bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bortezomib modulates surface CD20 in B-cell malignancies and affects rituximab-mediated complement-dependent cytotoxicity
Authors: Bil Jacek , Winiarska Magdalena , Nowis Dominika , Bojarczuk Kamil , Dąbrowska-Iwanicka Anna , Basak Grzegorz W. , Sułek Kazimierz , Jakobisiak Marek , Golab Jakub 
Published: March 2010

AbstractUnresponsiveness to rituximab treatment develops in many patients prompting elucidation of underlying molecular pathways. It was recently observed that rituximab-resistant lymphoma cells exhibit up-regulation of components of the ubiquitin-proteasome system (UPS). Therefore, we investigated in more detail the role of this system in the regulation of CD20 levels and the influence of proteasome inhibitors on rituximab-mediated complement-dependent cytotoxicity (R-CDC). We observed that incubation of Raji cells with rituximab leads to increased levels of ubiquitinated CD20. However, inhibition of the UPS was not associated with up-regulation of surface CD20 levels, although it significantly increased its ubiquitination. Short-term (24 hours) incubation of Raji cells with 10 or 20nM bortezomib did not change surface CD20 levels, but sensitized CD20+ lymphoma cells to R-CDC. Prolonged (48 hours) incubation with 20nM bortezomib, or incubation with 50nM bortezomib for 24 hours led to a significant decrease in surface CD20 levels as well as R-CDC. These effects were partly reversed by bafilomycin A1, an inhibitor of lysosomal/autophagosomal pathway of protein degradation. These studies indicate that CD20 levels are regulated by 2 proteolytic systems and that the use of proteasome inhibitors may be associated with unexpected negative influence on R-CDC.
Platelet interleukin-1α drives cerebrovascular inflammation
Authors: Thornton Peter , McColl Barry W. , Greenhalgh Andrew , Denes Adam , Allan Stuart M. , Rothwell Nancy J. 
Published: March 2010

AbstractWhite blood cell infiltration across an activated brain endothelium contributes to neurologic disease, including cerebral ischemia and multiple sclerosis. Identifying mechanisms of cerebrovascular activation is therefore critical to our understanding of brain disease. Platelet accumulation in microvessels of ischemic mouse brain was associated with endothelial activation in vivo. Mouse platelets expressed interleukin-1α (IL-1α), but not IL-1β, induced endothelial cell adhesion molecule expression (ICAM-1 and VCAM-1), and enhanced the release of CXC chemokine CXCL1 when incubated with primary cultures of brain endothelial cells from wild-type or IL-1α/β–deficient mice. A neutralizing antibody to IL-1α (but not IL-1β) or application of IL-1 receptor antagonist inhibited platelet-induced endothelial activation by more than 90%. Platelets from IL-1α/β–deficient mice did not induce expression of adhesion molecules in cerebrovascular endothelial cells and did not promote CXCL1 release in vitro. Conditioned medium from activated platelets induced an IL-1α–dependent activation of mouse brain endothelial cells and supported the transendothelial migration of neutrophils in vitro. Thus, we have identified platelets as a key source of IL-1α and propose that platelet activation of brain endothelium via IL-1α is a critical step for the entry of white blood cells, major contributors to inflammation-mediated injury in the brain.
Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved elements
Authors: Licastro Danilo , Gennarino Vincenzo A , Petrera Francesca , Sanges Remo , Banfi Sandro , Stupka Elia 
Published: March 2010

Abstract

Background
Ultraconserved elements (UCEs) are highly constrained elements of mammalian genomes, whose functional role has not been completely elucidated yet. Previous studies have shown that some of them act as enhancers in mouse, while some others are expressed in both normal and cancer-derived human tissues. Only one UCE element so far was shown to present these two functions concomitantly, as had been observed in other isolated instances of single, non ultraconserved enhancer elements.

Results
We used a custom microarray to assess the levels of UCE transcription during mouse development and integrated these data with published microarray and next-generation sequencing datasets as well as with newly produced PCR validation experiments. We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand. Although the nature of these transcripts remains a mistery, our meta-analysis of RNA-Seq datasets indicates that they are unlikely to be short RNAs and that some of them might encode nuclear transcripts. In the majority of cases this function overlaps with the already established enhancer function of these elements during mouse development. Utilizing several next-generation sequencing datasets, we were further able to show that the level of expression observed in non-exonic UCEs is significantly higher than in random regions of the genome and that this is also seen in other regions which act as enhancers.

Conclusion
Our data shows that the concurrent presence of enhancer and transcript function in non-exonic UCE elements is more widespread than previously shown. Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand.
Subarachnoidal Neurocysticercosis non-responsive to cysticidal drugs: a case series
Authors: Cárdenas Graciela , Carrillo-Mezo Roger , Jung Helgi , Sciutto Edda , Hernandez Jose Luis Soto , Fleury Agnès 
Published: March 2010

AbstractBackgroundNeurocysticercosis (NC) is one of the most frequent parasitic diseases of the central nervous system. Cysticidal drugs, albendazole and praziquantel, are generally effective when parasites localize in the parenchyma. In contrast, parasites lodged in the subarachnoid basal cisterns are less responsive to treatment.Case PresentationThe clinical and radiological pictures of six Mexican patients non-respondent to cysticidal treatment are presented.ConclusionsThe possible factors involved in the cysticidal non-response are discussed and hints are provided of potentially useful changes to therapeutic protocols.
Origin of measles virus: divergence from rinderpest virus between the 11th and 12th centuries
Authors: Furuse Yuki , Suzuki Akira , Oshitani Hitoshi 
Published: March 2010

AbstractMeasles, caused by measles virus (MeV), is a common infection in children. MeV is a member of the genusMorbillivirusand is most closely related to rinderpest virus (RPV), which is a pathogen of cattle. MeV is thought to have evolved in an environment where cattle and humans lived in close proximity. Understanding the evolutionary history of MeV could answer questions related to divergence times of MeV and RPV.We investigated divergence times using relaxed clock Bayesian phylogenetics. Our estimates reveal that MeV had an evolutionary rate of 6.0 - 6.5 × 10-4substitutions/site/year. It was concluded that the divergence time of the most recent common ancestor of current MeV was the early 20thcentury. And, divergence between MeV and RPV occurred around the 11thto 12thcenturies. The result was unexpected because emergence of MeV was previously considered to have occurred in the prehistoric age.MeV may have originated from virus of non-human species and caused emerging infectious diseases around the 11thto 12thcenturies. In such cases, investigating measles would give important information about the course of emerging infectious diseases.
Increased hematogones in an infant with bicytopenia and leucocytosis:a case report
Authors: Agarwal Kiran , Aggarwal Meenu , Aggarwal Vikas Kumar , Pujani Meenu , Nain Manupriya 
Published: March 2010

Abstract
Hematogones are the normal bone marrow constituents of bone marrow in children and their number decreases with age. As hematogones can resemble malignant lymphoblasts by their morphologic features and by expression of an immature B-cell phenotype, an accurate distinction of hematogone-rich lymphoid regeneration from leukemic lymphoblasts is critical for patient care. The increased number of hematogones had been reported in the bone marrow of children recovering from chemotherapy, aplastic conditions, other forms of bone marrow injury, infections like Cytomegalovirus, HIV and immune thrombocytopenia disorders. We describe here a case of one and half month old male infant with bicytopenia and leucocytosis associated with increased hematogones in the bone marrow due to an unknown probable viral infection.
Gram-negative bacteremia induces greater magnitude of inflammatory response than Gram-positive bacteremia
Authors: Abe Ryuzo , Oda Shigeto , Sadahiro Tomohito , Nakamura Masataka , Hirayama Yo , Tateishi Yoshihisa , Shinozaki Koichiro , Hirasawa Hiroyuki 
Published: March 2010

Abstract
Introduction
Bacteremia is recognized as a critical condition that influences the outcome of sepsis. Although large-scale surveillance studies of bacterial species causing bacteremia have been published, the pathophysiological differences in bacteremias with different causative bacterial species remain unclear. The objective of the present study is to investigate the differences in pathophysiology and the clinical course of bacteremia caused by different bacterial species.

Methods
We reviewed the medical records of all consecutive patients admitted to the general intensive care unit (ICU) of a university teaching hospital during the eight-year period since introduction of a rapid assay for interleukin (IL)-6 blood level to routine ICU practice in May 2000. White blood cell count, C-reactive protein (CRP), IL-6 blood level, and clinical course were compared among different pathogenic bacterial species.

Results
The 259 eligible patients, as well as 515 eligible culture-positive blood samples collected from them, were included in this study. CRP, IL-6 blood level, and mortality were significantly higher in the septic shock group (n = 57) than in the sepsis group (n = 127) (P < 0.001). The 515 eligible culture-positive blood samples harbored a total of 593 isolates of microorganisms (Gram-positive, 407; Gram-negative, 176; fungi, 10). The incidence of Gram-negative bacteremia was significantly higher in the septic shock group than in the sepsis group (P < 0.001) and in the severe sepsis group (n = 75, P < 0.01). CRP and IL-6 blood level were significantly higher in Gram-negative bacteremia (n = 176) than in Gram-positive bacteremia (n = 407) (P < 0.001, <0.0005, respectively).

Conclusions
The incidence of Gram-negative bacteremia was significantly higher in bacteremic ICU patients with septic shock than in those with sepsis or severe sepsis. Furthermore, CRP and IL-6 levels were significantly higher in Gram-negative bacteremia than in Gram-positive bacteremia. These findings suggest that differences in host responses and virulence mechanisms of different pathogenic microorganisms should be considered in treatment of bacteremic patients, and that new countermeasures beyond conventional antimicrobial medications are urgently needed.
Leukocyte function in the aging immune system
Authors: Desai Anjali , Grolleau-Julius Annabelle , Yung Raymond 
Published: March 2010

Abstract
Review of the current understanding of age-dependent changes in leukocyte function and their contribution to aging-related disease processes.
Aging is associated with a progressive dysregulation of immune responses. Whether these changes are solely responsible for the observed increased mortality and morbidity amongst the elderly is uncertain. Recent advances have highlighted the age-associated changes that occur beyond T and B lymphocytes. Additionally, multiple human and animal studies have identified a relationship between chronic low-grade inflammation and geriatric syndromes, such as frailty, suggesting that the phenomenon of “inflamm-aging” may provide a rationale for the increased vulnerability to chronic inflammatory diseases in older adults. In the present review, we broadly summarize our current understanding of age-dependent changes in leukocyte function and their contribution to aging-related disease processes.
MAPK-directed phosphatases preferentially regulate pro- and anti-inflammatory cytokines in experimental visceral leishmaniasis: involvement of distinct protein kinase C isoforms
Authors: Kar Susanta , Ukil Anindita , Sharma Gunjan , Das Pijush K 
Published: March 2010

Abstract
MAP kinase-directed phosphatases in the disease progression of leishmaniasis have a role in modulation of cytokine balance and iNOS expression.
The role of phosphatases in the impairment of MAPK signaling, which is directly responsible for Leishmania-induced macrophage dysfunction, is still poorly understood. Gene expression profiling revealed that Leishmania donovani infection markedly up-regulated the expression of three phosphatases: MKP1, MKP3, and PP2A. Inhibition of these phosphatases prior to infection points toward preferential induction of the Th2 response through deactivation of p38 by MKP1. On the other hand, MKP3 and PP2A might play significant roles in the inhibition of iNOS expression through deactivation of ERK1/2. Among various PKC isoforms, PKCζ was associated with induction of MKP3 and PP2A in infected macrophages, whereas PKCε was correlated with MKP1 induction. Inhibition of phosphatases in L. donovani-infected BALB/c mice shifted the cytokine balance in favor of the host by inducing TNF-α and iNOS expression. This was validated by cystatin, an immunomodulator and curing agent for experimental visceral leishmaniasis, which showed that inhibition of MKPs and PP2A activity may be necessary for a favorable T cell response and suppression of organ parasite burden. This study, for the first time, suggests the possibility of the involvement of MAPK-directed phosphatases in the establishment of L. donovani infection.
Apoptosis signal-regulating kinase 1 in peptidoglycan-induced COX-2 expression in macrophages
Authors: Hsu Ming-Jen , Chang Chia-Kai , Chen Mei-Chieh , Chen Bing-Chang , Ma Hon-Ping , Hong Chuang-Ye , Lin Chien-Huang 
Published: March 2010

Abstract
PGN activates TLR2-mediated PP2A-ASK1-JNK-AP-1-C/EBPβ cascade and subsequent COX-2 expression in macrophages.
In this study, we investigated the role of ASK1 in PGN-induced C/EBPβ activation and COX-2 expression in RAW 264.7 macrophages. The PGN-induced COX-2 expression was attenuated by the DNs of ASK1, JNK1, JNK2, a JNK inhibitor (SP600125), and an AP-1 inhibitor (curcumin). PGN caused ASK1 dephosphorylation time-dependently at Ser967, dissociation from the ASK1-14-3-3 complex, and subsequent ASK1 activation. In addition, PGN activated PP2A and suppression of PP2A by okadaic acid markedly inhibited PGN-induced ASK1 Ser967 dephosphorylation and COX-2 expression. PGN induced the activation of the JNK-AP-1 signaling cascade downstream of ASK1. PGN-increased C/EBPβ expression and DNA-binding activity were inhibited by the ASK1-JNK-AP-1 signaling blockade. COX-2 promoter luciferase activity induced by PGN was attenuated in cells transfected with the COX-2 reporter construct possessing the C/EBP-binding site mutation. In addition, the ASK1-JNK-AP-1-C/EBPβ cascade was activated in human peripheral mononuclear cells exposure to PGN. The TLR2 agonist Pam3CSK4 was also shown to induce ASK1 Ser967 dephosphorylation, JNK and c-jun phosphorylation, C/EBPβ activation, and COX-2 expression in RAW 264.7 macrophages. PGN-induced COX-2 promoter luciferase activity was prevented by selective inhibition of TLR2 and c-Jun in RAW 264.7 macrophages. Our data demonstrate that PGN might activate the TLR2-mediated PP2A-ASK1-JNK-AP-1-C/EBPβ cascade and subsequent COX-2 expression in RAW 264.7 macrophages.
Clostridium difficiletoxin B differentially affects GPCR-stimulated Ca2+ responses in macrophages: independent roles for Rho and PLA2
Authors: Rebres Robert A , Moon Christina , DeCamp Dianne , Lin Keng-Mean , Fraser Iain D , Milne Stephen B , Roach Tamara I A , Brown H Alex , Seaman William E 
Published: March 2010

AbstractDistinct activities of toxin B up-regulate PLCβ3 or down-regulate PLCβ4-dependent IP3-Ca2+ coupling.Clostridium difficile toxins cause acute colitis by disrupting the enterocyte barrier and promoting inflammation. ToxB from C. difficile inactivates Rho family GTPases and causes release of cytokines and eicosanoids by macrophages. We studied the effects of ToxB on GPCR signaling in murine RAW264.7 macrophages and found that ToxB elevated Ca2+ responses to Gαi-linked receptors, including the C5aR, but reduced responses to Gαq-linked receptors, including the UDP receptors. Other Rho inhibitors also reduced UDP Ca2+ responses, but they did not affect C5a responses, suggesting that ToxB inhibited UDP responses by inhibiting Rho but enhanced C5a responses by other mechanisms. By using PLCβ isoform-deficient BMDM, we found that ToxB inhibited Ca2+ signaling through PLCβ4 but enhanced signaling through PLCβ3. Effects of ToxB on GPCR Ca2+ responses correlated with GPCR use of PLCβ3 versus PLCβ4. ToxB inhibited UDP Ca2+ signaling without reducing InsP3 production or the sensitivity of cellular Ca2+ stores to exogenous InsP3, suggesting that ToxB impairs UDP signaling at the level of InsP3/Ca2+coupling. In contrast, ToxB elevated InsP3 production by C5a, and the enhancement of Ca2+ signaling by C5a was prevented by inhibition of PLA2 or 5-LOX but not COX, implicating LTs but not prostanoids in the mechanism. In sum, ToxB has opposing, independently regulated effects on Ca2+ signaling by different GPCR-linked PLCβ isoforms in macrophages.
Fospropofol Disodium
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E. 
Published: March 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent in print and are also available online. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The March 2009 monograph topics are plerixafor, degarelix, armodafinil, iloperidone, and lasofoxifene. The DUE is on degarelix.
Looking beyond the B-side from the G-side: the under- and misrepresentation of the Roma in the media
Authors: Tortajada Iolanda , Willem Cilia 
Published: March 2010

In this article we present the results of two different studies What Of Us Is In This? (carried out in 2006 at the University of Lleida and supported by the Catalan Audiovisual Council) and Roots&Routes (carried out between 2005 and 2008 at the University of Barcelona). These studies,
on the one hand, reach the same conclusions using different methodologies and, on the other, illustrate that the results obtained from engaging in a dialogue with Roma people about their media representation (using qualitative techniques with the intention of giving them a voice) are not any
different from the conclusions that have come out of more classical content and discourse analyses about minorities and the media performed to date.
When we asked the Roma about their perceptions and opinions of their representation in the media, we realized that they were quite conscious
and critical about media discourses that offer a stereotyped vision of them, constructing a definition of being Roma by using difference and conflict. The Roma who participated in our study described how the media make them invisible and represent them in a distorted way. Thus, we can affirm
the validity of a methodology that focuses its attention on giving a voice to the subjects, as this will not only contribute to reinforcing the results of other techniques, but also makes us think about the adequacy of research based exclusively on an analysis of the message (object), without
taking into account the groups that are marginalized, and not only by the media, but also by research itself (subjects).
Inventing rituals; inhabiting places ritual and community in public art
Authors: Jones Ruth 
Published: March 2010

In May 2008, five temporary art events were commissioned by Ruth Jones in public spaces in Cardigan (Wales) as part of the project Holy Hiatus. The project explored the possibilities for ritual to be employed creatively in public art practice, and to examine the ways that artists
can draw audiences into unexpected and potentially liminal experiences of place through ritual. Some people locally and from further a field knew about the events through publicity material or word of mouth, and made an active decision to attend, while others came across interventions unexpectedly
whilst going about their daily business: for example, Alastair MacLennan was working on the footbridge over the River Teifi for twelve hours, tying ribbon, greenery and paper boats to the railings and talking to curious users of the bridge; while Simon Whitehead worked with dancers Kate Willis
and Andrea Buckley to create an improvised dance Drift (which followed the flow of the tides) through the town over three days. A few people living in and around Cardigan became collaborators through their involvement in the artists' projects; Yvonne Buchheim created a public performance
at Cardigan swimming pool in collaboration with two local swimmers and two singers and Anna Lucas spent three weeks meeting teenagers in West Wales who were actively involved with working animals, in order to gather film footage for a new video installation that was exhibited in the Pendre
Art Gallery. Maura Hazelden collaborated with acoustic singer Lou Laurens and created a six-hour performance in the newly built Small World Theatre: a company deeply engaged with local communities. The temporary, mobile and in some cases, understated nature of the works meant that the impact
was often subtle, but the artworks nonetheless created a ripple of effect for both active and incidental audiences, leading witnesses to wonder what they had just seen and to what extent they had knowingly, or unknowingly, participated.
Following the completion of the projects, a series
of interviews with twelve audience members were carried out by researcher Sarah Pace from Safle (an independent public art consultancy based in Cardiff) in order to gain an insight into how the artworks were received. This article integrates the findings from these with theoretical understandings
of ritual from fields such as anthropology, sociology, cultural and communication theory. The article begins by laying out the arguments for and against the creative potential of ritual. The interviewees' experiences of the artworks for Holy Hiatus are then compared to find support
for the proposition that experiences of liminality are possible in public art projects that employ ritual. Finally, the article looks at how experiencing public rituals in places that are familiar to us might alter our perception of those places in both exciting and challenging ways.
The
names of the interviewees have been altered to maintain anonymity.