bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lessons from primary immunodeficiencies: Autoimmune regulator and autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy
Authors: Constantine Gregory M. , Lionakis Michail S. 
Published: December 2018

SummaryThe discovery of the autoimmune regulator (AIRE) protein and the delineation of its critical contributions in the establishment of central immune tolerance has significantly expanded our understanding of the immunological mechanisms that protect from the development of autoimmune disease. The parallel identification and characterization of patient cohorts with the monogenic disorder autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED), which is typically caused by biallelic AIRE mutations, has underscored the critical contribution of AIRE in fungal immune surveillance at mucosal surfaces and in prevention of multiorgan autoimmunity in humans. In this review, we synthesize the current clinical, genetic, molecular and immunological knowledge derived from basic studies in Aire‐deficient animals and from APECED patient cohorts. We also outline major advances and research endeavors that show promise for informing improved diagnostic and therapeutic approaches for patients with APECED.
CHAPLE syndrome uncovers the primary role of complement in a familial form of Waldmann's disease
Authors: Ozen Ahmet 
Published: December 2018

SummaryPrimary intestinal lymphangiectasia (PIL) or Waldmann's disease was described in 1961 as an important cause of protein‐losing enteropathy (PLE). PIL can be the sole finding in rare individuals or occur as part of a multisystemic genetic syndrome. Although genetic etiologies of many lymphatic dysplasia syndromes associated with PIL have been identified, the pathogenesis of isolated PIL (with no associated syndromic features) remains unknown. Familial cases and occurrence at birth suggest genetic etiologies in certain cases. Recently, CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and PLE (the CHAPLE syndrome) has been identified as a monogenic form of PIL. Surprisingly, loss of CD55, a key regulator of complement system leads to a predominantly gut condition. Similarly to other complement disorders, namely paroxysmal nocturnal and hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), CHAPLE disease involves pathogenic cross‐activation of the coagulation system, predisposing individuals to severe thrombosis. The observation that complement system is overly active in CHAPLE disease introduced a novel concept into the management of PLE; anti‐complement therapy. While CD55 deficiency constitutes a treatable subgroup in the larger pool of patients with isolated PIL, the etiology remains to be identified in the remaining patients with intact CD55.
WHIM syndrome: Immunopathogenesis, treatment and cure strategies
Authors: McDermott David H. , Murphy Philip M. 
Published: December 2018

SummaryWHIM syndrome is a rare, autosomal dominant immunodeficiency which is named for the four key manifestations: Warts, Hypogammaglobulinemia, Infections, and Myelokathexis. It results from heterozygous gain‐of‐function mutations in the chemokine receptor CXCR4 which is widely expressed on leukocytes and has profound influences on immune system homeostasis and organogenesis. New treatments for the disease using drugs to reduce CXCR4 function are excellent examples of precision medicine. Since CXCR4 and its ligand CXCL12 play an important role in a variety of infectious, inflammatory, autoimmune, and malignant diseases, the study of WHIM syndrome provides important insights into both the physiologic and disease roles of these molecules.
Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome
Authors: Su Helen C. , Jing Huie , Angelus Pam , Freeman Alexandra F. 
Published: December 2018

SummaryDOCK8 immunodeficiency syndrome (DIDS) is a progressive combined immunodeficiency that can be distinguished from other combined immunodeficiencies or hyperimmunoglobulinemia E syndromes in featuring (a) profound susceptibility to virus infections of the skin, with associated skin cancers, and (b) severe food allergies. The DOCK8 locus has many repetitive sequence elements that predispose to the generation of large germline deletions as well as recombination‐mediated somatic DNA repair. Residual DOCK8 protein contributes to the variable disease phenotype. The severe virus infections of the skin, and probably also VZV‐associated vasculopathy, reflect an important function of DOCK8, which is normally required to maintain lymphocyte shape integrity as the cells migrate through dense tissues. Loss of DOCK8 also causes immune deficits through other mechanisms including a milder generalized cell survival defect and skewing of T helper cell subsets. Recent work has uncovered the roles for DOCK8 in dendritic cell responses that can also help explain the virus susceptibility, as well as in regulatory T cells that might help explain autoimmunity in a minority of patients. Fortunately, hematopoietic stem cell transplantation cures the eczema and infection susceptibility of DIDS, but not necessarily the other disease manifestations including food allergies.
Early‐onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms
Authors: Pazmandi Julia , Kalinichenko Artem , Ardy Rico Chandra , Boztug Kaan 
Published: December 2018

SummaryRare, monogenetic diseases present unique models to dissect gene functions and biological pathways, concomitantly enhancing our understanding of the etiology of complex (and often more common) traits. Although inflammatory bowel disease (IBD) is a generally prototypic complex disease, it can also manifest in an early‐onset, monogenic fashion, often following Mendelian modes of inheritance. Recent advances in genomic technologies have spurred the identification of genetic defects underlying rare, very early‐onset IBD (VEO‐IBD) as a disease subgroup driven by strong genetic influence, pinpointing key players in the delicate homeostasis of the immune system in the gut and illustrating the intimate relationships between bowel inflammation, systemic immune dysregulation, and primary immunodeficiency with increased susceptibility to infections. As for other human diseases, it is likely that adult‐onset diseases may represent complex diseases integrating the effects of host genetic susceptibility and environmental triggers. Comparison of adult‐onset IBD and VEO‐IBD thus provides beautiful models to investigate the relationship between monogenic and multifactorial/polygenic diseases. This review discusses the present and novel findings regarding monogenic IBD as well as key questions and future directions of IBD research.
The clinical and mechanistic intersection of primary atopic disorders and inborn errors of growth and metabolism
Authors: Lyons Jonathan J. , Milner Joshua D. 
Published: December 2018

SummaryDynamic changes in metabolism have long been understood as critical for both the initiation and maintenance of innate and adaptive immune responses. A number of recent advances have clarified details of how metabolic pathways can specifically affect cellular function in immune cells. Critical to this understanding is ongoing study of the congenital disorders of glycosylation and other genetic disorders of metabolism that lead to altered immune function in humans. While there are a number of immune phenotypes associated with metabolic derangements caused by single gene disorders, several genetic mutations have begun to link discrete alterations in metabolism and growth specifically with allergic disease. This subset of primary atopic disorders is of particular interest as they illuminate how hypomorphic mutations which allow for some residual function of mutated protein products permit the “abnormal” allergic response. This review will highlight how mutations altering sugar metabolism and mTOR activation place similar constraints on T lymphocyte metabolism to engender atopy, and how alterations in JAK/STAT signaling can impair growth and cellular metabolism while concomitantly promoting allergic diseases and reactions in humans.
Functionally richer communities improve ecosystem functioning: Dung removal and secondary seed dispersal by dung beetles in the Western Palaearctic
Authors: Milotić Tanja , Baltzinger Christophe , Eichberg Carsten , Eycott Amy E. , Heurich Marco , Müller Jörg , Noriega Jorge A. , Menendez Rosa , Stadler Jutta , Ádám Réka , Bargmann Tessa , Bilger Isabelle , Buse Jörn , Calatayud Joaquín , Ciubuc Constantin , Boros Gergely , Jay‐Robert Pierre , Kruus Märt , Merivee Enno , Miessen Geoffrey , Must Anne , Ardali Elham , Preda Elena , Rahimi Iraj , Rohwedder Dirk , Rose Rob , Slade Eleanor M. , Somay László , Tahmasebi Pejman , Ziani Stefano , Hoffmann Maurice 
Published: December 2018

AbstractAimIn several ecosystems, the diversity of functional species traits has been shown to have a stronger effect on ecosystem functioning than taxonomic diversity alone. However, few studies have explored this idea at a large geographical scale. In a multisite experiment, we unravelled the relationship between ecosystem function and functional completeness of species assemblages using dung beetles as a model group, focusing on dung removal and secondary seed dispersal.LocationSeventeen grassland locations across the Western Palaearctic.MethodsWe used a randomized block design with different exclosure types to control the dung and seed removing activities of individual functional groups of the local dung beetle assemblage. We classified dung beetle species according to resource specialization and into functional groups based on dung processing behaviour (dwellers, tunnellers, rollers) and body size (small, large). Additionally, we assessed the role of other soil macro‐invertebrates. By sampling the dung beetle community and measuring the remaining dung and seeds after the experiment, the impact of each functional group was estimated.ResultsDung beetle assemblages differed along a north–south and east–west gradient. Dwellers dominated northernmost sites, whereas at lower latitudes we observed more tunnellers and rollers indicating a functional shift. Resource specialists were more abundant in southern and eastern areas. Overall, functional group diversity enhanced dung removal. More dung (+46.9%) and seeds (+32.1%) were removed in the southern sites and tunnellers and rollers were more effective. At the northernmost sites, where tunnellers were scarce or absent, other soil macro‐invertebrates removed the majority of dung.Main conclusionsThe conservation of functionally complete dung beetle assemblages is crucial to maintain the ecosystem functions provided by dung beetles. Given the latitudinal variation in functional group diversity, it is reasonable to expect compositional changes due to climate change. These changes could lead to increased dung removal and a higher secondary seed dispersal rate in northern regions.
Shifting global Larix distributions: Northern expansion and southern retraction as species respond to changing climate
Authors: Mamet Steven D. , Brown Carissa D. , Trant Andrew J. , Laroque Colin P. 
Published: December 2018

AbstractAimRecent and rapid warming is reorganizing terrestrial vegetation, creating novel species assemblages, and shifting range limits. Relative to the evergreen species that currently dominate much of the boreal forest landscape, Larix (larch) distributions may be particularly responsive to climatic change due to their deciduous habit, and quick growth and reproduction. Here, we amassed data from 83 studies to describe and explain observed patterns of Larix range shifts under contemporary climate change.LocationNorthern hemisphere.TaxonSpecies of the genus Larix, deciduous gymnosperms.MethodsWith 181 observations of Larix range limit dynamics, we used five distribution parameters (tree line advance, stand infilling, tree line recession, stand thinning, no response) and their determinants (climate, land use change, natural disturbance) to describe and explain observed patterns of Larix range shifts under contemporary climate change. We ran a redundancy analysis on the matrix of five distribution parameters considered with other climatic and nonclimatic parameters as explanatory variables. We also characterized the climatic niche of Larix species (temperature and precipitation) and how the niche has changed during the 20th century.ResultsOf 173 sites studied over the full distribution of Larix, 63% experienced Larix population increases, 18% had population decreases, and no response was detected at 19% of sites. Latitudinal Larix tree lines in Siberia and North America appear to be infilling and shifting their distributions northward, whereas Larix recession and thinning was more common in southern regions, suggesting southern populations may be experiencing greater drought stress than their northern counterparts. Climatic niches of most Larix species shifted towards warmer and wetter conditions, with tree line advance/forest infilling in cool/dry climate space, and recession/thinning in warm/dry space.Main conclusionsNorthern expansion is underway or seems imminent for boreal Larix species, primarily L. laricina in North America. Retraction in southern regions and disappearance of some mountainous populations may be inevitable due to their narrow ecological niches. Species restricted to mountainous habitats may expand locally, though will likely not contribute to broad scale range expansion. These changes will depend on suitable climate, disturbance, and dispersal mechanisms.
A sharp floristic discontinuity revealed by the biogeographic regionalization of African savannas
Authors: Fayolle Adeline , Swaine Michael D. , Aleman Julie , Azihou Akomian F. , Bauman David , te Beest Mariska , Chidumayo Emmanuel N. , Cromsigt Joris P. G. M. , Dessard Hélène , Finckh Manfred , Gonçalves Francisco Maiato P. , Gillet Jean‐Francois , Gorel Anais , Hick Aurélie , Holdo Ricardo , Kirunda Ben , Mahy Gregory , McNicol Iain , Ryan Casey M. , Revermann Rasmus , Plumptre Andrew , Pritchard Rose , Nieto‐Quintano Paula , Schmitt Christine B. , Seghieri Josiane , Swemmer Anthony , Talila Habte , Woollen Emily 
Published: December 2018

AbstractAimIn tropical Africa, savannas cover huge areas, have high plant species richness and are considered as a major natural resource for most countries. There is, however, little information available on their floristics and biogeography at the continental scale, despite the importance of such information for our understanding of the drivers of species diversity at various scales and for effective conservation and management. Here, we collated and analysed floristic data from across the continent in order to propose a biogeographical regionalization for African savannas.LocationWe collated floristic information (specifically woody species lists) for 298 samples of savanna vegetation across Africa, extending from 18° N to 33° S and from 17° W to 48° E.TaxaWe focused on native woody species.MethodsWe used ordination and clustering to identify the floristic discontinuities and gradual transitions across African savannas. Floristic relationships, specificity and turnover, within and between floristic clusters, were analysed using a (dis‐)similarity‐based approach.ResultsWe identified eight floristic clusters across African savannas which in turn were grouped into two larger macro‐units. Ordinations at species and genus levels showed a clear differentiation in woody species composition between the North/West macro‐unit and the South/East macro‐unit. This floristic discontinuity matches to the High (i.e. N&W) and Low (S&E) division of Africa previously proposed by White () and which tracks climatic and topographical variation. In the N&W savannas, the floristic gradient determined by rainfall was partitioned into the Sudanian (drier) and Guinean (wetter) clusters. Within the highly heterogeneous S&E savannas and woodlands, six clusters were identified: Ugandan, Ethiopian, Mozambican, Zambezian, Namibian and South African.Main conclusionsThe proposed pan‐African classification of savannas and woodlands might assist the development of coordinated management and conservation policies.
Processing of texts and videos: A strategy‐focused analysis
Authors: Lee Hye Yeon , List Alexandra 
Published: December 2018

AbstractThis study examined strategies used across two modalities of information presentation. Students were presented with two sources on endangered species, either as two texts or two videos. Then, participants were asked to annotate the two sources either using the track changes function in Microsoft Word, for the text condition, or using the VideoAnt, video annotation platform, for the video condition. Students' annotations were coded for the strategies evidenced. More strategies were reported in association with the text condition and a greater number of higher‐level strategies and emphasis‐related strategies were reported. Moreover, students were found to report consistent strategies when processing two different sources, on two different topics, and were found to report strategies disproportionately early during processing, particularly for the video condition.
Inhibition of miR‐148a‐3p resists hepatocellular carcinoma progress of hepatitis C virus infection through suppressing c‐Jun and MAPK pathway
Authors: Deng Yibin , Wang Jianchu , Huang Meijin , Xu Guidan , Wei Wujun , Qin Houji 
Published: December 2018

AbstractObjectivesThe present study was committed to investigate the role of miR‐148a‐3p in HCC infected with hepatitis C virus (HCV) and the regulatory mechanism of miR‐148a‐3p/c‐Jun/MAPK signalling pathway.MethodsDifferential analysis and GSEA analysis were performed with R packages. QRT‐PCR and Western blot were used to detect RNA or protein level, respectively. The targeted relationship between miR‐148a‐3p and c‐Jun was predicted by TargetScan database and determined by double luciferase reporter assay. MTT assay and flow cytometry were used to evaluate cell proliferation, cell cycle and cell apoptosis, respectively.ResultsC‐Jun was up‐regulated, and MAPK signalling pathway was activated in HCV‐infected HCC cells. C‐Jun expression regulated inflammation‐related gene expression and had an influence on cell proliferation, cell cycle and cell apoptosis. MiR‐148a‐3p, down‐regulated in HCV‐infected HCC cells, could target c‐Jun mRNA to suppress c‐Jun protein expression.ConclusionsMiR‐148a‐3p suppressed the proliferation of HCC cells infected with HCV through targeting c‐Jun mRNA.
Euroscepticism among Dutch Leftist and Rightist Populist Constituencies: How can the U‐Curve be Understood?
Authors: van Bohemen Samira , de Koster Willem , van der Waal Jeroen 
Published: December 2018

AbstractThe U‐curve in euroscepticism is well established: both leftist and rightist populist constituencies are more eurosceptic than voters for establishment parties. Using rich survey data on a country with both constituencies represented in parliament (the Netherlands; n=1,296), we examine why euroscepticism drives populist voting. Our analyses demonstrate that euroscepticism is part of the well‐established link between both 1) distrust in politics and politicians, and 2) support for protectionism on the one hand, and voting for both types of populist party on the other. It is also part of the well‐known relationship between 3) ethnocentrism and rightist populist voting. Surprisingly, euroscepticism is not part of the typical association between economic egalitarianism and voting for a leftist populist party. The concluding section discusses the implications of our findings and provides suggestions for further research.
The impact of the number of sellers on quantal response equilibrium predictions in Bertrand oligopolies
Authors: Bayer Ralph‐C , Dong Chaohua , Wu Hang 
Published: December 2018

AbstractThis paper studies how increasing the number of sellers in a Bertrand oligopoly with homogenous goods affects the equilibrium price level predicted by logistic quantal response equilibrium (LQRE) and power‐function QRE (PQRE). We show that increasing the number of sellers reduces the average posted price in a PQRE, but can increase the average posted price in an LQRE. Our results indicate that the comparative‐static predictions of QRE (McKelvey & Palfrey, 1995, Games Econ Behav, 10, 6–38) are not necessarily robust to changes of the quantal response function.
Effect of selective infiltration etching on the bond strength between zirconia and resin luting agents
Authors: Çakırbay Tanış Merve , Akay Canan , Şen Murat 
Published: December 2018

AbstractObjectiveTo evaluate the shear bond strength of resin cements to zirconia treated with the selective infiltration etching technique (SIE).Materials and MethodsForty‐seven zirconia specimens were prepared with a sequence of silicon carbide abrasives, cleaned in an ultrasonic bath. Three samples were separated for atomic force microscope (AFM) analyses (one nontreated for control, one sandblasted, and one selective infiltration etched) and the remaining were randomly distributed in four groups, according to the combination of surface treatment and resin cement: group 1a (sandblasting + Variolink II), group 1b (sandblasting + Panavia SA Plus), group 2a (SIE + Variolink II), group 2b (SIE + Panavia SA Plus). A composite resin cylinder (3 mm × 3 mm) was cemented to the zirconia surface, as per each group's specific protocol. After storing 24 hours in distilled water at 37°C, the specimens were tested for shear bond strength and the results were subjected to statistical analysis.ResultsAt 24 hours, the highest SBS values were observed in group 2b, where the SIE technique was used in conjunction with Panavia SA Plus. Lowest values were found in group 1a. Increased surface roughness was observed with SIE.ConclusionsSIE significantly enhanced the resin bond strength to zirconia. However, cement selection was also an important factor, for both surface treatments tested.Clinical SignificanceUse of SIE method combined with MDP monomer containing resin cement can provide clinically acceptable bond strength between zirconia and resin cement.