bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Fluorescence versus Forward Scatter Time-of-Flight and Increased Peak versus Integral Fluorescence Ratios Indicate Receptor Clustering in Flow Cytometry
Authors: Fürnrohr Barbara G. , Stein Merle , Rhodes Benjamin , Chana Prabhjoat S. , Schett Georg , Vyse Timothy J. , Herrmann Martin , Mielenz Dirk 
Published: May 2015

Abstract
Clustering of surface receptors is often required to initiate signal transduction, receptor internalization, and cellular activation. To study the kinetics of clustering, we developed an economic high-throughput method using flow cytometry. The quantification of receptor clustering by flow cytometry is based on the following two observations: first, the fluorescence signal length (FL time-of-flight [ToF]) decreases relative to the forward scatter signal length (FSc-ToF), and second, the peak FL (FL-peak) increases relative to the integral FL (FL-integral) upon clustering of FL-labeled surface receptors. Receptor macroclustering can therefore be quantified using the ratios FL-ToF/FSc-ToF (method ToF) or FL-peak/FL-integral (method Peak). We have used these methods to analyze clustering of two immune receptors known to undergo different conformational and oligomeric states: the BCR and the complement receptor 3 (CR3), on murine splenocytes, purified B cells, and human neutrophils. Engagement of both the BCR and CR3, on immortalized as well as primary murine B cells and human neutrophil, respectively, resulted in decreased FL-ToF/FSc-ToF and increased FL-peak/FL-integral ratios. Manipulation of the actin-myosin cytoskeleton altered BCR clustering which could be measured using the established parameters. To confirm clustering of CR3 on neutrophils, we applied imaging flow cytometry. Because receptor engagement is as a biological process dependent on cell viability, energy metabolism, and temperature, receptor clustering can only be quantified by gating on viable cells under physiological conditions. In summary, with this novel method, receptor clustering on nonadherent cells can easily be monitored by high-throughput conventional flow cytometry.
Deficiency of CD40 Reveals an Important Role for LIGHT in Anti-Leishmania Immunity
Authors: Okwor Ifeoma , Xu Guilian , Tang Haidong , Liang Yong , Fu Yang-Xin , Uzonna Jude E. 
Published: May 2015

Abstract
We previously showed that LIGHT and its receptor herpes virus entry mediator (HVEM) are important for development of optimal CD4+ Th1 cell immunity and resistance to primary Leishmania major infection in mice. In this study, we further characterized the contributions of this molecule in dendritic cell (DC) maturation, initiation, and maintenance of primary immunity and secondary anti-Leishmania immunity. Flow-cytometric studies showed that CD8α+ DC subset was mostly affected by HVEM-Ig and lymphotoxin β receptor-Ig treatment. LIGHT signaling is required at both the priming and the maintenance stages of primary anti-Leishmania immunity but is completely dispensable during secondary immunity in wild type mice. However, LIGHT blockade led to impaired IL-12 and IFN-γ responses and loss of resistance in healed CD40-deficient mice after L. major challenge. The protective effect of LIGHT was mediated primarily via its interaction with lymphotoxin β receptor on CD8α+ DCs. Collectively, our results show that although LIGHT is critical for maintenance of primary Th1 response, it is dispensable during secondary anti-Leishmania immunity in the presence of functional CD40 signaling as seen in wild type mice.
Structural Analysis of Der p 1–Antibody Complexes and Comparison with Complexes of Proteins or Peptides with Monoclonal Antibodies
Authors: Osinski Tomasz , Pomés Anna , Majorek Karolina A. , Glesner Jill , Offermann Lesa R. , Vailes Lisa D. , Chapman Martin D. , Minor Wladek , Chruszcz Maksymilian 
Published: May 2015

Abstract
Der p 1 is a major allergen from the house dust mite, Dermatophagoides pteronyssinus, that belongs to the papain-like cysteine protease family. To investigate the antigenic determinants of Der p 1, we determined two crystal structures of Der p 1 in complex with the Fab fragments of mAbs 5H8 or 10B9. Epitopes for these two Der p 1–specific Abs are located in different, nonoverlapping parts of the Der p 1 molecule. Nevertheless, surface area and identity of the amino acid residues involved in hydrogen bonds between allergen and Ab are similar. The epitope for mAb 10B9 only showed a partial overlap with the previously reported epitope for mAb 4C1, a cross-reactive mAb that binds Der p 1 and its homolog Der f 1 from Dermatophagoides farinae. Upon binding to Der p 1, the Fab fragment of mAb 10B9 was found to form a very rare α helix in its third CDR of the H chain. To provide an overview of the surface properties of the interfaces formed by the complexes of Der p 1–10B9 and Der p 1–5H8, along with the complexes of 4C1 with Der p 1 and Der f 1, a broad analysis of the surfaces and hydrogen bonds of all complexes of Fab–protein or Fab–peptide was performed. This work provides detailed insight into the cross-reactive and specific allergen–Ab interactions in group 1 mite allergens. The surface data of Fab–protein and Fab–peptide interfaces can be used in the design of conformational epitopes with reduced Ab binding for immunotherapy.
PRMT1 Upregulated by Epithelial Proinflammatory Cytokines Participates in COX2 Expression in Fibroblasts and Chronic Antigen-Induced Pulmonary Inflammation
Authors: Sun Qingzhu , Liu Li , Roth Michael , Tian Jia , He Qirui , Zhong Bo , Bao Ruanjuan , Lan Xi , Jiang Congshan , Sun Jian , Yang Xudong , Lu Shemin 
Published: May 2015

Abstract
Protein arginine methyltransferase (PRMT)1, methylating both histones and key cellular proteins, has emerged as a key regulator of various cellular processes. This study aimed to identify the mechanism that regulates PRMT1 in chronic Ag-induced pulmonary inflammation (AIPI) in the E3 rat asthma model. E3 rats were challenged with OVA for 1 or 8 wk to induce acute or chronic AIPI. Expression of mRNAs was detected by real-time quantitative PCR. PRMT1, TGF-β, COX2, and vascular endothelial growth factor protein expression in lung tissues was determined by immunohistochemistry staining and Western blotting. In the in vitro study, IL-4–stimulated lung epithelial cell (A549) medium (ISEM) with or without anti–TGF-β Ab was applied to human fibroblasts from lung (HFL1). The proliferation of HFL1 was determined by MTT. AMI-1 (pan-PRMT inhibitor) was administered intranasally to chronic AIPI rats to determine PRMT effects on asthmatic parameters. In lung tissue sections, PRMT1 expression was significantly upregulated, mainly in epithelial cells, in acute AIPI lungs, whereas it was significantly upregulated mainly in fibroblasts in chronic AIPI lungs. The in vitro study revealed that ISEM elevates PRMT1, COX2, and vascular endothelial growth factor expressions, and it promoted fibroblast proliferation. The application of anti–TGF-β Ab suppressed COX2 upregulation by ISEM. AMI-1 inhibited the expression of COX2 in TGF-β–stimulated cells. In the in vivo experiment, AMI-1 administered to AIPI rats reduced COX2 production and humoral immune response, and it abrogated mucus secretion and collagen generation. These findings suggested that TGF-β–induced PRMT1 expression participates in fibroblast proliferation and chronic airway inflammation in AIPI.
A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor β Subunit, Glycoprotein 130
Authors: Hong Soon-Sun , Choi Jung Ho , Lee Sung Yoon , Park Yeon-Hwa , Park Kyung-Yeon , Lee Joo Young , Kim Juyoung , Gajulapati Veeraswamy , Goo Ja-Il , Singh Sarbjit , Lee Kyeong , Kim Young-Kook , Im So Hee , Ahn Sung-Hoon , Rose-John Stefan , Heo Tae-Hwe , Choi Yongseok 
Published: May 2015

Abstract
IL-6 is a major causative factor of inflammatory disease. Although IL-6 and its signaling pathways are promising targets, orally available small-molecule drugs specific for IL-6 have not been developed. To discover IL-6 antagonists, we screened our in-house chemical library and identified LMT-28, a novel synthetic compound, as a candidate IL-6 blocker. The activity, mechanism of action, and direct molecular target of LMT-28 were investigated. A reporter gene assay showed that LMT-28 suppressed activation of STAT3 induced by IL-6, but not activation induced by leukemia inhibitory factor. In addition, LMT-28 downregulated IL-6–stimulated phosphorylation of STAT3, gp130, and JAK2 protein and substantially inhibited IL-6–dependent TF-1 cell proliferation. LMT-28 antagonized IL-6–induced TNF-α production in vivo. In pathologic models, oral administration of LMT-28 alleviated collagen-induced arthritis and acute pancreatitis in mice. Based on the observation of upstream IL-6 signal inhibition by LMT-28, we hypothesized IL-6, IL-6Rα, or gp130 to be putative molecular targets. We subsequently demonstrated direct interaction of LMT-28 with gp130 and specific reduction of IL-6/IL-6Rα complex binding to gp130 in the presence of LMT-28, which was measured by surface plasmon resonance analysis. Taken together, our data suggest that LMT-28 is a novel synthetic IL-6 inhibitor that functions through direct binding to gp130.
Airway-Resident Memory CD8 T Cells Provide Antigen-Specific Protection against Respiratory Virus Challenge through Rapid IFN-γ Production
Authors: McMaster Sean R. , Wilson Jarad J. , Wang Hong , Kohlmeier Jacob E. 
Published: May 2015

Abstract
CD8 airway resident memory T (TRM) cells are a distinctive TRM population with a high turnover rate and a unique phenotype influenced by their localization within the airways. Their role in mediating protective immunity to respiratory pathogens, although suggested by many studies, has not been directly proven. This study provides definitive evidence that airway CD8 TRM cells are sufficient to mediate protection against respiratory virus challenge. Despite being poorly cytolytic in vivo and failing to expand after encountering Ag, airway CD8 TRM cells rapidly express effector cytokines, with IFN-γ being produced most robustly. Notably, established airway CD8 TRM cells possess the ability to produce IFN-γ faster than systemic effector memory CD8 T cells. Furthermore, naive mice receiving intratracheal transfer of airway CD8 TRM cells lacking the ability to produce IFN-γ were less effective at controlling pathogen load upon heterologous challenge. This direct evidence of airway CD8 TRM cell–mediated protection demonstrates the importance of these cells as a first line of defense for optimal immunity against respiratory pathogens and suggests they should be considered in the development of future cell-mediated vaccines.
Reconstituted High-Density Lipoprotein Attenuates Cholesterol Crystal–Induced Inflammatory Responses by Reducing Complement Activation
Authors: Niyonzima Nathalie , Samstad Eivind O. , Aune Marie H. , Ryan Liv , Bakke Siril S. , Rokstad Anne Mari , Wright Samuel D. , Damås Jan K. , Mollnes Tom E. , Latz Eicke , Espevik Terje 
Published: May 2015

Abstract
Chronic inflammation of the arterial wall is a key element in the development of atherosclerosis, and cholesterol crystals (CC) that accumulate in plaques are associated with initiation and progression of the disease. We recently revealed a link between the complement system and CC-induced inflammasome caspase-1 activation, showing that the complement system is a key trigger in CC-induced inflammation. HDL exhibits cardioprotective and anti-inflammatory properties thought to explain its inverse correlation to cardiovascular risk. In this study, we sought to determine the effect of reconstituted HDL (rHDL) on CC-induced inflammation in a human whole blood model. rHDL bound to CC and inhibited the CC-induced complement activation as measured by soluble terminal C5b-9 formation and C3c deposition on the CC surface. rHDL attenuated the amount of CC-induced complement receptor 3 (CD11b/CD18) expression on monocytes and granulocytes, as well as reactive oxygen species generation. Moreover, addition of CC to whole blood resulted in release of proinflammatory cytokines that were inhibited by rHDL. Our results support and extend the notion that CC are potent triggers of inflammation, and that rHDL may have a beneficial role in controlling the CC-induced inflammatory responses by inhibiting complement deposition on the crystals.
Lymphoid Gene Upregulation on Circulating Progenitors Participates in Their T-Lineage Commitment
Authors: Zepponi Vanessa , Michaels Lopez Victoria , Martinez-Cingolani Carolina , Boudil Amine , Pasqualetto Valérie , Skhiri Lamia , Gautreau Laetitia , Legrand Agnès , Megret Jerome , Zavala Flora , Ezine Sophie 
Published: May 2015

Abstract
Extrathymic T cell precursors can be detected in many tissues and represent an immediately competent population for rapid T cell reconstitution in the event of immunodeficiencies. Blood T cell progenitors have been detected, but their source in the bone marrow (BM) remains unclear. Prospective purification of BM-resident and circulating progenitors, together with RT-PCR single-cell analysis, was used to evaluate and compare multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). Molecular analysis of circulating progenitors in comparison with BM-resident progenitors revealed that CCR9+ progenitors are more abundant in the blood than CCR7+ progenitors. Second, although Flt3− CLPs are less common in the BM, they are abundant in the blood and have reduced Cd25+-expressing cells and downregulated c-Kit and IL-7Rα intensities. Third, in contrast, stage 3 MPP (MPP3) cells, the unique circulating MPP subset, have upregulated Il7r, Gata3, and Notch1 in comparison with BM-resident counterparts. Evaluation of the populations’ respective abilities to generate splenic T cell precursors (Lin−Thy1.2+CD25+IL7Rα+) after grafting recipient nude mice revealed that MPP3 cells were the most effective subset (relative to CLPs). Although several lymphoid genes are expressed by MPP3 cells and Flt3− CLPs, the latter only give rise to B cells in the spleen, and Notch1 expression level is not modulated in the blood, as for MPP3 cells. We conclude that CLPs have reached the point where they cannot be a Notch1 target, a limiting condition on the path to T cell engagement.
The Tec Kinase–Regulated Phosphoproteome Reveals a Mechanism for the Regulation of Inhibitory Signals in Murine Macrophages
Authors: Tampella Giacomo , Kerns Hannah M. , Niu Deqiang , Singh Swati , Khim Socheath , Bosch Katherine A. , Garrett Meghan E. , Moguche Albanus , Evans Erica , Browning Beth , Jahan Tahmina A. , Nacht Mariana , Wolf-Yadlin Alejandro , Plebani Alessandro , Hamerman Jessica A. , Rawlings David J. , James Richard G. 
Published: May 2015

Abstract
Previous work has shown conflicting roles for Tec family kinases in regulation of TLR-dependent signaling in myeloid cells. In the present study, we performed a detailed investigation of the role of the Tec kinases Btk and Tec kinases in regulating TLR signaling in several types of primary murine macrophages. We demonstrate that primary resident peritoneal macrophages deficient for Btk and Tec secrete less proinflammatory cytokines in response to TLR stimulation than do wild-type cells. In contrast, we found that bone marrow–derived and thioglycollate-elicited peritoneal macrophages deficient for Btk and Tec secrete more proinflammatory cytokines than do wild-type cells. We then compared the phosphoproteome regulated by Tec kinases and LPS in primary peritoneal and bone marrow–derived macrophages. From this analysis we determined that Tec kinases regulate different signaling programs in these cell types. In additional studies using bone marrow–derived macrophages, we found that Tec and Btk promote phosphorylation events necessary for immunoreceptor-mediated inhibition of TLR signaling. Taken together, our results are consistent with a model where Tec kinases (Btk, Tec, Bmx) are required for TLR-dependent signaling in many types of myeloid cells. However, our data also support a cell type–specific TLR inhibitory role for Btk and Tec that is mediated by immunoreceptor activation and signaling via PI3K.
Fine-Needle Aspiration Biopsy of the Lymph Node: A Novel Tool for the Monitoring of Immune Responses after Skin Antigen Delivery
Authors: Tatovic Danijela , Young Philippa , Kochba Efrat , Levin Yotam , Wong F. Susan , Dayan Colin M. 
Published: May 2015

Abstract
Assessment of immune responses in lymph nodes (LNs) is routine in animals, but rarely done in humans. We have applied minimally invasive ultrasound-guided fine-needle aspiration of the LN to a before-and-after study of the immune response to intradermally delivered Ag in healthy volunteers (n = 25). By comparison with PBMCs from the same individual, LN cells (LNCs) were characterized by reduced numbers of effector memory cells, especially CD8+ TEMRA cells (3.37 ± 1.93 in LNCs versus 22.53 ± 7.65 in PBMCs; p = 0.01) and a marked increased in CD69 expression (27.67 ± 7.49 versus 3.49 ± 2.62%, LNCs and PBMCs, respectively; p &lt; 0.0001). At baseline, there was a striking absence of IFN-γ ELISPOT responses to recall Ags (purified protein derivative, Tetanus toxoid, or flu/EBV/CMV viral mix) in LN, despite strong responses in the peripheral blood. However, 48 h after tuberculin purified protein derivative administration in the ipsilateral forearm resulting in a positive skin reaction, a clear increase in IFN-γ ELISPOT counts was seen in the draining LN but not in PBMCs. This response was lost by 5 d. These data suggest that the low levels of effector memory cells in the LN may explain the low background of baseline ELISPOT responses in LNs as compared with PBMCs, and the appearance of a response after 48 h is likely to represent migration of effector memory cells from the skin to the LN. Hence, it appears that the combination of intradermal Ag administration and draining LN sampling can be used as a sensitive method to probe the effector memory T cell repertoire in the skin.
The nature of work family conflict: A review and agenda for future research
Authors: Kengatharan Navaneethakrishnan 
Published: May 2015

The main purpose of this research was to identify gaps in the existing literature on work family conflict from the past 30 years, and develop a viable research plan for further research. Research papers from peer-reviewed journals were collected from multiple databases including Proquest, Business Source Premier (EBSCOhost), Expanded Academic (Gale), Emerald, ISI Web Science, the Sloan Work and Family Research Network at Boston College, and Google Scholar. Full text papers published in English in the last three decades were included in this study. The collected papers were then classified and analysed using thematic content analysis. Factors influencing work family conflict, their consequences and the relevant constructs were systematically identified and summarised. The gaps in the extant literature from the past 30 years were identified and these were subsumed under a regional gap-theoretical cultural perspective, a measurement gap, cross cultural studies, organisational responsiveness, environmental factors and gender role theory. The present study serves as a springboard for future studies and theory building on the interaction between the work and family domains. This research is original in its nature as it has identified major strands of the extant literature on work family conflict and ipso facto it can guide research scholars towards the unknown terrain of the work family sphere. This research urges policy makers, practitioners and members of organisations to digest this knowledge and it aims to make them aware of the overarching area of work and family in the contemporary world. The major limitation of this study is the Tower of Babel Bias, to wit, research studies not published in English were excluded from this study.
Alhajaya, Mohammed Salem \ associate proffers \Sports Science Faculty \Mutah University
Authors: Alhajaya Mohammed Salem 
Published: May 2015

<p align="center"><strong>Effects of proprioception training on knee joint position sense in male soccer athletes.</strong></p><p><strong> </strong></p><p align="center"><strong>Abstract</strong></p><p align="center"><strong> </strong></p><p>The aim of this study was to examine the effect of proprioception training program on knee joint position sense in male soccer athletes. Reproduction of knee joint angle by a passive (by the examiner) - active (by the subjects) positioning was employed to measure joint position sense. Thirty male athletes (N=30) were participated in this study from Sports Science faculty at Mutah University whom registered in soccer course for Fall semester 2013/2014. The researcher used the non-dominant as an experimental limb and underwent proprioceptive training program and dominant as a control limb. The researcher used paired-sample and independent-samples-t- Test to analyse the absolute angles score of present study.</p><p>Results indicated that there was a significant difference of reproduction of the knee joint angle before and after intervention training for the non-dominant limb and a significant difference between dominant and non-dominant limb after intervention training program, (p ≤ 0.05).</p><p>It was suggested that using a proprioception training program may have a direct impact in decreasing knee joint injuries in male soccer athletes.</p><p> </p><p> </p><p><strong>Key words</strong>: proprioception, joint position sense, reproduce joint angle, male soccer athletes, training program.</p><p> </p>
Bystander Effect Fuels Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells to Quickly Attenuate Early Stage Neurological Deficits After Stroke
Authors: Eckert Auston , Huang Lei , Gonzalez Rodolfo , Kim Hye-Sun , Hamblin Milton H. , Lee Jean-Pyo 
Published: May 2015

Abstract

Present therapies for stroke rest with tissue plasminogen activator (tPA), the sole licensed antithrombotic on the market; however, tPA's effectiveness is limited in that the drug not only must be administered less than 3–5 hours after stroke but often exacerbates blood-brain barrier (BBB) leakage and increases hemorrhagic incidence. A potentially promising therapy for stroke is transplantation of human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSCs). To date, the effects of iPSCs on injuries that take place during early stage ischemic stroke have not been well studied. Consequently, we engrafted iPSC-NSCs into the ipsilesional hippocampus, a natural niche of NSCs, at 24 hours after stroke (prior to secondary BBB opening and when inflammatory signature is abundant). At 48 hours after stroke (24 hours after transplant), hiPSC-NSCs had migrated to the stroke lesion and quickly improved neurological function. Transplanted mice showed reduced expression of proinflammatory factors (tumor necrosis factor-α, interleukin 6 [IL-6], IL-1β, monocyte chemotactic protein 1, macrophage inflammatory protein 1α), microglial activation, and adhesion molecules (intercellular adhesion molecule 1, vascular cell adhesion molecule 1) and attenuated BBB damage. We are the first to report that engrafted hiPSC-NSCs rapidly improved neurological function (less than 24 hours after transplant). Rapid hiPSC-NSC therapeutic activity is mainly due to a bystander effect that elicits reduced inflammation and BBB damage.

Significance
Clinically, cerebral vessel occlusion is rarely permanent because of spontaneous or thrombolytic therapy-mediated reperfusion. These results have clinical implications indicating a much extended therapeutic window for transplantation of human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSCs; 24 hours after stroke as opposed to the 5-hour window with tissue plasminogen activator [tPA]). In addition, there is potential for a synergistic effect by combining hiPSC-NSC transplantation with tPA to attenuate stroke's adverse effects.