bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial-Mediated Apoptosis in Lymphoma Cells by the Diterpenoid Lactone Andrographolide, the Active Component of Andrographis paniculata
Authors: Yang Shuo , Evens Andrew M. , Prachand Sheila , Singh Amareshwar T.K. , Bhalla Savita , David Kevin , Gordon Leo I. 
Published: August 2010

Abstract
Purpose: Andrographolide is a diterpenoid lactone isolated from Andrographis paniculata (King of Bitters), an herbal medicine used in Asia. It has been reported to have anti-inflammatory, antihypertensive, antiviral, and immune-stimulant properties. Furthermore, it has been shown to inhibit cancer cell proliferation and induce apoptosis in leukemia and solid tumor cell lines.
Experimental Design: We studied the Burkitt p53-mutated Ramos cell line, the mantle cell lymphoma (MCL) line Granta, the follicular lymphoma (FL) cell line HF-1, and the diffuse large B-cell lymphoma (DLBCL) cell line SUDHL4, as well as primary cells from patients with FL, DLBCL, and MCL.
Results: We found that andrographolide resulted in dose- and time-dependent cell death as measured by MTT. Andrographolide significantly increased reactive oxygen species (ROS) production in all cell lines. To determine mechanism of cell death, we measured apoptosis by Annexin V/propidium iodide in the presence and absence of the antioxidant N-acetyl-l-cysteine (NAC), the glutathione (GSH)–depleting agent buthionine sulfoxamine (BSO), or caspase inhibitors. We found that apoptosis was greatly enhanced by BSO, blocked by NAC, and accompanied by poly(ADP-ribose) polymerase cleavage and activation of caspase-3, caspase-8, and caspase-9. We measured BAX conformational change and mitochondrial membrane potential, and using mouse embryonic fibroblast (MEF) Bax/Bak double knockouts (MEFBax−/−/Bak−/−), we found that apoptosis was mediated through mitochondrial pathways, but dependent on caspases in both cell lines and patient samples.
Conclusions: Andrographolide caused ROS-dependent apoptosis in lymphoma cell lines and in primary tumor samples, which was enhanced by depletion of GSH and inhibited by NAC or the pan-caspase inhibitor Z-VAD-FMK. Further studies of diterpenoid lactones in lymphoma are warranted. Clin Cancer Res; 16(19); 4755–68. ©2010 AACR.
Endothelin Receptor Type B Gene Promoter Hypermethylation in Salivary Rinses Is Independently Associated with Risk of Oral Cavity Cancer and Premalignancy
Authors: Pattani Kavita Malhotra , Zhang Zhe , Demokan Semra , Glazer Chad , Loyo Myriam , Goodman Steven , Sidransky David , Bermudez Francisco , Jean-Charles Germain , McCaffrey Thomas , Padhya Tapan , Phelan Joan , Spivakovsky Silvia , Bowne Helen Yoo , Goldberg Judith D. , Rolnitzky Linda , Robbins Miriam , Kerr A. Ross , Sirois David , Califano Joseph A. 
Published: August 2010

Abstract
Endothelin receptor type B (EDNRB) and kinesin family member 1A (KIF1A) are candidate tumor suppressor genes that are inactivated in cancers. In this study, we evaluated the promoter hypermethylation of EDNRB and KIF1A and their potential use for risk classification in prospectively collected salivary rinses from patients with premalignant/malignant oral cavity lesions. Quantitative methylation-specific PCR was performed to analyze the methylation status of EDNRB and KIF1A in salivary rinses of 191 patients. We proceeded to determine the association of methylation status with histologic diagnosis and estimate classification accuracy. On univariate analysis, diagnosis of dysplasia/cancer was associated with age and KIF1A or EDNRB methylation. Methylation of EDNRB highly correlated with that of KIF1A (P &lt; 0.0001). On multivariable modeling, histologic diagnosis was independently associated with EDNRB (P = 0.0003) or KIF1A (P = 0.027) methylation. A subset of patients analyzed (n = 161) without prior biopsy-proven malignancy received clinical risk classification based on examination. On univariate analysis, EDNRB and risk classification were associated with diagnosis of dysplasia/cancer and remained significant on multivariate analysis (EDNRB: P = 0.047, risk classification: P = 0.008). Clinical risk classification identified dysplasia/cancer with a sensitivity of 71% and a specificity of 58%. The sensitivity of clinical risk classification combined with EDNRB methylation improved to 75%. EDNRB methylation in salivary rinses was independently associated with histologic diagnosis of premalignancy and malignancy and may have potential in classifying patients at risk for oral premalignant and malignant lesions in settings without access to a skilled dental practitioner. This may also potentially identify patients with premalignant and malignant lesions that do not meet the criteria for high clinical risk based on skilled dental examination. Cancer Prev Res; 3(9); 1093–103. ©2010 AACR.
Local Regulation of Arterial L-Type Calcium Channels by Reactive Oxygen Species
Authors: Amberg Gregory C. , Earley Scott , Glapa Stephanie A. 
Published: August 2010

Rationale:Reactive oxygen species (ROS) are implicated in the development of cardiovascular disease, and oxidants are important signaling molecules in many cell types. Recent evidence suggests that localized subcellular compartmentalization of ROS generation is an important feature of ROS signaling. However, mechanisms that transduce localized subcellular changes in redox status to functionally relevant changes in cellular processes such as Ca2+influx are poorly understood.Objective:To test the hypothesis that ROS regulate L-type Ca2+channel activity in cerebral arterial smooth muscle.Methods and Results:Using a total internal reflection fluorescence imaging–based approach, we found that highly localized subplasmalemmal generation of endogenous ROS preceded and colocalized with sites of enhanced L-type Ca2+channel sparklet activity in isolated cerebral arterial smooth muscle cells. Consistent with this observation and our hypothesis, exogenous ROS increased localized L-type Ca2+channel sparklet activity in isolated arterial myocytes via activation of protein kinase Cα and when applied to intact cerebral arterial segments, exogenous ROS increased arterial tone in an L-type Ca2+channel–dependent fashion. Furthermore, angiotensin II–dependent stimulation of local L-type Ca2+channel sparklet activity in isolated cells and contraction of intact arteries was abolished following inhibition of NADPH oxidase.Conclusions:Our data support a novel model of local oxidative regulation of Ca2+influx where vasoconstrictors coupled to NAPDH oxidase (eg, angiotensin II) induce discrete sites of ROS generation resulting in oxidative activation of adjacent protein kinase Cα molecules that in turn promote local sites of enhanced L-type Ca2+channel activity, resulting in increased Ca2+influx and contraction.
Use of ς with the Future Participle in Herodotus as an Indicator of Unfulfilled Expectations
Authors: Welser Christopher S. 
Published: August 2010

AbstractAn examination of Herodotus’s use of the circumstantial participle in the future tense with and without the adverbial particle ς reveals that Herodotus reserves ς almost exclusively for those cases in which the expectations or intentions represented by the participle are ultimately disappointed. This observation should teach us to distrust the conventional assertion that the appearance of ς with the circumstantial participle has no implications for an author’s thoughts. It also suggests that, in those cases where we lack direct knowledge of historical outcomes, the presence of ς with a circumstantial participle may permit us to be reasonably certain that any expectations or intentions expressed by that participle are likely to have gone unfulfilled. Thus, Herodotus’s use of the phrase ς νασοντες at the end of the Histories to refer to the Athenians’ intentions to dedicate the equipment from Xerxes’ bridge (9.121) should probably be understood as implying that no such dedication ever took place.
Le Protrepticus ad nepotem d’Ausone: rhétorique et humour, ou Ausone est-il sérieux?
Authors: Amherdt David 
Published: August 2010

AbstractThis article deals with the rhetorical and literary wealth of Ausonius’ Protrepticus ad nepotem, and particularly with the poet’s irony and humor. Irony is an indispensable key to the correct interpretation of a text that was often misunderstood and whose actual addressee is the Gallo-Roman aristocracy. The aim of this exhortation is promoting a culture and a political vision in which classics play an essential role. Ausonius brings into play all his literary abilities to make his poem into a poetical celebration. The rhetorician of Bordeaux conveys a very serious message in a funny and charming way, in perfect consonance with the culture and the expectations of his readers: this is the power of persuasion of late Antiquity literature.
Deme Accounts and the Meaning of hosios Money in Fifth-Century Athens
Authors: Blok Josine H. 
Published: August 2010

AbstractComparing the accounts of the deme Ikarion (IG I3 253) with those of Rhamnous (IG I3 247 bis and 253; IRhamnous 181 and 182) and Plotheia (IG I3 258), this article argues that the adjective hosios applied to a fund in Ikarion indicates that this money was dêmosios and to be used in a way pleasing to the gods. The long-standing view that hosios when applied to money means ‘free for secular use’ or ‘secular’ (e.g. LSJ s.v. σιος) is shown to be unfounded, inviting a reassessment of the meanings of hosios. The use of public money for funding cults as attested in these deme accounts sheds new light on public finance in classical Athens.
A Mixed Scheme for Subgrid-Scale Fluxes in Cloud-Resolving Models
Authors: Moeng C.-H. , Sullivan P. P. , Khairoutdinov M. F. , Randall D. A. 
Published: August 2010

Abstract
A large-domain large-eddy simulation of a tropical deep convection system is used as a benchmark to derive and test a mixed subgrid-scale (SGS) scheme for scalar and momentum fluxes in cloud-resolving models (CRMs). The benchmark simulation resolves a broad range of scales ranging from mesoscale organizations, through gravity waves and individual clouds, down to energy-containing turbulent eddies. A spectral analysis shows that the vertical-velocity kinetic energy peaks at scales from hundreds of meters in the lower cloud layer to several kilometers higher up; these scales are typical grid sizes of today’s CRMs. The analysis also shows that a significant portion of the scalar and momentum fluxes in the benchmark simulation are carried by motions smaller than several kilometers (i.e., smaller than a typical grid resolution of CRMs). The broad range of scales of the benchmark simulation is split into two components: filter scale (mimicking CRM resolvable scale) and subfilter scale (mimicking CRM SGS), using filter widths characteristic of a typical CRM grid spacing. The local relationship of the subfilter-scale fluxes to the filter-scale variables is examined. This leads to a mixed SGS scheme to represent the SGS fluxes of scalars and momentum in CRMs. A priori tests show that the mixed SGS scheme yields spatial distributions of subfilter-scale fluxes that correlate much better with those retrieved from the benchmark when compared with an eddy viscosity/diffusivity scheme that is commonly used in today’s CRMs.
The Analysis and Prediction of the 8–9 May 2007 Oklahoma Tornadic Mesoscale Convective System by Assimilating WSR-88D and CASA Radar Data Using 3DVAR
Authors: Schenkman Alexander D. , Xue Ming , Shapiro Alan , Brewster Keith , Gao Jidong 
Published: August 2010

Abstract
The Advanced Regional Prediction System (ARPS) model is employed to perform high-resolution numerical simulations of a mesoscale convective system and associated cyclonic line-end vortex (LEV) that spawned several tornadoes in central Oklahoma on 8–9 May 2007. The simulation uses a 1000 km × 1000 km domain with 2-km horizontal grid spacing. The ARPS three-dimensional variational data assimilation (3DVAR) is used to assimilate a variety of data types. All experiments assimilate routine surface and upper-air observations as well as wind profiler and Oklahoma Mesonet data over a 1-h assimilation window. A subset of experiments assimilates radar data. Cloud and hydrometeor fields as well as in-cloud temperature are adjusted based on radar reflectivity data through the ARPS complex cloud analysis procedure. Radar data are assimilated from the Weather Surveillance Radar-1988 Doppler (WSR-88D) network as well as from the Engineering Research Center for Collaborative and Adaptive Sensing of the Atmosphere (CASA) network of four X-band Doppler radars. Three-hour forecasts are launched at the end of the assimilation window. The structure and evolution of the forecast MCS and LEV are markedly better throughout the forecast period in experiments in which radar data are assimilated. The assimilation of CASA radar data in addition to WSR-88D data increases the structural detail of the modeled squall line and MCS at the end of the assimilation window, which appears to yield a slightly better forecast track of the LEV.
The Group and the Individual in Conflict and War
Authors: Friedman Robi 
Published: August 2010

This article is an expression of gratitude to Malcolm Pines who has been both a personal mentor and a robust supporter of the Israeli Institute for Group Analysis. The firm friendship which we developed, as well as his strong links with Israel and his wish to see us well, secure and developing are a source of great comfort. I would not have started to write at all if he had not provided encouragement over a decade ago. Thus this article is not only an effort to use the group clinically and an attempt to overcome difficulties politically by group work, but is itself an outcome of Malcolm’s influence. Beyond many other possible citations, I use two of the most relevant: ‘My belief is that the therapist has always to earn the right to make any interpretation. Truths are always personal. There is no objective, impersonal truth given by a therapist pronouncing objective truth about the patient. To speak out what you believe to be true about another person’s life is to engage with them in a shared encounter . . .’ (Pines, 1993: 101); and, ‘A new group has a limited range of communication, as its capacity to contain, to hold and ultimately to understand what people are expressing in their illnesses is limited. Over the time the range of responsiveness and understanding greatly widens . . . ’ (Pines, 1993: 102). This article is about the difficulties of painfully working through our own truths and the advantages and limitations of group development.
The Phenomenon of Silence
Authors: Urlić Ivan 
Published: August 2010

The phenomena of silence and quietness have been omnipresent in human life since its beginning. Nevertheless, they are rarely explored in their comprehensive and particular meanings. The author explores the meanings of silence and quietness in psychotherapy and in everyday life through theoretical considerations, clinical and social life examples, bearing in mind the psychodynamic/group analytic frame of reference. The dynamics of the transformation of non-verbal communication into verbal, the many meanings of an apparent lack of communication, and its understanding and differentiation from the culture of keeping silent are discussed, as well as the roles of internal and external group influences. In conclusion, the author refers to the phenomena of silence and quietness as regressive, repressive, transitional, transferential and countertransferential, as well as progressive phenomena spectrum. This article is dedicated to Malcolm Pines for the pleasant and thought provoking encounters, both personally and through his works, and for his sharp eye in perceiving messages and nuances of verbal and silent communications in depth and width, that inspired me to examine the contents of silences.
A novel adaptive design strategy increases the efficiency of clinical trials in secondary progressive multiple sclerosis
Authors: Chataway Jeremy , Nicholas Richard , Todd Susan , Miller David H , Parsons Nicholas , Valdés-Márquez Elsa , Stallard Nigel , Friede Tim 
Published: August 2010

Background:Adaptive seamless designs (ASDs) have been proposed to test multiple candidate compounds using an interim decision point which allows potentially effective therapies to be taken into the next design stage and to be assessed using a phase III outcome. Objective:To determine whether ASDs are feasible in secondary progressive multiple sclerosis (SPMS) and to compare them with conventional trial designs. Methods:We develop an innovative adaptive trial design for SPMS, which builds on recent developments in statistical methodology. A literature search and individual clinical datasets were used to inform a framework to run simulations to evaluate the proposed design. Results:ASDs are feasible in SPMS with MRI informing an interim decision point and Expanded Disability Status Scale (EDSS) as the final disability endpoint. Furthermore ASDs are more efficient than conventional designs with sample size savings of up to 40%. Sample sizes of 1000–1250 patients are sufficient to test up to four experimental treatments. Controlled recruitment is important to realize the full benefits of ASDs. Conclusions:Although more complex in design, ASDs have the potential to be more efficient and more powerful than conventional designs.
Parkinson's disease candidate gene prioritization based on expression profile of midbrain dopaminergic neurons
Authors: Vahedi Shahrooz , Rajabian Mehrnoosh , Misaghian Arman , Grbec Daniel , Simon Horst H , Alavian Kambiz N 
Published: August 2010

Abstract

Background
Parkinson's disease is the second most common neurodegenerative disorder. The pathological hallmark of the disease is degeneration of midbrain dopaminergic neurons. Genetic association studies have linked 13 human chromosomal loci to Parkinson's disease. Identification of gene(s), as part of the etiology of Parkinson's disease, within the large number of genes residing in these loci can be achieved through several approaches, including screening methods, and considering appropriate criteria. Since several of the indentified Parkinson's disease genes are expressed in substantia nigra pars compact of the midbrain, expression within the neurons of this area could be a suitable criterion to limit the number of candidates and identify PD genes.

Methods
In this work we have used the combination of findings from six rodent transcriptome analysis studies on the gene expression profile of midbrain dopaminergic neurons and the PARK loci in OMIM (Online Mendelian Inheritance in Man) database, to identify new candidate genes for Parkinson's disease.

Results
Merging the two datasets, we identified 20 genes within PARK loci, 7 of which are located in an orphan Parkinson's disease locus and one, which had been identified as a disease gene. In addition to identifying a set of candidates for further genetic association studies, these results show that the criteria of expression in midbrain dopaminergic neurons may be used to narrow down the number of genes in PARK loci for such studies.
Proteomic identification of secreted proteins of Propionibacterium acnes
Authors: Holland Carsten , Mak Tim N , Zimny-Arndt Ursula , Schmid Monika , Meyer Thomas F , Jungblut Peter R , Brüggemann Holger 
Published: August 2010

Abstract

Background
The anaerobic Gram-positive bacterium Propionibacterium acnes is a human skin commensal that resides preferentially within sebaceous follicles; however, it also exhibits many traits of an opportunistic pathogen, playing roles in a variety of inflammatory diseases such as acne vulgaris. To date, the underlying disease-causing mechanisms remain ill-defined and knowledge of P. acnes virulence factors remains scarce. Here, we identified proteins secreted during anaerobic cultivation of a range of skin and clinical P. acnes isolates, spanning the four known phylogenetic groups.

Results
Culture supernatant proteins of P. acnes were separated by two-dimensional electrophoresis (2-DE) and all Coomassie-stained spots were subsequently identified by MALDI mass spectrometry (MALDI-MS). A set of 20 proteins was secreted in the mid-exponential growth phase by the majority of strains tested. Functional annotation revealed that many of these common proteins possess degrading activities, including glycoside hydrolases with similarities to endoglycoceramidase, β-N-acetylglucosaminidase and muramidase; esterases such as lysophospholipase and triacylglycerol lipase; and several proteases. Other secreted factors included Christie-Atkins-Munch-Petersen (CAMP) factors, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and several hypothetical proteins, a few of which are unique to P. acnes. Strain-specific differences were apparent, mostly in the secretion of putative adhesins, whose genes exhibit variable phase variation-like sequence signatures.

Conclusions
Our proteomic investigations have revealed that the P. acnes secretome harbors several proteins likely to play a role in host-tissue degradation and inflammation. Despite a large overlap between the secretomes of all four P. acnes phylotypes, distinct differences between predicted host-tissue interacting proteins were identified, providing potential insight into the differential virulence properties of P. acnes isolates. Thus, our data presents a rich resource for guiding much-needed investigations on P. acnes virulence factors and host interacting properties.
Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a ‘whip-brake’ system of the endocrine heart
Authors: Tota Bruno , Cerra Maria Carmela , Gattuso Alfonsina 
Published: August 2010

SummaryIn the past 50 years, extensive evidence has shown the ability of vertebrate cardiac non-neuronal cells to synthesize and release catecholamines (CA). This formed the mindset behind the search for the intrinsic endocrine heart properties, culminating in 1981 with the discovery of the natriuretic peptides (NP). CA and NP, co-existing in the endocrine secretion granules and acting as major cardiovascular regulators in health and disease, have become of great biomedical relevance for their potent diagnostic and therapeutic use. The concept of the endocrine heart was later enriched by the identification of a growing number of cardiac hormonal substances involved in organ modulation under normal and stress-induced conditions. Recently, chromogranin A (CgA), a major constituent of the secretory granules, and its derived cardio-suppressive and antiadrenergic peptides, vasostatin-1 and catestatin, were shown as new players in this framework, functioning as cardiac counter-regulators in ‘zero steady-state error’ homeostasis, particularly under intense excitatory stimuli, e.g. CA-induced myocardial stress. Here, we present evidence for the hypothesis that is gaining support, particularly among human cardiologists. The actions of CA, NP and CgA, we argue, may be viewed as a hallmark of the cardiac capacity to organize ‘whip-brake’ connection-integration processes in spatio-temporal networks. The involvement of the nitric oxide synthase (NOS)/nitric oxide (NO) system in this configuration is discussed. The use of fish and amphibian paradigms will illustrate the ways that incipient endocrine-humoral agents have evolved as components of cardiac molecular loops and important intermediates during evolutionary transitions, or in a distinct phylogenetic lineage, or under stress challenges. This may help to grasp the old evolutionary roots of these intracardiac endocrine/paracrine networks and how they have evolved from relatively less complicated designs. The latter can also be used as an intellectual tool to disentangle the experimental complexity of the mammalian and human endocrine hearts, suggesting future investigational avenues.