bluuebunny/crossref_metadata_2025_split huggingface dataset:
Francisella tularensisInduces Ubiquitin-Dependent Major Histocompatibility Complex Class II Degradation in Activated Macrophages
Authors: Wilson Justin E. , Katkere Bhuvana , Drake James R. 
Published: August 2009

ABSTRACTThe intracellular bacteriumFrancisella tularensissurvives and replicates within macrophages, ultimately killing the host cell. Resolution of infection requires the development of adaptive immunity through presentation ofF. tularensisantigens to CD4+and CD8+T cells. We have previously established thatF. tularensisinduces macrophage prostaglandin E2(PGE2) production, leading to skewed T-cell responses. PGE2can also downregulate macrophage major histocompatibility complex (MHC) class II expression, suggesting thatF. tularensis-elicited PGE2may further alter T-cell responses via inhibition of class II expression. To test this hypothesis, gamma interferon (IFN-γ)-activated reporter macrophages were exposed to supernatants fromF. tularensis-infected macrophages, and the class II levels were measured. Exposure of macrophages to infection supernatants results in essentially complete clearance of surface class II and CD86, compromising the macrophage's ability to present antigens to CD4 T cells. Biochemical analysis revealed that infection supernatants elicit ubiquitin-dependent class II downregulation and degradation within intracellular acidic compartments. By comparison, exposure to PGE2alone only leads to a minor decrease in macrophage class II expression, demonstrating that a factor distinct from PGE2is eliciting the majority of class II degradation. However, production of this non-PGE2factor is dependent on macrophage cyclooxygenase activity and is induced by PGE2. These results establish thatF. tularensisinduces the production of a PGE2-dependent factor that elicits MHC class II downregulation in IFN-γ-activated macrophages through ubiquitin-mediated delivery of class II to lysosomes, establishing another mechanism for the modulation of macrophage antigen presentation duringF. tularensisinfection.
Susceptibility to Infectious Diseases Based on Antimicrobial Peptide Production
Authors: Rivas-Santiago Bruno , Serrano Carmen J. , Enciso-Moreno J. Antonio 
Published: August 2009

ABSTRACTIn the last few years, the great impact of antimicrobial peptides on infectious disease susceptibility and natural resistance has been reported. In some cases, susceptibility to diseases is related to antimicrobial peptide polymorphisms and gene copy numbers, but for the vast majority of infectious diseases, these phenomena need to be elucidated. This review is focused on the current knowledge about susceptibility and resistance conferred by genetic variations in antimicrobial peptide expression in infectious diseases.
Facial protection and head injuries in ice hockey: a systematic review
Authors: Asplund C , Bettcher S , Borchers J 
Published: August 2009

Objective:To summarise the best available evidence to determine if facial protection reduces head injury in ice hockey.Data Sources:MEDLINE and Cochrane databases through January 2009.Review Methods:Utilising terms: “head injuries,” “craniocerebral trauma [MeSH]”, “head injuries, closed [MeSH]”, head injuries, penetrating [MeSH]”, “face mask”, “face shield”, “visor” and “hockey”, 24 articles were identified through our systematic literature search. Of these, six studies met the inclusion criteria. Three independent reviewers reviewed the articles. The study results and generated conclusions were extracted and agreed upon.Results:Studies reviewed suggest that facial protection reduces overall head injuries in ice hockey. Facial protection showed a statistically significant (p<0.05) reduction in the number and type of facial injuries. In studies evaluating full facial protection (FFP) versus half facial protection (HFP), FFP offered a significantly higher level of protection against facial injuries and lacerations than HFP (relative risk (RR) 2.31, CI 1.53 to 3.48). There was no significant difference in the rate of concussion (RR 0.97, CI 0.61 to 1.54) or neck injury (CI 0.43 to 3.16) between full and partial protection. In those who sustained concussion players with FFP returned to practice or games sooner than players with partial facial protection (PFP) (1.7 sessions, CI 1.32 to 2.18).Conclusions:There is good evidence that FFP reduces the number and risk of overall head and facial injuries in ice hockey compared with PFP and no facial protection. PFP, while not as protective as FFP, appears to offer more risk reduction than no protection.
Associational Resistance and Associational Susceptibility: Having Right or Wrong Neighbors
Authors: Barbosa Pedro , Hines Jessica , Kaplan Ian , Martinson Holly , Szczepaniec Adrianna , Szendrei Zsofia 
Published: August 2009

Specific plant associations may decrease (associational resistance, AR) or increase (associational susceptibility, AS) the likelihood of detection by, and/or vulnerability to, herbivores. We discuss presumed mechanisms leading to AR and AS, suggest others, and conduct meta-analyses on plant and herbivore traits affecting AR and AS, and the effects of habitat.Specific plant associations determine the likelihood of detection and/or vulnerability of focal plants to herbivores. AS is more likely with insects and AR more likely with mammals. Unpalatable neighbors increase the likelihood of AR. An herbivore's feeding guild, diet breadth, and habitat type do not influence the likelihood of AR or AS. The effectiveness of AR in reducing herbivore abundance is independent of whether neighboring plants are within a plot of focal crops or along the edge of a plot. AR and AS may be applicable to associations among herbivores, and may be appropriately studied from a landscape perspective.
Behavioral Oncology and the War on Cancer: Partnering with Biomedicine
Authors: Stefanek Michael E. , Andrykowski Michael A. , Lerman Caryn , Manne Sharon , Glanz Karen ,   on behalf of the AACR Behavioral Science Task Force
Published: August 2009

Abstract
The call for interdisciplinary research in the war on cancer has escalated over the past several years. Behavioral science has played a key role in cancer control, and several exciting opportunities exist and will develop with the ongoing significant advances made in biomedical science. The current article briefly reviews the maturity of behavioral science in the areas of prevention, early detection, and survivorship and how the partnership of behavioral and biomedical science can effectively impact cancer incidence, morbidity, and mortality. [Cancer Res 2009;69(18):7151–6]
Harnessing the physiology of lymphopenia to support adoptive immunotherapy in lymphoreplete hosts
Authors: Cui Yongzhi , Zhang Hua , Meadors Joanna , Poon Rita , Guimond Martin , Mackall Crystal L. 
Published: August 2009

AbstractLymphopenia enhances the effectiveness of adoptive immunotherapy by facilitating expansion of transferred T cells but also limits the T-cell repertoire available to mediate immune responses and, in humans, is associated with chronic immune dysfunction. Previous studies concluded that lymphopenia augments adoptive immunotherapy by diminishing Tregs and increasing homeostatic cytokines. We sought to determine whether targeted therapies that replicate the physiology of lymphopenia in lymphoreplete hosts could provide a similarly supportive milieu. Pmel-1 T cells were transferred to B16-bearing lymphopenic versus lymphoreplete mice receiving αCD25 and/or recombinant human interleukin-7. Although CD25-based Treg depletion was inefficient because of peripheral expansion of CD4+CD25−FOXP3+ cells, outcomes were better in αCD25-treated lymphoreplete hosts than in lymphopenic hosts, and adoptive immunotherapy was most effective in lymphoreplete hosts receiving αCD25 plus recombinant human interleukin-7. Lymphopenic hosts supported increased proliferation of adoptively transferred antigen-specific T cells, but cells transferred to lymphoreplete recipients receiving targeted therapies showed superior function. Further, determinant spreading was substantial in lymphoreplete hosts but absent in lymphopenic hosts. These results demonstrate that targeted therapies delivered to mimic the “physiology of lymphopenia” enhance the efficacy of adoptive immunotherapy in lymphoreplete hosts and provide a potentially superior alternative to the induction of lymphopenia.
MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy
Authors: Savage Kerry J. , Johnson Nathalie A. , Ben-Neriah Susana , Connors Joseph M. , Sehn Laurie H. , Farinha Pedro , Horsman Douglas E. , Gascoyne Randy D. 
Published: August 2009

AbstractApproximately 5% to 10% of diffuse large B-cell lymphomas (DLBCLs) harbor an MYC oncogene rearrangement (MYC+). The prognostic significance of MYC+ DLBCL was determined in an unselected population of patients with newly diagnosed DLBCL treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP). Using a Vysis break-apart fluorescence in situ hybridization probe, 12 of 135 (8.8%) cases of MYC+ DLBCL were identified that had no defining high-risk features. MYC+ DLBCL was associated with an inferior 5-year progression-free survival (66% vs 31%, P = .006) and overall survival (72% vs 33%, P = .016). Multivariate analysis confirmed the prognostic importance of MYC for both progression-free survival (hazard ratio = 3.28; 95% confidence interval, 1.49-7.21, P = .003) and overall survival (hazard ratio = 2.98; 95% confidence interval, 1.28-6.95, P = .011). Cases of MYC+ DLBCL also had a higher risk of central nervous system relapse (P = .023), independent of other risk factors. The diagnosis of MYC+ DLBCL is likely underappreciated; and given the lack of defining risk factors, fluorescence in situ hybridization for MYC rearrangements should be performed in all patients with DLBCL. In the R-CHOP treatment era, MYC+ DLBCLs have an inferior prognosis. Treatment regimens similar to those used in Burkitt lymphoma may be more appropriate in this patient population and need to be prospectively tested.
ABO blood group glycans modulate sialic acid recognition on erythrocytes
Authors: Cohen Miriam , Hurtado-Ziola Nancy , Varki Ajit 
Published: August 2009

AbstractABH(O) blood group polymorphisms are based on well-known intraspecies variations in structures of neutral blood cell surface glycans in humans and other primates. Whereas natural antibodies against these glycans can act as barriers to blood transfusion and transplantation, the normal functions of this long-standing evolutionary polymorphism remain largely unknown. Although microbial interactions have been suggested as a selective force, direct binding of lethal pathogens to ABH antigens has not been reported. We show in this study that ABH antigens found on human erythrocytes modulate the specific interactions of 3 sialic acid-recognizing proteins (human Siglec-2, 1918SC influenza hemagglutinin, and Sambucus nigra agglutinin) with sialylated glycans on the same cell surface. Using specific glycosidases that convert A and B glycans to the underlying H(O) structure, we show ABH antigens stabilize sialylated glycan clusters on erythrocyte membranes uniquely for each blood type, generating differential interactions of the 3 sialic acid-binding proteins with erythrocytes from each blood type. We further show that by stabilizing such structures ABH antigens can also modulate sialic acid-mediated interaction of pathogens such as Plasmodium falciparum malarial parasite. Thus, ABH antigens can noncovalently alter the presentation of other cell surface glycans to cognate-binding proteins, without themselves being a direct ligand.
Escalated regeneration in sciatic nerve crush injury by the combined therapy of human amniotic fluid mesenchymal stem cells and fermented soybean extracts, Natto
Authors: Pan Hung-Chuan , Yang Dar-Yu , Ho Shu-Peng , Sheu Meei-Ling , Chen Chung-Jung , Hwang Shiaw-Min , Chang Ming-Hong , Cheng Fu-Chou 
Published: August 2009

AbstractAttenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto) was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS) was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days); Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits.
Characterization of a novel Nav1.5 channel mutation, A551T, associated with Brugada syndrome
Authors: Chiang Kun-Chi , Lai Ling-Ping , Shieh Ru-Chi 
Published: August 2009

Abstract
Brugada syndrome is a life-threatening, inherited arrhythmia disorder associated with autosomal dominant mutations in SCN5A, the gene encoding the human cardiac Na+ channel α subunit (Nav1.5). Here, we characterized the biophysical properties of a novel Brugada syndrome-associated Nav1.5 mutation, A551T, identified in a proband who was successfully resuscitated from an episode of ventricular fibrillation with sudden collapse. Whole-cell currents through wild-type (WT) Nav1.5 and mutant (A551T) channels were recorded and compared in the human embryonic kidney cell line HEK293T transfected with SCN5A cDNA and SCN1B cDNA, using the patch-clamp technique. Current density was decreased in the A551T mutant compared to the WT. In addition, the A551T mutation reduced Nav1.5 activity by promoting entry of the channel into fast inactivation from the closed state, thereby shifting the steady-state inactivation curve by -5 mV. Furthermore, when evaluated at -90 mV, the resting membrane potential, but not at the conventionally used -120 mV, both the percentage, and rate, of channel recovery from inactivation were reduced in the mutant. These results suggest that the DI-DII linker may be involved in the stability of inactivation gating process. This study supports the notion that a reduction in Nav1.5 channel function is involved in the pathogenesis of Brugada syndrome. The structural-functional study of the Nav1.5 channel advances our understanding of its pathophysiolgocial function.
Comparison of exhaled breath condensate pH using two commercially available devices in healthy controls, asthma and COPD patients
Authors: Koczulla Rembert , Dragonieri Silvano , Schot Robert , Bals Robert , Gauw Stefanie A , Vogelmeier Claus , Rabe Klaus F , Sterk Peter J , Hiemstra Pieter S 
Published: August 2009

Abstract

Background
Analysis of exhaled breath condensate (EBC) is a non-invasive method for studying the acidity (pH) of airway secretions in patients with inflammatory lung diseases.

Aim
To assess the reproducibility of EBC pH for two commercially available devices (portable RTube and non-portable ECoScreen) in healthy controls, patients with asthma or COPD, and subjects suffering from an acute cold with lower-airway symptoms. In addition, we assessed the repeatability in healthy controls.

Methods
EBC was collected from 40 subjects (n = 10 in each of the above groups) using RTube and ECoScreen. EBC was collected from controls on two separate occasions within 5 days. pH in EBC was assessed after degasification with argon for 20 min.

Results
In controls, pH-measurements in EBC collected by RTube or ECoScreen showed no significant difference between devices (p = 0.754) or between days (repeatability coefficient RTube: 0.47; ECoScreen: 0.42) of collection. A comparison between EBC pH collected by the two devices in asthma, COPD and cold patients also showed good reproducibility. No differences in pH values were observed between controls (mean pH 8.27; RTube) and patients with COPD (pH 7.97) or asthma (pH 8.20), but lower values were found using both devices in patients with a cold (pH 7.56; RTube, p < 0.01; ECoScreen, p < 0.05).

Conclusion
We conclude that pH measurements in EBC collected by RTube and ECoScreen are repeatable and reproducible in healthy controls, and are reproducible and comparable in healthy controls, COPD and asthma patients, and subjects with a common cold.
Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice
Authors: Li Yu-Tao , He Bei , Wang Yu-Zhu , Wang Jing 
Published: August 2009

AbstractTo determine if nuclear factor-κB (NF-κB) activation may be a key factor in lung inflammation and respiratory dysfunction, we investigated whether NF-κB can be blocked by intratracheal administration of NF-κB decoy oligodeoxynucleotides (ODNs), and whether decoy ODN-mediated NF-κB inhibition can prevent smoke-induced lung inflammation, respiratory dysfunction, and improve pathological alteration in the small airways and lung parenchyma in the long-term smoke-induced mouse model system. We also detected changes in transcriptional factors. In vivo, the transfection efficiency of NF-κB decoy ODNs to alveolar macrophages in BALF was measured by fluorescein isothiocyanate (FITC)-labeled NF-κB decoy ODNs and flow cytometry post intratracheal ODN administration. Pulmonary function was measured by pressure sensors, and pathological changes were assessed using histology and the pathological Mias software. NF-κB and activator protein 1(AP-1) activity was detected by the electrophoretic motility shift assay (EMSA). Mouse cytokine and chemokine pulmonary expression profiles were investigated by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and lung tissue homogenates, respectively, after repeated exposure to cigarette smoke. After 24 h, the percentage of transfected alveolar macrophages was 30.00 ± 3.30%. Analysis of respiratory function indicated that transfection of NF-κB decoy ODNs significantly impacted peak expiratory flow (PEF), and bronchoalveolar lavage cytology displayed evidence of decreased macrophage infiltration in airways compared to normal saline-treated or scramble NF-κB decoy ODNs smoke exposed mice. NF-κB decoy ODNs inhibited significantly level of macrophage inflammatory protein (MIP) 1α and monocyte chemoattractant protein 1(MCP-1) in lung homogenates compared to normal saline-treated smoke exposed mice. In contrast, these NF-κB decoy ODNs-treated mice showed significant increase in the level of tumor necrosis factor-α(TNF-α) and pro-MMP-9(pro-matrix metalloproteinase-9) in mice BALF. Further measurement revealed administration of NF-κB decoy ODNs did not prevent pathological changes. These findings indicate that NF-κB activation play an important role on the recruitment of macrophages and pulmonary dysfunction in smoke-induced chronic lung inflammation, and with the exception of NF-κB pathway, there might be complex mechanism governing molecular dynamics of pro-inflammatory cytokines expression and structural changes in small airways and pulmonary parenchyma in vivo.
Identification of a nuclear localization motif in the serine/arginine protein kinase PSRPK of physarum polycephalum
Authors: Liu Shide , Zhou Zhuolong , Lin Ziyang , Ouyang Qiuling , Zhang Jianhua , Tian Shengli , Xing Miao 
Published: August 2009

Abstract

Background
Serine/arginine (SR) protein-specific kinases (SRPKs) are conserved in a wide range of organisms, from humans to yeast. Studies showed that SRPKs can regulate the nuclear import of SR proteins in cytoplasm, and regulate the sub-localization of SR proteins in the nucleus. But no nuclear localization signal (NLS) of SRPKs was found. We isolated an SRPK-like protein PSRPK (GenBank accession No. DQ140379) from Physarum polycephalum previously, and identified a NLS of PSRPK in this study.

Results
We carried out a thorough molecular dissection of the different domains of the PSRPK protein involved in its nuclear localization. By truncation of PSRPK protein, deletion of and single amino acid substitution in a putative NLS and transfection of mammalian cells, we observed the distribution of PSRPK fluorescent fusion protein in mammalian cells using confocal microscopy and found that the protein was mainly accumulated in the nucleus; this indicated that the motif contained a nuclear localization signal (NLS). Further investigation with truncated PSPRK peptides showed that the NLS (318PKKGDKYDKTD328) was localized in the alkaline Ω-loop of a helix-loop-helix motif (HLHM) of the C-terminal conserved domain. If the 318PKKGDK322 sequence was deleted from the loop or K320 was mutated to T320, the PSRPK fluorescent fusion protein could not enter and accumulate in the nucleus.

Conclusion
This study demonstrated that the 318PKKGDKYDKTD328 peptides localized in the C-terminal conserved domain of PSRPK with the Ω-loop structure could play a crucial role in the NLS function of PSRPK.
GEOGLE: context mining tool for the correlation between gene expression and the phenotypic distinction
Authors: Yu Yao , Tu Kang , Zheng Siyuan , Li Yun , Ding Guohui , Ping Jie , Hao Pei , Li Yixue 
Published: August 2009

Abstract

Background
In the post-genomic era, the development of high-throughput gene expression detection technology provides huge amounts of experimental data, which challenges the traditional pipelines for data processing and analyzing in scientific researches.

Results
In our work, we integrated gene expression information from Gene Expression Omnibus (GEO), biomedical ontology from Medical Subject Headings (MeSH) and signaling pathway knowledge from sigPathway entries to develop a context mining tool for gene expression analysis – GEOGLE. GEOGLE offers a rapid and convenient way for searching relevant experimental datasets, pathways and biological terms according to multiple types of queries: including biomedical vocabularies, GDS IDs, gene IDs, pathway names and signature list. Moreover, GEOGLE summarizes the signature genes from a subset of GDSes and estimates the correlation between gene expression and the phenotypic distinction with an integrated p value.

Conclusion
This approach performing global searching of expression data may expand the traditional way of collecting heterogeneous gene expression experiment data. GEOGLE is a novel tool that provides researchers a quantitative way to understand the correlation between gene expression and phenotypic distinction through meta-analysis of gene expression datasets from different experiments, as well as the biological meaning behind. The web site and user guide of GEOGLE are available at: http://omics.biosino.org:14000/kweb/workflow.jsp?id=00020