bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperphosphorylation of Histone Deacetylase 2 by Alphaherpesvirus US3 Kinases
Authors: Walters Matthew S. , Kinchington Paul R. , Banfield Bruce W. , Silverstein Saul 
Published: July 2010

ABSTRACT

A serine/threonine (S/T) kinase encoded by the
US3
gene of herpes simplex virus type 1 (HSV-1) is conserved in varicella-zoster virus (VZV) and pseudorabies virus (PRV). Expression of US3 kinase in cells transformed with US3 expression plasmids or infected with each virus results in hyperphosphorylation of histone deacetylase 2 (HDAC2). Mapping studies revealed that each US3 kinase phosphorylates HDAC2 at the same unique conserved Ser residue in its C terminus. HDAC2 was also hyperphosphorylated in cells infected with PRV lacking US3 kinase, indicating that hyperphosphorylation of HDAC2 by PRV occurs in a US3-independent manner. Specific chemical inhibition of class I HDAC activity increases the plaquing efficiency of VZV and PRV lacking
US3
or its enzymatic activity, whereas only minimal effects are observed with wild-type viruses, suggesting that VZV and PRV US3 kinase activities target HDACs to reduce viral genome silencing and allow efficient viral replication. However, no effect was observed for wild-type or
US3
null HSV-1. Thus, we have demonstrated that while HDAC2 is a conserved target of alphaherpesvirus US3 kinases, the functional significance of these events is virus specific.
Interwoven Roles of Cyclin D3 and cdk4 Recruited by ICP0 and ICP4 in the Expression of Herpes Simplex Virus Genes
Authors: Kalamvoki Maria , Roizman Bernard 
Published: July 2010

ABSTRACT
Elsewhere this laboratory reported that (i) ICP0 interacts with cyclin D3 but not D1 or D2. The 3 cyclins independently partially rescue ΔICP0 mutants. (ii) Interaction with cyclin D3 is required for the switch from nuclear to cytoplasmic accumulation of ICP0. (iii) In infected cells cdk4 is activated whereas cdk2 is not. Inhibition of cdk4 results in nuclear retention of ICP0. Overexpression of cyclin D3 reverses the effect of the inhibitor. Here we report the following. (i) cdk4 interacts with ICP0, ICP4, and possibly with ICP8. This interaction is required to recruit cdk4 initially to ND10 and later to the viral replication compartments. (ii) cdk4 inhibitor I reduced or delayed the transcription and ultimately translation of mRNAs of ICP4, ICP27, or ICP8 and to a lesser extent that of the ICP0 gene in wild-type virus-infected cells. (iii) Overexpression of cyclin D3 resulted in a more rapid transcription of these genes. In the presence of inhibitor, the rates of accumulation of the products of these genes resemble those of wild-type virus in the absence of inhibitor. (iv) Overexpression of cyclin D3 also results in mobilization of cdk6 in nuclei of infected cells. We conclude that ICP0 encodes a function that enhances the recruitment of cyclin D3 to ND10 structures to activate cdk4 and that ICP0 along with other viral proteins recruits cdk4 to ND10 structures and ultimately to replication compartments for enhanced expression of viral genes and viral DNA synthesis.
Haloperidol promotes proliferation but inhibits differentiation in rat oligodendrocyte progenitor cell culturesThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.
Authors: Niu Jianqin , Mei Feng , Li Nan , Wang Hanzhi , Li Xinmin , Kong Jiming , Xiao Lan 
Published: July 2010

Haloperidol is a commonly used, typical, antipsychotic drug (APD) that acts strongly against positive symptoms, but has fewer therapeutic effects on, or may even aggravate, negative symptoms and cognitive deficits in patients with schizophrenia. Loss of oligodendrocytes has been suggested as a factor associated with the negative symptoms of schizophrenia. Recent study shows that chronic haloperidol treatment induced down-regulation of oligodendrocyte-related genes in certain brain regions of mouse. In this study, we used primary oligodendrocyte progenitor cell cultures from 1- to 3-day-postnatal rats to investigate the direct effects of haloperidol on the proliferation and differentiation of oligodendrocyte progenitor cells. Our results showed that (i) haloperidol (0–10.0 µmol·L–1) facilitated the proliferation of oligodendrocyte progenitor cells, (ii) chronic haloperidol (0.5 µmol·L–1) treatment decreased the number of myelin basic protein positive oligodendrocytes and reduced the oligodendrocytes cells possessing myelin-like membranes, resulting in inhibition of the terminal differentiation of oligodendrocytes, and (iii) D3 receptor mRNA was detected in oligodendrocyte progenitor cells, and haloperidol treatment induced a down-regulation of D3 receptor mRNA. These results suggest that the typical antipsychotic drug haloperidol affects the development of oligodendrocyte progenitor cells, and that D3 receptor down regulation may be involved. Our observations provide new insight into possible cellular mechanisms responsible for the side effects of typical antipsychotic drugs and support the concept that abnormality of oligodendrocytes may be involved in the pathogenesis of schizophrenia.
Effect of sodium houttuyfonate on inhibiting ventricular remodeling induced by abdominal aortic banding in rats
Authors: Gao Jian Ping , Chen Chang Xun , Wu Qi , Gu Wei Liang , Li Xiang 
Published: July 2010

Ventricular remodeling is an independent risk factor for many cardiovascular events. Inhibiting ventricular remodeling early may be an effective way to postpone heart failure for patients with cardiovascular illness. The study was designed to examine the effect of sodium houttuyfonate on ventricular remodeling induced by pressure overload in rats, as well as to explore the mechanisms involved. The model rats in which ventricular remodeling was induced abdominal aortic banding (AAB) were randomly divided into 4 groups: AAB control, AAB plus captopril (40 mg/kg), AAB plus low dose of sodium houttuyfonate (50 mg/kg), and AAB plus high dose of sodium houttuyfonate (100 mg/kg). One month after operation, hemodynamic parameters, heart mass indexes, size of cardiomyocytes, myocardial collagen volume, angiotensin II content in ventricular tissue, and serum concentrations of aldosterone and tumor necrosis factor (TNF)-α were evaluated. Sodium houttuyfonate significantly reduced heart mass indexes, the size of cardiomyocytes, and the myocardial collagen volume and decreased the levels of angiotensin II, aldosterone, and TNF-α. At the high dose, it decreased blood pressure and heart rate. In conclusion, sodium houttuyfonate attenuates ventricular remodeling induced by pressure overload in rats. The beneficial effects are in part associated with its alleviating the activation of renin–angiotensin–aldosterone system and decreasing the TNF-α level. Furthermore, its function seems to correlate with reduced blood pressure and heart rate.
Evaluation of the endothelin receptor antagonists ambrisentan, darusentan, bosentan, and sitaxsentan as substrates and inhibitors of hepatobiliary transporters in sandwich-cultured human hepatocytesThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.
Authors: Hartman J. Craig , Brouwer Kenneth , Mandagere Arun , Melvin Lawrence , Gorczynski Richard 
Published: July 2010

To evaluate potential mechanisms of clinical hepatotoxicity, 4 endothelin receptor antagonists (ERAs) were examined for substrate activity and inhibition of hepatic uptake and efflux transporters in sandwich-cultured human hepatocytes. The 4 transporters studied were sodium-dependent taurocholate cotransporter (NTCP), organic anion transporter (OATP), bile salt export pump (BSEP), and multidrug resistance-associated protein 2 (MRP2). ERA transporter inhibition was examined using the substrates taurocholate (for NTCP and BSEP), [3H]estradiol-17β-d-glucuronide (for OATP), and [2-d-penicillamine, 5-d-penicillamine]enkephalin (for MRP2). ERA substrate activity was evaluated using probe inhibitors ritonavir (OATP and BSEP), bromosulfalein (OATP), erythromycin (P-glycoprotein), probenecid (MRP2 and OATP), and cyclosporin (NTCP). ERAs were tested at 2, 20, and 100 µmol·L–1for inhibition and at 2 µmol·L–1as substrates. OATP, NTCP, or BSEP transport activity was not reduced by ambrisentan or darusentan. Bosentan and sitaxsentan attenuated NTCP transport at higher concentrations. Only sitaxsentan decreased OATP transport (52%), and only bosentan reduced BSEP transport (78%). MRP2 transport activity was unaltered. OATP inhibitors decreased influx of all ERAs. Darusentan influx was least affected (84%–100% of control), whereas bosentan was most affected (32%–58% of control). NTCP did not contribute to influx of ERAs. Only bosentan and darusentan were shown as substrates for both BSEP and P-glycoprotein efflux. All ERAs tested were substrates for at least one hepatic transporter. Bosentan and sitaxsentan, but not ambrisentan and darusentan, inhibited human hepatic transporters, which provides a potential mechanism for the increased hepatotoxicity observed for these agents in the clinical setting.
Apocynin attenuates pressure overload-induced cardiac hypertrophy in rats by reducing levels of reactive oxygen species
Authors: Liu Jinjun , Zhou Juan , An Wenjiao , Lin Yuanxi , Yang Yubai , Zang Weijin 
Published: July 2010

It has been shown that angiotensin II (Ang II) is involved in cardiac remodeling mediated by NADPH oxidase-dependent reactive oxygen species (ROS). Accordingly, NADPH oxidase-dependent ROS may play a role in cardiac hypertrophy induced by pressure overload. In the present study, we sought to determine whether inhibition of NADPH oxidase prevents cardiac hypertrophy. After abdominal aorta banding to induce cardiac hypertrophy, rats were treated for 8 weeks with apocynin (Apo) or captopril (Cap). Measures of cardiac hypertrophy were evaluated. Treatment with Cap or Apo reduced the left ventricle / body weight ratio (LV/BW), LV transnuclear myocyte diameter, and atrial natriuretic factor (ANF) mRNA expression relative to those of untreated rats subjected to aorta banding. The activity of NADPH oxidase and the ROS levels were decreased in treated animals. Cap, but not Apo, decreased Ang II levels and inhibited expression of p22phox and p67phox in LVs. In conclusion, local expression of Ang II appears to contribute to pressure overload-induced cardiac hypertrophy by upregulating NADPH oxidase expression and promoting ROS synthesis. Inhibition of NADPH oxidase and elimination of ROS may prevent or repair damage due to cardiac hypertrophy.
Recurrent landslides predisposed by fault-induced weathering of flysch in the Western Carpathians
Authors: Pánek T. , Hradecký J. , Minár J. , Šilhán K. 
Published: July 2010

Abstract
The interrelationship between slope deformation and fault-induced weathering as a predisposing factor for the development of sliding is analysed through several case studies from the Western Carpathians in the Czech Republic. The study area comprises flysch nappes with alternating sandstone and shale of different permeability. These lithological structures are affected by systems of faults. Recurring slope instability is found associated with zones of deep weathering in tectonically weakened areas. Climatic variability of landslide activity can be identified during the Holocene by means of radiocarbon dating and pollen analysis. Areas affected by recurring landsliding suggest gradual and cyclic landslide frequency.
Very deep weathering and related landslides
Authors: Ollier C. D. 
Published: July 2010

Abstract
Some huge landslides have occurred in deeply weathered rock, but most geologists and engineers do not appreciate the great depths that weathering can attain. Rocks can be weathered to depths of hundreds of metres, often in a very irregular manner. Fresh rock is converted to weathered rock called saprolite by isometric chemical alteration. Some saprolite is later eroded, and fresh rock appears in the landscape in distinctive landforms. This erosion of an irregularly weathered landscape is called stripping (meaning the stripping of saprolite from fresh rock). The age of the weathering may be measured in geological periods, as can the age of stripping, and may be related to past climate different from that of today. Deep weathering occurs basically by hydrolysis, which requires groundwater. Slope failure in saprolite depends on the engineering property of the material, and its relation to bedrock and corestones, and relationship to degree of weathering of adjacent saprolite. This paper emphasizes the deep weathering phenomenon itself, but a few examples are given to illustrate the variety of landslides in deeply weathered material.
Deterioration processes of hard clays and clay shales
Authors: Picarelli L. , Di Maio C. 
Published: July 2010

Abstract
Soil deterioration is one of the main causes of slope failure in hard clays and clay shales, but so far a clear general framework of the causes of deterioration is still missing. Based on laboratory data, field observations and speculation, this paper examines some processes of deterioration of stiff overconsolidated clays and clay shales with particular regard to their influence on the stability of slopes. In particular, deterioration localized within soil bands or involving large soil masses is described with reference to its mechanical or physico-chemical causes. Coupling between mechanical and physico-chemical processes is considered.
Mass movement and landscape evolution in weathered granite and gneiss terrains
Authors: Migoń Piotr 
Published: July 2010

Abstract
The paper assesses the contribution of mass movement to the development of landforms in weathered granite and gneiss terrain, using examples from SE Brazil, southern Mexico, SE China, and other locations. The style of slope failures varies depending on local relief and the grade of weathering, which mutually influence each other. Shallow debris slides and boulder falls are common in less weathered rock and steep terrain, whereas rotational slides appear to dominate in highly weathered rock and in more subdued topography. In certain topographic circumstances, slides may turn into debris flows or earthflows. Extreme rainfall is a typical trigger of mass movement in weathered terrain. Mapping of past landslides may considerably assist in hazard assessment, as they usually leave a clear geomorphological record.
Degradation of marls; two case studies from the Iberian Peninsula
Authors: Alonso E. E. , Pineda J. A. , Cardoso R. 
Published: July 2010

Abstract
The strength degradation of two marl formations (Pamplona marls in Spain and Abadia marls in Portugal) is analysed in the paper. In the case of Pamplona marls, a number of large-scale direct shear tests on natural and saturated specimens of the undisturbed material were performed. Tests on marl–concrete interfaces were performed and are also presented. Both cases analysed show that the saturation of the marl leads to a strong reduction of friction and effective cohesion. Negative effects of suction changes on the mechanical behaviour of the marls were investigated in more detail in suction controlled tests on Abadia marls, a more plastic material. A numerical simulation of wetting effects on a marl fragment of finite size helps to identify the nature of degradation mechanisms, which are associated with the development of tensile surfaces inside the marl matrix. They, in turn, are due to the expansive behaviour of the clay fraction of the marl relative to suction changes.
Weathering processes, structural degradation and slope-structure stability of rock-hewn churches of Lalibela (Ethiopia)
Authors: Delmonaco G. , Margottini C. , Spizzichino D. 
Published: July 2010

Abstract

Lalibela is located in the northern–central part of Ethiopia,
c
. 600 km north of Addis Ababa in Northern Wollo (Ahmara Region). The town, which has about 12 000 inhabitants, is situated at an altitude of 2500 m. In its centre a unique complex of 11 rock-hewn Christian Orthodox churches is located, cut out of the rock some 800 years ago. Their construction is attributed to King Lalibela (1167–1207). All the churches exhibit widespread evidence of structural damage and weathering processes, which are posing a serious problem for the preservation of the monuments. Preliminary geological field surveys,
in situ
geotechnical analyses and laboratory tests have been carried out in the area to understand the cause of weathering and the likely consequences on the structural stability of the churches. Laboratory tests on volcanic materials detected a deep alteration of rocks as a result of the widespread presence of montmorillonite. This is the primary cause of the progressive deterioration of the physical and mechanical characteristics of the slope-forming rocks in Lalibela. Major consequences are the alveolar weathering of churches' façade, the degradation of the roofs and a reduction of rock strength, which are causing a progressive structural instability in some rock-hewn monuments. Also, sliding of façades along bedding joints was detected. Understanding the weathering processes affecting the Lalibela churches allows the detection of problems and the timely implementation of medium- to long-term protection strategies for conservation of the monuments.
Role of CAAT/Enhancer Binding Protein Homologous Protein in Panobinostat-Mediated Potentiation of Bortezomib-Induced Lethal Endoplasmic Reticulum Stress in Mantle Cell Lymphoma Cells
Authors: Rao Rekha , Nalluri Srilatha , Fiskus Warren , Savoie Andrew , Buckley Kathleen M. , Ha Kyungsoo , Balusu Ramesh , Joshi Atul , Coothankandaswamy Veena , Tao Jianguo , Sotomayor Eduardo , Atadja Peter , Bhalla Kapil N. 
Published: July 2010

Abstract
Purpose: Bortezomib induces unfolded protein response (UPR) and endoplasmic reticulum stress, as well as exhibits clinical activity in patients with relapsed and refractory mantle cell lymphoma (MCL). Here, we determined the molecular basis of the improved in vitro and in vivo activity of the combination of the pan-histone deacetylase inhibitor panobinostat and bortezomib against human, cultured, and primary MCL cells.
Experimental Design: Immunoblot analyses, reverse transcription-PCR, and immunofluorescent and electron microscopy were used to determine the effects of panobinostat on bortezomib-induced aggresome formation and endoplasmic reticulum stress in MCL cells.
Results: Treatment with panobinostat induced heat shock protein 90 acetylation; depleted the levels of heat shock protein 90 client proteins, cyclin-dependent kinase 4, c-RAF, and AKT; and abrogated bortezomib-induced aggresome formation in MCL cells. Panobinostat also induced lethal UPR, associated with induction of CAAT/enhancer binding protein homologous protein (CHOP). Conversely, knockdown of CHOP attenuated panobinostat-induced cell death of MCL cells. Compared with each agent alone, cotreatment with panobinostat increased bortezomib-induced expression of CHOP and NOXA, as well as increased bortezomib-induced UPR and apoptosis of cultured and primary MCL cells. Cotreatment with panobinostat also increased bortezomib-mediated in vivo tumor growth inhibition and improved survival of mice bearing human Z138C MCL cell xenograft.
Conclusion: These findings suggest that increased UPR and induction of CHOP are involved in enhanced anti-MCL activity of the combination of panobinostat and bortezomib. Clin Cancer Res; 16(19); 4742–54. ©2010 AACR.
Predictive Value of Multislice Computed Tomography Variables of Atherosclerosis for Ischemia on Stress-Rest Single-Photon Emission Computed Tomography
Authors: van Velzen Joëlla E. , Schuijf Joanne D. , van Werkhoven Jacob M. , Herzog Bernhard A. , Pazhenkottil Aju P. , Boersma Eric , de Graaf Fleur R. , Scholte Arthur J. , Kroft Lucia J. , de Roos Albert , Stokkel Marcel P. , Jukema J. Wouter , Kaufmann Philipp A. , van der Wall Ernst E. , Bax Jeroen J. 
Published: July 2010

Background—
Previous studies have shown that the presence of stenosis alone on multislice computed tomography (MSCT) has a limited positive predictive value for the presence of ischemia on myocardial perfusion imaging (MPI). The purpose of this study was to assess which variables of atherosclerosis on MSCT angiography are related to ischemia on MPI.

Methods and Results—
Both MSCT and MPI were performed in 514 patients. On MSCT, the calcium score, degree of stenosis (≥50% and ≥70% stenosis), and plaque extent and location were determined. Plaque composition was classified as noncalcified, mixed, or calcified. Ischemia was defined as a summed difference score (≥2 on a per-patient basis. Ischemia was observed in 137 patients (27%). On a per-patient basis, multivariate analysis showed that the degree of stenosis (presence of (≥70% stenosis, odds ratio=3.5), plaque extent and composition (mixed plaques (≥3, odds ratio=1.7; calcified plaques ≥3, odds ratio=2.0), and location (atherosclerotic disease in the left main coronary artery and/or proximal left anterior descending coronary artery, odds ratio=1.6) were independent predictors for ischemia on MPI. In addition, MSCT variables of atherosclerosis, such as plaque extent, composition, and location, had significant incremental value for the prediction of ischemia over the presence of ≥70% stenosis.

Conclusions—
In addition to the degree of stenosis, MSCT variables of atherosclerosis describing plaque extent, composition, and location are predictive of the presence of ischemia on MPI.
HypE: An Algorithm for Fast Hypervolume-Based Many-Objective Optimization
Authors: Bader Johannes , Zitzler Eckart 
Published: July 2010

In the field of evolutionary multi-criterion optimization, the hypervolume indicator is the only single set quality measure that is known to be strictly monotonic with regard to Pareto dominance: whenever a Pareto set approximation entirely dominates another one, then the indicator value of the dominant set will also be better. This property is of high interest and relevance for problems involving a large number of objective functions. However, the high computational effort required for hypervolume calculation has so far prevented the full exploitation of this indicator's potential; current hypervolume-based search algorithms are limited to problems with only a few objectives. This paper addresses this issue and proposes a fast search algorithm that uses Monte Carlo simulation to approximate the exact hypervolume values. The main idea is not that the actual indicator values are important, but rather that the rankings of solutions induced by the hypervolume indicator. In detail, we present HypE, a hypervolume estimation algorithm for multi-objective optimization, by which the accuracy of the estimates and the available computing resources can be traded off; thereby, not only do many-objective problems become feasible with hypervolume-based search, but also the runtime can be flexibly adapted. Moreover, we show how the same principle can be used to statistically compare the outcomes of different multi-objective optimizers with respect to the hypervolume—so far, statistical testing has been restricted to scenarios with few objectives. The experimental results indicate that HypE is highly effective for many-objective problems in comparison to existing multi-objective evolutionary algorithms. HypE is available for download at http://www.tik.ee.ethz.ch/sop/download/supplementary/hype/ .