bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy proteins in antigen processing for presentation on MHC molecules
Authors: Münz Christian 
Published: June 2016

SummaryAutophagy describes catabolic pathways that deliver cytoplasmic constituents for lysosomal degradation. Since major histocompatibility complex (MHC) molecules sample protein degradation products and present them to T cells for adaptive immunity, it is maybe not too surprising that autophagy contributes to this protein antigen processing for MHC presentation. However, the recently recognized breath of pathways, by which autophagy contributes to MHC antigen processing, is exciting. Macroautophagy does not only seem to deliver intracellular but facilitates also extracellular antigen processing by lysosomal hydrolysis for MHC class II presentation. Moreover, even MHC class I molecules that usually display proteasomal products are regulated by macroautophagy, probably using a pool of these molecules outside the endoplasmic reticulum, where MHC class I molecules are loaded with peptide during canonical MHC class I antigen processing. This review aims to summarize these recent developments and point out gaps of knowledge, which should be filled by further investigation, in order to harness the different antigen‐processing pathways via autophagy for vaccine improvement.
MHC class I‐related molecule, MR1, and mucosal‐associated invariant T cells
Authors: Franciszkiewicz Katarzyna , Salou Marion , Legoux Francois , Zhou Qian , Cui Yue , Bessoles Stéphanie , Lantz Olivier 
Published: June 2016

SummaryThe MHC‐related 1, MR1, molecule presents a new class of microbial antigens (derivatives of the riboflavin [Vitamin B2] biosynthesis pathway) to mucosal‐associated invariant T (MAIT) cells. This raises many questions regarding antigens loading and intracellular trafficking of the MR1/ligand complexes. The MR1/MAIT field is also important because MAIT cells are very abundant in humans and their frequency is modified in many infectious and non‐infectious diseases. Both MR1 and the invariant TCRα chain expressed by MAIT cells are strikingly conserved among species, indicating important functions. Riboflavin is synthesized by plants and most bacteria and yeasts but not animals, and its precursor derivatives activating MAIT cells are short‐lived unless bound to MR1. The recognition of MR1 loaded with these compounds is therefore an exquisite manner to detect invasive bacteria. Herein, we provide an historical perspective of the field before describing the main characteristics of MR1, its ligands, and the few available data regarding its cellular biology. We then summarize the current knowledge of MAIT cell differentiation and discuss the definition of MAIT cells in comparison to related subsets. Finally, we describe the phenotype and effector activities of MAIT cells.
CD4+ T‐cell help amplifies innate signals for primary CD8+ T‐cell immunity
Authors: Bedoui Sammy , Heath William R. , Mueller Scott N. 
Published: June 2016

SummaryCD8+ T cells provide an important component of protection against intracellular infections and cancer. Immune responses by these T cells involve a primary phase of effector expansion and differentiation, followed by a contraction phase leading to memory formation and, if antigen is re‐encountered, a secondary expansion phase with more rapid differentiation. Both primary and secondary phases of CD8+ T‐cell immunity have been shown to depend on CD4+ T‐cell help, although during certain infections the primary phase is variable in this requirement. One explanation for such variability relates to the strength of associated inflammatory signals, with weak signals requiring help. Here, we focus on our studies that have dissected the requirements for help in the primary phase of the CTL response to herpes simplex virus, elucidating intricate interactions and communications between CD4+ T cells, various dendritic cell subsets, and CD8+ T cells. We place our studies in the context of others and describe a simple model of help where CD40 signaling amplifies innate signals to enable efficient CD8+ T‐cell expansion and differentiation. This model facilitates CTL induction to various different agents, without altering the qualitative innate signals that direct other important arms of immunity.
The comings and goings of MHC class I molecules herald a new dawn in cross‐presentation
Authors: Blander J. Magarian 
Published: June 2016

SummaryMHC class I (MHC‐I) molecules are the centerpieces of cross‐presentation. They are loaded with peptides derived from exogenous sources and displayed on the plasma membrane to communicate with CD8 T cells, relaying a message of tolerance or attack. The study of cross‐presentation has been focused on the relative contributions of the vacuolar versus cytosolic pathways of antigen processing and the location where MHC‐I molecules are loaded. While vacuolar processing generates peptides loaded onto vacuolar MHC‐I molecules, how and where exogenous peptides generated by the proteasome and transported by TAP meet MHC‐I molecules for loading has been a matter of debate. The source and trafficking of MHC‐I molecules in dendritic cells have largely been ignored under the expectation that these molecules came from the Endoplasmic reticulum (ER) or the plasma membrane. New studies reveal a concentrated pool of MHC‐I molecules in the endocytic recycling compartment (ERC). These pools are rapidly mobilized to phagosomes carrying microbial antigens, and in a signal‐dependent manner under the control of Toll‐like receptors. The phagosome becomes a dynamic hub receiving traffic from multiple sources, the ER–Golgi intermediate compartment for delivering the peptide‐loading machinery and the ERC for deploying MHC‐I molecules that alert CD8 T cells of infection.
Dendritic cell maturation and cross‐presentation: timing matters!
Authors: Alloatti Andrés , Kotsias Fiorella , Magalhaes Joao Gamelas , Amigorena Sebastian 
Published: June 2016

SummaryAs a population, dendritic cells (DCs) appear to be the best cross‐presenters of internalized antigens on major histocompatibility complex class I molecules in the mouse. To do this, DCs have developed a number of unique and dedicated means to control their endocytic and phagocytic pathways: among them, the capacity to limit acidification of their phagosomes, to prevent proteolytic degradation, to delay fusion of phagosomes to lysosomes, to recruit ER proteins to phagosomes, and to export phagocytosed antigens to the cytosol. The regulation of phagocytic functions, and thereby of antigen processing and presentation by innate signaling, represents a critical level of integration of adaptive and innate immune responses. Understanding how innate signals control antigen cross‐presentation is critical to define effective vaccination strategies for CD8+ T‐cell responses.
Mechanistic understanding and significance of small peptides interaction with MHC class II molecules for therapeutic applications
Authors: Afridi Saifullah , Hoessli Daniel C. , Hameed Muhammad Waqar 
Published: June 2016

SummaryMajor histocompatibility complex (MHC) class II molecules are expressed by antigen‐presenting cells and stimulate CD4+ T cells, which initiate humoral immune responses. Over the past decade, interest has developed to therapeutically impact the peptides to be exposed to CD4+ T cells. Structurally diverse small molecules have been discovered that act on the endogenous peptide exchanger HLA‐DM by different mechanisms. Exogenously delivered peptides are highly susceptible to proteolytic cleavage in vivo; however, it is only when successfully incorporated into stable MHC II–peptide complexes that these peptides can induce an immune response. Many of the small molecules so far discovered have highlighted the molecular interactions mediating the formation of MHC II–peptide complexes. As potential drugs, these small molecules open new therapeutic approaches to modulate MHC II antigen presentation pathways and influence the quality and specificity of immune responses. This review briefly introduces how CD4+ T cells recognize antigen when displayed by MHC class II molecules, as well as MHC class II–peptide‐loading pathways, structural basis of peptide binding and stabilization of the peptide–MHC complexes. We discuss the concept of MHC‐loading enhancers, how they could modulate immune responses and how these molecules have been identified. Finally, we suggest mechanisms whereby MHC‐loading enhancers could act upon MHC class II molecules.
Factors influencing decision‐making around family presence during resuscitation: a grounded theory study
Authors: Giles Tracey , de Lacey Sheryl , Muir‐Cochrane Eimear 
Published: June 2016

AbstractAimThe aim of this study was to examine factors impacting family presence during resuscitation practices in the acute care setting.BackgroundFamily presence during resuscitation was introduced in the 1980s, so family members/significant others could be with their loved ones during life‐threatening events. Evidence demonstrates important benefits; yet despite growing support from the public and endorsement from professional groups, family presence is practiced inconsistently and rationales for poor uptake are unclear.DesignConstructivist grounded theory design.MethodsTwenty‐five health professionals, family members and patients informed the study. In‐depth interviews were undertaken between October 2013–November 2014 to interpret and explain their meanings and actions when deciding whether to practice or participate in FPDR.FindingsThe Social Construction of Conditional Permission explains the social processes at work when deciding to adopt or reject family presence during resuscitation. These processes included claiming ownership, prioritizing preferences and rights, assessing suitability, setting boundaries and protecting others/self. In the absence of formal policies, decision‐making was influenced primarily by peoples’ values, preferences and pre‐existing expectations around societal roles and associated status between health professionals and consumers. As a result, practices were sporadic, inconsistent and often paternalistic rather than collaborative.ConclusionAn increased awareness of the important benefits of family presence and the implementation of clinical protocols are recommended as an important starting point to address current variations and inconsistencies in practice. These measures would ensure future practice is guided by evidence and standards for health consumer safety and welfare rather than personal values and preferences of the individuals ‘in charge’ of permissions.
“You are either out on the court, or sitting on the bench”: understanding accountability from the perspectives of nurses and nursing managers
Authors: Leonenko Marina , Drach‐Zahavy Anat 
Published: June 2016

AbstractAimsThe aims of this study were: (1) to understand the implicit and explicit perceptions of accountability from the perspective of bedside nurses and their managers; (2) to identify the factors that facilitate accountability behaviours.BackgroundDespite the importance attributed to accountability in nursing education and practice, empirical research lacks clarity regarding how nurses perceive accountability and decide whether or not to act accountably.DesignQualitative study.MethodData of a purposeful sample of 23 nurses were collected through in‐depth semi‐structured interviews during 2015. They were tape‐recorded, transcribed verbatim and content analysed.ResultsNurses agreed that accountability, more particularly responsibility, was crucial to nursing professionalism. However, they perceived the demands for transparency and answerability as unjustified. Bedside nurses held this view more than nursing managers. Still, accountability was not considered an integral organizational norm but the choice of each nurse and his or her assessment of risks or benefits of acting accountably.ConclusionsNurses’ individual accountability was insufficient to generate accountability behaviours. They tended to weigh up the unit's accountability level in gauging risks and benefits before acting accountably. Risks of accountability behaviour included isolation, resistance and bullying, while benefits included professionalism, empowerment and pride.
Transformational leadership in nursing: a concept analysis
Authors: Fischer Shelly A. 
Published: June 2016

AbstractAimTo analyse the concept of transformational leadership in the nursing context.BackgroundTasked with improving patient outcomes while decreasing the cost of care provision, nurses need strategies for implementing reform in health care and one promising strategy is transformational leadership. Exploration and greater understanding of transformational leadership and the potential it holds is integral to performance improvement and patient safety.DesignConcept analysis using Walker and Avant's (2005) concept analysis method.Data sourcesPubMed, CINAHL and PsychINFO.MethodsThis report draws on extant literature on transformational leadership, management, and nursing to effectively analyze the concept of transformational leadership in the nursing context.Implications for nursingThis report proposes a new operational definition for transformational leadership and identifies model cases and defining attributes that are specific to the nursing context. The influence of transformational leadership on organizational culture and patient outcomes is evident. Of particular interest is the finding that transformational leadership can be defined as a set of teachable competencies. However, the mechanism by which transformational leadership influences patient outcomes remains unclear.ConclusionTransformational leadership in nursing has been associated with high‐performing teams and improved patient care, but rarely has it been considered as a set of competencies that can be taught. Also, further research is warranted to strengthen empirical referents; this can be done by improving the operational definition, reducing ambiguity in key constructs and exploring the specific mechanisms by which transformational leadership influences healthcare outcomes to validate subscale measures.
Beware of “reducing prejudice”: imagined contact may backfire if applied with a prevention focus
Authors: West Keon , Greenland Katy 
Published: June 2016

AbstractImagined intergroup contact—the mental simulation of a (positive) interaction with a member of another group—is a recently developed, low‐risk, prejudice‐reducing intervention. However, regulatory focus can moderate of the effects of prejudice‐reducing interventions: a prevention focus (as opposed to a promotion focus) can lead to more negative outcomes. In two experiments we found that a prevention focus altered imagined contact's effects, causing the intervention to backfire. In Experiment 1, participants who reported a strong prevention‐focus during imagined contact subsequently reported higher intergroup anxiety and (indirectly) less positive attitudes toward Asians. We found similar moderating effects in Experiment 2, using a different outgroup (gay men) and a subtle regulatory focus manipulation. Theoretical and practical implications for imagined contact are discussed.
Analysis of Red Sea fish species' introductions into the Mediterranean reveals shifts in introduction patterns
Authors: Samaha Carol , zu Dohna Heinrich , Bariche Michel 
Published: June 2016

AbstractAimThe Mediterranean Sea is one of the most threatened marine systems in the world. One of the major threats is the introduction of alien species from the Red Sea through the Suez Canal into the Mediterranean. The aim of our study was to address two interrelated questions, namely which traits of Red Sea fish species are associated with the species' introduction into the Mediterranean Sea and how the introduction patterns changed over time.LocationRed Sea and Mediterranean SeaMethodsWe used Cox regressions to identify traits of Red Sea species that are associated with the rate at which new alien Red Sea species are recorded in the Mediterranean (hazard rate) and to identify groups of species with different temporal trends of their baseline hazard rates. We fitted latent‐variable models to determine whether different trends in baseline hazard rates can be attributed to trends in detection or introduction.ResultsOur results showed that the highest hazard rate occurred among pelagic species, species living over soft bottoms, species present in small families and species recorded in the Red Sea close to the Suez Canal. We also found that alien species could be separated into three groups with different temporal trends in baseline hazard rates. The different trends were due to changes in introduction rate rather than detection. Two groups with historically low introduction rate showed an increase in introduction rate over time.Main conclusionsOur results provide novel biogeographical explanations for introduction patterns that were previously attributed to the effects of sea surface temperature and interspecific competition. The trends uncovered by our analysis indicate that the profile of introduced species is changing with potentially profound consequences for the Mediterranean Sea.
Dominance has a biogeographical component: do plants tend to exert stronger impacts in their invaded rather than native range?
Authors: Hejda Martin , Štajerová Kateřina , Pyšek Petr 
Published: June 2016

AbstractAimUsing three North American species invading Europe (Aster novi‐belgii, Lupinus polyphyllus and Solidago canadensis) and three European species invading North America (Agrostis capillaris, Bromus tectorum and Cirsium arvense), we tested (1) whether the dominant species impact differs between its native and invaded ranges and (2) whether the impacts differ according to the direction of invasion (from Europe to North America and vice versa).LocationNorth America (USA) and central Europe (Czech Republic).MethodsThe dominance of the selected species was expressed as its relative cover, and its relationship to species richness was tested using marginal and mixed‐effect regression models.ResultsAll the three North American species invading Europe suppressed species richness in the native range, while only two (A. novi‐belgii and L. polyphyllus) impacted native species richness in the invaded range. On the contrary, of the three European species invading North America, only A. capillaris was found to suppress species richness in its native range, while all three suppressed it in the invaded range. Overall, the richness of native species responded significantly more negatively to the dominant species cover in its invaded rather than native range, regardless of the identity of the dominant species.Main conclusionsInvasive species suppress diversity more in the invaded range, and European invaders have more profound impacts in North America than North American invaders in Europe. We suggest that long‐term coexistence and species filtering are responsible for the lower impacts in the native range, while large‐scale evolutionary patterns are likely to be associated with the more profound impacts of selected European species as invaders in North America than vice versa.
Biogeography of anurans and squamates in the Cerrado hotspot: coincident endemism patterns in the richest and most impacted savanna on the globe
Authors: Azevedo Josué A. R. , Valdujo Paula H. , de C. Nogueira Cristiano 
Published: June 2016

AbstractAimTo analyse ranges of endemic squamates and anurans in the Cerrado hotspot, searching for coincident distributional patterns in two ecologically distinct clades, and proposing a testable and comprehensive regionalization scheme for the richest and most threatened savanna on the planet.LocationCerrado region, central South America.MethodsWe updated previous point‐locality compilations for endemic species of the Cerrado herpetofauna, gathering 4588 unique occurrence records. Using a 1° grid cell, we compared regionalization results of biotic element (BE) and endemicity analyses. To search for a unified regionalization pattern, we compared analyses with a combined dataset (anurans + squamates) with those obtained in single‐group analyses.ResultsThe analysis with the combined dataset recovered more complete results than those in taxon‐specific analyses. We found 13 main biogeographical units formed by anurans and squamates that were recovered in both analyses with the combined dataset, and formed our general regionalization scheme. In general, biogeographical units defined by BEs correspond to those recovered by endemicity analysis with the combined dataset. Most recovered biogeographical units were formed both by anurans and squamates, with fewer areas determined solely by one group.Main conclusionsCommon regionalization processes operated on both anurans and squamates, shaping general biogeographical patterns for the Cerrado. The general regionalization pattern recovered with anurans and squamates may be valid for other taxa, and should be tested in future studies. As in previous results, most biogeographical units are found over ancient plateaus, separated by peripheral depressions. These major topographical barriers may explain major coincident patterns, linking the evolution of Cerrado biotas to the geomorphological history of the Brazilian shield.
The effect of elevation and time on mountain spider diversity: a view of two aspects in the Cederberg mountains of South Africa
Authors: Foord Stefan H. , Dippenaar‐Schoeman Anna S. 
Published: June 2016

AbstractAimOur aim is to test if long‐term patterns in α alpha and β beta diversity along an elevational transect on two aspects of a mountain are consistent through time using spiders as model organisms, quantify the role of elevation and time (seasonal and inter‐annual) in explaining these patterns and partition the relative contribution of nestedness, species turnover and species loss in explaining these diversity patterns.LocationThe transect is across the Cederberg mountains in the Cape Floristic Kingdom, Western Cape, South Africa and is constituted by 17 sites with an elevational range of 1900 m on two aspects of the mountain (east and west).MethodsSpider assemblages were sampled biannually (wet and dry seasons) over 6 years. Four replicates per site, each consisting of a 5 × 2 pitfall grid, were sampled for 5 days sessions. Generalized linear mixed models with Poisson error structure for species richness (alpha diversity), binomial error structure for beta diversity (Jaccard dissimilarity βccand its partitioned components, β‐3and βrich), and Gaussian error structure for beta diversity values standardized by a null model (SES) were used to model the effects of elevation and season on these two indices respectively.ResultsAlthough varying considerably between years, spider alpha diversity had a hump‐shaped pattern on the western aspect and U‐shaped on the eastern aspect. However, season interacted with elevation to produce more complex patterns during the dry season. There was no significant nestedness except for two instances on the western aspect. Replacement accounted for 60–70% of beta diversity between sites, and elevational distance decay in beta diversity was the result of increased turnover on the western aspect and increased species loss on the eastern aspect. Standardized patterns suggest that there are no effects of season on beta diversity except for a decreased distance decay during the dry season on the western aspect.Main conclusionsLarge‐scale predictors of spider alpha diversity explained small amounts variation in spider diversity, pointing to the importance of local and stochastic processes. Regional turnover of spider diversity is mainly the result of niche processes, suggesting localized adaptation of taxa, further supported by the lack of nestedness in assemblages.