bluuebunny/crossref_metadata_2025_split huggingface dataset:
DUSP3 Genetic Deletion Confers M2-like Macrophage–Dependent Tolerance to Septic Shock
Authors: Singh Pratibha , Dejager Lien , Amand Mathieu , Theatre Emilie , Vandereyken Maud , Zurashvili Tinatin , Singh Maneesh , Mack Matthias , Timmermans Steven , Musumeci Lucia , Dejardin Emmanuel , Mustelin Tomas , Van Ginderachter Jo A. , Moutschen Michel , Oury Cécile , Libert Claude , Rahmouni Souad 
Published: April 2015

Abstract
DUSP3 is a small dual-specificity protein phosphatase with an unknown physiological function. We report that DUSP3 is strongly expressed in human and mouse monocytes and macrophages, and that its deficiency in mice promotes tolerance to LPS-induced endotoxin shock and to polymicrobial septic shock after cecal ligation and puncture. By using adoptive transfer experiments, we demonstrate that resistance to endotoxin is macrophage dependent and transferable, and that this protection is associated with a striking increase of M2-like macrophages in DUSP3−/− mice in both the LPS and cecal ligation and puncture models. We show that the altered response of DUSP3−/− mice to sepsis is reflected in decreased TNF production and impaired ERK1/2 activation. Our results demonstrate that DUSP3 plays a key and nonredundant role as a regulator of innate immune responses by mechanisms involving the control of ERK1/2 activation, TNF secretion, and macrophage polarization.
Integrated Innate Mechanisms Involved in Airway Allergic Inflammation to the Serine Protease Subtilisin
Authors: Florsheim Esther , Yu Shuang , Bragatto Ivan , Faustino Lucas , Gomes Eliane , Ramos Rodrigo N. , Barbuto José Alexandre M. , Medzhitov Ruslan , Russo Momtchilo 
Published: April 2015

Abstract
Proteases are recognized environmental allergens, but little is known about the mechanisms responsible for sensing enzyme activity and initiating the development of allergic inflammation. Because usage of the serine protease subtilisin in the detergent industry resulted in an outbreak of occupational asthma in workers, we sought to develop an experimental model of allergic lung inflammation to subtilisin and to determine the immunological mechanisms involved in type 2 responses. By using a mouse model of allergic airway disease, we have defined in this study that s.c. or intranasal sensitization followed by airway challenge to subtilisin induces prototypic allergic lung inflammation, characterized by airway eosinophilia, type 2 cytokine release, mucus production, high levels of serum IgE, and airway reactivity. These allergic responses were dependent on subtilisin protease activity, protease-activated receptor-2, IL-33R ST2, and MyD88 signaling. Also, subtilisin stimulated the expression of the proallergic cytokines IL-1α, IL-33, thymic stromal lymphopoietin, and the growth factor amphiregulin in a human bronchial epithelial cell line. Notably, acute administration of subtilisin into the airways increased lung IL-5–producing type 2 innate lymphoid cells, which required protease-activated receptor-2 expression. Finally, subtilisin activity acted as a Th2 adjuvant to an unrelated airborne Ag-promoting allergic inflammation to inhaled OVA. Therefore, we established a murine model of occupational asthma to a serine protease and characterized the main molecular pathways involved in allergic sensitization to subtilisin that potentially contribute to initiate allergic airway disease.
Intratumoral Delivery of IL-21 Overcomes Anti-Her2/Neu Resistance through Shifting Tumor-Associated Macrophages from M2 to M1 Phenotype
Authors: Xu Meng , Liu Mingyue , Du Xuexiang , Li Sirui , Li Hang , Li Xiaozhu , Li Ying , Wang Yang , Qin Zhihai , Fu Yang-Xin , Wang Shengdian 
Published: April 2015

Abstract
Tumor resistance is a major hurdle to anti-Her2/neu Ab–based cancer therapy. Current strategies to overcome tumor resistance focus on tumor cell–intrinsic resistance. However, the extrinsic mechanisms, especially the tumor microenvironment, also play important roles in modulating the therapeutic response and resistance of the Ab. In this study, we demonstrate that tumor progression is highly associated with TAMs with immune-suppressive M2 phenotypes, and deletion of TAMs markedly enhanced the therapeutic effects of anti-Her2/neu Ab in a HER2/neu-dependent breast cancer cell TUBO model. Tumor local delivery of IL-21 can skew TAM polarization away from the M2 phenotype to a tumor-inhibiting M1 phenotype, which rapidly stimulates T cell responses against tumor and dramatically promotes the therapeutic effect of anti-Her2 Ab. Skewing of TAM polarization by IL-21 relies substantially on direct action of IL-21 on TAMs rather than stimulation of T and NK cells. Thus, our findings identify the abundant TAMs as a major extrinsic barrier for anti-Her2/neu Ab therapy and present a novel approach to combat this extrinsic resistance by tumor local delivery of IL-21 to skew TAM polarization. This study offers a therapeutic strategy to modulate the tumor microenvironment to overcome tumor-extrinsic resistance.
Bordetella pertussis Adenylate Cyclase Toxin Blocks Induction of Bactericidal Nitric Oxide in Macrophages through cAMP-Dependent Activation of the SHP-1 Phosphatase
Authors: Cerny Ondrej , Kamanova Jana , Masin Jiri , Bibova Ilona , Skopova Karolina , Sebo Peter 
Published: April 2015

Abstract
The adenylate cyclase toxin–hemolysin (CyaA) plays a key role in the virulence of Bordetella pertussis. CyaA penetrates complement receptor 3–expressing phagocytes and catalyzes uncontrolled conversion of cytosolic ATP to the key second messenger molecule cAMP. This paralyzes the capacity of neutrophils and macrophages to kill bacteria by complement-dependent oxidative burst and opsonophagocytic mechanisms. We show that cAMP signaling through the protein kinase A (PKA) pathway activates Src homology domain 2 containing protein tyrosine phosphatase (SHP) 1 and suppresses production of bactericidal NO in macrophage cells. Selective activation of PKA by the cell-permeable analog N6-benzoyladenosine-3′,5′-cyclic monophosphate interfered with LPS-induced inducible NO synthase (iNOS) expression in RAW264.7 macrophages, whereas inhibition of PKA by H-89 largely restored the production of iNOS in CyaA-treated murine macrophages. CyaA/cAMP signaling induced SHP phosphatase–dependent dephosphorylation of the c-Fos subunit of the transcription factor AP-1 and thereby inhibited TLR4-triggered induction of iNOS gene expression. Selective small interfering RNA knockdown of SHP-1, but not of the SHP-2 phosphatase, rescued production of TLR-inducible NO in toxin-treated cells. Finally, inhibition of SHP phosphatase activity by NSC87877 abrogated B. pertussis survival inside murine macrophages. These results reveal that an as yet unknown cAMP-activated signaling pathway controls SHP-1 phosphatase activity and may regulate numerous receptor signaling pathways in leukocytes. Hijacking of SHP-1 by CyaA action then enables B. pertussis to evade NO-mediated killing in sentinel cells of innate immunity.
Distinctive Structural Hallmarks and Biological Activities of the Multiple Cathelicidin Antimicrobial Peptides in a Primitive Teleost Fish
Authors: Zhang Xu-Jie , Zhang Xiang-Yang , Zhang Nu , Guo Xia , Peng Kai-Song , Wu Han , Lu Long-Feng , Wu Nan , Chen Dan-Dan , Li Shun , Nie Pin , Zhang Yong-An 
Published: April 2015

Abstract
Cathelicidin antimicrobial peptides (CAMPs) represent a crucial component of the innate immune system in vertebrates. Although widely studied in mammals, little is known about the structure and function of fish CAMPs. Further to the previous findings, two more cathelicidin genes and multiple transcripts from rainbow trout were identified in the present study. Interestingly, we found that trout have evolved energy-saving forms of cathelicidins with the total deletion of the characteristic cathelin-like domain. Sequence analysis revealed that salmonid CAMPs have formed a special class of antimicrobial peptides in vertebrates with three distinctive hallmarks: the N terminus is intensified by positive charges, the central region consists of repetitive motifs based on RPGGGS, and the C terminus is lowly charged. Immunofluorescence localization of trout CAMPs demonstrated that these peptides expressed mainly at the mucosal layer of gut. Meanwhile, signals around sinusoids were also detected in head kidney. Moreover, the biological activities of trout CAMPs were proved to be mediated by the N terminus. Additionally, the repetitive motifs characteristically existing in Salmonidae increased the structural flexibilities of peptides and further increased the antibacterial and IL-8–stimulating activities. Unlike most α helical and cytotoxic mammalian CAMPs, trout CAMPs, mainly consisting of β-sheet and random coil, exhibited no cytotoxic activities. The distinctive structural features of trout CAMPs provide new insights into the understanding of the evolution of CAMPs in vertebrates. Moreover, the high bacterial membrane selectivity of trout CAMPs will help to design excellent peptide antibiotics.
Smart apps for the smart plastic surgeon
Authors: Venkataram Aniketh , Ellur Sunderraj , Kujur Abha Rani , Joseph Vijay 
Published: April 2015

ABSTRACTSmartphones have the ability to benefit plastic surgeons in all aspects of patient care and education. With the sheer number of applications available and more being created everyday, it is easy to miss out on apps which could be of great relevance. Moreover, the range of android applications available has not been extensively discussed in the literature. To this end, we have compiled an exhaustive list of android smartphone applications, which we feel can help our day to day functioning. The apps have been extensively reviewed and neatly described along with all their potential uses. In addition, we have made an effort to highlight ‘non-medical’ or efficiency apps which can improve departmental functioning. These apps have not been described in prior articles, and their functionality might not be known to all. We believe that the technology savvy plastic surgeon can make maximum use of these apps to his benefit.
Review of clinical and endoscopic features of metastatic tumors of the gastrointestinal tract
Authors: Bashir Showkat , Borum Marie 
Published: April 2015

AbstractMetastatic tumors may occur at any site within the digestive tract. Most of these metastasis are observed in the stomach, small bowel, duodenum, and rarely in the esophagus and colon. The progress in cancer treatment, improved survival of cancer patients combined with increased use of endoscopy is likely going to increase the findings of secondary tumors of the gastrointestinal tract. As such the endoscopist has to be aware about the clinical and endoscopic features of these lesions, maintain high index of suspicion in proper clinical settings and alert the pathologist about the possibility of metastatic tumor.
2009 American Anthropological Association Meeting, New Orleans, LA, Session on Culture, Health and Aging in Native North American Communities
Authors: Warry Wayne 
Published: April 2015

Introduction: Wayne WarryMarie’s Story Of Aging Well: Toward New Perspectives on the Experience Of Aging For Aboriginal Seniors in CanadaSyvia Abonyi Marie Favel, Ile a la CrosseMistreatment and the Meaning of Respect for Native EldersLori L. Jervis William Sconzert HallForgetting and Forgotten: Dementia in Aboriginal SeniorsKristen Jacklin and Wayne WarryUnderstanding Aging: Culture, Cognitive Health and Contemporary Aboriginal People’s Experience with DementiaJessica PacePerspectives on Brain Autopsy, Diabetic Amputation, and End-of-Life Issues among Elderly American Indian People Neil Henderson, L. Carson Henderson, Ryan Blanton and Steven GomezDiscussion: Robert C. Harman and Wayne Warry
Young Adults’ Perceptions of Intergenerational Communication: Mongolian and American Data
Authors: Choi Charles W. , Giles Howard , Hajek Christopher 
Published: April 2015

This study examines Mongolian and American young adults’ perceptions of intergenerational communication, specifically with respect to age stereotypes, norms of respect, communication behavior, and communication satisfaction. Using the Communication Predicament of Aging Model as a theoretical framework, the relationships between these variables are investigated using regression analyses. Young adults from both cultural contexts were asked to evaluate prior interactions with both middle-aged and older adults. The findings indicate a difference between how each generation is perceived, and the unique role of the middle-aged generation in Mongolia is evident.
Aging, Gender and Sexuality in Brazilian Society
Authors: Debert Guita Grin 
Published: April 2015

Drawing on the interplay between gender, aging, and sexuality, the aim of this article is twofold: (1) to show how Brazilian gerontologists treat gender differences and sexual activity in old age; (2) to analyze the ways discourses regarding the aging body and sexuality are perceived and evaluated by older women and men . I argue that attempts of gerontologists’ to eroticize old age have to contend with the widespread notion that the desire for sex is inevitably lost with age. Thus, in the retiree associations that were studied, men had a tendency to assume they are not ‘old’ because their erectile function was still in good condition, and divorced or widowed women, in senior citizen associations, tend to regard themselves as happy due to having freed themselves from the sexual obligations imposed by marriage. In both cases, the dominant belief that there is a loss of sexual desire in old age was reproduced.
A model for electric field enhancement in lightning leader tips to levels allowing X‐ray and γ ray emissions
Authors: Babich L. P. , Bochkov E. I. , Kutsyk I. M. , Neubert T. , Chanrion O. 
Published: April 2015

AbstractA model is proposed capable of accounting for the local electric field increase in front of the lightning stepped leader up to magnitudes allowing front electrons to overcome the runaway energy threshold and thus to initiate relativistic runaway electron avalanches capable of generating X‐ray and γ ray bursts observed in negative lightning leader. The model is based on an idea that an ionization wave, propagating in a preionized channel, is being focused, such that its front remains narrow and the front electric field is being enhanced. It is proposed that when a space leader segment, formed ahead of a negative lightning leader, connects to the leader, the electric potential of the leader is transferred through the space leader in an ionizing wave that continues into the partly ionized channels of preexisting streamers of the space leader. It is shown with numerical simulations that the ionization channels of streamers limit the lateral expansion of the ionization wave, thereby enhancing the peak electric field to values allowing an acceleration of low‐energy electrons into the runaway regime where electrons efficiently generate bremsstrahlung. The results suggest that the inhomogeneous ionization environment at the new leader tip amplifies the production rate of energetic electrons relative to a homogeneous environment considered in the past studies.
A forward operator and its adjoint for GPS slant total delays
Authors: Zus Florian , Dick Galina , Heise Stefan , Wickert Jens 
Published: April 2015

AbstractIn a recent study we developed a fast and accurate algorithm to compute Global Positioning System (GPS) Slant Total Delay (STDs) utilizing numerical weather model data. Having developed a forward operator we construct in this study the tangent linear (adjoint) operator by application of the chain rule of differential calculus in forward (reverse) mode. Armed with these operators we show in a simulation study the potential benefit of GPS STDs in inverse modeling. We conclude that the developed operators are tailored for three (four)‐dimensional variational data assimilation and/or travel time tomography.
Robust signals of future projections of Indian summer monsoon rainfall by IPCC AR5 climate models: Role of seasonal cycle and interannual variability
Authors: Jayasankar C. B. , Surendran Sajani , Rajendran Kavirajan 
Published: April 2015

AbstractCoupled Model Intercomparison Project phase 5 (Fifth Assessment Report of Intergovernmental Panel on Climate Change) coupled global climate model Representative Concentration Pathway 8.5 simulations are analyzed to derive robust signals of projected changes in Indian summer monsoon rainfall (ISMR) and its variability. Models project clear future temperature increase but diverse changes in ISMR with substantial intermodel spread. Objective measures of interannual variability (IAV) yields nearly equal chance for future increase or decrease. This leads to discrepancy in quantifying changes in ISMR and variability. However, based primarily on the physical association between mean changes in ISMR and its IAV, and objective methods such as k‐means clustering with Dunn's validity index, mean seasonal cycle, and reliability ensemble averaging, projections fall into distinct groups. Physically consistent groups of models with the highest reliability project future reduction in the frequency of light rainfall but increase in high to extreme rainfall and thereby future increase in ISMR by 0.74 ± 0.36 mm d−1, along with increased future IAV. These robust estimates of future changes are important for useful impact assessments.
Physical mechanism of initial breakdown pulses and narrow bipolar events in lightning discharges
Authors: da Silva Caitano L. , Pasko Victor P. 
Published: April 2015

AbstractTo date the true nature of initial breakdown pulses (IBPs) and narrow bipolar events (NBEs) in lightning discharges remains a mystery. Recent experimental evidence has correlated IBPs to the initial development of lightning leaders inside the thundercloud. NBE wideband waveforms resemble classic IBPs in both amplitude and duration. Most NBEs are quite peculiar in the sense that very frequently they occur in isolation from other lightning processes. The remaining fraction, 16% of positive polarity NBEs, according to Wu et al. (2014), happens as the first event in an otherwise regular intracloud lightning discharge. These authors point out that the initiator type of NBEs has no difference with other NBEs that did not start lightning, except for the fact that they occur deeper inside the thunderstorm (i.e., at lower altitudes). In this paper, we propose a new physical mechanism to explain the source of both IBPs and NBEs. We propose that IBPs and NBEs are the electromagnetic transients associated with the sudden (i.e., stepwise) elongation of the initial negative leader extremity in the thunderstorm electric field. To demonstrate our hypothesis a novel computational/numerical model of the bidirectional lightning leader tree is developed, consisting of a generalization of electrostatic and transmission line approximations found in the literature. Finally, we show how the IBP and NBE waveform characteristics directly reflect the properties of the bidirectional lightning leader (such as step length, for example) and amplitude of the thunderstorm electric field.
Diagnostic algorithm for unilateral sinus disease: a 15‐year retrospective review
Authors: Paz Silva Marianella , Pinto Jayant M. , Corey Jacquelynne P. , Mhoon Ernest E. , Baroody Fuad M. , Naclerio Robert M. 
Published: April 2015

BackgroundPatients presenting with unilateral sinus symptoms or nasal polyps raise concerns about sinister pathology. Yet despite the relatively common occurrence of this presentation, and its potential severity, an organized diagnostic approach to unilateral sinus disease (USD) has never been defined. The purpose of this work was to propose a diagnostic algorithm for managing patients with USD based on prior experience.MethodsWe performed a retrospective review of the medical records of all patients with USD who underwent surgical intervention and had pathological specimens during a 15‐year period at an urban academic center. Nasal endoscopy and computed tomography (CT) scan findings, demographic characteristics, presenting symptoms, medical histories, and previous treatments were analyzed.ResultsA total of 191 patients met the inclusion criteria, 153 of whom were initially diagnosed at our center. Among the latter group, 51 (33%) presented with a nasal mass or polyp observed by endoscopy. Inverted papilloma was present in 16% of those cases, and malignant tumors comprised 14%. In contrast, of patients without an obvious nasal polyp (n = 102), 2% had inverted papilloma and 3% had malignancies. Overall, chronic rhinosinusitis was the most common diagnosis both in patients with polyps (67%) and those without nasal polyps (69%).ConclusionAlthough USD is most likely to represent chronic inflammation, there exists a fair likelihood of finding malignant pathology, particularly in cases where patients have a unilateral polyp. Based on this review, we propose a strategy for the management of new presentations of USD.
Benzannulation of Triynes to Generate Functionalized Arenes by Spontaneous Incorporation of Nucleophiles
Authors: Karmakar Rajdip , Yun Sang Young , Chen Jiajia , Xia Yuanzhi , Lee Daesung 
Published: April 2015

AbstractThe thermal reaction of ester‐tethered 1,3,8‐triynes provides novel benzannulation products with concomitant incorporation of a nucleophile. Evidence suggests that this reaction proceeds via an allene‐enyne intermediate generated by an Alder‐ene reaction in the first step. Depending on the substituent of the alkyne moiety on the allene‐enyne intermediate, the subsequent transformation can take one of two different paths, each leading to discrete aromatization products. The benzannulation of a silane‐substituted 1,3,8‐triynes provides arene products with a nucleophile incorporated onto the newly formed benzene core, whereas an aryl substituent leads to nucleophile trapping at the benzylic carbon atom connected to the aryl substituent. The formation of these two different products results from the involvement of two regioisomeric allene‐enyne intermediates.
Synthesis and characterization of acid–base polyimides bearing pendant sulfoalkoxy groups for direct methanol fuel cell applications
Authors: Qi Zhigang , Gong Chenliang , Liang Yu , Li Hui , Wu Zhongying , Zhang Shujiang , Li Yanfeng 
Published: April 2015

ABSTRACTA series of acid–base polyimides with sulfonic acid groups in the side chains have been prepared, based on a new synthesized sulfonated diamine monomer containing pyridine functional group. The effect of the introduction of pyridine groups into copolymer backbone on the properties of membrane were evaluated through the investigation of membrane parameters. The copolymers produced flexible, tough, and transparent membranes by solvent casting method. All the prepared membranes displayed high thermal stability, great oxidative stability and good mechanical properties. They exhibited appropriate water uptake (15.8–30.2 wt % at 80°C) and remarkable dimensional stability (2.5–6.9% at 80°C). The proton conductivity of SPI‐80 was 1.01 × 10−2 S cm−1 at room temperature. Moreover, the methanol permeability of SPI‐80 membrane was 1.22 × 10−7 cm2 s−1, which was lower than 23.8 × 10−7 cm2 s−1 of Nafion 117. Therefore, these acid‐base polyimides materials have a promising prospect for direct methanol fuel cell applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42238.