bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD40L Induces Functional Tunneling Nanotube Networks Exclusively in Dendritic Cells Programmed by Mediators of Type 1 Immunity
Authors: Zaccard Colleen R. , Watkins Simon C. , Kalinski Pawel , Fecek Ronald J. , Yates Aarika L. , Salter Russell D. , Ayyavoo Velpandi , Rinaldo Charles R. , Mailliard Robbie B. 
Published: December 2014

Abstract
The ability of dendritic cells (DC) to mediate CD4+ T cell help for cellular immunity is guided by instructive signals received during DC maturation, as well as the resulting pattern of DC responsiveness to the Th signal, CD40L. Furthermore, the professional transfer of antigenic information from migratory DC to lymph node–residing DC is critical for the effective induction of cellular immune responses. In this study we report that, in addition to their enhanced IL-12p70 producing capacity, human DC matured in the presence of inflammatory mediators of type 1 immunity are uniquely programmed to form networks of tunneling nanotube-like structures in response to CD40L-expressing Th cells or rCD40L. This immunologic process of DC reticulation facilitates intercellular trafficking of endosome-associated vesicles and Ag, but also pathogens such HIV-1, and is regulated by the opposing roles of IFN-γ and IL-4. The initiation of DC reticulation represents a novel helper function of CD40L and a superior mechanism of intercellular communication possessed by type 1 polarized DC, as well as a target for exploitation by pathogens to enhance direct cell-to-cell spread.
IRAK4 as a Molecular Target in the Amelioration of Innate Immunity–Related Endotoxic Shock and Acute Liver Injury by Chlorogenic Acid
Authors: Park Sun Hong , Baek Seung-Il , Yun Jieun , Lee Seungmin , Yoon Da Young , Jung Jae-Kyung , Jung Sang-Hun , Hwang Bang Yeon , Hong Jin Tae , Han Sang-Bae , Kim Youngsoo 
Published: December 2014

Abstract
Mice lacking the IL-1R–associated kinase 4 (IRAK4) are completely resistant to LPS-induced endotoxic disorder or the TLR9 agonist CpG DNA plus d-galactosamine–induced acute liver injury (ALI), whereas wild-type strains succumb. However, translational drugs against sepsis or ALI remain elusive. Lonicerae flos extract is undergoing the clinical trial phase I in LPS-injected healthy human volunteers for sepsis treatment. In the current study, chlorogenic acid (CGA), a major anti-inflammatory constituent of lonicerae flos extract, rescued endotoxic mortality of LPS-intoxicated C57BL/6 mice, as well as ameliorated ALI of LPS/d-galactosamine–challenged C57BL/6 mice. As a mechanism, CGA inhibited various TLR agonist–, IL-1α–, or high-mobility group box-1–stimulated autophosphorylation (activation) of IRAK4 in peritoneal macrophages from C57BL/6 or C3H/HeJ mice via directly affecting the kinase activity of IRAK4, a proximal signal transducer in the MyD88-mediated innate immunity that enhances transcriptional activity of NF-κB or AP-1. CGA consequently attenuated protein or mRNA levels of NF-κB/AP-1 target genes encoding TNF-α, IL-1α, IL-6, and high-mobility group box-1 in vivo under endotoxemia or ALI. Finally, this study suggests IRAK4 as a molecular target of CGA in the treatment of innate immunity–related shock and organ dysfunction following insult of various TLR pathogens from bacteria and viruses.
CD26-Mediated Induction of EGR2 and IL-10 as Potential Regulatory Mechanism for CD26 Costimulatory Pathway
Authors: Hatano Ryo , Ohnuma Kei , Otsuka Haruna , Komiya Eriko , Taki Izumi , Iwata Satoshi , Dang Nam H. , Okumura Ko , Morimoto Chikao 
Published: December 2014

Abstract
CD26 is associated with T cell signal transduction processes as a costimulatory molecule, and CD26+ T cells have been suggested to be involved in the pathophysiology of diverse autoimmune diseases. Although the cellular and molecular mechanisms involved in CD26-mediated T cell activation have been extensively evaluated by our group and others, potential negative feedback mechanisms to regulate CD26-mediated activation still remain to be elucidated. In the present study, we examine the expression of inhibitory molecules induced via CD26-mediated costimulation. We show that coengagement of CD3 and CD26 induces preferential production of IL-10 in human CD4+ T cells, mediated through NFAT and Raf-MEK-ERK pathways. A high level of early growth response 2 (EGR2) is also induced following CD26 costimulation, possibly via NFAT and AP-1–mediated signaling, and knockdown of EGR2 leads to decreased IL-10 production. Furthermore, CD3/CD26-stimulated CD4+ T cells clearly suppress proliferative activity and effector cytokine production of bystander T cells in an IL-10–dependent manner. Taken together, our data suggest that robust CD26 costimulatory signaling induces preferential expression of EGR2 and IL-10 as a potential mechanism for regulating CD26-mediated activation.
Survival of Human Circulating Antigen-Induced Plasma Cells Is Supported by Plasma Cell–Niche Cytokines and T Follicular Helper Lymphocytes
Authors: Ramos-Amaya Ana , Rodríguez-Bayona Beatriz , López-Blanco Rubén , Andújar Eloisa , Pérez-Alegre Mónica , Campos-Caro Antonio , Brieva José A. 
Published: December 2014

Abstract
Human circulating Ag-induced plasma cells (PCs) contain a high proportion of cycling cells. This study reveals that these PCs spontaneously proliferate in culture during 72 h, as determined by BrdU-uptake detection. Transcriptome analysis indicates that, in comparison with tonsil and bone marrow (BM) PCs, these PCs distinctively upregulate genes involved in cell division. Blood PC proliferation occurs simultaneously with increasing apoptosis rates, and is associated with PC survival. In addition, the proliferating activity of these PCs is enhanced by the addition of cytokines present in PC survival niches. Moreover, blood Ag-induced, but not BM, PCs exhibit the expression of molecules involved in the interaction between memory B cells and T follicular helper (Tfh) cells. In fact, purified circulating and tonsil Tfh cells increased IgG secretion by blood Ag-induced, but not by BM, PCs. This effect is exerted by augmenting blood PC survival through a mechanism partly dependent on cell contact. These results strongly suggest that the proliferating capacity of circulating Ag-induced PCs contributes to their competitive migration to survival niches, either to long-living PC niches or to temporal niches present in reactive lymphoid organs and inflamed tissues, structures where Tfh cells appear to participate.
Complement Deficiency Promotes Cutaneous Wound Healing in Mice
Authors: Rafail Stavros , Kourtzelis Ioannis , Foukas Periklis G. , Markiewski Maciej M. , DeAngelis Robert A. , Guariento Mara , Ricklin Daniel , Grice Elizabeth A. , Lambris John D. 
Published: December 2014

Abstract
Wound healing is a complex homeostatic response to injury that engages numerous cellular activities, processes, and cell-to-cell interactions. The complement system, an intricate network of proteins with important roles in immune surveillance and homeostasis, has been implicated in many physiological processes; however, its role in wound healing remains largely unexplored. In this study, we employ a murine model of excisional cutaneous wound healing and show that C3−/− mice exhibit accelerated early stages of wound healing. Reconstitution of C3−/− mice with serum from C3+/+ mice or purified human C3 abrogated the accelerated wound-healing phenotype. Wound histology of C3−/− mice revealed a reduction in inflammatory infiltrate compared with C3+/+ mice. C3 deficiency also resulted in increased accumulation of mast cells and advanced angiogenesis. We further show that mice deficient in the downstream complement effector C5 exhibit a similar wound-healing phenotype, which is recapitulated in C5aR1−/− mice, but not C3aR−/− or C5aR2−/− mice. Taken together, these data suggest that C5a signaling through C5aR may in part play a pivotal role in recruitment and activation of inflammatory cells to the wound environment, which in turn could delay the early stages of cutaneous wound healing. These findings also suggest a previously underappreciated role for complement in wound healing, and may have therapeutic implications for conditions of delayed wound healing.
Endogenous Intracellular Cathelicidin Enhances TLR9 Activation in Dendritic Cells and Macrophages
Authors: Nakagawa Yukinobu , Gallo Richard L. 
Published: December 2014

Abstract
Cathelicidins are a gene family best known for their antimicrobial action, but the diverse mature peptides they encode also have other host defense functions. The human cathelicidin peptide LL-37 enhances recognition of nucleic acids, an action whose significance is seen in human diseases such as psoriasis where it is associated with increased type 1 IFN production. This function has been attributed to the extracellular action of the peptide to facilitate uptake of nucleic acids. In this study, we demonstrate that the murine mature cathelicidin peptide (CRAMP), encoded by the mouse gene (Camp), is functionally distinct from the human mature peptide (LL-37), as it does not facilitate CpG entry. However, mouse cathelicidin does influence recognition of CpG as bone marrow–derived dendritic cells from Camp−/− mice have impaired CpG responses and Camp−/− mice had impaired response to CpG given i.v. or s.c. We show that cathelicidin concentrates in Lamp1 positive compartments, is colocalized with CpG in the endolysosome, can be immunoprecipitated with TLR9, and binds to CpG intracellulary. Collectively, these results indicate that the functions of cathelicidin in control of TLR9 activation may include both intracellular and extracellular effects.
Distinct Cellular Sources of Hepoxilin A3 and Leukotriene B4 Are Used To Coordinate Bacterial-Induced Neutrophil Transepithelial Migration
Authors: Pazos Michael A. , Pirzai Waheed , Yonker Lael M. , Morisseau Christophe , Gronert Karsten , Hurley Bryan P. 
Published: December 2014

Abstract
Neutrophilic infiltration is a leading contributor to pathology in a number of pulmonary disease states, including cystic fibrosis. Hepoxilin A3 (HXA3) is a chemotactic eicosanoid shown to mediate the transepithelial passage of neutrophils in response to infection in several model systems and at multiple mucosal surfaces. Another well-known eicosanoid mediating general neutrophil chemotaxis is leukotriene B4 (LTB4). We sought to distinguish the roles of each eicosanoid in the context of infection of lung epithelial monolayers by Pseudomonas aeruginosa. Using human and mouse in vitro transwell model systems, we used a combination of biosynthetic inhibitors, receptor antagonists, as well as mutant sources of neutrophils to assess the contribution of each chemoattractant in driving neutrophil transepithelial migration. We found that following chemotaxis to epithelial-derived HXA3 signals, neutrophil-derived LTB4 is required to amplify the magnitude of neutrophil migration. LTB4 signaling is not required for migration to HXA3 signals, but LTB4 generation by migrated neutrophils plays a significant role in augmenting the initial HXA3-mediated migration. We conclude that HXA3 and LTB4 serve independent roles to collectively coordinate an effective neutrophilic transepithelial migratory response.
Biogenic amines in smear and mould-ripened cheeses
Authors: Pleva Pavel , Buňková Leona , Theimrová Eva , Bartošáková Vendula , Buňka František , Purevdorj Khatantuul 
Published: December 2014

The aim of the study was the monitoring of six biogenic amines (histamine, tyramine, phenylethylamine, tryptamine, putrescine, and cadaverine) and two polyamines (spermidine and spermine) in 30 samples of dairy products purchased in the Czech Republic, namely in 15 samples of mould-ripened cheeses and in 15 samples of smear-ripened cheeses. A further goal was the microbiological analysis of the individual samples of cheeses (total count of microorganisms, number of enterobacteria, enterococci, lactic acid bacteria, yeasts and moulds). The monitored biogenic amines were analyzed by a high performance liquid chromatography equipped with a UV/VIS DAD detector. The amount of enterobacteria in fresh cheese exceeded 105 CFU.g‑1. In smear-ripened cheese flavourless (Romadur type), the amount was >103 CFU.g-1 and 104-105 CFU.g-1 in smear-ripened cheese with flavour. Biogenic amines were observed in two groups of blue cheeses (white veined cheese and blue veined cheese) and smear-ripened cheeses. In both groups, there is a possibility of the presence of biogenic amines because the number of microorganisms and concentration of free amino acids increase during ripening.In ten samples of soft smear-ripening acid cheese and in smear-ripened cheese, the total content of biogenic amines were 22-1000 mg.kg-1 and in 5 samples of these cheeses, it was in range 1000-6000 mg.kg-1. The total amount of biogenic amines in the blue cheeses were in range 40-600 mg.kg-1. The presense of the tyramine was observed in the all analysed cheeses. The tyramine producing strains generated more than 900 mg.kg-1 of this biogenic amine. The production of tryptamine in the analysed cheeses was not proved by this study. The results of this study show that biogenic amines and polyamines are common in cheese. However, in some cases, they can pose a significant health danger for consumers. Any legislative control authority does not monitor them, as they are secondary metabolites even though they are potential health risks.
Clinical Research Skills Development Program in Cell-Based Regenerative Medicine
Authors: Schulman Ivonne Hernandez , Suncion Viky , Karantalis Vasileios , Balkan Wayne , Hare Joshua M. ,   for the Cardiovascular Cell Therapy Research Network
Published: December 2014

Abstract

Summary
Cell-based therapy aimed at restoring organ function is one of the most exciting and promising areas of medical research. However, a novel intervention like cell-based therapy requires physician education and training. An increasing number of physicians untrained in regenerative medicine are using cell-based therapy to treat patients for a wide variety of chronic illnesses. The current lack of training for physicians in this area combined with the sharply increasing practice of regenerative medicine is concerning for a number of reasons, namely potential harm to patients and avoidable conflicts between governmental regulatory agencies and physicians. Academic medical fellowship training programs are needed that specifically prepare physicians for treating patients with cell-based therapies for various organ systems and chronic diseases. The National Heart, Lung, and Blood Institute established the Cardiovascular Cell Therapy Network to design and conduct clinical trials that advance the field of cell-based therapy for patients with cardiovascular disease. As part of the network, a two-year Clinical Research Skills Development Program was supported at two centers with the goal of training early career investigators in cell-based clinical and translational research. In this review, we describe the implementation of this training program at our institution with the purpose of promoting the further development of academic fellowship programs in cell-based regenerative medicine.
Medical Group Visits: A Feasibility Study to Manage Patients with Chronic Pain in an Underserved Urban Clinic
Authors: Gardiner Paula , Dresner Danielle , Barnett Katherine Gergen , Sadikova Ekaterina , Saper Robert 
Published: December 2014

Background: Chronic pain affects millions of racially diverse Americans. Evidence suggests that group medical visits are effective for treating chronic pain; similarly, a number of studies demonstrate the effectiveness of certain evidence-based complementary therapies in managing pain. Objectives: The primary goal of this study is to evaluate the feasibility of the integrative medical group visit (IMGV) care model in an inner-city racially diverse outpatient clinic. IMGV combines patient-centered, non-pharmacologic strategies and principles of mindfulness-based stress-reduction with a group medical visit to reduce pain and associated symptoms. Methods: We surveyed patients pre and post an 8-session IMGV program to evaluate changes in pain in the last week (0—10 point scale) and comorbid symptoms including depression (Patient Health Questionaire-8 [PHQ-8]), perceived stress, and sleep quality. We also recorded referrals to the program, patients screened for eligibility, total enrollment, loss to follow-up, and attendance. Results: Seventy patients joined IMGV, and of these, 65 (93%) enrolled in the study. Over the course of 12 months, 7 groups met (median 9 patients/group; range 8—13 participants). Mean difference in pain level for all patients between baseline and 8 weeks was 0.7 (SD=2.0, P=.005). Mean diference in PHQ-8 depression score for patients with baseline score ≥5 was 2.6 (SD=4.6, P<.001). Statistically significant improvements were also seen in sleep quality and perceived stress. Conclusion: A group visits program combining conventional and integrative medicine for predominantly racially diverse patients is feasible.
Observed multivariable signals of late 20th and early 21st century volcanic activity
Authors: Santer Benjamin D. , Solomon Susan , Bonfils Céline , Zelinka Mark D. , Painter Jeffrey F. , Beltran Francisco , Fyfe John C. , Johannesson Gardar , Mears Carl , Ridley David A. , Vernier Jean‐Paul , Wentz Frank J. 
Published: December 2014

AbstractThe relatively muted warming of the surface and lower troposphere since 1998 has attracted considerable attention. One contributory factor to this “warming hiatus” is an increase in volcanically induced cooling over the early 21st century. Here we identify the signals of late 20th and early 21st century volcanic activity in multiple observed climate variables. Volcanic signals are statistically discernible in spatial averages of tropical and near‐global SST, tropospheric temperature, net clear‐sky short‐wave radiation, and atmospheric water vapor. Signals of late 20th and early 21st century volcanic eruptions are also detectable in near‐global averages of rainfall. In tropical average rainfall, however, only a Pinatubo‐caused drying signal is identifiable. Successful volcanic signal detection is critically dependent on removal of variability induced by the El Niño–Southern Oscillation.
Tidal modulation and triggering of low‐frequency earthquakes in northern Cascadia
Authors: Royer A. A. , Thomas A. M. , Bostock M. G. 
Published: December 2014

AbstractWe analyze the influence of Earth and ocean tides on the triggering of low‐frequency earthquakes (LFEs) in northern Cascadia using three LFE catalogs for southern Vancouver Island and Washington state from episodic tremor and slip events between 2003 and 2013. Sensitivities of LFE families to tidally induced fault normal stress, updip shear stress (UDSS), and corresponding time derivatives are computed and their geographic variability is mapped. We find localized areas showing higher sensitivity to UDSS than their surroundings, suggesting that tidal sensitivity depends on laterally heterogeneous physical properties such as variable pore fluid pressures and frictional properties along the plate interface. We observe that sensitivity of LFEs to UDSS rises dramatically from near zero on the first day of strong activity to a maximum ∼4 days later. In addition, the peak LFE rate transitions from a correlation with peak tidal shear stress rate to a correlation with peak tidal shear stress through large slow slip events. We identify 64 Rapid‐Tremor‐Reversals (RTRs) that start a few days after the main slip front. The RTRs have an average stress drop of ∼0.8 kPa and a majority (72%) occurs during periods of large positive UDSS. The combined observations imply that RTRs play an important role in slow slip processes and that modulation of creep rate due to tidal stress and tidal triggering of secondary events are jointly responsible for the observed tidal sensitivity.
Dynamics of the surface layer diurnal cycle in the equatorial Atlantic Ocean (0°, 23°W)
Authors: Wenegrat Jacob O. , McPhaden Michael J. 
Published: December 2014

AbstractA 15 year time series (1999–2014) from the 0°, 23°W Prediction and Research Moored Array in the Tropical Atlantic (PIRATA) mooring, which includes an 8 month record (October 2008 to June 2009) of high‐resolution near‐surface velocity data, is used to analyze the diurnal variability of sea surface temperature, shear, and stratification in the central equatorial Atlantic. The ocean diurnal cycle exhibits pronounced seasonality that is linked to seasonal variations in the surface wind field. In boreal summer and fall, steady trade winds and clear skies dominate, with limited diurnal variability in sea surface temperature. Diurnal shear layers, with reduced Richardson numbers, are regularly observed descending into the marginally unstable equatorial undercurrent below the mixed layer, conditions favorable for the generation of deep‐cycle turbulence. In contrast, in boreal winter and spring, winds are lighter and more variable, mixed layers are shallow, and diurnal variability of sea surface temperature is large. During these conditions, diurnal shear layers are less prominent, and the stability of the undercurrent increases, suggesting seasonal covariance between diurnal near‐surface shear and deep‐cycle turbulence. Modulation of the ocean diurnal cycle by tropical instability waves is also identified. This work provides the first observational assessment of the diurnal cycle of near‐surface shear, stratification, and marginal instability in the equatorial Atlantic, confirming previous modeling results and offering a complementary perspective on similar work in the equatorial Pacific.
Observational study of surface spectral radiation and corresponding albedo over Gobi, desert, and bare loess surfaces in northwestern China
Authors: Zheng Zhiyuan , Dong Wenjie , Li Zhenchao , Zhao Wei , Hu Shanshan , Yan Xiaodong , Zhao Jiaqi , Wei Zhigang 
Published: December 2014

AbstractIn this paper, the field experiments on ground surface spectral broadband solar radiation (SR) and corresponding albedo were introduced at three man‐made sites at Gobi, desert, and bare loess zones during three different intensive observational periods (IOP) from 2010 to 2013 in Gansu Province, respectively. The continuous and high temporal resolution records of ground surface solar radiation are presented, including global (GR), ultraviolet (UV), visible (VIS), and near‐infrared radiation (NIR). The corresponding albedos are analyzed over three typical nonvegetated underlying surfaces in arid and semiarid and semihumid regions of northwestern China. The preliminary investigations were carried out. The results show that the variation trends of UV, VIS, and NIR are coincident with the GR, and the irradiances are gradually decreasing throughout the IOP at each site; the energy ratios of VIS/GR are all approximately 40.2%, and the ratios of NIR/GR are all approximately 54.4% at the Gobi, desert, and bare loess zones; and the averaged albedos of the soil for VIS are 0.231, 0.211, and 0.142 and for the NIR are 0.266, 0.252, and 0.255 over the Gobi, desert, and bare loess land surfaces, respectively. The energy ratios of VIS/GR and NIR/GR are not 50% as prescribed for all of the soil color classes in most of land surface models (LSMs). The observational soil albedo values for NIR are not twice to that of the VIS as predicted in some LSMs for the underlying surface at the three sites. GR albedo is determined by the energy ratios of SR/GR and SR albedos.