Highly Divergent T-cell Receptor Binding Modes Underlie Specific Recognition of a Bulged Viral Peptide bound to a Human Leukocyte Antigen Class I Molecule

Human leukocyte antigen (HLA)-I molecules can present long peptides, yet the mechanisms by which T-cell receptors (TCRs) recognize featured pHLA-I landscapes are unclear. We compared the binding modes of three distinct human TCRs, CA5, SB27, and SB47, complexed with a “super-bulged” viral peptide (LPEPLPQGQLTAY) restricted by HLA-B*35:08. The CA5 and SB27 TCRs engaged HLA-B*35:08^LPEP similarly, straddling the central region of the peptide but making limited contacts with HLA-B*35:08. Remarkably, the CA5 TCR did not contact the α1-helix of HLA-B*35:08. Differences in the CDR3β loop between the CA5 and SB27 TCRs caused altered fine specificities. Surprisingly, the SB47 TCR engaged HLA-B*35:08^LPEP using a completely distinct binding mechanism, namely “bypassing” the bulged peptide and making extensive contacts with the extreme N-terminal end of HLA-B*35:08. This docking footprint included HLA-I residues not observed previously as TCR contact sites. The three TCRs exhibited differing patterns of alloreactivity toward closely related or distinct HLA-I allotypes. Thus, the human T-cell repertoire comprises a range of TCRs that can interact with “bulged” pHLA-I epitopes using unpredictable strategies, including the adoption of atypical footprints on the MHC-I.     

STOCHASTIC TEMPERATURES IMPEDE RNA VIRUS ADAPTATION

Constant environments are often assumed to favor the evolution of specialization whereas exposure to changing environments may favor the evolution of generalists. Here we explored the phenotypic and molecular changes associated with evolving an RNA virus in constant versus fluctuating temperature environments. We used vesicular stomatitis virus (VSV) to determine whether selection at a constant temperature entails a performance trade‐off at an unselected temperature, whether virus populations evolve to be generalists when selected in deterministically changing temperature environments, and whether selection under stochastically changing temperatures prevents evolved generalization, such as by constraining the ability for viruses to adaptively improve. We observed that all VSV lineages evolved at constant temperatures showed fitness gains in their selected temperature with little evidence for trade‐offs in performance in the unselected environment. Evolution in deterministically and stochastically changing temperatures led to populations with the highest and lowest overall fitness gains, respectively. Sequence analysis revealed little evidence for convergent molecular evolution among lineages within the same treatment. Across all temperature treatments, the majority of genome substitutions occurred in the G (glycoprotein) gene, suggesting that this locus for the cell‐binding protein plays a key role in dictating VSV performance under changing temperature.     

EVOLUTIONARY CONSTRAINTS AND THE MAINTENANCE OF INDIVIDUAL SPECIALIZATION THROUGHOUT SUCCESSION

Constraints on life‐history traits, with their close links to fitness, are widely invoked as limits to niche expansion at most organizational levels. Theoretically, such constraints can maintain individual specialization by preventing adaptation to all niches available, but empirical evidence of them remains elusive for natural populations. This problem may be compounded by a tendency to seek constraints involving multiple traits, neglecting their added potential to manifest in trait expression across environments (i.e., within reaction norms). By replicating genotypes of a colonial marine invertebrate across successional stages in its local community, and taking a holistic approach to the analysis of ensuing reaction norms for fitness, we show the potential for individual specialization to be maintained by genetic constraints associated with these norms, which limit the potential for fitness at one successional stage to improve without loss of fitness at others. Our study provides new insight into the evolutionary maintenance of individual specialization in natural populations and reinforces the importance of reaction norms for studying this phenomenon.     

SIZE VARIATION,GROWTH STRATEGIES,AND THE EVOLUTION OF MODULARITY IN THE MAMMALIAN SKULL

Allometry is a major determinant of within‐population patterns of association among traits and, therefore, a major component of morphological integration studies. Even so, the influence of size variation over evolutionary change has been largely unappreciated. Here, we explore the interplay between allometric size variation, modularity, and life‐history strategies in the skull from representatives of 35 mammalian families. We start by removing size variation from within‐species data and analyzing its influence on integration magnitudes, modularity patterns, and responses to selection. We also carry out a simulation in which we artificially alter the influence of size variation in within‐taxa matrices. Finally, we explore the relationship between size variation and different growth strategies. We demonstrate that a large portion of the evolution of modularity in the mammalian skull is associated to the evolution of growth strategies. Lineages with highly altricial neonates have adult variation patterns dominated by size variation, leading to high correlations among traits regardless of any underlying modular process and impacting directly their potential to respond to selection. Greater influence of size variation is associated to larger intermodule correlations, less individualized modules, and less flexible responses to natural selection.     

Rates of dinosaur limb evolution provide evidence for exceptional radiation in Mesozoic birds

Birds are the most diverse living tetrapod group and are a model of large-scale adaptive radiation. Neontological studies suggest a radiation within the avian crown group, long after the origin of flight. However, deep time patterns of bird evolution remain obscure because only limited fossil data have been considered. We analyse cladogenesis and limb evolution on the entire tree of Mesozoic theropods, documenting the dinosaur–bird transition and immediate origins of powered flight. Mesozoic birds inherited constraints on forelimb evolution from non-flying ancestors, and species diversification rates did not accelerate in the earliest flying taxa. However, Early Cretaceous short-tailed birds exhibit both phenotypic release of the hindlimb and increased diversification rates, unparalleled in magnitude at any other time in the first 155 Myr of theropod evolution. Thus, a Cretaceous adaptive radiation of stem-group birds was enabled by restructuring of the terrestrial locomotor module, which represents a key innovation. Our results suggest two phases of radiation in Avialae: with the Cretaceous diversification overwritten by extinctions of stem-group birds at the Cretaceous–Palaeogene boundary, and subsequent diversification of the crown group. Our findings illustrate the importance of fossil data for understanding the macroevolutionary processes generating modern biodiversity.     

Trade-offs in interspecific comparisons in plant ecology and how plants overcome proposed constraints

Comparative studies on plant species have not distinguished between two inherently different applications of the idea of a trade-off. In the first case, the theoretical trade-off between two variables leads to a trend line, about which there is a degree of scatter. Any two species in the study are expected, in theory, to show a true trade-off, i.e. feature A must decrease for feature B to increase. This I call the ‘trend line’ type of plot. In the second case, the species are expected to fill a considerable part of the space defined by two axes and the theoretical trade-off leads to a boundary line which limits the extent of the cloud of points. In this case, many interspecific comparisons are not expected to show evidence of a trade-off, but those on the boundary line are expected to do so. This I call the ‘boundary line’ type of plot. In both types of plot, species within a given clade may show a true trade-off, while large numbers of unrelated species do not.

First, I undertake to show, by means of examples, the reality of the distinction made above, and to demonstrate that statistically significant and ecologically important negative correlations between features A and B in the ‘trend line’ type of plot can be accompanied by huge variation from the trend line. Second, for plots of the ‘boundary line’ type, I undertake to show that authors have not always tested sufficiently rigorously the constraint lines concerning combinations of supposedly incompatible tolerances, and have not allowed for the absence of certain combinations of unfavourable conditions in the field and consequent lack of selection pressure for the evolution of species with a combination of extreme tolerances.

I review two examples of each kind of constrained evolution. First, I take the worldwide leaf economics spectrum and the negative correlation between growth rate in high light and survival rate in deep shade. Second, I review the supposed incompatibilities between shade tolerance and drought tolerance, and between waterlogging tolerance and drought tolerance.

I conclude that the term ‘trade-off’ is used too loosely. The common lack of true trade-offs has made possible the species richness of present-day vegetation. Also, small numbers of species have evolved combinations of tolerances that might seem improbable. Not enough research is being aimed at understanding the mechanistic basis of variation about trend lines, and the crossing of supposed boundary lines.     

Midpoint attractors and species richness: Modelling the interaction between environmental drivers and geometric constraints

We introduce a novel framework for conceptualising, quantifying and unifying discordant patterns of species richness along geographical gradients. While not itself explicitly mechanistic, this approach offers a path towards understanding mechanisms. In this study, we focused on the diverse patterns of species richness on mountainsides. We conjectured that elevational range midpoints of species may be drawn towards a single midpoint attractor – a unimodal gradient of environmental favourability. The midpoint attractor interacts with geometric constraints imposed by sea level and the mountaintop to produce taxon‐specific patterns of species richness. We developed a Bayesian simulation model to estimate the location and strength of the midpoint attractor from species occurrence data sampled along mountainsides. We also constructed midpoint predictor models to test whether environmental variables could directly account for the observed patterns of species range midpoints. We challenged these models with 16 elevational data sets, comprising 4500 species of insects, vertebrates and plants. The midpoint predictor models generally failed to predict the pattern of species midpoints. In contrast, the midpoint attractor model closely reproduced empirical spatial patterns of species richness and range midpoints. Gradients of environmental favourability, subject to geometric constraints, may parsimoniously account for elevational and other patterns of species richness.     

早期心电图QRS 波宽度对急性ST 段抬高型心肌梗死患者心脏不良事件的影响

目的:探讨早期心电图QRS波宽度(QRSw)对急性ST段抬高型心肌梗死(STEMI)患者近期主要心脏不良事件(MACE)的影响。方法:选取我院收治的135例STEMI患者为研究对象,按照入院时的心电图QRSw将患者分为A组(QRSw为60 ms≤QRSw≤80 ms)、B组(QRSw为80 msQRSw100 ms)、C组(QRSw为QRSw≥100 ms),将是否发生MACE分为MACE组和非MACE组,比较各组相关指标的差异,分析QRSw与MACE发生的关系。结果:A、B及C组三组患者在梗死面积、肌酸激酶同工酶(CK-MB)、肌钙蛋白I(c Tn I)、B型脑钠肽(BNP)、高敏C反应蛋白(hs-CRP)、左室射血分数(LVEF)方面存在显著的统计学差异(P0.05),与A组及B组比较,C组血清hs-CRP、BNP、c Tn I、CK-MB较高,梗死面积大、LVEF偏低。三组患者在MACE发生率方面亦存在显著的统计学差异(P0.05),C组高于A组及B组。MACE组患者QRSw高于非MACE组(P0.05),其含有QRSw≥100 ms患者的比例亦高于非MACE组(P0.05);QRSw(OR=1.214,CI:1.104~1.441,P0.05)是STEMI患者近期MACE发生的独立危险因素。结论:STEMI患者随着QRSw增大,MACE的发生风险亦增加,QRSw可能是STEMI患者近期MACE发生的独立危险因素,应当引起临床重视。     

A screening method to analyse the sensitivity of a lower limb multibody kinematic model

The study presents a screening method used to identify the influential parameters of a lower limb model including ligaments, at low numerical cost. Concerning multibody kinematics optimisation, the ligament parameters (isometric length) were found the most influential ones in a previous study. The screening method tested if they remain influential with minimised length variations. The most important parameters for tibiofemoral kinematics were the skin markers, segment lengths and joint parameters, including two ligaments. This was confirmed by a quantitative sensitivity analysis. The screening method has the potential to be used as a stand-alone procedure for a sensitivity analysis.     

Heritabilities,social environment effects and genetic correlations of social behaviours in a cooperatively breeding vertebrate

Social animals interact frequently with conspecifics, and their behaviour is influenced by social context, environmental cues and the behaviours of interaction partners, allowing for adaptive, flexible adjustments to social encounters. This flexibility can be limited by part of the behavioural variation being genetically determined. Furthermore, behaviours can be genetically correlated, potentially constraining independent evolution. Understanding social behaviour thus requires carefully disentangling genetic, environmental, maternal and social sources of variations as well as the correlation structure between behaviours. Here, we assessed heritability, maternal, common environment and social effects of eight social behaviours in Neolamprologus pulcher, a cooperatively breeding cichlid. We bred wild‐caught fish in a paternal half‐sibling design and scored ability to defend a resource against conspecifics, to integrate into a group and the propensity to help defending the group territory (“helping behaviour”). We assessed genetic, social and phenotypic correlations within clusters of behaviours predicted to be functionally related, namely “competition,” “aggression,” “aggression‐sociability,” “integration” and “integration‐help.” Helping behaviour and two affiliative behaviours were heritable, whereas there was little evidence for a genetic basis in all other traits. Phenotypic social effects explained part of the variation in a sociable and a submissive behaviour, but there were no maternal or common environment effects. Genetic and phenotypic correlation within clusters was mostly positive. A group's social environment influenced covariances of social behaviours. Genetic correlations were similar in magnitude but usually exceeding the phenotypic ones, indicating that conclusions about the evolution of social behaviours in this species could be provisionally drawn from phenotypic data in cases where data for genetic analyses are unobtainable.