bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid and Rigorous IL-17A Production by a Distinct Subpopulation of Effector Memory T Lymphocytes Constitutes a Novel Mechanism of Toxic Shock Syndrome Immunopathology
Authors: Szabo Peter A. , Goswami Ankur , Mazzuca Delfina M. , Kim Kyoungok , O’Gorman David B. , Hess David A. , Welch Ian D. , Young Howard A. , Singh Bhagirath , McCormick John K. , Haeryfar S. M. Mansour 
Published: November 2017

Abstract
Toxic shock syndrome (TSS) is caused by staphylococcal and streptococcal superantigens (SAgs) that provoke a swift hyperinflammatory response typified by a cytokine storm. The precipitous decline in the host’s clinical status and the lack of targeted therapies for TSS emphasize the need to identify key players of the storm’s initial wave. Using a humanized mouse model of TSS and human cells, we herein demonstrate that SAgs elicit in vitro and in vivo IL-17A responses within hours. SAg-triggered human IL-17A production was characterized by remarkably high mRNA stability for this cytokine. A distinct subpopulation of CD4+ effector memory T (TEM) cells that secrete IL-17A, but not IFN-γ, was responsible for early IL-17A production. We found mouse “TEM-17” cells to be enriched within the intestinal epithelium and among lamina propria lymphocytes. Furthermore, interfering with IL-17A receptor signaling in human PBMCs attenuated the expression of numerous inflammatory mediators implicated in the TSS-associated cytokine storm. IL-17A receptor blockade also abrogated the secondary effect of SAg-stimulated PBMCs on human dermal fibroblasts as judged by C/EBP δ expression. Finally, the early IL-17A response to SAgs was pathogenic because in vivo neutralization of IL-17A in humanized mice ameliorated hepatic and intestinal damage and reduced mortality. Together, our findings identify CD4+ TEM cells as a key effector of TSS and reveal a novel role for IL-17A in TSS immunopathogenesis. Our work thus elucidates a pathogenic, as opposed to protective, role for IL-17A during Gram-positive bacterial infections. Accordingly, the IL-17–IL-17R axis may provide an attractive target for the management of SAg-mediated illnesses.
Local TNFR1 Signaling Licenses Murine Neutrophils for Increased TLR-Dependent Cytokine and Eicosanoid Production
Authors: Deguine Jacques , Wei Jessica , Barbalat Roman , Gronert Karsten , Barton Gregory M. 
Published: November 2017

Abstract
Neutrophils are generally the first immune cells recruited during the development of sterile or microbial inflammation. As these cells express many innate immune receptors with the potential to directly recognize microbial or endogenous signals, we set out to assess whether their functions are locally influenced by the signals present at the onset of inflammation. Using a mouse model of peritonitis, we demonstrate that neutrophils elicited in the presence of C-type lectin receptor ligands have an increased ability to produce cytokines, chemokines, and lipid mediators in response to subsequent TLR stimulation. Importantly, we found that licensing of cytokine production was mediated by paracrine TNF-α-TNFR1 signaling rather than direct ligand sensing, suggesting a form of quorum sensing among neutrophils. Mechanistically, licensing was largely imparted by changes in the posttranscriptional regulation of inflammatory cytokines, whereas production of IL-10 was regulated at the transcriptional level. Altogether, our data suggest that neutrophils rapidly adapt their functions to the local inflammatory milieu. These phenotypic changes may promote rapid neutrophil recruitment in the presence of pathogens but limit inflammation in their absence.
Dependence of Glomerulonephritis Induction on Novel Intraglomerular Alternatively Activated Bone Marrow–Derived Macrophages and Mac-1 and PD-L1 in Lupus-Prone NZM2328 Mice
Authors: Sung Sun-sang J. , Ge Yan , Dai Chao , Wang Hongyang , Fu Shu Man , Sharma Rahul , Hahn Young S. , Yu Jing , Le Thu H. , Okusa Mark D. , Bolton Warren K. , Lawler Jessica R. 
Published: November 2017

Abstract
Glomerular damage mediated by glomerulus-infiltrating myeloid-derived cells is a key pathogenic event in lupus nephritis (LN), but the process is poorly understood. Confocal microscopy of kidney sections and flow cytometry analysis of glomerular cells from magnetic bead–purified glomeruli have identified glomerulus-infiltrating leukocyte populations in NZM2328 (NZM) lupus-prone mice with spontaneous chronic glomerulonephritis (GN) and anti–glomerular basement membrane-induced nephritis. The occurrence of a major glomerulus-infiltrating CD11b+F4/80−I-A− macrophage population exhibiting the markers programmed death ligand-1 (PD-L1), Mac-2, and macrophage mannose receptor (CD206) and producing Klf4, Il10, Retnla, Tnf, and Il6 mRNA, which are known to be expressed by alternatively activated (M2b) macrophages, correlated with proteinuria status. In NZM mice with spontaneous LN, glomerular macrophage infiltration is predominant. CD11b+F4/80−I-A− intraglomerular macrophages and polymorphonuclear neutrophils (PMN) are important in inducing GN, as anti-CD11b and –ICAM-1 mAb inhibited both proteinuria and macrophage and PMN infiltration. The predominant and high expression of PD-L1 by CD11b+F4/80−I-A− glomerular macrophages in kidneys of mice with GN and the inhibition of proteinuria by anti–PD-L1 mAb supported the pathogenic role of these macrophages but not the PD-L1− PMN in GN development and in inducing podocyte damage. In NZM mice with spontaneous chronic GN and severe proteinuria, few glomerulus-infiltrating PMN were found, leaving macrophages and, to a less extent, dendritic cells as the major infiltrating leukocytes. Taken together, these data support the important pathogenic effect of CD11b+F4/80−I-A− M2b-like glomerulus-infiltrating macrophages in LN and reinforce macrophages as a promising target for GN treatment.
Essential Neuroscience in Immunology
Authors: Chavan Sangeeta S. , Tracey Kevin J. 
Published: November 2017

Abstract
The field of immunology is principally focused on the molecular mechanisms by which hematopoietic cells initiate and maintain innate and adaptive immunity. That cornerstone of attention has been expanded by recent discoveries that neuronal signals occupy a critical regulatory niche in immunity. The discovery is that neuronal circuits operating reflexively regulate innate and adaptive immunity. One particularly well-characterized circuit regulating innate immunity, the inflammatory reflex, is dependent upon action potentials transmitted to the reticuloendothelial system via the vagus and splenic nerves. This field has grown significantly with the identification of several other reflexes regulating discrete immune functions. As outlined in this review, the delineation of these mechanisms revealed a new understanding of immunity, enabled a first-in-class clinical trial using bioelectronic devices to inhibit cytokines and inflammation in rheumatoid arthritis patients, and provided a mosaic view of immunity as the integration of hematopoietic and neural responses to infection and injury.
Two Strikes and You’re Out? The Pathogenic Interplay of Coinhibitor Deficiency and Lymphopenia-Induced Proliferation
Authors: Ellestad Kristofor K. , Anderson Colin C. 
Published: November 2017

Abstract
Lymphopenia-induced proliferation (LIP) occurs when resources for T cell survival in a host are in excess. LIP has been associated with the development of inflammatory disease in situations where an additional disease-predisposing cofactor is present during LIP. This has led to the view of LIP-driven autoimmunity as a two hit model; however, not all cofactors have equal ability to precipitate autoimmunity and we have recently shown that in some circumstances, such as the absence of the coinhibitory molecule PD-1, additional hits are required. Herein we review factors controlling LIP, including coinhibitory molecules and other attenuators of TCR signaling, with a focus on their contribution to LIP-driven autoimmunity. Rather than viewing LIP-associated autoimmunity as an n-hit model, we suggest a more quantitative view of lymphopenia with respect to the factors that promote LIP as a tool to predict autoimmune potential and to inform tumor immunotherapy approaches.
An Infectious Disease–Associated Il12b Polymorphism Regulates IL-12/23 p40 Transcription Involving Poly(ADP-Ribose) Polymerase 1
Authors: Zhao Quanju , Du Qinglin , Wei Fang , Xie Jianping , Ma Xiaojing 
Published: November 2017

Abstract
IL-12 and IL-23 are important host defense factors produced by APCs against certain intracellular and extracellular pathogens. Their dysregulation has also been implicated in several autoimmune diseases. The nucleotide polymorphism in the promoter region of Il12b (rs41292470 consisting of the long or short allele) encoding the shared subunit of IL-12 and IL-23, p40, has been reported to associate with susceptibility to infectious diseases and autoimmune disorders. How these genetic variants impact Il12b expression at the molecular level was unclear. We established an Il12b promoter-luciferase reporter system containing the long or short allele driving the reporter gene expression and found that the long allele (infection-resistant) displayed ∼2-fold higher transcriptional activity than the short allele (infection-susceptible), associated with a selective and differential nuclear binding activity to the two alleles in activated macrophages. DNA pull-down assays coupled with mass spectrometry analyses identified the specific DNA binding activity as poly(ADP-ribose) polymerase 1 (PARP-1). Small hairpin RNA–mediated knockdown of the endogenous PARP-1 expression resulted in reduced p40 mRNA expression and Il12b promoter activity. Bone marrow–derived macrophages from PARP-1–deficient mice had decreased p40 expression at both mRNA and protein levels. Furthermore, selective PARP-1 inhibitors resulted in impaired production of IL-12p40 and IL-23 in bone–marrow derived macrophages and PBMCs. Chromatin immunoprecipitation assay revealed that PARP-1 could bind specifically to Il12b in LPS-stimulated macrophages. Our study opens the way for further elucidating the molecular mechanism whereby allele-specific immune responses to foreign and self-antigens mediated by IL-12/IL-23 are controlled in an individually variable manner.
Descriptive Values for Dancers on Baseline Concussion Tools
Authors: McIntyre Lauren , Campo Marc 
Published: November 2017

Context: Capturing baseline data before a concussion can be a valuable tool in individualized care. However, not all athletes, including dancers, have access to baseline testing. When baseline examinations were not performed, clinicians consult normative values. Dancers are unique athletes; therefore, describing values specific to dancers may assist those working with these athletes in making more informed decisions.Objective: To describe values for key concussion measures of dancers. Our secondary aim was to examine whether differences existed between sexes and professional status. Finally, we explored factors that may affect dancers' scores.Design: Cross-sectional study.Setting: Professional dance companies and a collegiate dance conservatory.Patients or Other Participants: A total of 238 dancers (university = 153, professional = 85; women = 171; men = 67; age = 21.1 ± 4.8 years).Main Outcome Measure(s): We calculated the total symptom severity from the Sport Concussion Assessment Tool–3rd edition; the Standardized Assessment of Concussion score; the modified Balance Error Scoring System score; and the King-Devick score for each participant. Group differences were analyzed with Mann-Whitney or t tests, depending on the data distribution. We used bivariate correlations to explore the effects of other potential influencing factors.Results: Participants demonstrated the following baseline outcomes: symptom severity = 16.6 ± 12.8; Standardized Assessment of Concussion = 27.5 ± 1.8; modified Balance Error Scoring System = 3.2 ± 3.1 errors; and King-Devick = 41.5 ± 8.2 seconds. A Mann-Whitney test revealed differences in King-Devick scores between female (40.8 ± 8.0 seconds) and male (43.4 ± 8.4 seconds) dancers (P = .04). An independent-samples t test also demonstrated a difference in modified Balance Error Scoring System scores between female (2.95 ± 3.1 errors) and male (3.8 ± 3.1 errors) dancers (P = .02). Age, hours of sleep, height, and history of concussion, depression, or injury did not display moderate or strong associations with any of the outcome measures.Conclusions: Dancers' symptom severity scores appeared to be higher than the values reported for other athletes. Additional studies are needed to establish normative values and develop a model for predicting baseline scores.
Evolution and Functional Diversification of the GLI Family of Transcription Factors in Vertebrates
Authors: Abbasi Amir Ali , Goode Debbie K. , Amir Saneela , Grzeschik Karl-Heinz 
Published: November 2017

Background In vertebrates the “SONIC HEDGEHOG” signalling pathway has been implicated in cell-fate determination, proliferation and the patterning of many different cell types and organs. As the GLI family members (GLI1, GLI2 and GLI3) are key mediators of hedgehog morphogenetic signals, over the past couple of decades they have been extensively scrutinized by genetic, molecular and biochemical means. Thus, a great deal of information is currently available about the functional aspects of GLI proteins in various vertebrate species. To address the roles of GLI genes in diversifying the repertoire of the Hh signalling and deploying them for the vertebrate specifications, in this study we have examined the evolutionary patterns of vertebrate GLI sequences within and between species. Results Phylogenetic tree analysis suggests that the vertebrate GLI1, GLI2 and GLI3 genes diverged after the separation of urochordates from vertebrates and before the tetrapods-bony fishes split. Lineage specific duplication events were also detected. Estimation of mode and strength of selection acting on GLI orthologs demonstrated that all members of the GLI gene family experienced more relaxed selection in teleost fish than in the mammalian lineage. Furthermore, the GLI1 gene appeared to have been exposed to different functional constraints in fish and tetrapod lineages, whilst a similar level of functional constraints on GLI2 and GLI3 was suggested by comparable average non-synonymous (Ka) substitutions across the lineages. A relative rate test suggested that the majority of the paralogous copies of the GLI family analyzed evolved with similar evolutionary rates except GLI1 which evolved at a significantly faster rate than its paralogous counterparts in tetrapods. Conclusions Our analysis shows that sequence evolutionary patterns of GLI family members are largely correlated with the reported similarities and differences in the functionality of GLI proteins within and between the various vertebrate species. We propose that duplication and divergence of GLI genes has increased in the complexity of vertebrate body plan by recruiting the hedgehog signalling for the novel developmental tasks.
A QSAR/QSTR Study on the Environmental Health Impact by the Rocket Fuel 1,1-Dimethyl Hydrazine and its Transformation Products
Authors: Carlsen Lars , Kenessov Bulat N. , Batyrbekova Svetlana Ye. 
Published: November 2017

QSAR/QSTR modelling constitutes an attractive approach to preliminary assessment of the impact on environmental health by a primary pollutant and the suite of transformation products that may be persistent in and toxic to the environment. The present paper studies the impact on environmental health by residuals of the rocket fuel 1,1-dimethyl hydrazine (heptyl) and its transformation products. The transformation products, comprising a variety of nitrogen containing compounds are suggested all to possess a significant migration potential. In all cases the compounds were found being rapidly biodegradable. However, unexpected low microbial activity may cause significant changes. None of the studied compounds appear to be bioaccumulating. Apart from substances with an intact hydrazine structure or hydrazone structure the transformation products in general display rather low environmental toxicities. Thus, it is concluded that apparently further attention should be given to tri- and tetramethyl hydrazine and 1-formyl 2,2-dimethyl hydrazine as well as to the hydrazones of formaldehyde and acetaldehyde as these five compounds may contribute to the overall environmental toxicity of residual rocket fuel and its transformation products.
Is the Pen really Mightier than the Scalpel?
Authors: Choudhary Nilookumari 
Published: November 2017

How to cite this article
Sarode GS, Choudhary N, Sarode SC, Patil S. Is the Pen really Mightier than the Scalpel? J Contemp Dent Pract 2017;18(11):987-988.
Prevalence of Dental Caries and Oral Hygiene Status among Juvenile Prisoners in the Kingdom of Saudi Arabia
Authors: Alkhadra Thamer 
Published: November 2017

ABSTRACT

Aim
The aim of the study was to determine the prevalence of dental caries and oral hygiene status among juvenile prisoners in Riyadh, Kingdom of Saudi Arabia.

Materials and methods
A total of 105 prisoners aged between 12 and 17 years of age from the Juvenile Detention Center were included in the study. Any prisoner with systemic illness and being noncooperative were excluded from the study. Clinical examinations were performed under an artificial light source using a disposable mouth mirror and explorer while seated on a portable chair. The dental caries experience was measured as the number of decayed, missing, or filled permanent teeth (DMFT) using DMFT score. The oral hygiene index (OHI) was assessed by the Greene and Vermillion method. The data collected were analyzed using Statistical Package for the Social Sciences version 16.

Results
The mean age of the sample was 16.33 years, with 74.3% of the prisoners in the 16 to 17-year-old group. The dental caries index measured by calculating the mean DMFT of the juvenile prisoners increased with age. The DMFT scores of 9.09 (4.388) for 78 juvenile prisoners aged 16 to 17 years followed by 9.00 (2.925) for 19 prisoners aged 14 to 15 years and 7.13 (1.808) for 8 prisoners aged 12 to 13 years were observed. The oral hygiene status of the prisoners showed that more than half of the juvenile prisoners included in the study had poor (53.3%) oral hygiene and less than half had fair (45.7%) oral hygiene and only one participant demonstrated good oral hygiene.

Conclusion
The juvenile prisoners had high prevalence of dental caries and fair-to-bad oral hygiene, indicating poor oral health status. Furthermore, the study emphasizes the need for special attention from the concerned health authorities, voluntary organizations, and surrounding dental colleges in meeting the oral health needs of this group.

Clinical significance
The study provides an important database for decision makers to take on the challenge of reducing dental caries among juvenile prisoners.

How to cite this article
Alkhadra T. Prevalence of Dental Caries and Oral Hygiene Status among Juvenile Prisoners in the Kingdom of Saudi Arabia. J Contemp Dent Pract 2017;18(11):991-995.
In situ Effect of Nanohydroxyapatite Paste in Enamel Teeth Bleaching
Authors: Silva Cecy Martins , de Lima Gomes Yasmin SB , Alexandrino Larissa D , de M Alencar Cristiane , Alves Eliane B , Faial Kelson CF 
Published: November 2017

ABSTRACTAimEvaluatein situthe effect of nanohydroxyapatite paste (nano-HAP) before bleaching with hydrogen peroxide 35% (HP35%) by ion chromatography (IC) Knoop hardness number (KHN) and tristimulus colorimetry (TC).Materials and methodsA total of 60 fragments were obtained from third molars included (3 mm × 3 mm × 3 mm) and the specimens were divided into three groups (n = 20): Gas chromatography (CG) (negative control group) = no bleaching; HP35% (positive control group) = HP35% whitening (whiteness HP35%); nano-HAP = application for 10 minutes before bleaching treatment + HP35%. The specimens were fixed to the volunteers’ molars. The KHN and TC were measured before and after bleaching. For IC, the dentin layer was removed, leaving the enamel that was crushed, and autoclaved for chemical quantification (calcium, fluorine, and phosphorus). The results of KHN and TC were analyzed statistically by analysis of variance (ANOVA) followed by Tukey test (p < 0.05).ResultsThe HP35% group showed reduction of the Ca, F, and P ions. The initial and final KHN mean of the CG and nano-HAP did not differ statistically; however, the group of HP35% did differ statistically. The mean ∆E of the HP35% and nano-HAP groups did not differ statistically from each other. However, they differed from the CG.ConclusionThe nano-HAP paste preserved the KHN, promoted the lower loss of Ca and P ions and an increase of F ions when compared with the CG, but did not influence the effectiveness of the bleaching treatment.Clinical significanceNano-HA is a biomaterial that has shown positive results in the prevention of deleterious effects on the enamel by the action of the office bleaching treatment.How to cite this articleGomes YSBL, Alexandrino LD, Alencar CDM, Alves EB, Faial KCF, Silva CM.In situEffect of Nanohydroxyapatite Paste in Enamel Teeth Bleaching. J Contemp Dent Pract 2017;18(11):996-1003.
Antimicrobial Effect of Ginger, Garlic, Honey, and Lemon Extracts on Streptococcus mutans
Authors: Aravind A , Mathai Kiran , Anand Swathy , Dinatius Praveen , Krishnan Anandhu V , Mathai Meera 
Published: November 2017

ABSTRACTAimThe aim of this study was to evaluate the effect of lemon, ginger, garlic, and honey extracts onStreptococcus mutans.Materials and methodsCommercially obtained honey, ginger, garlic, and lemon were included in the study to evaluate its efficacy in isolation and in combination againstS. mutans. The efficacies of extracts were tested using well diffusion method, and its effect was evaluated by measuring the zone of inhibition around the well. Antimicrobial activity of the extracts was carried out individually and compared considering triplicates of all the extracts.ResultsWhen individual comparison of the extracts was made, garlic showed greatest antimicrobial activity with a mean zone of inhibition (34.9 ± 0.58 mm) and honey showed least antimicrobial activity (0.5 ± 0.6 mm). When combinations of extracts were tested againstS. mutans, lemon and garlic combination showed the greatest zone of inhibition (27.6 ± 0.43 mm) compared with other combinations, and ginger + lemon combinations showed the least zone of inhibition (12.6 ± 0.43 mm).ConclusionThis study concluded that garlic showed a greatest antimicrobial effect againstS. mutanswhen compared with preparations individually and garlic and lemon showed greatest zone of inhibition in combination than other preparations.Clinical significanceAntibiotics and other chemical agents are mainly used to treat the common dental infections. However, due to the excessive use, it can result in antibiotic resistance. Hence, herbal medicines with medicinal values should be replaced with conventional methods.How to cite this articleMathai K, Anand S, Aravind A, Dinatius P, Krishnan AV, Mathai M. Antimicrobial Effect of Ginger, Garlic, Honey, and Lemon Extracts onStreptococcus mutans. J Contemp Dent Pract 2017;18(11):1004-1008.