Interaction of αVβ3 and αVβ6 Integrins with Human Parechovirus 1

Human parechovirus (HPEV) infections are very common in early childhood and can be severe in neonates. It has been shown that integrins are important for cellular infectivity of HPEV1 through experiments using peptide blocking assays and function-blocking antibodies to α_V integrins. The interaction of HPEV1 with α_V integrins is presumably mediated by a C-terminal RGD motif in the capsid protein VP1. We characterized the binding of integrins α_Vβ₃ and α_Vβ₆ to HPEV1 by biochemical and structural studies. We showed that although HPEV1 bound efficiently to immobilized integrins, α_Vβ₆ bound more efficiently than α_Vβ₃ to immobilized HPEV1. Moreover, soluble α_Vβ₆, but not α_Vβ₃, blocked HPEV1 cellular infectivity, indicating that it is a high-affinity receptor for HPEV1. We also showed that HPEV1 binding to integrins in vitro could be partially blocked by RGD peptides. Using electron cryo-microscopy and image reconstruction, we showed that HPEV1 has the typical T=1 (pseudo T=3) organization of a picornavirus. Complexes of HPEV1 and integrins indicated that both integrin footprints reside between the 5-fold and 3-fold symmetry axes. This result does not match the RGD position predicted from the coxsackievirus A9 X-ray structure but is consistent with the predicted location of this motif in the shorter C terminus found in HPEV1. This first structural characterization of a parechovirus indicates that the differences in receptor binding are due to the amino acid differences in the integrins rather than to significantly different viral footprints.Picornaviruses consist of a positive-sense, single-stranded infectious RNA genome of approximately 7.3 kb enclosed in a capsid composed of 60 copies of each of the three or four capsid proteins (VP1 to VP4). Human parechovirus 1 (HPEV1) is a member of the Parechovirus genus of the Picornaviridae family (38, 70). There are currently eight completely sequenced human parechovirus types and 14 described types (4, 19, 24, 30, 38, 39, 51, 58, 78). In addition, the Parechovirus genus currently has four Ljungan virus members that infect rodents. HPEV1 exhibits several distinct molecular characteristics compared to other picornaviruses (38, 71). These include the lack of the maturation cleavage of the capsid proteins VP0 to VP4 (N-terminal) and VP2 (C-terminal), existence of an approximately 30-amino-acid-long extension to the N terminus of VP3, a unique nonstructural protein 2A, and a 5′ untranslated region that is more closely related to picornaviruses infecting animals than those infecting humans.HPEV infections are common during the first years of life and are often mild or asymptomatic (20, 28, 42, 73, 80). Recently, a number of new types have been identified, and their prevalence in stool samples, for example, highlights their clinical importance. Normally, they cause gastroenteritis and respiratory infections, but severe illnesses, such as infections of the central nervous system, generalized infections of neonates, and myocarditis, have also been associated with HPEV infections (1, 8, 10, 28, 80). Currently, the role of the unique molecular, structural, and antigenic characteristics of HPEVs in the pathogenesis of infection is unknown.HPEV types 1, 2, 4, 5, and 6 are known to possess an RGD motif near the C terminus of VP1 that is known to facilitate binding of cellular ligands (e.g., fibronectin) to α_v integrins. The motif is in an analogous position to motifs in coxsackievirus A9 (CAV9) and echovirus 9 (EV9; Barty strain) (Fig. ​(Fig.1).1). The role of the RGD sequence in cellular entry and subsequent replication of HPEV1 has been shown through blocking assays with RGD-containing peptides, mutation of the sequence, and function-blocking antibodies to α_v integrins (11, 43, 62, 71). These results strongly suggested that α_v integrins play a central role in the initiation of HPEV1 infection. Direct involvement of α_v integrins in the infectious entry of HPEV1 was further confirmed by overexpression of human α_vβ₁ and α_vβ₃ integrins in Chinese hamster ovary (CHO) cells, allowing successful virus infection (74). There are no reports yet on the identification of receptors for the HPEV types lacking the RGD motif (HPEV3, HPEV7, and HPEV8) (19, 39, 51).Open in a separate windowFIG. 1.Sequence alignments. Amino acid sequence alignment of the viral coat protein VP1 from different picornaviruses with the CAV9 secondary structure derived from the atomic model displayed above the alignment (34). The columns boxed in blue with red letters signify similarity, and the red column signifies identity. There is limited similarity between HPEV and other picornaviruses. C-terminal RGD motifs are boxed in red.Although the crystal structures of several picornaviruses have been determined (3, 26, 34, 35, 44, 57, 59, 65, 68, 72) and the receptor interactions have been studied in detail by X-ray crystallography, electron cryo-microscopy (cryo-EM), and three-dimensional (3D) image reconstruction (6, 9, 23, 31, 32, 47, 83), there is no structural information available for the parechoviruses or parechovirus-receptor complexes. Here, we compare the binding of α_Vβ₃ and α_Vβ₆ to HPEV1 in vitro by biochemical assays and determine the structures of HPEV1 and the corresponding HPEV1-integrin complexes.     

Resting‐state networks of the neonate brain identified using independent component analysis

Resting‐state functional magnetic resonance imaging (rs‐fMRI) has been successfully used to probe the intrinsic functional organization of the brain and to study brain development. Here, we implemented a combination of individual and group independent component analysis (ICA) of FSL on a 6‐min resting‐state data set acquired from 21 naturally sleeping term‐born (age 26 ± 6.7 d), healthy neonates to investigate the emerging functional resting‐state networks (RSNs). In line with the previous literature, we found evidence of sensorimotor, auditory/language, visual, cerebellar, thalmic, parietal, prefrontal, anterior cingulate as well as dorsal and ventral aspects of the default‐mode‐network. Additionally, we identified RSNs in frontal, parietal, and temporal regions that have not been previously described in this age group and correspond to the canonical RSNs established in adults. Importantly, we found that careful ICA‐based denoising of fMRI data increased the number of networks identified with group‐ICA, whereas the degree of spatial smoothing did not change the number of identified networks. Our results show that the infant brain has an established set of RSNs soon after birth.     

Redefining metabolic syndrome as a fat storage condition based on studies of comparative physiology

Objective: The metabolic syndrome refers to a constellation of signs including abdominal obesity, elevated serum triglycerides, low HDL‐cholesterol, elevated blood pressure, and insulin resistance. Today approximately one third of the adult population has the metabolic syndrome. While there is little doubt that the signs constituting the metabolic syndrome frequently cluster, much controversy exists over the definition, pathogenesis, or clinical utility. Design and Methods: Here we present evidence from the field of comparative physiology that the metabolic syndrome is similar to the biological process that animals engage to store fat in preparation for periods of food shortage. Results: We propose that the metabolic syndrome be changed to fat storage condition to more clearly align with its etiology. Obesity in humans is likely the consequences of both genetic predisposition (driven in part by thrifty genes) and environment. Recent studies suggest that the loss of the uricase gene may be one factor that predisposes humans to obesity today. Conclusion: Understanding the process animals engage to switch from a lean insulin‐sensitive to an obese insulin‐resistant state may provide novel insights into the cause of obesity and diabetes in humans, and unique opportunities for reversing their pathology.     

Does dispersal ability affect the relative importance of environmental control and spatial structuring of littoral macroinvertebrate communities?

Both spatial processes and environmental control may structure metacommunities, but their relative importance may be contingent on the dispersal ability of organisms. I examined the roles of spatial and environmental factors for the structuring of littoral macroinvertebrate communities across a set of lakes in a boreal drainage basin. I hypothesized that dispersal ability would affect the relative importance of spatial processes and environmental control, and thus the biological data were divided into four groups of species differing in dispersal ability. In general, the group of the strongest aerial dispersers showed greatest relative pure environmental control and least pure spatial structuring of community structure and species richness, while spatial processes seemed to be more important for the other three dispersal ability groups. However, these results were contingent on the indirect measure of spatial processes, with the spatial variables and connectivity variables providing slightly different insights into the spatial processes and environmental control of metacommunity structuring. It appears, however, that dispersal ability has effects on the spatial processes and environmental control important in metacommunity organization, with strong dispersers being more under environmental control and less affected by spatial processes compared to weak dispersers.     

A new species of Peltidium Philippi, 1839 (Crustacea,Copepoda, Harpacticoida) from the Pacific coast of Mexico

During the analysis of phytal meiobenthic samples collected from a rocky-sandy beach in the state of Nayarit, in the Mexican Pacific, several specimens of harpacticoid copepods were obtained and taxonomically examined. These specimens were found to represent an undescribed species of the peltidiid genus Peltidium Philippi, 1839. The new species, Peltidium nayarit sp. n. is described herein. It resembles Peltidium nichollsi Geddes and Peltidium lerneri Geddes from Bahamas but also the widespread Peltidium speciosum Thompson & Scott and Peltidium purpureum Philippi. The new species from the Mexican Pacific differs from its known congeners by its possession of a unique combination of characters, including a modified pectinate seta on the antennary exopod, three terminal setae on the second endopodal segment of leg 1, third exopodal segment of leg 1 with three elements, inner terminal claw twice as long as outer claw, female fifth leg with 5 exopodal setae, exopodal setae I-III stout, spinulose and seta IV being as long as seta V. This is the second species of the family known to be distributed in the Eastern Tropical Pacific and in Mexico. Pending additional data, the distribution of this species appears to be restricted to this area of the Mexican Pacific.     

Regional decline in growth rates of massive Porites corals in Southeast Asia

This study reports the first well‐replicated analysis of continuous coral growth records from warmer water reefs (mean annual sea surface temperatures (SST) >28.5 °C) around the Thai–Malay Peninsula in Southeast Asia. Based on analyses of 70 colonies sampled from 15 reefs within six locations, region‐wide declines in coral calcification rate (ca. 18.6%), linear extension rate (ca. 15.4%) and skeletal bulk density (ca. 3.9%) were observed over a 31‐year period from 1980 to 2010. Decreases in calcification and linear extension rates were observed at five of the six locations and ranged from ca. 17.2–21.6% and ca. 11.4–19.6%, respectively, whereas decline in skeletal bulk density was a consequence of significant reductions at only two locations (ca. 6.9% and 10.7%). A significant link between region‐wide growth rates and average annual SST was found, and Porites spp. demonstrated a high thermal threshold of ca. 29.4 °C before calcification rates declined. Responses at individual locations within the region were more variable with links between SST and calcification rates being significant at only four locations. Rates of sea temperature warming at locations in the Andaman Sea (Indian Ocean) (ca. 1.3 °C per decade) were almost twice those in the South China Sea (Pacific Ocean) (ca. 0.7 °C per decade), but this was not reflected in the magnitude of calcification declines at corresponding locations. Considering that massive Porites spp. are major reef builders around Southeast Asia, this region‐wide growth decline is a cause for concern for future reef accretion rates and resilience. However, this study suggests that the future rates and patterns of change within the region are unlikely to be uniform or dependent solely on the rates of change in the thermal environment.     

Metacommunity structuring in stream networks: roles of dispersal mode,distance type,and regional environmental context

Within a metacommunity, both environmental and spatial processes regulate variation in local community structure. The strength of these processes may vary depending on species traits (e.g., dispersal mode) or the characteristics of the regions studied (e.g., spatial extent, environmental heterogeneity). We studied the metacommunity structuring of three groups of stream macroinvertebrates differing in their overland dispersal mode (passive dispersers with aquatic adults; passive dispersers with terrestrial adults; active dispersers with terrestrial adults). We predicted that environmental structuring should be more important for active dispersers, because of their better ability to track environmental variability, and that spatial structuring should be more important for species with aquatic adults, because of stronger dispersal limitation. We sampled a total of 70 stream riffle sites in three drainage basins. Environmental heterogeneity was unrelated to spatial extent among our study regions, allowing us to examine the effects of these two factors on metacommunity structuring. We used partial redundancy analysis and Moran's eigenvector maps based on overland and watercourse distances to study the relative importance of environmental control and spatial structuring. We found that, compared with environmental control, spatial structuring was generally negligible, and it did not vary according to our predictions. In general, active dispersers with terrestrial adults showed stronger environmental control than the two passively dispersing groups, suggesting that the species dispersing actively are better able to track environmental variability. There were no clear differences in the results based on watercourse and overland distances. The variability in metacommunity structuring among basins was not related to the differences in the environmental heterogeneity and spatial extent. Our study emphasized that (1) environmental control is prevailing in stream metacommunities, (2) dispersal mode may have an important effect on metacommunity structuring, and (3) some factors other than spatial extent or environmental heterogeneity contributed to the differences among the basins.     

Scale-related patterns in the spatial and environmental components of stream macroinvertebrate assemblage variation

Aim We examined the relative contributions of spatial gradients and local environmental conditions to macroinvertebrate assemblages of boreal headwater streams at three hierarchical extents: bioregion, ecoregion and drainage system. We also aimed to identify the environmental variables most strongly related to assemblage structure at each study scale, and to assess how the importance of these variables is related to regional context and spatial structuring at different scales. Location Northern Finland ( 62 – 68° N, 25–32° E). Methods Variation in macroinvertebrate data was partitioned using partial canonical correspondence analysis into components explained by spatial variables (nine terms from the cubic trend surface regression), local environmental variables (15 variables) and spatially structured environmental variation. Results The strength of the relationship between assemblage structure and local environmental variables increased with decreasing spatial extent, whereas assemblage variation related to spatial variables and spatially structured environmental variation showed the opposite pattern. At the largest extents, spatial variation was related to latitudinal gradients, whereas spatial autocorrelation among neighbouring streams was the likely mechanism creating spatial structure within drainage systems. Only stream size and water acidity were consistently important in explaining assemblage structure at all study scales, while the importance of other environmental variables was more context‐dependent. Main conclusions The importance of local environmental factors in explaining macroinvertebrate assemblage structure increases with decreasing spatial extent. This scale‐related pattern is not caused solely by changes in study extent, however, but also by variable sample sizes at different regional extents. The importance of environmental gradients is context‐dependent and few factors are likely to be universally important correlates of macroinvertebrate assemblage structure. Finally, our results suggest that bioassessment should give due attention to spatial structuring of stream assemblages, because important assemblage gradients may not only be related to local factors but also to biogeographical constraints and neighbourhood dispersal processes.