bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Oncogenic MicroRNA OncomiR-21 Overexpressed during Marek's Disease Lymphomagenesis Is Transactivated by the Viral Oncoprotein Meq
Authors: Stik Grégoire , Dambrine Ginette , Pfeffer Sébastien , Rasschaert Denis 
Published: October 2012

ABSTRACT

Gallid herpesvirus 2 (GaHV-2) is an oncogenic herpesvirus that causes T lymphoma in chicken. GaHV-2 encodes a basic leucine zipper (bZIP) protein of the AP-1 family, Meq. Upon formation of homo- or heterodimers with c-Jun, Meq may modulate the expression of viral and cellular genes involved in lymphomagenesis. GaHV-2 also encodes viral microRNAs (miRNAs) involved in latency and apoptosis escape. However, little is known about cellular miRNA deregulation during the development of GaHV-2-associated lymphoma. We determined the cellular miRNA expression profiles of chickens infected with a very virulent strain (RB-1B) or a vaccine strain (CVI988) or noninfected. Among the most deregulated cellular miRNAs, we focused our efforts on gga-miR-21, which is upregulated during GaHV-2 infection. We mapped the gga-miR-21 promoter to the 10th intron of the
TMEM49
gene and found it to be driven by AP-1- and Ets-responsive elements. We show here that the viral oncoprotein Meq binds to this promoter, thereby transactivating gga-miR-21 expression. We confirmed that this miRNA targets chicken programmed death cell 4 (PDCD4) and promotes tumor cell growth and apoptosis escape. Finally, gga-miR-21 was overexpressed only during infection with a very virulent strain (RB-1B) and not during infection with a nononcogenic strain (CVI988), providing further evidence for its role in GaHV-2 lymphomagenesis. Our data therefore suggest an additional role for Meq in GaHV-2-mediated lymphomagenesis through the induction of miR-21 expression.
Rethinking DRAM design and organization for energy-constrained multi-cores
Authors: Udipi Aniruddha N. , Muralimanohar Naveen , Chatterjee Niladrish , Balasubramonian Rajeev , Davis Al , Jouppi Norman P. 
Published: October 2012

DRAM vendors have traditionally optimized the cost-per-bit metric, often making design decisions that incur energy penalties. A prime example is the overfetch feature in DRAM, where a single request activates thousands of bit-lines in many DRAM chips, only to return a single cache line to the CPU. The focus on cost-per-bit is questionable in modern-day servers where operating costs can easily exceed the purchase cost. Modern technology trends are also placing very different demands on the memory system: (i)queuing delays are a significant component of memory access time, (ii) there is a high energy premium for the level of reliability expected for business-critical computing, and (iii) the memory access stream emerging from multi-core systems exhibits limited locality. All of these trends necessitate an overhaul of DRAM architecture, even if it means a slight compromise in the cost-per-bit metric.
This paper examines three primary innovations. The first is a modification to DRAM chip microarchitecture that re tains the traditional DDRx SDRAMinterface. Selective Bit-line Activation (SBA) waits for both RAS (row address) and CAS (column address) signals to arrive before activating exactly those bitlines that provide the requested cache line. SBA reduces energy consumption while incurring slight area and performance penalties. The second innovation, Single Subarray Access (SSA), fundamentally re-organizes the layout of DRAM arrays and the mapping of data to these arrays so that an entire cache line is fetched from a single subarray. It requires a different interface to the memory controller, reduces dynamic and background energy (by about 6X), incurs a slight area penalty (4%), and can even lead to performance improvements (54% on average) by reducing queuing delays. The third innovation further penalizes the cost-per-bit metric by adding a checksum feature to each cache line. This checksum error-detection feature can then be used to build stronger RAID-like fault tolerance, including chipkill-level reliability. Such a technique is especially crucial for the SSA architecture where the entire cache line is localized to a single chip. This DRAM chip microarchitectural change leads to a dramatic reduction in the energy and storage overheads for reliability. The proposed architectures will also apply to other emerging memory technologies (such as resistive memories) and will be less disruptive to standards, interfaces, and the design flow if they can be incorporated into first-generation designs.
Improving the future by examining the past
Authors: Thacker Charles P. 
Published: October 2012

During the last fifty years, the technology underlying computer systems has improved dramatically. As technology has evolved, designers have made a series of choices in the way it was applied in computers. In some cases, decisions that were made in the twentieth century make less sense in the twenty-first. Conversely, paths not taken might now be more attractive given the state of technology today, particularly in light of the limits the field is facing, such as the increasing gap between processor speed and storage access times and the difficulty of cooling today's computers.
In this talk, I'll discuss some of these choices and suggest some possible changes that might make computing better in the twenty-first century.
The role of tetrahydrobiopterin in inflammation and cardiovascular disease
Authors: McNeill Eileen , Channon Keith 
Published: October 2012

SummaryThe cofactor tetrahydrobiopterin (BH4) is required for nitric oxide (NO) production by all nitric oxide synthase (NOS) enzymes and is a key regulator of cellular redox signalling. When BH4 levels become limiting NOS enzymes become ‘uncoupled’ and produce superoxide rather than NO. Endothelial cell BH4 is required for the maintenance of vascular function through NO production, and reduced BH4 levels are associated with vascular dysfunction. Evidence increasingly points to important roles for BH4 and NOS enzymes in other vascular cell types. Leukocytes have a fundamental role in atherosclerosis, and new evidence points to a role in the control of hypertension. Leukocytes are a major site of iNOS expression, and the regulation of this isoform is another mechanism by which BH4 availability may modulate disease. This review provides an overview of BH4 control of NOS function in both endothelial cells and leukocytes in the context of vascular disease and current therapeutic evaluations.
Long-Term Frequency Gradients During Persistent Atrial Fibrillation in Sheep Are Associated With Stable Sources in the Left Atrium
Authors: Filgueiras-Rama David , Price Nicholas F. , Martins Raphael P. , Yamazaki Masatoshi , Avula Uma Mahesh R. , Kaur Kuljeet , Kalifa Jérôme , Ennis Steven R. , Hwang Elliot , Devabhaktuni Vijay , Jalife Jose , Berenfeld Omer 
Published: October 2012

Background—
Dominant frequencies (DFs) of activation are higher in the atria of patients with persistent than paroxysmal atrial fibrillation (AF), and left atrial (LA)-to-right atrial (RA) DF gradients have been identified in both. However, whether such gradients are maintained as long-term persistent AF is established remains unexplored. We aimed at determining in vivo the time course in atrial DF values from paroxysmal to persistent AF in sheep and testing the hypothesis that an LA-to-RA DF difference is associated with LA drivers in persistent AF.

Methods and Results—

AF was induced using RA tachypacing (n=8). Electrograms were obtained weekly from an RA lead and an implantable loop recorder implanted near the LA. DFs were determined for 5-second-long electrograms (QRST subtracted) during AF in vivo and in ex vivo optical mapping. Underlying structural changes were compared with weight-matched controls (n=4). After the first AF episode, DF increased gradually during a 2-week period (7±0.21 to 9.92±0.31 Hz; n=6;
P
<0.05). During 9 to 24 weeks of AF, the DF values on the implantable loop recorder were higher than the RA (10.6±0.08 versus 9.3±0.1 Hz, respectively; n=7;
P
<0.0001). Subsequent optical mapping confirmed a DF gradient from posterior LA-to-RA (9.1±1.0 to 6.9±0.9 Hz;
P
<0.05) and demonstrated patterns of activation compatible with drifting rotors in the posterior LA. Persistent AF sheep showed significant enlargement of the posterior LA compared with controls.

Conclusions—
In the sheep, transition from paroxysmal to persistent AF shows continuous LA-to-RA DF gradients in vivo together with enlargement of the posterior LA, which harbors the highest frequency domains and patterns of activation compatible with drifting rotors.
Automated Vulnerability Testing Identifies Patients With Inadequate Defibrillation Safety Margin
Authors: Birgersdotter-Green Ulrika , Ruetz Linda L. , Anand Kishlay , Monir George , Abeyratne Athula I. , Bailey J. Russell , Shorofsky Stephen R. , Hsia Henry H. , Friedman Paul A. 
Published: October 2012

Background—
Implantable cardioverter-defibrillator system efficacy is tested at implant by induction of ventricular fibrillation (VF). Defibrillation safety margin can be assessed without VF induction using upper limit of vulnerability methods, but these methods have required manual determination of T-wave timing.

Methods and Results—
To test the feasibility of an inductionless system of implant testing, a multicenter prospective study of an automated vulnerability safety margin system was conducted, which measured T-wave timing using an intracardiac electrogram during a ventricular pacing train. The system delivered up to 4 T-wave shocks of 18 J. Lack of VF induction by all 4 shocks was considered evidence of defibrillation adequacy. Patients subsequently underwent conventional defibrillation testing to meet a standard implant criterion. The 95% lower CI for defibrillation success at 25 J for noninduced patients was found using Bayesian statistics. Sixty patients were enrolled at 6 centers. Vulnerability testing and defibrillation success results were obtained from 54 patients. Vulnerability testing induced VF in 10 (19%) patients, of whom 2 required system revision. All patients not induced by vulnerability testing were successfully defibrillated twice at ≤25 J. The Bayesian credible interval was 97% to 100% for the population success rate of defibrillation at 25 J for automated vulnerability safety margin noninduced patients.

Conclusions—
An automated system identified all patients who failed conventional safety margin testing, while inducing only 19% of patients. Although limited by sample size, this study suggests the feasibility of automated implant testing that substantially reduces the need for VF induction in patients receiving implantable cardioverter-defibrillators.
Mean Platelet Volume and Platelet Distribution Width in Patients With Chronic Obstructive Pulmonary Disease
Authors: Steiropoulos P. , Papanas N. , Nena E. , Xanthoudaki M. , Goula T. , Froudarakis M. , Pita E. , Maltezos E. , Bouros D. 
Published: October 2012

We evaluated mean platelet volume (MPV; an indicator of vascular risk) and platelet distribution width in patients with stable chronic obstructive pulmonary disease (COPD; n = 85). We also included a control group of 34 smokers without airflow limitation. Mean platelet volume was significantly higher in patients with COPD (10.69 ± 1.0 vs 9.96 ± 1.10 fL, P < .001) than in the smoker controls. White blood cell (WBC) count was also significantly higher in patients with COPD than in the smoker controls (10 642 ± 1247 vs 7136 ± 1887/μL, P < .001). There was a correlation between MPV and WBC in patients with COPD, especially in those at stage III ( r = .530, P = .004) and IV ( r = .389, P = .023). Mean platelet volume did not correlate with any indices of COPD severity. In patients with COPD, MPV and WBC levels are higher than those of smokers with normal pulmonary function and are significantly correlated. Whether these effects relate to vascular risk in patients with COPD remain to be established.
The adjacent positioning of co-regulated gene pairs is widely conserved across eukaryotes
Authors: Arnone James T , Robbins-Pianka Adam , Arace Jeffrey R , Kass-Gergi Sara , McAlear Michael A 
Published: October 2012

Abstract

Background
Coordinated cell growth and development requires that cells regulate the expression of large sets of genes in an appropriate manner, and one of the most complex and metabolically demanding pathways that cells must manage is that of ribosome biogenesis. Ribosome biosynthesis depends upon the activity of hundreds of gene products, and it is subject to extensive regulation in response to changing cellular conditions. We previously described an unusual property of the genes that are involved in ribosome biogenesis in yeast; a significant fraction of the genes exist on the chromosomes as immediately adjacent gene pairs. The incidence of gene pairing can be as high as 24% in some species, and the gene pairs are found in all of the possible tandem, divergent, and convergent orientations.

Results
We investigated co-regulated gene sets in S. cerevisiae beyond those related to ribosome biogenesis, and found that a number of these regulons, including those involved in DNA metabolism, heat shock, and the response to cellular stressors were also significantly enriched for adjacent gene pairs. We found that as a whole, adjacent gene pairs were more tightly co-regulated than unpaired genes, and that the specific gene pairing relationships that were most widely conserved across divergent fungal lineages were correlated with those genes that exhibited the highest levels of transcription. Finally, we investigated the gene positions of ribosome related genes across a widely divergent set of eukaryotes, and found a significant level of adjacent gene pairing well beyond yeast species.

Conclusion
While it has long been understood that there are connections between genomic organization and transcriptional regulation, this study reveals that the strategy of organizing genes from related, co-regulated pathways into pairs of immediately adjacent genes is widespread, evolutionarily conserved, and functionally significant.
The SbSOS1 gene from the extreme halophyte Salicornia brachiata enhances Na+loading in xylem and confers salt tolerance in transgenic tobacco
Authors: Yadav Narendra Singh , Shukla Pushp Sheel , Jha Anupama , Agarwal Pradeep K , Jha Bhavanath 
Published: October 2012

Abstract

Background
Soil salinity adversely affects plant growth and development and disturbs intracellular ion homeostasis resulting cellular toxicity. The Salt Overly Sensitive 1 (SOS1) gene encodes a plasma membrane Na+/H+ antiporter that plays an important role in imparting salt stress tolerance to plants. Here, we report the cloning and characterisation of the SbSOS1 gene from Salicornia brachiata, an extreme halophyte.

Results
The SbSOS1 gene is 3774 bp long and encodes a protein of 1159 amino acids. SbSOS1 exhibited a greater level of constitutive expression in roots than in shoots and was further increased by salt stress. Overexpressing the S. brachiata SbSOS1 gene in tobacco conferred high salt tolerance, promoted seed germination and increased root length, shoot length, leaf area, fresh weight, dry weight, relative water content (RWC), chlorophyll, K+/Na+ ratio, membrane stability index, soluble sugar, proline and amino acid content relative to wild type (WT) plants. Transgenic plants exhibited reductions in electrolyte leakage, reactive oxygen species (ROS) and MDA content in response to salt stress, which probably occurred because of reduced cytosolic Na+ content and oxidative damage. At higher salt stress, transgenic tobacco plants exhibited reduced Na+ content in root and leaf and higher concentrations in stem and xylem sap relative to WT, which suggests a role of SbSOS1 in Na+ loading to xylem from root and leaf tissues. Transgenic lines also showed increased K+ and Ca2+ content in root tissue compared to WT, which reflect that SbSOS1 indirectly affects the other transporters activity.

Conclusions
Overexpression of SbSOS1 in tobacco conferred a high degree of salt tolerance, enhanced plant growth and altered physiological and biochemical parameters in response to salt stress. In addition to Na+ efflux outside the plasma membrane, SbSOS1 also helps to maintain variable Na+ content in different organs and also affect the other transporters activity indirectly. These results broaden the role of SbSOS1 in planta and suggest that this gene could be used to develop salt-tolerant transgenic crops.
Iron deficiency affects nitrogen metabolism in cucumber (Cucumis sativusL.) plants
Authors: Borlotti Andrea , Vigani Gianpiero , Zocchi Graziano 
Published: October 2012

AbstractBackgroundNitrogen is a principal limiting nutrient in plant growth and development. Among factors that may limit NO3-assimilation, Fe potentially plays a crucial role being a metal cofactor of enzymes of the reductive assimilatory pathway. Very few information is available about the changes of nitrogen metabolism occurring under Fe deficiency in Strategy I plants. The aim of this work was to study how cucumber (Cucumis sativusL.) plants modify their nitrogen metabolism when grown under iron deficiency.ResultsThe activity of enzymes involved in the reductive assimilation of nitrate and the reactions that produce the substrates for the ammonium assimilation both at root and at leaf levels in Fe-deficient cucumber plants were investigated. Under Fe deficiency, only nitrate reductase (EC 1.7.1.1) activity decreased both at the root and leaf level, whilst for glutamine synthetase (EC 6.3.1.2) and glutamate synthase (EC 1.4.1.14) an increase was found. Accordingly, the transcript analysis for these enzymes showed the same behaviour except for root nitrate reductase which increased. Furthermore, it was found that amino acid concentration greatly decreased in Fe-deficient roots, whilst it increased in the corresponding leaves. Moreover, amino acids increased in the xylem sap of Fe-deficient plants.ConclusionsThe data obtained in this work provided new insights on the responses of plants to Fe deficiency, suggesting that this nutritional disorder differentially affected N metabolism in root and in leaf. Indeed under Fe deficiency, roots respond more efficiently, sustaining the whole plant by furnishing metabolites (i.e.aa, organic acids) to the leaves.
Prostate specific antigen testing policy worldwide varies greatly and seems not to be in accordance with guidelines: a systematic review
Authors: Van der Meer Saskia , Löwik Sabine AM , Hirdes Willem H , Nijman Rien M , Van der Meer Klaas , Hoekstra-Weebers Josette EHM , Blanker Marco H 
Published: October 2012

Abstract

Background
Prostate specific antigen (PSA) testing is widely used, but guidelines on follow-up are unclear.

Methods
We performed a systematic review of the literature to determine follow-up policy after PSA testing by general practitioners (GPs) and non-urologic hospitalists, the use of a cut-off value for this policy, the reasons for repeating a PSA test after an initial normal result, the existence of a general cut-off value below which a PSA result is considered normal, and the time frame for repeating a test.

Data sources. MEDLINE, Embase, PsychInfo and the Cochrane library from January 1950 until May 2011.

Study eligibility criteria. Studies describing follow-up policy by GPs or non-urologic hospitalists after a primary PSA test, excluding urologists and patients with prostate cancer. Studies written in Dutch, English, French, German, Italian or Spanish were included. Excluded were studies describing follow-up policy by urologists and follow-up of patients with prostate cancer. The quality of each study was structurally assessed.

Results
Fifteen articles met the inclusion criteria. Three studies were of high quality. Follow-up differed greatly both after a normal and an abnormal PSA test result. Only one study described the reasons for not performing follow-up after an abnormal PSA result.

Conclusions
Based on the available literature, we cannot adequately assess physicians’ follow-up policy after a primary PSA test. Follow-up after a normal or raised PSA test by GPs and non-urologic hospitalists seems to a large extent not in accordance with the guidelines.
Impact of Salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro
Authors: Lieke Thorsten , Ramackers Wolf , Bergmann Sabine , Klempnauer Jürgen , Winkler Michael , Klose Johannes 
Published: October 2012

AbstractBackgroundCholangiocarcinoma (CC) is a primary liver cancer with increasing incidence worldwide. Despite all efforts made in past years, prognosis remains to be poor. At least in part, this might be explained by a pronounced resistance of CC cells to undergo apoptosis. Thus, new therapeutic strategies are imperatively required. In this study we investigated the effect of Salinomycin, a polyether ionophore antibiotic, on CC cells as an appropriate agent to treat CC. Salinomycin was quite recently identified to induce apoptosis in cancer stem cells and to overcome apoptosis-resistance in several leukemia-cells and other cancer cell lines of different origin.MethodsTo delineate the effects of Salinomycin on CC, we established anin vitrocell culture model using three different human CC cell lines. After treatment apoptosis as well as migration and proliferation behavior was assessed and additional cell cycle analyses were performed by flowcytometry.ResultsBy demonstrating Annexin V and TUNEL positivity of human CC cells, we provide evidence that Salinomycin reveals the capacity to break apoptosis-resistance in CC cells. Furthermore, we are able to demonstrate that the non-apoptotic cell fraction is characterized by sustainable impaired migration and proliferation. Cell cycle analyses revealed G2-phase accumulation of human CC cells after treatment with Salinomycin. Even though apoptosis is induced in two of three cell lines of CC cells, one cell line remained unaffected in regard of apoptosis but revealed as the other CC cells decreased proliferation and migration.ConclusionIn this study, we are able to demonstrate that Salinomycin is an effective agent against previously resistant CC cells and might be a potential candidate for the treatment of CC in the future.
Globular adiponectin protects H9c2 cells from palmitate-induced apoptosis via Akt and ERK1/2 signaling pathways
Authors: Wei Chuan Dong , Li Yan , Zheng Hong Yun , Sun Kai Sheng , Tong Yong Qing , Dai Wen , Wu Wei , Bao An Yu 
Published: October 2012

Abstract

Background
Cardiomyocytes apoptosis is an important contributor to myocardial dysfunction and heart failure. Adiponectin has cardioprotective effects, potential mechanisms behind it are not clear in cardiomyocytes. The purpose of the study was to investigate whether adiponectin can block palmitate-induced apoptosis and the underlying biochemical mechanism in H9c2 cells.

Methods
H9c2 cells were treated with palmitate presence or absence of 2.5 μg/mL globular adiponectin. The effect on the cell viability of H9c2 cells was evaluated using MTT assay, and cell apoptosis was determined by Hoechst 33342 staining. Protein expression was measured using the western blot method.

Results
Our results showed that the palmitate treatment induced apoptosis in H9c2 cells, which was associated with increasing the level of cleaved caspase-3 and cleaved PARP. Meanwhile, palmitate-induced apoptosis increased the protein level of p-ERK1/2, and decreased the protein level of p-Akt significantly. However, levels of both of these proteins were restored to the normal when pretreated with adiponectin, and followed with the decrease of cleaved caspase-3 and cleaved PARP. In line with these results, the protective effect of adiponectin can be blocked by PI3K/Akt inhibitor LY294002, and palmitate-induced apoptosis can be attenuated by ERK1/2 inhibitor U0126.

Conclusions
Taken together, the present study demonstrated that adiponectin protects H9c2 cells from palmitate-induced apoptosis via PI3K/Akt and ERK1/2 signaling pathways. Our results reveal a link between adiponectin and cardiomyocytes apoptosis, suggesting that adioponectin may be a promising therapeutic for the treatment of lipotoxicity cardiomyopathy.