bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutively Activated Nuclear Factor-κB, but not Induced NF-κB, Leads to TRAIL Resistance by Up-Regulation of X-Linked Inhibitor of Apoptosis Protein in Human Cancer Cells
Authors: Braeuer Susanne J. , Büneker Chirlei , Mohr Andrea , Zwacka Ralf Michael 
Published: October 2006

AbstractThe tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in most, but not all, cancer cells. The molecular factors regulating the sensitivity to TRAIL are still incompletely understood. The transcription factor nuclear factor-κB (NF-κB) has been implicated, but its exact role is controversial. We studied different cell lines displaying varying responses to TRAIL and found that TRAIL can activate NF-κB in all our cancer cell lines regardless of their TRAIL sensitivity. Inhibition of NF-κB via adenoviral expression of the IκB-α super-repressor only sensitized the TRAIL-resistant pancreatic cancer cell line Panc-1. Panc-1 cells harbor constitutively activated NF-κB, pointing to a possible role of preactivated NF-κB in protection from TRAIL. Furthermore, we could reduce X-linked inhibitor of apoptosis protein (XIAP) levels in Panc-1 cells by inhibition of constitutively activated NF-κB and sensitize Panc-1 cells to TRAIL by RNA interference against XIAP. These results implicate elevated XIAP levels caused by high basal NF-κB activity in TRAIL resistance and suggest that therapeutic strategies involving TRAIL can be abetted by inhibition of NF-κB and/or XIAP only in tumor cells with constitutively activated NF-κB. (Mol Cancer Res 2006;4(10):715–28)
Considering the Rationality of Ritual Behavior
Authors: MortSlone JoelD. Jason 
Published: October 2006

AbstractEngagement in religious ritual acts is, from a scientific point of view, a surprising feature of human behavior given the inherent commitment to counterintuitive worlds, including, generally invisible entities such as superhuman agents. Why people engage in such behaviors has preoccupied many scholars in the history of the study of religion (including scholars from within anthropology, psychology, sociology, and numerous other disciplines). These scholars have engaged in the Rationality Debate; the goal of which is to determine standards that could be used to make judgments about the rationality of human behavior. While ritual behavior might be ineffective for the achievement of purported goals and fail to conform to principles of reasoning based on rules of logic, the simple fact that this behavior is widespread, transmitted in a stable fashion, and the result (at least indirectly) of evolutionary processes suggest that considering its rationality or lack thereof is largely irrelevant. The question should not be “if” ritual behavior is rational but rather “why” this behavior is consistently exhibited. We argue that in order to answer this question anthropologists ultimately depend on heuristics recast as postulated entities. These are conceived as causal variable(s) governing patterned human behavior and consequently circle back and affirm a fallacious Durkheimian description of ritual behavior. This is a major and fundamental flaw in the current anthropological research tradition; the correction of which requires fundamental shifts in the philosophical commitments held—knowingly or unknowingly—by anthropologists.
Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection
Authors: Wang Xiaolei , Rasmussen Terri , Pahar Bapi , Poonia Bhawna , Alvarez Xavier , Lackner Andrew A. , Veazey Ronald S. 
Published: October 2006

AbstractRapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)–infected adult macaques and human immunodeficiency virus (HIV)–infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that “activated” central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques.
Comparison of protein interaction networks reveals species conservation and divergence
Authors: Liang Zhi , Xu Meng , Teng Maikun , Niu Liwen 
Published: October 2006

Abstract

Background
Recent progresses in high-throughput proteomics have provided us with a first chance to characterize protein interaction networks (PINs), but also raised new challenges in interpreting the accumulating data.

Results
Motivated by the need of analyzing and interpreting the fast-growing data in the field of proteomics, we propose a comparative strategy to carry out global analysis of PINs. We compare two PINs by combining interaction topology and sequence similarity to identify conserved network substructures (CoNSs). Using this approach we perform twenty-one pairwise comparisons among the seven recently available PINs of E.coli, H.pylori, S.cerevisiae, C.elegans, D.melanogaster, M.musculus and H.sapiens. In spite of the incompleteness of data, PIN comparison discloses species conservation at the network level and the identified CoNSs are also functionally conserved and involve in basic cellular functions. We investigate the yeast CoNSs and find that many of them correspond to known complexes. We also find that different species harbor many conserved interaction regions that are topologically identical and these regions can constitute larger interaction regions that are topologically different but similar in framework. Based on the species-to-species difference in CoNSs, we infer potential species divergence. It seems that different species organize orthologs in similar but not necessarily the same topology to achieve similar or the same function. This attributes much to duplication and divergence of genes and their associated interactions. Finally, as the application of CoNSs, we predict 101 protein-protein interactions (PPIs), annotate 339 new protein functions and deduce 170 pairs of orthologs.

Conclusion
Our result demonstrates that the cross-species comparison strategy we adopt is powerful for the exploration of biological problems from the perspective of networks.
Use of CFSE staining of borreliae in studies on the interaction between borreliae and human neutrophils
Authors: Tuominen-Gustafsson Helena , Penttinen Markus , Hytönen Jukka , Viljanen Matti K 
Published: October 2006

AbstractBackgroundSpecies of the tick-transmitted spirochete groupBorrelia burgdorferisensu lato (B. burgdorferi) cause Lyme borreliosis. Acute borrelial infection of the skin has unusual characteristics with only a mild local inflammatory response suggesting that the interaction between borreliae and the cells of the first-line defence might differ from that of other bacteria. It has been reported that human neutrophils phagocytose motile borreliae through an unconventional mechanism (tube phagocytosis) which is not observed with non-motile borreliae. Therefore, it would be of great interest to visualise the bacteria by a method not affecting motility and viability of borreliae to be able to study their interaction with the cells of the innate immunity. Carboxyfluorescein diacetate, succinimidyl ester (CFSE) labelling has been previously used for studying the adhesion of labelled bacteria to host cells and the uptake of labelled substrates by various cells using flow cytometry.ResultsIn this study, CFSE was shown to efficiently stain different genospecies ofB. burgdorferiwithout affecting bacterial viability or motility. Use of CFSE staining allowed subsequent quantification of borreliae associated with human neutrophils with flow cytometry and confocal microscopy. As a result, no difference in association between different borrelial genospecies (Borrelia burgdorferisensu stricto,Borrelia afzelii,Borrelia garinii), or between borreliae and the pyogenic bacteriumStreptococcus pyogenes, with neutrophils could be detected. Borrelial virulence, on the other hand, affected association with neutrophils, with significantly higher association of a non-virulent mutantB. burgdorferisensu stricto strain compared to the parental virulent wild type strain.ConclusionThese results suggest that the flow cytometric assay using CFSE labelled borreliae is a valuable tool in the analysis of the interaction between borreliae and human neutrophils. The results also indicate a clear difference in the association with neutrophils between virulent and non-virulent borrelial strains.
Evaluation of a 'virtual' approach to commissioning health research
Authors: McCourt Christine A , Morgan Philip A , Youll Penny 
Published: October 2006

Abstract
Background
The objective of this study was to evaluate the implementation of a 'virtual' (computer-mediated) approach to health research commissioning. This had been introduced experimentally in a DOH programme – the 'Health of Londoners Programme' – in order to assess whether is could enhance the accessibility, transparency and effectiveness of commissioning health research. The study described here was commissioned to evaluate this novel approach, addressing these key questions.

Methods
A naturalistic-experimental approach was combined with principles of action research. The different commissioning groups within the programme were randomly allocated to either the traditional face-to-face mode or the novel 'virtual' mode. Mainly qualitative data were gathered including observation of all (virtual and face-to-face) commissioning meetings; semi-structured interviews with a purposive sample of participants (n = 32/66); structured questionnaires and interviews with lead researchers of early commissioned projects. All members of the commissioning groups were invited to participate in collaborative enquiry groups which participated actively in the analysis process.

Results
The virtual process functioned as intended, reaching timely and relatively transparent decisions that participants had confidence in. Despite the potential for greater access using a virtual approach, few differences were found in practice. Key advantages included physical access, a more flexible and extended time period for discussion, reflection and information gathering and a more transparent decision-making process. Key challenges were the reduction of social cues available in a computer-mediated medium that require novel ways of ensuring appropriate dialogue, feedback and interaction. However, in both modes, the process was influenced by a range of factors and was not technology driven.

Conclusion
There is potential for using computer-mediated communication within the research commissioning process. This may enhance access, effectiveness and transparency of decision-making but further development is needed for this to be fully realised, including attention to process as well as the computer-mediated medium.
Analysis of bronchoalveolar lavage fluid proteome from systemic sclerosis patients with or without functional, clinical and radiological signs of lung fibrosis
Authors: Fietta AM , Bardoni AM , Salvini R , Passadore I , Morosini M , Cavagna L , Codullo V , Pozzi E , Meloni F , Montecucco C 
Published: October 2006

AbstractLung fibrosis is a major cause of mortality and morbidity in systemic sclerosis (SSc). However, its pathogenesis still needs to be elucidated. We examined whether the alteration of certain proteins in bronchoalveolar lavage fluid (BALF) might have a protective or a causative role in the lung fibrogenesis process. For this purpose we compared the BALF protein profile obtained from nine SSc patients with lung fibrosis (SScFib+) with that obtained from six SSc patients without pulmonary fibrosis (SScFib-) by two-dimensional gel electrophoresis (2-DE). Only spots and spot-trains that were consistently expressed in a different way in the two study groups were taken into consideration. In total, 47 spots and spot-trains, corresponding to 30 previously identified proteins in human BALF, showed no significant variation between SScFib+ patients and SScFib- patients, whereas 24 spots showed a reproducible significant variation in the two study groups. These latter spots corresponded to 11 proteins or protein fragments, including serum albumin fragments (13 spots), 5 previously recognized proteins (7 spots), and 4 proteins (3 spots) that had not been previously described in human BALF maps, namely calumenin, cytohesin-2, cystatin SN, and mitochondrial DNA topoisomerase 1 (mtDNA TOP1). Mass analysis did not determine one protein-spot. The two study groups revealed a significant difference in BALF protein composition. Whereas levels of glutathione S-transferase P (GSTP), Cu–Zn superoxide dismutase (SOD) and cystatin SN were downregulated in SScFib+ patients compared with SScFib- patients, we observed a significant upregulation of α1-acid glycoprotein, haptoglobin-α chain, calgranulin (Cal) B, cytohesin-2, calumenin, and mtDNA TOP1 in SScFib+ patients. Some of these proteins (GSTP, Cu–Zn SOD, and cystatin SN) seem to be involved in mechanisms that protect lungs against injury or inflammation, whereas others (Cal B, cytohesin-2, and calumenin) seem to be involved in mechanisms that drive lung fibrogenesis. Even if the 2-DE analysis of BALF did not provide an exhaustive identification of all BALF proteins, especially those of low molecular mass, it allows the identification of proteins that might have a role in lung fibrogenesis. Further longitudinal studies on larger cohorts of patients will be necessary to assess their usefulness as predictive markers of disease.
NF-κB is required for STAT-4 expression during dendritic cell maturation
Authors: Remoli Maria Elena , Ragimbeau Josiane , Giacomini Elena , Gafa Valerie , Severa Martina , Lande Roberto , Pellegrini Sandra , Coccia Eliana M 
Published: October 2006

AbstractThe transcription factor STAT-4 plays a pivotal role in the IL-12-mediated development of naive CD4+ T cells into the Th1 phenotype. Initially thought to be restricted to the lymphoid lineage, STAT-4 was subsequently shown to be expressed in the myeloid compartment, mainly in activated monocytes, macrophages, and dendritic cells (DC). Here, we have studied STAT-4 in human monocyte-derived DC, and we demonstrated that its expression can be induced by multiple stimuli, such as the ligands for TLR-4, TLR-2, and TLR-3, different pathogens, CD40 ligand, and the proinflammatory cytokines TNF-α and IL-1β. It is interesting that we found that STAT-4 is tyrosine-phosphorylated in response to type I IFN but not IL-12 in human mature DC. Cloning and functional analysis of the STAT-4 promoter showed that a NF-κB binding site, localized at –969/–959 bp upstream of the transcriptional start site, is involved in the regulation of this gene in primary human DC. EMSAs using a probe containing this NF-κB binding sequence and chromatin immunoprecipitation indicated that p65/p50 and p50/p50 dimers were the main NF-κB/Rel proteins involved in STAT-4 gene expression in maturing DC. The mutation of this κB site or the overexpression of the repressor IκBα exerted an inhibitory effect on a STAT-4 promoter-driven reporter as well as on STAT-4 expression. Altogether, these results indicate that STAT-4 can be finely tuned along with DC maturation through NF-κB activation and that its induction may be involved in preparing the DC to be receptive to the cytokine environment present in lymphoid organs.
Impact and Perceptions of Mandatory Tumor Biopsies for Correlative Studies in Clinical Trials of Novel Anticancer Agents
Authors: Agulnik Mark , Oza Amit M. , Pond Gregory R. , Siu Lillian L. 
Published: October 2006

Purpose To assess the impact and perceptions of patients, physicians, and institutional review board members (IRBs) on the issue of mandatory serial tumor biopsies to acquire tissues for correlative studies. Patients and Methods Complementary, self-administered questionnaires were circulated to trial patients who had previously undergone serial research-related biopsies (TPs), clinic patients who had prior diagnostic but not research-related biopsies (CPs), academic medical oncologists in Canada (MOs), and IRBs at the affiliated academic centers. Results Ten (72%) of 14 TPs, 265 (82%) of 325 CPs, 137 (66%) of 209 MOs, and 142 (49%) of 291 IRBs responded. A 5% to 10% risk of a major biopsy complication was acceptable to 22% of CPs but only to 1% of MOs or IRBs. Anxiety was reported by 30% of TPs and 45% of CPs before their biopsies. More than 82% of MOs or IRBs believed the average patient would have at least borderline anxiety before their biopsy. Among the patients, 84% would authorize their samples for additional unrelated research and 75% would agree to genetic testing. Nearly all MOs and 86% of IRBs considered it ethical to request for additional unrelated research testing. With respect to genetic testing, 82% of MOs and 72% of IRBs would request it. Conclusion Although nearly all MOs and IRBs see the value in the biopsy, their threshold for acceptable risk is lower and they anticipate more associated anxiety than patients. Most patients recalled a tendency to tolerate their biopsies well with an average associated anxiety, and would allow their specimens to be tested for research purposes.
Bone Sialoprotein Is Predictive of Bone Metastases in Resectable Non–Small-Cell Lung Cancer: A Retrospective Case-Control Study
Authors: Papotti Mauro , Kalebic Thea , Volante Marco , Chiusa Luigi , Bacillo Elisa , Cappia Susanna , Lausi Paolo , Novello Silvia , Borasio Piero , Scagliotti Giorgio V. 
Published: October 2006

PurposeBone metastases (BM) in non–small-cell lung cancer (NSCLC) may be detected at diagnosis or during the course of the disease, and are associated with a worse prognosis. Currently, there are no predictive or diagnostic markers to identify high-risk patients for metastatic bone dissemination.Patients and MethodsThirty patients with resected NSCLC who subsequently developed BM were matched for clinicopathologic parameters to 30 control patients with resected NSCLC without any metastases and 26 patients with resected NSCLC and non-BM lesions. Primary tumors were investigated by immunohistochemistry for 10 markers involved in bone resorption or development of metastases. Differences among groups were estimated by χ2test, whereas the prognostic impact of clinicopathologic parameters and marker expression was evaluated by univariate (Wilcoxon and Mantel-Cox tests) and multivariate (Cox proportional hazards regression model) analyses.ResultsThe presence of bone sialoprotein (BSP) was strongly associated with bone dissemination (P < .001) and, independently, with worse outcome (P = .02, Mantel-Cox test), as defined by overall survival. To evaluate BSP protein expression in nonselected NSCLC, a series of 120 consecutive resected lung carcinomas was added to the study, and BSP prevalence reached 40%. No other markers showed a statistically significant difference among the three groups or demonstrated a prognostic impact, in terms of both overall survival and time interval to metastases.ConclusionBSP protein expression in the primary resected NSCLC is strongly associated with BM progression and could be useful in identifying high-risk patients who could benefit from novel modalities of surveillance and preventive treatment.
An Anatomical Evaluation of the Mini-Supraorbital Approach and Comparison with Standard Craniotomies
Authors: Figueiredo Eberval G. , Deshmukh Vivek , Nakaji Peter , Deshmukh Pushpa , Crusius Marcelo U. , Crawford Neil , Spetzler Robert F. , Preul Mark C. 
Published: October 2006

Abstract

OBJECTIVE:
To compare anatomically the surgical exposure provided by pterional (PT), orbitozygomatic (OZ), and minisupraorbital (SO) craniotomies. @@METHODS:@@ Seven sides of six fixed cadaver heads injected with silicone were used. The mini-SO craniotomy followed by the PT and OZ approaches were performed sequentially. The bony flaps were attached with miniplates and screws, allowing easy conversion between the approaches. A frameless stereotactic device was used to calculate an area of surgical exposure and the angles of approach for six different anatomic targets. An image guidance system was used to demonstrate the limits of the surgical exposure for each technique.

RESULTS:
No significant differences were observed in the total area of surgical exposure when comparing the mini-SO (A = 1831.2 ± 415.3 mm2), PT (A = 1860.0 ± 617.2 mm2), and OZ approaches (A = 1843.3 ± 358.1 mm2; P &gt; 0.05). Angular exposure was greater for the OZ and PT approaches than for the mini-SO approach, either in the vertical and horizontal axes, considering all of the six targets studied (P&lt; 0.05). Except for the distal segment of the ipsilateral sylvian fissure, no practical differences in the limits of the exposure were detected.

CONCLUSION:
The mini-SO approach may offer a similar surgical working area compared with that provided by standard craniotomies and constitutes an excellent alternative to the OZ and PT craniotomies in selected patients. Selection should not be based primarily on the area to be exposed, but rather on the working angles that are anticipated to be required. The key point is to use the most adequate technique for a particular patient, rather than using a one-size-fits-all approach for all patients.
Endovascular Treatment of Spinal Cord Arteriovenous Malformations
Authors: Veznedaroglu Erol , Nelson Peter K. , Jabbour Pascal M. , Rosenwasser Robert H. 
Published: October 2006

Abstract
SPINAL CORD ARTERIOVENOUS malformations are rare lesions that represent one-tenth of the brain arteriovenous malformations. Depending on their location and relationship to the dura, these lesions are divided into four categories. Their clinical manifestations may vary from mild symptoms to severe motor deficits. Spinal angiography remains the “gold standard” for diagnosing spinal cord vascular lesions. Although the type of shunting remains difficult to determine by the magnetic resonance imaging, it is well analyzed by spinal angiography. The cure of the shunting is not by itself a therapeutic goal, but the objective is the creation of a new hemodynamic equilibrium between the lesion and the spinal cord to decrease the risk of hemorrhage and prevent the progression of the spinal cord ischemia. The endovascular tools seem to be a reasonable therapeutic option for the treatment of the majority of the spinal cord arteriovenous malformations.