a PARP inhibitor approved for human testing such as olaparib blocks already-established chronic asthma traits in response to house dust mite (HDM), a true human allergen, in mice and to examine whether the drug modulates human cluster of differentiation type 4 (CD4+) T-cell function. To conduct the study, human lung specimens and peripheral blood mononuclear cells (PBMCs) and a HDM-based mouse asthma model were used. Our results show that PARP is activated in PBMCs and lung tissues of asthmatics. PARP inhibition by olaparib or gene knockout blocked established asthma-like traits in mice chronically exposed to HDM including airway eosinophilia and hyper-responsiveness. These effects were linked to a marked reduction in T helper 2 (Th2) cytokine production without a prominent effect on interferon (IFN)-γ or interleukin (IL)-10. PARP inhibition prevented HDM-induced increase in overall cellularity, weight and CD4+ T-cell population in spleens of treated mice whereas it increased the T-regulatory cell population. In CD3/CD28-stimulated human CD4 +T-cells, olaparib treatment reduced Th2 cytokine production potentially by modulating GATA binding protein-3 (gata-3)/IL-4 expression while moderately affecting T-cell proliferation. PARP inhibition inconsistently increased IL-17 in HDM-exposed mice and CD3/CD28-stimulated CD4+ T cells without a concomitant increase in factors that can be influenced by IL-17. In the present study, we provide evidence for the first time that PARP-1 is activated in human asthma and that its inhibition is effective in blocking established asthma in mice.
Fluidic beam steering in parasitically coupled patch antenna arrays
Authors: Bhattacharjee T. , Jiang H. , Behdad N. 
Published: July 2015

A technique for designing a parasitic patch antenna array whose beam can be steered dynamically using a fluidic tuning mechanism is presented. Using this technique, a three‐element patch antenna array operating at 5 GHz is designed and fabricated using 3D printing. Two oil‐filled channels are placed in the substrate of the antenna along the radiating edges of the patches and filled with movable metal cylinders and glass balls. The parasitic elements are mutually coupled to the centre element in the H‐plane. As the train of metal cylinders and glass balls are moved from the left or right with respect to the centre‐driven patch element, the beam is steered towards the opposite direction. The proposed parasitic patch array is able to steer the beam ±22.5° with maintained impedance matching.
High Prevalence of Hypertension in a Danish Population Telemedical Home Measurement of Blood Pressure in Citizens Aged 55–64 Years in Holstebro County
Authors: Hoffmann-Petersen Nikolai , Lauritzen Torsten , Bech Jesper Nørgaard , Pedersen Erling Bjerregaard 
Published: July 2015

Abstract

BACKGROUND
Home blood pressure (HBP) is prognostically superior to office BP (OBP) and similar to ambulatory BP measurements. We determined the prevalence of hypertension using HBP with telemedical data transmission in the municipality of Holstebro, Denmark (57,000 citizens).

METHODS
Using the Civil Registration System, we invited citizens aged 55–64 years to have their OBP and HBP measured using telemedical data transmission. Elevated OBP was defined as ≥140/90mm Hg. HBP was measured 3 times daily on 3 consecutive days with 3 measurements on each occasion. HBP was the mean of all measurements on day 1 and 3, and hypertension was defined as ≥135/85mm Hg.

RESULTS
We included 3,102 citizens who had performed at least 12 HBP measurements during day 2 and 3. Group 1: ( n = 1,464, 47%) had both normal OBP and HBP. Group 2: ( n = 838, 27%) had both elevated OBP and HBP indicating persistent hypertension. Group 3: ( n = 560, 18%) had elevated OBP and normal HBP indicating white coat hypertension (WCH). Group 4: ( n = 240, 8%) had normal OBP and elevated HBP indicating masked hypertension (MH). Thus, 1,078 (35%, groups 2 and 4) were untreated or insufficiently treated. Awareness of hypertension was registered in 950 patients (31%) and of these 49% had a normal HBP.

CONCLUSIONS
This is the first large-scale study to eliminate completely reporting bias by using telemedical transmission of BP data. One third of citizens in the age group 55–64 years had an abnormally high HBP, and one fourth either had WCH or MH.

CLINICAL TRIALS REGISTRATION
ClinicalTrials.gov identification number: NCT02355392
Relationship Between Prehypertension/Hypertension and Periodontal Disease: A
Prospective Cohort Study
Authors: Kawabata Yuya , Ekuni Daisuke , Miyai Hisataka , Kataoka Kota , Yamane Mayu , Mizutani Shinsuke , Irie Koichiro , Azuma Tetsuji , Tomofuji Takaaki , Iwasaki Yoshiaki , Morita Manabu 
Published: July 2015

Abstract

BACKGROUND
Most cross-sectional studies have found a significant positive relationship between periodontal disease and prehypertension/hypertension. However, these studies had limitations and there are few prospective cohort studies in young adults. The purpose of this prospective cohort study was to investigate whether periodontal disease was related to prehypertension/hypertension in Japanese university students.

METHODS
Students ( n = 2,588), who underwent health examinations before entering university and before graduation, were included in the analysis. The association between periodontal disease such as the percentage of bleeding on probing (BOP) and community periodontal index (CPI) scores, and change in blood pressure status was determined.

RESULTS
At the reexamination, the numbers of participants with prehypertension (systolic blood pressure 120–139mm Hg or diastolic blood pressure 80–89mm Hg) and hypertension (≥140/90mm Hg) were 882 (34.1%) and 109 (4.2%), respectively. In a logistic regression model, the risk of hypertension was significantly associated with male (odds ratio (OR): 6.31; 95% confidence interval (CI): 2.63–15.13; P &lt; 0.001), no habitual physical activity at baseline (OR: 2.90; 95% CI: 1.56–5.38; P &lt; 0.01) and periodontal disease defined as the presence of both probing pocket depth (PPD) ≥ 4mm and BOP ≥ 30% at baseline (OR: 2.74; 95% CI: 1.19–6.29; P = 0.02) in participants with prehypertension at baseline. On the other hand, the risk of prehypertension was not associated with presence of periodontal disease (OR: 0.93; 95% CI: 0.51–1.70; P = 0.82).

CONCLUSION
In the short-term prospective cohort study, a significant association between presence of periodontal disease and hypertension was observed in Japanese university students.
Change in Systolic Blood Pressure During Stroke, Functional Status, and Long-Term Mortality in an Elderly Population
Authors: Weiss Avraham , Beloosesky Yichayaou , Kenett Ron S. , Grossman Ehud 
Published: July 2015

Abstract

BACKGROUND
Elevated systolic blood pressure (SBP) recorded by 24-hour blood pressure monitoring (24H BPM) on the first day of acute stroke is associated in elderly patients, with an unfavorable outcome. Herein, we assessed, by 24H BPM, the impact of the change in SBP levels during the first week of stroke on short-term functional status and long-term mortality in elderly patients.

METHODS
One hundred and fifty acute stroke patients (69 males), mean age at admission 83.6±5.5 years, 82% with ischemic stroke, were investigated. 24H BPM was recorded within 24 hours of admission and 1 week later. After 7 days, patients were assessed for functional status according to the modified Rankin scale (mRS) and were subsequently followed for mortality up to 7.5 years (mean 3.16±2.29).

RESULTS
After 7 days, SBP decreased from 147±21 to 140±20mm Hg ( P &lt; 0.001). Functional status improved and mRS decreased from 4.2 to 3.7. During follow-up, 58 patients (17 males and 41 females) had died. Mortality rate was higher in females (69% vs. 45%; P &lt; 0.01) and in patients with a history of congestive heart failure. The average admission SBP predicted short-term functional status and long-term mortality. However, the change in SBP corrected for admission levels, gender, age and other variables was not associated with short-term functional status and long-term mortality.

CONCLUSION
There is no evidence of association between change in SBP during the first week of stroke and short-term functional status and long-term mortality in this group of stroke patients.
The microRNA-221/-222 cluster balances the antiviral and inflammatory response in viral myocarditis
Authors: Corsten Maarten F , Heggermont Ward , Papageorgiou Anna-Pia , Deckx Sophie , Tijsma Aloys , Verhesen Wouter , van Leeuwen Rick , Carai Paolo , Thibaut Hendrik-Jan , Custers Kevin , Summer Georg , Hazebroek Mark , Verheyen Fons , Neyts Johan , Schroen Blanche , Heymans Stephane 
Published: July 2015

Abstract

Aims
Viral myocarditis (VM) is an important cause of heart failure and sudden cardiac death in young healthy adults; it is also an aetiological precursor of dilated cardiomyopathy. We explored the role of the miR-221/-222 family that is up-regulated in VM.

Methods and results
Here, we show that microRNA-221 (miR-221) and miR-222 levels are significantly elevated during acute VM caused by Coxsackievirus B3 (CVB3). Both miRs are expressed by different cardiac cells and by infiltrating inflammatory cells, but their up-regulation upon myocarditis is mostly exclusive for the cardiomyocyte. Systemic inhibition of miR-221/-222 in mice increased cardiac viral load, prolonged the viraemic state, and strongly aggravated cardiac injury and inflammation. Similarly, in vitro, overexpression of miR-221 and miR-222 inhibited enteroviral replication, whereas knockdown of this miR-cluster augmented viral replication. We identified and confirmed a number of miR-221/-222 targets that co-orchestrate the increased viral replication and inflammation, including ETS1/2, IRF2, BCL2L11, TOX, BMF, and CXCL12. In vitro inhibition of IRF2, TOX, or CXCL12 in cardiomyocytes significantly dampened their inflammatory response to CVB3 infection, confirming the functionality of these targets in VM and highlighting the importance of miR-221/-222 as regulators of the cardiac response to VM.

Conclusions
The miR-221/-222 cluster orchestrates the antiviral and inflammatory immune response to viral infection of the heart. Its inhibition increases viral load, inflammation, and overall cardiac injury upon VM.
The High-Frequency Trading Arms Race: Frequent Batch Auctions as a Market Design Response *
Authors: Budish Eric , Cramton Peter , Shim John 
Published: July 2015

AbstractThe high-frequency trading arms race is a symptom of flawed market design. Instead of the continuous limit order book market design that is currently predominant, we argue that financial exchanges should use frequent batch auctions: uniform price double auctions conducted, for example, every tenth of a second. That is, time should be treated as discrete instead of continuous, and orders should be processed in a batch auction instead of serially. Our argument has three parts. First, we use millisecond-level direct-feed data from exchanges to document a series of stylized facts about how the continuous market works at high-frequency time horizons: (i) correlations completely break down; which (ii) leads to obvious mechanical arbitrage opportunities; and (iii) competition has not affected the size or frequency of the arbitrage opportunities, it has only raised the bar for how fast one has to be to capture them. Second, we introduce a simple theory model which is motivated by and helps explain the empirical facts. The key insight is that obvious mechanical arbitrage opportunities, like those observed in the data, are built into the market design—continuous-time serial-processing implies that even symmetrically observed public information creates arbitrage rents. These rents harm liquidity provision and induce a never-ending socially wasteful arms race for speed. Last, we show that frequent batch auctions directly address the flaws of the continuous limit order book. Discrete time reduces the value of tiny speed advantages, and the auction transforms competition on speed into competition on price. Consequently, frequent batch auctions eliminate the mechanical arbitrage rents, enhance liquidity for investors, and stop the high-frequency trading arms race.
Hospital employment of physicians and supply chain performance
Authors: Young Gary J. , Nyaga Gilbert N. , Zepeda E. David 
Published: July 2015

Background:
As hospital employment of physicians becomes increasingly common in the United States, much speculation exists as to whether this type of arrangement will promote hospital operating efficiency in such areas as supply chain management. Little empirical research has been conducted to address this question.

Purpose:
The aim of this study was to provide an exploratory assessment of whether hospital employment of physicians is associated with better supply chain performance. Drawing from both agency and stewardship theories, we examined whether hospitals with a higher proportion of employed medical staff members have relatively better supply chain performance based on two performance measures, supply chain expenses and inventory costs.

Approach:
We conducted the study using a pooled, cross-sectional sample of hospitals located in California between 2007 and 2009. Key data sources were hospital annual financial reports from California’s Office of Statewide Health Policy and Development and the American Hospital Association annual survey of hospitals. To examine the relationship between physician employment and supply chain performance, we specified physician employment as the proportion of total employed medical staff members as well as the proportion of employed medical staff members within key physician subgroups. We analyzed the data using generalized estimating equations.

Findings:
Study results generally supported our hypothesis that hospital employment of physicians is associated with better supply chain performance.

Practical Implications:
Although the results of our study should be viewed as preliminary, the trend in the United States toward hospital employment of physicians may be a positive development for improved hospital operating efficiency. Hospital managers should also be attentive to training and educational resources that medical staff members may need to strengthen their role in supply chain activities.