bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of the Nlrp3 Inflammasome by Streptococcus pyogenes Requires Streptolysin O and NF-κB Activation but Proceeds Independently of TLR Signaling and P2X7 Receptor
Authors: Harder Jürgen , Franchi Luigi , Muñoz-Planillo Raúl , Park Jong-Hwan , Reimer Thornik , Núñez Gabriel 
Published: October 2009

Abstract
Macrophages play a crucial role in the innate immune response against the human pathogen Streptococcus pyogenes, yet the innate immune response against the bacterium is poorly characterized. In the present study, we show that caspase-1 activation and IL-1β secretion were induced by live, but not killed, S. pyogenes, and required expression of the pore-forming toxin streptolysin O. Using macrophages deficient in inflammasome components, we found that both NLR family pyrin domain-containing 3 (Nlrp3) and apoptosis-associated speck-like protein (Asc) were crucial for caspase-1 activation and IL-1β secretion, but dispensable for pro-IL-1β induction, in response to S. pyogenes infection. Conversely, macrophages deficient in the essential TLR adaptors Myd88 and Trif showed normal activation of caspase-1, but impaired induction of pro-IL-1β and secretion of IL-1β. Notably, activation of caspase-1 by TLR2 and TLR4 ligands in the presence of streptolysin O required Myd88/Trif, whereas that induced by S. pyogenes was blocked by inhibition of NF-κB. Unlike activation of the Nlrp3 inflammasome by TLR ligands, the induction of caspase-1 activation by S. pyogenes did not require exogenous ATP or the P2X7R. In vivo experiments revealed that Nlrp3 was critical for the production of IL-1β but was not important for survival in a mouse model of S. pyogenes peritoneal infection. These results indicate that caspase-1 activation in response to S. pyogenes infection requires NF-κB and the virulence factor streptolysin O, but proceeds independently of P2X7R and TLR signaling.
Helminth Antigens Modulate Immune Responses in Cells from Multiple Sclerosis Patients through TLR2-Dependent Mechanisms
Authors: Correale Jorge , Farez Mauricio 
Published: October 2009

Abstract
To better understand the link between parasite infections and the course of multiple sclerosis (MS), we studied the role of TLRs in helminth product recognition by dendritic cells (DCs) and B cells. Baseline expression of TLR2 was significantly higher in infected-MS patients compared with uninfected MS subjects or healthy controls. Moreover, cells exposed to TLR2 agonists or to soluble egg Ag (SEA) from Schistosoma mansoni resulted in significant TLR2 up-regulation. SEA suppressed the LPS-induced DCs production of IL-1β, IL-6, IL-12, and TNF-α and enhanced TGF-β as well as IL-10 production. Similarly, after exposure to SEA, anti-CD40-activated B cells increased IL-10 production. Both processes were MyD88 dependent. In addition, SEA down-regulated the expression of LPS-induced costimulatory molecules on DCs in a MyD88-independent manner. DCs stimulation by SEA and TLR2 agonists induced increasing phosphorylation of the MAPK ERK1/2. Neither stimulus showed an effect on p38 and JNK1/2 phosphorylation, however. Addition of the ERK1/2 inhibitor U0126 was associated with dose-dependent inhibition of IL-10 and reciprocal enhancement of IL-12. Finally, cytokine effects and changes observed in DCs costimulatory molecule expression after SEA exposure were lost when TLR2 expression was silenced. Overall, these findings indicate that helminth molecules exert potent regulatory effects on both DCs and B cells through TLR2 regulation conducted via different signaling pathways. This knowledge could prove critical in developing novel therapeutic approaches for the treatment of autoimmune diseases such as MS.
Reducing Epitope Spread during Affinity Maturation of an Anti-Ganglioside GD2 Antibody
Authors: Hu Jian , Huang Xiaodong , Ling Chang-Chun , Bundle David R. , Cheung Nai-Kong V. 
Published: October 2009

Abstract
Ab affinity maturation in vivo is always accompanied by negative selection to maintain Ag specificity. In contrast, in vitro affinity maturation can lead to epitope spread, resulting in loss of specificity. Anti-ganglioside-GD2 mAbs are clinically effective against neuroblastoma; pain and neuropathy are major side effects. We used structural relatives of GD2 to define epitope spread during in vitro affinity maturation of an anti-GD2 single-chain variable fragment (scFv) called 5F11-scFv. Clonal dominance identified by polyclonal sequencing was confirmed by analyzing individual clones. Affinity-matured mutations were introduced into scFv-streptavidin for functional studies. Without a negative selector, 19-fold affinity improvement (clone Q, where Q is the symbol for glutamine) was associated with strong cross-reactivity with GM2 and GD1b and moderate cross-reactivity with GD3, resulting in positive immunohistochemical staining of all 13 non-neural normal human tissues, in contrast to none of 13 tissues with parental clone P. With GM2 as a negative selector, clone Y (where Y is the symbol for tyrosine) was generated with only weak cross-reactivity with GD1b, adrenal and thyroid glands, and no staining of other non-neural normal tissues. Even though there was only a 3-fold affinity improvement, clone Y showed significantly higher tumor uptake over parental clone P (134%, p = 0.04), whereas clone Q was inferior (54% of clone P; p = 0.05) as confirmed by tumor-to-normal tissue ratios across 16 organs (41% of clone P; p &lt; 0.0001). Using the less efficient negative selector GD3, a clone mixture (Q, V, and Y, where V is the symbol for valine) emerged. We conclude that epitope spread during affinity maturation can be reduced by negative selection. Furthermore, efficiency of the negative selector depends on its cross-reactive affinity with the matured scFv.
IL-17/Th17 Promotes Type 1 T Cell Immunity against Pulmonary Intracellular Bacterial Infection through Modulating Dendritic Cell Function
Authors: Bai Hong , Cheng Jianjun , Gao Xiaoling , Joyee Antony George , Fan Yijun , Wang Shuhe , Jiao Lei , Yao Zhi , Yang Xi 
Published: October 2009

Abstract
Although their contribution to host defense against extracellular infections has been well defined, IL-17 and Th17 are generally thought to have limited impact on intracellular infections. In this study, we investigated the role and mechanisms of IL-17/Th17 in host defense against Chlamydia muridarum, an obligate intracellular bacterium, lung infection. Our data showed rapid increase in IL-17 production and expansion of Th17 cells following C. muridarum infection and significant detrimental impact of in vivo IL-17 neutralization by anti-IL-17 mAb on disease course, immune response, and dendritic cell (DC) function. Specifically, IL-17-neutralized mice exhibited significantly greater body weight loss, higher organism growth, and much more severe pathological changes in the lung compared with sham-treated control mice. Immunological analysis showed that IL-17 neutralization significantly reduced Chlamydia-specific Th1 responses, but increased Th2 responses. Interestingly, the DC isolated from IL-17-neutralized mice showed lower CD40 and MHC II expression and IL-12 production, but higher IL-10 production compared with those from sham-treated mice. In two DC-T cell coculture systems, DC isolated from IL-17-neutralized mice induced higher IL-4, but lower IFN-γ production by Ag-specific T cells than those from sham-treated mice in cell priming and reaction settings. Adoptive transfer of DC isolated from IL-17-neutralized mice, unlike those from sham-treated mice, failed to protect the recipients against challenge infection. These findings provide in vivo evidence that IL-17/Th17 plays an important role in host defense against intracellular bacterial infection, and suggest that IL-17/Th17 can promote type 1 T cell immunity through modulating DC function.
Cognitive assessment of children with acute lymphoblastic leukemia: Preliminary findings
Authors: Abraham Anna , Appaji L 
Published: October 2009

Abstract
Aim:The objective of this study was to assess the cognitive functions of Indian children with acute lymphoblastic leukemia (ALL), periodically after initiation of treatment since prospective longitudinal research in this area on the Indian population has not been adequately documented. Unlike many western studies that have targeted survivors of ALL, we aimed to bring out the cognitive outcome after initiation of treatment.Materials and Methods:The cognitive functions of 19 patients diagnosed to have ALL were assessed using standardized tests after induction chemotherapy, and periodically thereafter following the second course of treatment comprising central nervous system-directed radiotherapy, and chemotherapy using intrathecal methotrexate.Results:The study found a statistically significant decline in the intelligence quotient and a deficit in the cognitive function of analytical reasoning.Conclusion:This preliminary study supports findings of an earlier Indian study and many studies conducted in the west. Since the life expectancy of these children has increased and most of them have long-term survival, and even cure, we suggest that identifying and managing children with cognitive difficulties are important in the rehabilitation of these children.
Primary pancreatic lymphoma: Report of three cases with review of literature
Authors: Haji Altaf Gauhar , Sharma Shekhar , Majeed K Abdul , Vijaykumar D K , Pavithran K , Dinesh M 
Published: October 2009

Abstract
Background:Primary pancreatic lymphoma (PPL) is an extremely rare neoplasm, which may be confused with pancreatic adenocarcinoma. So far only about 150 cases of PPL have been reported.Materials and Methods:We present our experience of 3 cases of PPL over a 4-year period.Results:All the patients presented with vague abdominal pain of duration ranging from 1½ months to 3 months. Two patients had diagnosis confirmed histologically by CT-guided core biopsy or Fine needle aspiration procedure. We were able to avoid unnecessary laparotomy in 2 patients using preoperative guided Fine needle aspiration Cytology, although the third patient did undergo a Whipple′s procedure as the diagnosis of PPL was not considered during the initial workup.Conclusions:There is no significant difference noted with regard to patient′s age or duration of symptoms between patients with either pancreatic adenocarcinoma or PPL. The differential diagnosis of PPL includes pancreatic adenocarcinoma and secondary involvement of pancreas from extra-nodal lymphoma. Combination of two things is suggestive of Pancreatic lymphoma: (1) Bulky localized tumor in pancreatic head (2) Absence of significant dilatation of main pancreatic duct strengthens a diagnosis of pancreatic lymphoma over adenocarcinoma. Majority of patients can be managed with chemotherapy with much better prognosis compared to patients with pancreatic adenocarcinoma. Larger series of patients are needed to evaluate whether chemotherapy, eventually followed by involved-field radiation therapy, is the treatment of choice for PPL.
Primary mammary small-cell carcinoma: A case report and review of the literature
Authors: Haji Altaf Gauhar , Sharma Shekhar , Vijaykumar D K , Mukherjee Poulome , Babu R , Chitrathara K 
Published: October 2009

AbstractOnly a few cases of primary small-cell carcinoma of the breast have been documented in the current medical literature. A confident diagnosis can only be made if a nonmammary site is excluded or if an in-situ component can be demonstrated histologically. These criteria have been met only in a very few of the published cases, including this case report. We describe a case of a 68-year-old lady with left breast lump, which was diagnosed as breast cancer on fine-needle aspiration and core biopsy. Metastatic workup was negative for disease elsewhere, and she received 3 cycles of neoadjuvant chemotherapy followed by surgery (modified radical mastectomy). However, the disease behaved very aggressively in the postoperative period. There is a lack of consensus regarding the management of the primary tumor. Present surgical treatment options are similar to those in cases of invasive ductal breast cancer, as appropriate for the size and stage of the lesion. A review of current literature on his rare entity is also presented.
Carcinoma in situ of true vocal cord in a nonsmoker adolescent female
Authors: Mondal Dodul , Kundu Sayan , Chattopadhyay Subrata , De Sumitava , Dastidar A Ghosh , Roy Amitabha 
Published: October 2009

AbstractCarcinoma in situ (precancerous lesion) of true vocal cord in a nonsmoker adolescent female without any history of prior neck irradiation is rare. A 16-year-old female patient without any of the known risk factors presented with history of gradual-onset hoarseness of voice unrelieved by symptomatic treatments for 1 year. Contrast-enhanced CT scan of neck and laryngoscopy and histopathology of the tissue from irregular lesions along the medial margin of the left vocal cord diagnosed it as a case of carcinoma in situ of vocal cord. Absence of known risk factors and very young age of the patient made this case a rarity and hence the case is being reported.
Spontaneous Current Oscillations during Hard Anodization of Aluminum under Potentiostatic Conditions
Authors: Lee Woo , Kim Jae‐Cheon , Gösele Ulrich 
Published: October 2009

AbstractNanoporous anodic aluminum oxide is prepared by hard anodization of aluminum under potentiostatic conditions using 0.3 M H2C2O4. Under unstirred electrolyte condition, spontaneous current oscillations are observed. The amplitude and period of these current oscillations are observed to increase with anodization time. As a consequence of the oscillatory behavior, the resulting anodic alumina exhibits modulated pore structures, in which the diameter contrast and the length of pore modulation increase with the amplitude and the period of current oscillations, respectively, and the current peak profile determines the internal geometry of oxide nanopores. The mechanism responsible for the oscillatory behavior is suggested to be a diffusion‐controlled anodic oxidation of aluminum.
Customized Electronic Coupling in Self‐Assembled Donor–Acceptor Nanostructures
Authors: de Oteyza Dimas G. , García‐Lastra Juan M. , Corso Martina , Doyle Bryan P. , Floreano Luca , Morgante Alberto , Wakayama Yutaka , Rubio Angel , Ortega J. Enrique 
Published: October 2009

AbstractCharge transfer processes between donor–acceptor complexes and metallic electrodes are at the heart of novel organic optoelectronic devices such as solar cells. Here, a combined approach of surface‐sensitive microscopy, synchrotron radiation spectroscopy, and state‐of‐the‐art ab initio calculations is used to demonstrate the delicate balance that exists between intermolecular and molecule–substrate interactions, hybridization, and charge transfer in model donor–acceptor assemblies at metal‐organic interfaces. It is shown that charge transfer and chemical properties of interfaces based on single component layers cannot be naively extrapolated to binary donor–acceptor assemblies. In particular, studying the self‐assembly of supramolecular nanostructures on Cu(111), composed of fluorinated copper‐phthalocyanines (F16CuPc) and diindenoperylene (DIP), it is found that, in reference to the associated single component layers, the donor (DIP) decouples electronically from the metal surface, while the acceptor (F16CuPc) suffers strong hybridization with the substrate.
Novel microfibrous‐structured silver catalyst for high efficiency gas‐phase oxidation of alcohols
Authors: Mao Jiping , Deng Miaomiao , Chen Li , Liu Ye , Lu Yong 
Published: October 2009

AbstractNovel microfibrous‐structured silver catalysts were developed for gas‐phase selective oxidation of mono‐/aromatic‐/di‐alcohols. Sinter‐locked three‐dimensional microfibrous networks consisting of 5 vol % 8‐μm‐Ni (or 12‐μm‐SS‐316L) fibers and 95 vol % void volume were built up by the papermaking/sintering processes. Silver was then deposited onto the surface of the sinter‐locked fibers by incipient wetness impregnation method. At relatively low temperatures (e.g., 380°C), the microfibrous‐structured silver catalysts provided quite higher activity/selectivity compared to the electrolytic silver. The microfibrous Ag/Ni‐fiber offered much better low‐temperature activity than the Ag/SS‐fiber. The interaction at Ag particles and Ni‐fiber interface not only visibly increased the active/selective sites of Ag+ ions and Agnδ+ clusters but also significantly promoted their low‐temperature reducibility and ability for O2 activation. In addition, the microfibrous structure provided a unique combination of large void volume, entirely open structure, high thermal conductivity and high permeability. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Proinflammatory phenotype with imbalance of KLF2 and RelA: Risk of childhood stroke with sickle cell anemia
Authors: Enenstein Judy , Milbauer Liming , Domingo Evidio , Wells Alexandra , Roney Mark , Kiley Jim , Wei Peng , Hebbel Robert P. 
Published: October 2009

AbstractAltered inflammation signaling within the cerebral vasculature may be an important risk factor for stroke in children with sickle cell anemia (SCA). This study examines how differential expression of NFκB/p65 (RelA), KLF2, and other transcription factors may act as switches in inflammation signaling leading to observed differences between non‐SCA (NS) African Americans and African Americans with SCA who are either at risk (AR) or not at risk (NAR) of childhood stroke based on occurrence of Circle of Willis disease. Clover/Transfac analysis was used to identify overrepresented transcription factor binding motifs on genes associated with inflammation. Transcription factor binding motifs for the NFκB family and RFX1 were overrepresented on inflammation signaling gene set analysis. Variations in protein expression were determined by flow cytometry of blood outgrowth endothelial cells (BOECs) from NS, AR, and NAR donors and Western blots of protein extracts from both unstimulated and TNFα/IL1β‐stimulated BOECs. BOECs from patients with SCA had more cytoplasmic‐derived RelA compared with NS BOECs. Sickle BOECs also had heightened responses to inflammatory stimuli compared with NS BOECs, as shown by increased nuclear RelA, and intracellular adhesion molecule (ICAM) response to TNFα/IL1β stimulation. Multiple control points in RelA signaling were associated with risk of childhood stroke. The ratio of proinflammatory factor RelA to anti‐inflammatory factor KLF2 was greater in BOECs from AR donors than NS donors. Group risk of childhood stroke with SCA was greatest among individuals who exhibited increased expression of proinflammatory transcription factors and decreased expression of transcription factors that suppress inflammation. Am. J. Hematol. 2010. © 2009 Wiley‐Liss, Inc.
Workers are people too: Societal aspects of occupational health disparities—an ecosocial perspective
Authors: Krieger Nancy 
Published: October 2009

AbstractWorkers are people too. What else is new? This seemingly self‐evident proposition, however, takes on new meaning when considering the challenging and deeply important issue of occupational health disparities—the topic that is the focus of 12 articles in this special issue of theAmerican Journal of Industrial Medicine. In this commentary, I highlight some of the myriad ways that societal determinants of health intertwine with each and every aspect of occupation‐related health inequities, as analyzed from an ecosocial perspective. The engagement extends from basic surveillance to etiologic research, from conceptualization and measurement of variables to analysis and interpretation of data, from causal inference to preventive action, and from the political economy of work to the political economy of health. A basic point is that who is employed (or not) in what kinds of jobs, with what kinds of exposures, what kinds of treatment, and what kinds of job stability, benefits, and pay—as well as what evidence exists about these conditions and what action is taken to address them—depends on societal context. At issue are diverse aspects of people's social location within their societies, in relation to their jointly experienced—and embodied—realities of socioeconomic position, race/ethnicity, nationality, nativity, immigration and citizen status, age, gender, and sexuality, among others. Reviewing the papers' findings, I discuss the scientific and real‐world action challenges they pose. Recommendations include better conceptualization and measurement of socioeconomic position and race/ethnicity and also use of the health and human rights framework to further the public health mission of ensuring the conditions that enable people—including workers—to live healthy and dignified lives. Am. J. Ind. Med. 53:104–115 2010. © 2009 Wiley‐Liss, Inc.
New route to synthesis of PVP‐stabilized palladium(0) nanoclusters and their enhanced catalytic activity in Heck and Suzuki cross‐coupling reactions
Authors: Durap Feyyaz , Metin Önder , Aydemir Murat , Özkar Saim 
Published: October 2009

AbstractHerein we report a new method for the synthesis and characterization of PVP‐stabilized palladium(0) nanoclusters and their enhanced catalytic activity in Suzuki coupling and Heck reactions of aryl bromides with phenylboronic acid and styrene, respectively, under mild conditions. The PVP‐stabilized palladium(0) nanoclusters with a particle size of 4.5 ± 1.1 nm were prepared using a new method: refluxing a mixture of potassium tetrachloropalladate(II) and PVP in methanol at 80 °C for 1 h followed by reduction with sodium borohydride. Palladium(0) nanoclusters prepared in this way were stable in solution for weeks, could be isolated as solid materials and were characterized by TEM, XPS, UV–vis, and XRD techniques. The PVP‐stabilized palladium(0) nanoclusters were active catalysts in Heck and Suzuki coupling reactions of arylbromides with styrene and phenylboronic acid affording stilbenes and biphenyls, respectively, in high yield. Recycling experiments showed that PVP‐stabilized palladium(0) nanoclusters could be used five times with essentially no loss in activity in the Heck and Suzuki coupling reactions. Copyright © 2009 John Wiley & Sons, Ltd.
Access to scientific literature in India
Authors: Gaulé Patrick 
Published: October 2009

AbstractThis article uses an evidence‐based approach to assess the difficulties faced by developing country scientists in accessing scientific literature. I compare the backward citation patterns of Swiss and Indian scientists in a database of 43,150 scientific papers published by scientists from either country in 2007. Controlling for fields and quality with citing journal fixed effects, I find that Indian scientists have shorter reference lists (−6%) and are more likely to cite articles from open access journals (+50%). Moreover, the difference in the length of the reference list is more pronounced in biology and medicine, where circulation of (free) preprints and conference proceedings is non‐existent. Informal file‐sharing practices among scientists mitigate the effects of access restrictions.