bluuebunny/crossref_metadata_2025 huggingface dataset:
Three New Compounds from Aspergillus terreus PT06-2 Grown in a High Salt Medium
Authors: Wang Yi , Zheng Jinkai , Liu Peipei , Wang Wei , Zhu Weiming
Published: August 2011

To investigate the structurally novel and bioactive natural compounds from marine-derived microorganisms under high salinity, the fungus Aspergillus terreus PT06-2 was isolated from the sediment of the Putian Sea Saltern, Fujian, China. Three new compounds, terremides A (1) and B (2) and terrelactone A (3), along with twelve known compounds (4–15) were isolated and identified from the fermentation broth of A. terreus PT06-2 at 10% salinity. Among these metabolites, compounds 4 and 15 only produced in the 10% salinity culture, were identified as methyl 3,4,5-trimethoxy-2-(2-(nicotinamido) benzamido) benzoate, and (+)-terrein, respectively. The new compounds 1 and 2 exhibited antibacterial activity against Pseudomonas aeruginosa and Enterobacter aerogenes with MIC values of 63.9 and 33.5 μM, respectively. Compounds 5 showed moderate anti-H1N1 activity and lower cytotoxicity with IC50 and CC50 values of and 143.1 and 976.4 μM, respectively.
Diversity and Antibacterial Activities of Fungi Derived from the Gorgonian Echinogorgia rebekka from the South China Sea
Authors: Wang Ya-Nan , Shao Chang-Lun , Zheng Cai-Juan , Chen Yi-Yan , Wang Chang-Yun
Published: August 2011

The diversity of symbiotic fungi associated with the gorgonian coral Echinogorgia rebekka from the Weizhou coral reef in the South China Sea was investigated. Combined with morphologic traits, ITS-rDNA sequences revealed 18 fungal strains from this gorgonian. All of the 18 fungi belonged to the phylum Ascomycota and were distributed among seven genera in five orders: Eurotiales (Aspergillus and Penicillium), Pleosporales (Alternaria), Capnodiales (Cladosporium), Trichosphaeriales (Nigrospora) and Hypocreales (Hypocrea and Nectria). Antibacterial activities of these fungal strains were investigated with five pathogenic bacteria. All of the 18 fungal strains displayed different levels of antibacterial activities, most of which exhibited moderate to high antibacterial activities to the Gram-positive pathogens Staphylococcus aureus and Micrococcus tetragenus, and showed relatively low bioactivities to other three pathogenic bacteria. Several fungal strains in the genera Penicillium and Cladosporium with strong antibacterial activities provide potential for further research on isolation of bioactive secondary metabolites.
Identification of the Antibacterial Compound Produced by the Marine Epiphytic Bacterium Pseudovibrio sp. D323 and Related Sponge-Associated Bacteria
Authors: Penesyan Anahit , Tebben Jan , Lee Matthew , Thomas Torsten , Kjelleberg Staffan , Harder Tilmann , Egan Suhelen
Published: August 2011

Surface-associated marine bacteria often produce secondary metabolites with antagonistic activities. In this study, tropodithietic acid (TDA) was identified to be responsible for the antibacterial activity of the marine epiphytic bacterium Pseudovibrio sp. D323 and related strains. Phenol was also produced by these bacteria but was not directly related to the antibacterial activity. TDA was shown to effectively inhibit a range of marine bacteria from various phylogenetic groups. However TDA-producers themselves were resistant and are likely to possess resistance mechanism preventing autoinhibition. We propose that TDA in isolate D323 and related eukaryote-associated bacteria plays a role in defending the host organism against unwanted microbial colonisation and, possibly, bacterial pathogens.
High Functionalization of 5-Nitro-1H-imidazole Derivatives: The TDAE Approach
Authors: Juspin Thierry , Zink Laura , Crozet Maxime D. , Terme Thierry , Vanelle Patrice
Published: August 2011

We report herein the synthesis of substituted 2-[4-(1,2-dimethyl-5-nitro-1H-imidazol-4-yl)phenyl]-1-arylethanols, ethyl 3-[4-(1,2-dimethyl-5-nitro-1H-imidazol-4-yl)-phenyl]-2-hydroxypropanoate and 2-[4-(1,2-dimethyl-5-nitro-1H-imidazol-4-yl)benzyl]-2-hydroxy-acenaphthylen-1(2H)-one from the reactions of 4-[4-(chloromethyl)phenyl]-1,2-dimethyl-5-nitro-1H-imidazole with various aromatic carbonyl and a-carbonyl ester derivatives using tetrakis(dimethylamino)ethylene (TDAE) methodology.
Synthesis of Quinoxaline 1,4-di-N-Oxide Analogues and Crystal Structure of 2-Carbomethoxy-3-hydroxyquinoxaline-di-N-oxide
Authors: Xu Yingjun , Wu Fanhong , Yao Zhiyi , Zhang Minmin , Jiang Sheng
Published: August 2011

A series of quinoxaline 1,4-di-N-oxide analogues were prepared from benzofurazan N-oxide derivatives and β-diketone ester compounds by the improved Beirut reaction. The structures of the target products were characterized by NMR, MS, IR and elemental analysis measurements, and that of 2-carbomethoxy-3-hydroxyquinoxaline- di-N-oxide was further confirmed by single-crystal X-ray diffraction. Its crystal structure belongs to the monoclinic system, space group C2/c with a = 14.4320 (12) Å, b = 10.7514 (9) Å, c = 13.2728 (11) Å, V = 1958.5 (3) Å 3, Z = 8. The X-ray crystallographic analysis reveals that quinoxaline 1,4-di-N-oxide displays acyloin-endiol tautomerism.
Activity and Export of Engineered Nisin-(1-22) Analogs
Authors: Plat Annechien , Kuipers Anneke , Lange Jacobien G. de , Moll Gert N. , Rink Rick
Published: August 2011

The pentacyclic peptide antibiotic nisin, produced by Lactococcus lactis is ubiquitously applied as a food preservative. We previously demonstrated that the truncated nisin-(1-22) has only 10-fold lower activity than nisin. Here we aimed at further developing this tricyclic nisin analog to reach activity comparable to that of nisin. Our data demonstrate that: (1) ring A has a large mutational freedom; (2) the composition of residues 20–22 strongly affects production levels of nisin-(1-22); (3) a positively charged C-terminus of nisin-(1-22) significantly enhances its antimicrobial activity; (4) nisin-(1-22) inhibits in vitro growth of a target strain using different dynamics than nisin.
Scientific Report: Highlights of 24th ICAR, 8–11 May 2011, Sofia, Bulgaria
Authors: Hodge Anthony Vere
Published: August 2011

The 24th ICAR meeting was held in Sofia, Bulgaria, 8–11 May 2011. This report summarizes the presentations by the ICAR award winners, Earl Kern and Brian Gowen; the keynote address by Albert (ADME) Osterhaus; the Plenary lectures by Raina Fichorova, Ralf Bartenschlager and Esteban Domingo; the invited speakers for the symposia; and a few of those by contributors.

This report aims to reflect the diversity of topics across different disciplines (chemistry to biology) discussed at ICAR: old viruses (smallpox), emerging viruses (SARS, new strains of influenza and flaviviruses), problematic viruses (HIV and HCV), sporadic viruses (arenaviruses), neglected viruses (enteroviruses), new research targets (for HCV) and new approaches (lethal mutagenesis). There were timely reports on promising compounds against adenoviruses, cytomegalovirus, HCV and HIV in clinical trials. This conference illuminated the constantly evolving field of antiviral chemotherapy by providing a forum to present and discuss new antiviral compounds, new uses for old compounds and exciting clinical results. This ICAR was a fitting testament to the ‘father of antiviral chemotherapy’, Bill Prusoff, who died aged 90 in April 2011.
A case series and review of sporotrichosis in Sikkim
Authors: Bhutia Pema Yoden , Gurung Shrijana , Yegneswaran Prakash Peralam , Pradhan Jagat , Pradhan Uttam , Peggy Tshering , Pradhan Prakash Kumar , Bhutia Chewang Doma
Published: August 2011

Sporotrichosis caused by the fungus Sporothrix schenckii has been widely reported from the northern Himalayan belt and the north eastern region of India. Three autochthonous cases of lymphocutaneous sporotrichosis from east and south districts of Sikkim are reported. Fluid aspirate from the nodulo-ulcerative lesions were sent for cytology and fungal culture. S. schenckii was isolated on culture and cytological examination in all three cases showed granulomatous reaction. Thermal dimorphism was demonstrated and animal pathogenicity testing was performed. Saturated solution of potassium iodide was used for treatment and the last case was treated with itraconazole and potassium iodide. Awareness of this disease and an extensive environmental study is required to understand the actual burden of this disease.
Cytomegalovirus infection in non-immunosuppressed critically ill patients
Authors: Jain Manisha , Duggal Shalini , Chugh Tulsi Das
Published: August 2011

Cytomegalovirus (CMV) is an important and common cause of mortality and morbidity in immunocompromised patients such as those with HIV/AIDS, transplant recipients on immunosuppressive therapy, and malignant hematological disease. After primary infection with CMV the virus becomes latent in multiple organs and can later be reactivated during severe dysregulation of the immune system. A large population carry dormant virus and are thus at risk for reactivation. However, reactivation of CMV has been reported in "non-immunosuppressed patients" such as severe trauma, sepsis, shock, burns, cirrhosis and other critically ill patients lying in the intensive care units. Therefore, the intensivists are increasingly facing a dilemma of identifying such patients to treat and there is a debate if there is a scientific justification for prophylaxis in such immunocompetent patients.
Genital tract group B streptococcal colonization in pregnant women: a South Indian perspective
Authors: Sharmila Vijayan , Joseph Noyal Mariya , Arun Babu Thirunavukkarasu , Chaturvedula Latha , Sistla Sujatha
Published: August 2011

Introduction: During the last few decades, group B Streptococcus (GBS) has emerged as an important pathogen. The major reservoirs for GBS are the vagina and the peri-anal regions/rectum, and the colonization of these regions is a risk factor for subsequent infection in pregnant women and newborns. Methodology: A prospective study was performed to determine the prevalence of GBS colonization in the vagina and rectum of pregnant women and the antibiotic susceptibility pattern of the isolates. We also aimed to identify risk factors associated with GBS colonization. The vaginal and rectal swabs were inoculated in Todd-Hewitt broth and later subcultured on blood agar for isolation of GBS. Results: A total of 300 pregnant women were enrolled in the study. GBS strains were isolated from seven out of 300 patients, corresponding to a colonization rate of 2.3%. Of the seven patients carrying GBS, isolates were cultured only from vaginal swabs in two cases (28.6%), only from rectal swabs in two cases (28.6%) from both vaginal and rectal swabs in three cases (42.9%). Heavy colonization was present only in 42.9% (3/7) of antenatal women. None of the seven isolates were resistant to penicillin or clindamycin, while one isolate (14.3%) was resistant to erythromycin and five isolates (71.4%) were resistant to tetracycline. Multigravid women and those with previous spontaneous abortion were more frequently colonized by GBS. Conclusion: The GBS colonization rate in our study was low. No resistance to penicillin or clindamycin was seen, while the majority of the isolates were resistant to tetracycline.
Community-associated methicillin-resistant Staphylococcus aureus infections in a pediatric intensive care unit
Authors: Menif Khaled , Bouziri Asma , Khaldi Ammar , Hamdi Asma , Belhadj Sarra , Borgi Aida , Fitouri Zahra , Ben Jaballah Najla
Published: August 2011

Introduction: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection is an increasing problem worldwide. In developing countries, there is little data on CA-MRSA infection in children. This study reviewed the clinical features and outcomes of children admitted in a Tunisian pediatric intensive care unit with severe CA-MRSA infections. Methodology: Retrospective chart review of patients coded for CA-MRSA over 10 years. Results: There were 14 (0.32% of all admissions) patients identified with severe CA-MRSA infections. The median age was three months (range, 0.5-156 months). All patients had pulmonary involvement. Six children (42.8%) developed septic shock. Two (14.3%) patients had multifocal infection with deep venous thrombosis. Two (14.3%) patients died. Conclusions: Severe CA-MRSA pneumonia dominated presentation. The mortality of CA-MRSA infection in our series is lower than that previously reported.
First-Year Experience of Chemotherapy for Advanced Retinoblastoma in Tanzania: Disease Profile, Outcomes, and Challenges in 2008
Authors: Carrim Zia I. , Kajaige Jane , Bowman Richard J. , Lavy Tim E. , Scanlan Patricia
Published: August 2011

Purpose:

To examine the profile of retinoblastoma in a national tertiary referral center in Tanzania and to report first-year outcomes of its treatment using chemotherapy.

Methods:

All patients with retinoblastoma referred in 2008 were included. Disease was classified on clinical grounds as ocular, orbital, or metastatic. Those with ocular and orbital disease received chemotherapy. Remission was the main outcome measure and defined as absence of disease at the end of treatment.

Results:

In 2008, 37 patients (20 males and 17 females) with retinoblastoma were referred to Ocean Road Cancer Institute. The mean delay from the first sign of disease to presentation at hospital was 10.4 ± 8.7 months. Disease was ocular in 32% (12 of 37), orbital in 57% (21 of 37), and metastatic in 11% (4 of 37). Of those with ocular disease, 67% (8 of 12) completed chemotherapy and all (8 of 8) achieved remission. In contrast, 48% (10 of 21) with orbital disease completed chemotherapy and only 50% (5 of 10) achieved remission. The difference in outcome between the groups was statistically significant (
P
= .001, Fisher exact test).

Conclusion:

The profile of retinoblastoma in Tanzania is skewed toward severe invasive disease. Despite the introduction of chemotherapy, further improvements in mortality and morbidity can only be achieved through emphasis on early detection.
Visual Field Constriction With Relatively Preserved Central Vision: An Unusual Case of Early-Onset Retinal Dystrophy
Authors: Heng Sijie , McCulloch Daphne L. , Dutton Gordon N.
Published: August 2011

The authors report a case of visual field constriction with relatively preserved central visual acuity caused by early-onset retinal dystrophy in a 17-year-old girl. Although uncommon, such a phenomenon associated with Leber’s congenital amaurosis, retinitis pigmentosa, and related diseases should be considered in early-onset visual field constriction.
MAPK Kinase 3 Specifically Regulates FcεRI-Mediated IL-4 Production by Mast Cells
Authors: MacNeil Adam J. , Yang Yong Jun , Lin Tong-Jun
Published: August 2011

Mast cells play a central role in allergic inflammation and are activated through cross-linking of FcεRI receptor-bound IgE, initiating a signaling cascade resulting in production of biologically potent mediators. Signaling pathways in the regulation of specific mediators remain incompletely defined. In this study, we examined the role of MAPK kinase 3 (MKK3) in IgE-dependent mast cell activation. In an in vivo model of passive cutaneous anaphylaxis, MKK3-deficient mice showed a deficit in late-phase IgE-dependent inflammation. To characterize the mechanism of this deficiency, we cultured bone marrow-derived mast cells (BMMCs) from wild-type and MKK3-deficient mice. We found that FcεRI-mediated mast cell activation induced rapid MKK3 phosphorylation by 5 min, diminishing slowly after 6 h. In MKK3-deficient BMMCs, phosphorylation of p38 was reduced at early and later time points. Among 40 cytokines tested using a protein array, IL-4 was the only cytokine specifically downregulated in MKK3-deficient BMMCs. Reduced IL-4 expression was seen in the local skin of MKK3-deficient mice following passive cutaneous allergic reaction. Furthermore, early growth response-1 (Egr1) bound to the promoter of IL-4 in FcεRI-activated mast cells, and Egr1 transcription factor activity was diminished in MKK3-deficient BMMCs. Finally, mast cell-deficient mice reconstituted with MKK3-deficient BMMCs displayed a significantly impaired late-phase allergic inflammatory response. Thus, mast cell MKK3 signaling contributes to IgE-dependent allergic inflammation and is a specific regulator of FcεRI-induced IL-4 production.
Species-Specific Determinants in the IgG CH3 Domain Enable Fab-Arm Exchange by Affecting the Noncovalent CH3–CH3 Interaction Strength
Authors: Labrijn Aran F. , Rispens Theo , Meesters Joyce , Rose Rebecca J. , den Bleker Tamara H. , Loverix Stefan , van den Bremer Ewald T. J. , Neijssen Joost , Vink Tom , Lasters Ignace , Aalberse Rob C. , Heck Albert J. R. , van de Winkel Jan G. J. , Schuurman Janine , Parren Paul W. H. I.
Published: August 2011

A distinctive feature of human IgG4 is its ability to recombine half molecules (H chain and attached L chain) through a dynamic process termed Fab-arm exchange, which results in bispecific Abs. It is becoming evident that the process of Fab-arm exchange is conserved in several mammalian species, and thereby represents a mechanism that impacts humoral immunity more generally than previously thought. In humans, Fab-arm exchange has been attributed to the IgG4 core-hinge sequence (226-CPSCP-230) in combination with unknown determinants in the third constant H chain domain (CH3). In this study, we investigated the role of the CH3 domain in the mechanism of Fab-arm exchange, and thus identified amino acid position 409 as the critical CH3 determinant in human IgG, with R409 resulting in exchange and K409 resulting in stable IgG. Interestingly, studies with IgG from various species showed that Fab-arm exchange could not be assigned to a common CH3 domain amino acid motif. Accordingly, in rhesus monkeys (Macaca mulatta), aa 405 was identified as the CH3 determinant responsible (in combination with 226-CPACP-230). Using native mass spectrometry, we demonstrated that the ability to exchange Fab-arms correlated with the CH3–CH3 dissociation constant. Species-specific adaptations in the CH3 domain thus enable Fab-arm exchange by affecting the inter-CH3 domain interaction strength. The redistribution of Ag-binding domains between molecules may constitute a general immunological and evolutionary advantage. The current insights impact our view of humoral immunity and should furthermore be considered in the design and evaluation of Ab-based studies and therapeutics.
Blocking IL-17A Promotes the Resolution of Pulmonary Inflammation and Fibrosis Via TGF-β1–Dependent and –Independent Mechanisms
Authors: Mi Su , Li Zhe , Yang Hong-Zhen , Liu Hong , Wang Jia-Ping , Ma Yong-Gang , Wang Xiao-Xing , Liu Han-Zhi , Sun Wei , Hu Zhuo-Wei
Published: August 2011

Pulmonary fibrosis is the pathologic basis for a variety of incurable human chronic lung diseases. IL-17A, a glycoprotein secreted from IL-17–producing cells, has recently been shown to be a proinflammatory cytokine involved in chronic inflammation and autoimmune disease. In this study, we report that IL-17A increased the synthesis and secretion of collagen and promoted the epithelial–mesenchymal transition in alveolar epithelial cells in a TGF-β1–dependent manner. Using in vivo fibrotic models, we found IL-17A expression to be elevated and IL-17A–associated signaling pathways to be activated in fibrotic lung tissues. Neutralization of IL-17A in vivo promoted the resolution of bleomycin-induced acute inflammation, attenuated pulmonary fibrosis, and increased survival. Additionally, IL-17A antagonism inhibited silica-induced chronic inflammation and pulmonary fibrosis. Targeting IL-17A resulted in a shift of the suppressive immune response in fibrotic lung tissue toward a Th1-type immune response, and it effectively induced autophagy, which promoted the autophagic degradation of collagen and autophagy-associated cell death. Moreover, IL-17A was found to attenuate the starvation-induced autophagy, and autophagy modulators regulated collagen degradation in the alveolar epithelial cells in a TGF-β1–independent manner. Administration of 3-methylamphetamine, an autophagy inhibitor, reversed the therapeutic efficacy of IL-17A antagonism in pulmonary fibrosis. Our studies indicate that IL-17A participates in the development and progression of pulmonary fibrosis in both TGF-β1–dependent and –independent manners and that the components of the IL-17A signaling pathway are potential therapeutic targets for the treatment of fibroproliferative lung diseases.
Activation of TLR2 Enhances Tight Junction Barrier in Epidermal Keratinocytes
Authors: Yuki Takuo , Yoshida Hiroyuki , Akazawa Yumiko , Komiya Aya , Sugiyama Yoshinori , Inoue Shintaro
Published: August 2011

The epidermis has developed physical and immunological barriers that prevent infiltration of deleterious chemicals and pathogens. As a first step to understanding the relationship between these barriers, we investigated whether TLR2 activation functionally alters tight junctions (TJs) in cultured human keratinocytes. Stimulation with peptidoglycan, a ligand for TLR2, elevated the TJ-associated barrier in the space of 3 h. The increase in TJ-associated barrier function due to peptidoglycan stimulation was suppressed by the knockdown of TLR adaptor MyD88 or the pretreatment with TLR2-neutralizing Ab, indicating that TLR2 activation enhanced TJ-associated barrier. One and 3 h after peptidoglycan stimulation, expression levels of the TJ proteins occludin, claudin-1, claudin-4, and ZO-1 were unchanged. However, immunoprecipitation studies demonstrated that the association of phospho-atypical protein kinase Cζ/ι, crucial for TJ biogenesis, with occludin was increased. Significantly, inhibition of atypical protein kinase Cζ/ι activity completely blocked the immediate elevation of the TJ-associated barrier. Finally, peptidoglycan was applied to the stratum corneum surface of a human skin equivalent, and the TJ barrier was evaluated. In the space of 3 h after the stimulation, the amount of intercellular tracer in the stratum corneum incubated from the dermal side was reduced, indicating that the TJ barrier is strengthened via TLR2 activation. Taken together, our findings indicated that infiltration of pathogens into the epidermis immediately enhanced TJ function via TLR2 signaling. Furthermore, the dynamically controlled TJs in skin are considered fundamental in preventing further invasion of pathogens and maintaining cutaneous barrier homeostasis.
B Cells and TCR Avidity Determine Distinct Functions of CD4+ T Cells in Retroviral Infection
Authors: Ploquin Mickaël J.-Y. , Eksmond Urszula , Kassiotis George
Published: August 2011

The T cell-dependent B cell response relies on cognate interaction between B cells and CD4+ Th cells. However, the consequences of this interaction for CD4+ T cells are not entirely known. B cells generally promote CD4+ T cell responses to pathogens, albeit to a variable degree. In contrast, CD4+ T cell responses to self- or tumor Ags are often suppressed by B cells. In this study, we demonstrated that interaction with B cells dramatically inhibited the function of virus-specific CD4+ T cells in retroviral infection. We have used Friend virus infection of mice as a model for retroviral infection, in which the behavior of virus-specific CD4+ T cells was monitored according to their TCR avidity. We report that avidity for Ag and interaction with B cells determine distinct aspects of the primary CD4+ T cell response to Friend virus infection. Virus-specific CD4+ T cells followed exclusive Th1 and T follicular helper (Tfh) differentiation. High avidity for Ag facilitated expansion during priming and enhanced the capacity for IFN-γ and IL-21 production. In contrast, Tfh differentiation was not affected by avidity for Ag. By reducing or preventing B cell interaction, we found that B cells promoted Tfh differentiation, induced programmed death 1 expression, and inhibited IFN-γ production by virus-specific CD4+ T cells. Ultimately, B cells protected hosts from CD4+ T cell-mediated immune pathology, at the detriment of CD4+ T cell-mediated protective immunity. Our results suggest that B cell presentation of vaccine Ags could be manipulated to direct the appropriate CD4+ T cell response.
Mutations in a Dominant Nef Epitope of Simian Immunodeficiency Virus Diminish TCR:Epitope Peptide Affinity but not Epitope Peptide:MHC Class I Binding
Authors: Cale Evan M. , Bazick Heidi S. , Rianprakaisang Tony A. , Alam S. Munir , Letvin Norman L.
Published: August 2011

Viruses like HIV and SIV escape from containment by CD8+ T lymphocytes through generating mutations that interfere with epitope peptide:MHC class I binding. However, mutations in some viral epitopes are selected for that have no impact on this binding. We explored the mechanism underlying the evolution of such epitopes by studying CD8+ T lymphocyte recognition of a dominant Nef epitope of SIVmac251 in infected Mamu-A*02+ rhesus monkeys. Clonal analysis of the p199RY-specific CD8+ T lymphocyte repertoire in these monkeys indicated that identical T cell clones were capable of recognizing wild-type (WT) and mutant epitope sequences. However, we found that the functional avidity of these CD8+ T lymphocytes for the mutant peptide:Mamu-A*02 complex was diminished. Using surface plasmon resonance to measure the binding affinity of the p199RY-specific TCR repertoire for WT and mutant p199RY peptide:Mamu-A*02 monomeric complexes, we found that the mutant p199RY peptide:Mamu-A*02 complexes had a lower affinity for TCRs purified from CD8+ T lymphocytes than did the WT p199RY peptide:Mamu-A*02 complexes. These studies demonstrated that differences in TCR affinity for peptide:MHC class I ligands can alter functional p199RY-specific CD8+ T lymphocyte responses to mutated epitopes, decreasing the capacity of these cells to contain SIVmac251 replication.
Cytoplasmic Igα Serine/Threonines Fine-Tune Igα Tyrosine Phosphorylation and Limit Bone Marrow Plasma Cell Formation
Authors: Patterson Heide Christine , Kraus Manfred , Wang Donghai , Shahsafaei Aliakbar , Henderson Joel M. , Seagal Jane , Otipoby Kevin L. , Thai To-Ha , Rajewsky Klaus
Published: August 2011

Igα serine 191 and 197 and threonine 203, which are located in proximity of the Igα ITAM, dampen Igα ITAM tyrosine phosphorylation. In this study, we show that mice with targeted mutations of Igα S191, 197, and T203 displayed elevated serum IgG2c and IgG2b concentrations and had elevated numbers of IgG2c- and IgG2b-secreting cells in the bone marrow. BCR-induced Igα tyrosine phosphorylation was slightly increased in splenic B cells. Our results suggest that Igα serine/threonines limit formation of IgG2c- and IgG2b-secreting bone marrow plasma cells, possibly by fine-tuning Igα tyrosine-mediated BCR signaling.
Loss of CD20 and Bound CD20 Antibody from Opsonized B Cells Occurs More Rapidly Because of Trogocytosis Mediated by Fc Receptor-Expressing Effector Cells Than Direct Internalization by the B Cells
Authors: Beum Paul V. , Peek Elizabeth M. , Lindorfer Margaret A. , Beurskens Frank J. , Engelberts Patrick J. , Parren Paul W. H. I. , van de Winkel Jan G. J. , Taylor Ronald P.
Published: August 2011

We previously reported that 1 h after infusion of CD20 mAb rituximab in patients with chronic lymphocytic leukemia (CLL), >80% of CD20 was removed from circulating B cells, and we replicated this finding, based on in vitro models. This reaction occurs via an endocytic process called shaving/trogocytosis, mediated by FcγR on acceptor cells including monocytes/macrophages, which remove and internalize rituximab–CD20 immune complexes from B cells. Beers et al. reported that CD20 mAb-induced antigenic modulation occurs as a result of internalization of B cell-bound mAb–CD20 complexes by the B cells themselves, with internalization of ∼40% observed after 2 h at 37°C. These findings raise fundamental questions regarding the relative importance of shaving versus internalization in promoting CD20 loss and have substantial implications for the design of mAb-based cancer therapies. Therefore, we performed direct comparisons, based on flow cytometry, to determine the relative rates and extent of shaving versus internalization. B cells, from cell lines, from patients with CLL, and from normal donors, were opsonized with CD20 mAbs rituximab or ofatumumab and incubated for varying times and then reacted with acceptor THP-1 monocytes to promote shaving. We find that shaving induces considerably greater loss of CD20 and bound mAb from opsonized B cells in much shorter time periods (75–90% in <45 min) than is observed for internalization. Both shaving/trogocytosis and internalization could contribute to CD20 loss when CLL patients receive rituximab therapy, but shaving should occur more rapidly and is most likely to be the key mechanism of CD20 loss.
Intra-Golgi Formation of IgM–Glycosaminoglycan Complexes Promotes Ig Deposition
Authors: Khan Salar N. , Cox John V. , Nishimoto Satoru K. , Chen Ching , Fritzler Marvin J. , Hendershot Linda M. , Weigert Martin , Radic Marko
Published: August 2011

Immune complexes arise from interactions between secreted Ab and Ags in the surrounding milieu. However, it is not known whether intracellular Ag–Ab interactions also contribute to the formation of extracellular immune complexes. In this study, we report that certain murine B cell hybridomas accumulate intracellular IgM and release large, spherical IgM complexes. The complexes (termed “spherons”) reach 2 μm in diameter, detach from the cell surface, and settle out of solution. The spherons contain IgM multimers that incorporate the J chain and resist degradation by endoglycosidase H, arguing for IgM passage through the Golgi. Treatment of cells with inhibitors of proteoglycan synthesis, or incubation of spherons with chondroitinase ABC, degrades spherons, indicating that spheron formation and growth depend on interactions between IgM and glycosaminoglycans. This inference is supported by direct binding of IgM to heparin and hyaluronic acid. We conclude that, as a consequence of IgM binding to glycosaminoglycans, multivalent IgM–glycan complexes form in transit of IgM to the cell surface. Intra-Golgi formation of immune complexes could represent a new pathogenic mechanism for immune complex deposition disorders.
On the Importance of the Stokes-Brinkman Equations for Computing Effective Permeability in Karst Reservoirs
Authors: Krotkiewski Marcin , Ligaarden Ingeborg S. , Lie Knut-Andreas , Schmid Daniel W.
Published: August 2011

Cavities and fractures significantly affect the flow paths in carbonate reservoirs and should be accurately accounted for in numerical models. Herein, we consider the problem of computing the effective permeability of rock samples based on high-resolution 3D CT scans containing millions of voxels. We use the Stokes-Brinkman equations in the entire domain, covering regions of free flow governed by the Stokes equations, porous Darcy flow, and transitions between them. The presence of different length scales and large (ten orders of magnitude) contrasts in permeability leads to highly ill-conditioned linear systems of equations, which are difficult to solve. To obtain a problem that is computationally tractable, we first analyze the relative importance of the Stokes and Darcy terms for a set of idealized 2D models. We find that, in terms of effective permeability, the Stokes-Brinkman equations are only applicable for a special parameter set where the effective free-flow permeability is less than four orders of magnitude different from the matrix permeability. All other cases can be accurately modeled with either the Stokes or the Darcy end-member flows, depending on if there do or do not exist percolating free-flow regions. The insights obtained are used to perform a direct computation of the effective permeability of a rock sample model with more than 8 million cells.
Novas midias, cidadania e exclusão digital no contexto da sociedade da informação
Authors: Mota Francisca Rosaline Leite
Published: August 2011

O artigo aborda questões relativas ao papel das Novas Mídias para a conquista da Cidadania na chamada Sociedade da Informação. Aponta alguns dos principais fatores que contribuem para agravar a Exclusão Digital e relata iniciativas que objetivam promover a cidadania por meio da info-inclusão no Brasil, dando ênfase especial a algumas experiências no contexto cearense.
Inteligência social e inteligência competitiva
Authors: Tarapanoff Kira
Published: August 2011

Coloca os conceitos de inteligência social e coletiva no contexto da Sociedade da informação e do Conhecimento. Traça o desenvolvimento da inteligência econômica nos países e a aplicação da inteligência competitiva nas organizações. Defende que a ação conjunta do processo de gestão da informação e gestão do conhecimento, ambas em apoio às estratégia e missão organizacional, apresentam para o processo de tomada de decisão uma propriedade emergente que é a inteligência institucional.
A contribuição da inteligência competitiva para o desenvolvimento de arranjos produtivos locais: caso Jaú-SP
Authors: Hoffmann Wanda A. M. , Gregolin José A.R. , Oprime Pedro C.
Published: August 2011

O contexto econômico atual tem provocado a maior exposição das empresas brasileiras à concorrência internacional, impondo desafios e oportunidades. As pequenas e médias empresas brasileiras (PMEs), são as mais vulneráveis face a escassez de recursos e custos de produção, dentre outros aspectos. Os arranjos produtivos locais (APLs) ou clusters são importantes modos de organização da produção das PMEs. Esses modos de produção são considerados vitais na geração de emprego e renda para o país. As características desses arranjos que dimensionam a sua dinâmica e crescimento são temas relevantes de pesquisa em várias regiões e países, pela importância econômica e social, amplamente difundidos nos últimos anos por pesquisadores e entidades. O presente estudo aborda a contribuição da inteligência competitiva para o fortalecimento de APLs. Nesse contexto, a dinâmica de APLs e os seus gargalos tecnológicos e de gestão são identificados focalizando o segmento de calçados e couros de Jaú no Estado de São Paulo. Vários aspectos são abordados em relação à dinâmica desse arranjo produtivo local, através da sua análise comparativa com pólos internacionais, especialmente o italiano. Indicando sinais de uma estratégia típica de clusters industriais, explicitada pela sinergia obtida pela interatividade de troca de informações intra-cluster e o esforço em incrementar sua capacidade competitiva.
Immersion mode heterogeneous ice nucleation by an illite rich powder representative of atmospheric mineral dust
Authors: Broadley S. L. , Murray B. J. , Herbert R. J. , Atkinson J. D. , Dobbie S. , Condliffe E. , Neve L.
Published: August 2011

Abstract. Atmospheric dust rich in illite is transported globally from arid regions and may impact cloud properties through the nucleation of ice. We present measurements of ice nucleation in water droplets containing known quantities of an illite rich powder under atmospherically relevant conditions. The illite rich powder used here, NX illite, has a similar mineralogical composition to atmospheric mineral dust sampled in remote locations, i.e. dust which has been subject to long range transport, cloud processing and sedimentation. Arizona Test Dust has a significantly different mineralogical composition and we suggest that NX illite is a better surrogate of natural atmospheric dust. Heterogeneous nucleation by NX illite was observed, using optical microscopy, to occur dominantly between 246 K and the homogeneous freezing limit and higher freezing temperatures were observed with larger surface areas of NX illite present within the droplets. It is shown that there is strong particle to particle variability in terms of ice nucleating ability with a few particles dominating ice nucleation at high surface areas. In fact, this work suggests that the bulk of atmospheric mineral dust particles are less efficient at nucleating ice than assumed in parameterisation currently used in models. For droplets containing ≤2 × 10−6 cm2 of NX illite, freezing temperatures did not noticeably change when the cooling rate was varied by an order of magnitude. The data obtained during cooling experiments (with surface areas ≤2 × 10−6 cm2) is shown to be inconsistent with the single component stochastic model, but is well described by the singular model (ns(236.2 K ≤ T ≤ 247.5 K) = exp(6.53043 × 104 − 8.2153088 × 102 T + 3.446885376 T 2 − 4.822268 × 10−3 T3). However, droplets continued to freeze when the temperature was held constant, which is inconsistent with the time independent singular model. We show that this apparent discrepancy can be resolved using a multiple component stochastic model in which it is assumed there are many types of nucleation sites, each with a unique temperature dependent nucleation coefficient. Cooling rate independence can be achieved with this time dependent model if the nucleation rate coefficients increase very rapidly with decreasing temperature, thus reconciling our measurement of nucleation at constant temperature with the cooling rate independence.
Carbon dioxide emissions from an Acacia plantation on peatland in Sumatra, Indonesia
Authors: Jauhiainen J. , Hooijer A. , Page S. E.
Published: August 2011

Abstract. Peat surface CO2 emission, groundwater table depth and peat temperature were monitored for two years along transects in an Acacia plantation on thick tropical peat (>4 m) in Sumatra, Indonesia. A total of 2300 emission measurements were taken at 144 locations. The autotrophic root respiration component of the CO2 emission was separated from heterotrophic emissions caused by peat oxidation in three ways: (i) by comparing CO2 emissions within and beyond the tree rooting zone, (ii) by comparing CO2 emissions with and without peat trenching (i.e. cutting any roots remaining in the peat beyond the tree rooting zone), and (iii) by comparing CO2 emissions before and after Acacia tree harvesting. On average, the contribution of root respiration to daytime CO2 emission is 21 % along transects in mature tree stands. At locations 0.5 m from trees this is up to 80 % of the total emissions, but it is negligible at locations more than 1.3 m away. This means that CO2 emission measurements well away from trees are free of any root respiration contribution and thus represent only peat oxidation emission. We find daytime mean annual CO2 emission from peat oxidation alone of 94 t ha−1 yr−1 at a mean water table depth of 0.8 m, and a minimum emission value of 80 t ha−1 yr−1 after correction for the effect of diurnal temperature fluctuations, which resulted in a 14.5 % reduction of the daytime emission. There is a positive correlation between mean long-term water table depths and peat oxidation CO2 emission. However, no such relation is found for instantaneous emission/water table depth within transects and it is clear that factors other than water table depth also affect peat oxidation and total CO2 emissions. The increase in the temperature of the surface peat due to plantation development may explain over 50 % of peat oxidation emissions.
Benchmarking monthly homogenization algorithms
Authors: Venema V. K. C. , Mestre O. , Aguilar E. , Auer I. , Guijarro J. A. , Domonkos P. , Vertacnik G. , Szentimrey T. , Stepanek P. , Zahradnicek P. , Viarre J. , Müller-Westermeier G. , Lakatos M. , Williams C. N. , Menne M. , Lindau R. , Rasol D. , Rustemeier E. , Kolokythas K. , Marinova T. , Andresen L. , Acquaotta F. , Fratianni S. , Cheval S. , Klancar M. , Brunetti M. , Gruber C. , Prohom Duran M. , Likso T. , Esteban P. , Brandsma T.
Published: August 2011

Abstract. The COST (European Cooperation in Science and Technology) Action ES0601: Advances in homogenization methods of climate series: an integrated approach (HOME) has executed a blind intercomparison and validation study for monthly homogenization algorithms. Time series of monthly temperature and precipitation were evaluated because of their importance for climate studies and because they represent two important types of statistics (additive and multiplicative). The algorithms were validated against a realistic benchmark dataset. The benchmark contains real inhomogeneous data as well as simulated data with inserted inhomogeneities. Random break-type inhomogeneities were added to the simulated datasets modeled as a Poisson process with normally distributed breakpoint sizes. To approximate real world conditions, breaks were introduced that occur simultaneously in multiple station series within a simulated network of station data. The simulated time series also contained outliers, missing data periods and local station trends. Further, a stochastic nonlinear global (network-wide) trend was added. Participants provided 25 separate homogenized contributions as part of the blind study as well as 22 additional solutions submitted after the details of the imposed inhomogeneities were revealed. These homogenized datasets were assessed by a number of performance metrics including (i) the centered root mean square error relative to the true homogeneous value at various averaging scales, (ii) the error in linear trend estimates and (iii) traditional contingency skill scores. The metrics were computed both using the individual station series as well as the network average regional series. The performance of the contributions depends significantly on the error metric considered. Contingency scores by themselves are not very informative. Although relative homogenization algorithms typically improve the homogeneity of temperature data, only the best ones improve precipitation data. Training was found to be very important. Moreover, state-of-the-art relative homogenization algorithms developed to work with an inhomogeneous reference are shown to perform best. The study showed that currently automatic algorithms can perform as well as manual ones.
Status of organochlorine pesticides in the drinking water well-field located in the Delhi region of the flood plains of river Yamuna
Authors: Mutiyar P. K. , Mittal A. K. , Pekdeger A.
Published: August 2011

Abstract. This study presents the occurrence of pesticides in a well-field located in Yamuna flood plain of Delhi region. Ground water sampling campaigns were carried out during pre-monsoon and post-monsoon periods covering 21 bore-wells and 5 Ranney wells. Major 17 organochlorine pesticides (OCP's) along with other water quality parameters were monitored during this period. Pesticide concentrations were determined using GC- ECD, while GC-MS was used for confirmatory purposes. OCP's groups like ∑HCH, ∑DDT, endosulfan and aldrin were observed in this well-field. Concentration of OCPs from Ranney wells exceeded the limit (1 μg l−1) prescribed by the Bureau of Indian Standards (BIS) in pre-monsoon season, though OCP levels in bore wells were within BIS limits. However, these levels were very close to the World Health Organisation (WHO) and European Union (EU) limit of for pesticides (0.5 μg l−1) in many samples. Bore well produced better quality water compared to the water from Ranney wells. Although, the level of OCP's was slightly lower than prescribed limit of national regulatory agency but such low doses may cause long-term damage to human populations if such water is consumed for longer durations. At low doses OCP's acts as endocrine disrupting agent and cause metabolic disorders in local population.
Towards direct coupling of regional climate models and ice sheet models by mass balance gradients: application to the Greenland Ice Sheet
Authors: Helsen M. M. , van de Wal R. S. W. , van den Broeke M. R. , van de Berg W. J. , Oerlemans J.
Published: August 2011

Abstract. It is notoriously difficult to couple surface mass balance (SMB) results from climate models to the changing geometry of an ice sheet model. This problem is traditionally avoided by using only accumulation fields from a climate model, and deriving SMB by parameterizing the run-off as a function of temperature, which is often related to surface elevation. In this study, a new parameterization of SMB is presented, designed for use in ice dynamical models to allow a direct adjustment of SMB as a result of a change in elevation (Hs) or a change in climate forcing. This method is based on spatial gradients in the present-day SMB field as computed by a regional climate model. Separate linear relations are derived for ablation and accumulation regimes, using only those pairs of Hs an SMB that are found within a minimum search radius. This approach enables a dynamic SMB forcing of ice sheet models, also for initially non-glaciated areas in the peripheral areas of an ice sheet, and circumvents traditional temperature lapse rate assumptions. The method is applied to the Greenland Ice Sheet (GrIS). Model experiments using both steady-state forcing and more realistic glacial-interglacial forcing result in ice sheet reconstructions and behavior that compare favorably with present-day observations of ice thickness.
Looking on Policy and Social Policy in the Context of Public Administration and Management
Authors: Ali Irani Farhad Nezhad Haj , Noruzi Mohammad Reza
Published: August 2011

The role of policy is important in economic, social and political related issues. The search for coordination and coherence of policies should take into account the fact that ideas about policy and its role in development have changed over time, indicating the difficulty to find clarity on the approaches to social investment, poverty alleviation and equity. This paper aims to study the importance of the policy, social policy and its related materials.
Democratization and Women’s Political Space in Nigeria: A Critical Appraisal
Authors: Chukwuemeka Emma , C.Eze Sunday
Published: August 2011

The study investigates the extent women participate in politics in Nigeria. Abia and Imo states were closely studied. Two hypotheses were formulated. The instruments used for data collection were questionnaire, interview and focus group discussion. A total of 354 copies of questionnaire were distributed, out of this number, 349 copies were completed and returned by the respondents. Z-test statistical tool was used to analyze the data, Based on the analysis, the major findings revealed that violence against women deter women from getting actively involved in politics in Nigeria. Also culture and traditional ethos prevent the advancement of women in politics also. Based on these findings, the following recommendations among others were proffered: Political mobilization should be carried into the villages to sensitize the women on the need to get involved in politics. More so new laws should be enacted on political thuggery and violence. They should be pursued vigorously to curb the high level of violence meted out to women by their male political counterparts in Nigeria.
Relationships between capabilities-strategy alignment and accountability-emphasis in government business enterprises
Authors: Seng Cheaseth
Published: August 2011

This study introduces a new research perspective to the investigation of factors affecting management’s attention to the rendering of their organisation’s managerial and public accountabilities. It draws on management studies of the fit between organisational strategy-types and capabilities and extends this literature to a new organisational context of government-owned business enterprises (GBEs) that act as fully competitive profit-making enterprises, but are made strongly accountable to the government minister, the parliament and the public. Sets of capabilities-strategy alignments are modelled, including prospecting GBEs with technology strengths, defender GBEs with market-linking capabilities and analyser GBEs with a balance of capabilities. These sets are then assessed in terms of their consequences for the emphasis given by management to processes and systems for discharging the GBE’s accountability outcomes. Data is collected through a questionnaire to senior managers of 141 GBEs in Australia. The findings are mostly consistent with prior studies conducted in private sector companies, even though strategy-capabilities alignments are related to accountability rather than financial performance. The findings provide insights to GBEs’ management and relevant government ministers concerning the continuing need to appropriately align strategies and capabilities of GBEs and the consequences of such alignment for the rendering of accountability.