Local host specialization,host-switching,and dispersal shape the regional distributions of avian haemosporidian parasites

The drivers of regional parasite distributions are poorly understood, especially in comparison with those of free-living species. For vector-transmitted parasites, in particular, distributions might be influenced by host-switching and by parasite dispersal with primary hosts and vectors. We surveyed haemosporidian blood parasites (Plasmodium and Haemoproteus) of small land birds in eastern North America to characterize a regional parasite community. Distributions of parasite populations generally reflected distributions of their hosts across the region. However, when the interdependence between hosts and parasites was controlled statistically, local host assemblages were related to regional climatic gradients, but parasite assemblages were not. Moreover, because parasite assemblage similarity does not decrease with distance when controlling for host assemblages and climate, parasites evidently disperse readily within the distributions of their hosts. The degree of specialization on hosts varied in some parasite lineages over short periods and small geographic distances independently of the diversity of available hosts and potentially competing parasite lineages. Nonrandom spatial turnover was apparent in parasite lineages infecting one host species that was well-sampled within a single year across its range, plausibly reflecting localized adaptations of hosts and parasites. Overall, populations of avian hosts generally determine the geographic distributions of haemosporidian parasites. However, parasites are not dispersal-limited within their host distributions, and they may switch hosts readily.A regional community can be thought of as a set of species whose distributions partially overlap within a large geographic area (1, 2). The structure of the regional community (i.e., the relative abundances of species across space and the degree to which populations cooccur) is governed by local (e.g., interspecific competition) and regional (e.g., species diversification and dispersal) processes (3). Although regional communities include all species, parasites and pathogens are rarely considered integral community members (4). Indeed, impacts of parasites on community structure are frequently associated with epidemics—often following introductions to nonnative regions—that have driven naïve hosts to extinction or near extinction (5–7). However, parasites likely play a critical role in shaping regional community structure. Parasites can comprise a large proportion of the community biomass (8), form the majority of links in a community food web (9), and influence regional diversity by variously accelerating (10) or slowing (11) host diversification.Nevertheless, few studies have investigated the processes influencing the regional community structure of both parasites and their hosts. Parasite populations are integrated into community studies with difficulty, partly because these populations are distributed across multiple dimensions—space, host species, and host individuals (12)—and also because parasites are difficult to sample. Moreover, although parasites tend to specialize on one or a few host species, host-breadth may vary across a parasite’s range (13).Regional studies of birds and their dipteran-vectored haemosporidian (“malaria”) blood parasites (14–19) have shown that many parasites are heterogeneously distributed across space despite the availability of suitable hosts. Specialized associations between specific parasites and vectors (20–22) may drive such heterogeneity, although a recent analysis suggests that parasite–host compatibility is also important (23), and local coevolutionary relationships between parasites and their hosts likely influence geographic distributions of both host and parasite populations (11, 14, 15). However, most regional studies of these parasites have focused on individual host species (24–30).Here, we investigate the regional community structure of avian hosts and their haemosporidian parasites with respect to abiotic and biotic drivers of both host and parasite distributions. We surveyed local assemblages of avian haemosporidian parasites across eastern North America and related the distributions of individual parasite lineages to regional climate variation and to the distributions and abundances of their avian hosts. Community dissimilarities between sampling locations based on host assemblage structure (i.e., the relative abundances of potential host species) were positively correlated with those based on parasite assemblage structure, suggesting interdependence of host and parasite population distributions. However, when controlling statistically for that interdependence, local host assemblages responded strongly to environmental gradients and differed more with increasing geographic separation, whereas parasite assemblages did not. This finding suggests that haemosporidian parasites disperse readily across the distributions of their host populations in eastern North America, independently of difference in climate and geographic distance. The degree to which some parasite lineages specialized on particular hosts varied across years and locations, and the nonrandom parasite lineage turnover across the distribution of one well-sampled host species suggested that adaptations of hosts and parasites may also shape regional community structure. Despite evidence of pathogenicity of haemosporidian parasites in birds (31), correlations between host abundances and parasite relative abundances across the region were statistically indistinguishable from random. Taken together, these results suggest that the distributions of parasite populations largely follow the distributions of their hosts but that parasites readily switch hosts and may replace each other across the ranges of individual hosts, resulting in a complex and dynamic regional community.     

Organogenesis in deep time: A problem in genomics,development, and paleontology

The fossil record is a unique repository of information on major morphological transitions. Increasingly, developmental, embryological, and functional genomic approaches have also conspired to reveal evolutionary trajectory of phenotypic shifts. Here, we use the vertebrate appendage to demonstrate how these disciplines can mutually reinforce each other to facilitate the generation and testing of hypotheses of morphological evolution. We discuss classical theories on the origins of paired fins, recent data on regulatory modulations of fish fins and tetrapod limbs, and case studies exploring the mechanisms of digit loss in tetrapods. We envision an era of research in which the deep history of morphological evolution can be revealed by integrating fossils of transitional forms with direct experimentation in the laboratory via genome manipulation, thereby shedding light on the relationship between genes, developmental processes, and the evolving phenotype.Paleontologists in recent decades have discovered a host of new taxa that reveal transitional stages in the evolution of birds, whales, mammals, tetrapods, frogs, salamanders, and arthropods (1–9). This pulse of discovery is not an accident, but the result of an elaboration of our ability to identify likely sites for fossil recovery by using increasingly refined phylogenies, stratigraphic maps, and geological records. Likewise, imaging techniques, such as high-energy CT, have opened up old and understudied fossil collections as new vehicles for discovery. With advances in both fieldwork and imaging, the discovery of the phenotypic basis for morphological innovation is at a critical moment in its long history: Novel perspectives on classical questions of anatomical evolution are within our reach.Fossils, when placed in a phylogenetic context, can reveal taxa with novel combinations of characters that could not be predicted by studying extant creatures alone. If we lacked fossil evidence of mammal-like reptiles, for example, then the physiological and morphological similarities of birds and mammals would likely be interpreted as homologies rather than examples of parallel evolution (e.g., the discredited “Haemothermia” clade) (10, 11). In addition to identifying solid taxonomic groupings, these same fossils reveal transitional series in the origin of the mammalian dentition, ear, and cranium (3). Our understanding of numerous other transformations, from the origin of birds to the origin of tetrapods, is seriously limited without the knowledge of extinct stem taxa.A rich fossil record permits us to document robustly supported transformation series in the evolution of an anatomical feature, organ system, or body plan. However, to understand the pattern and process of evolutionary transitions, paleontologists have increasingly turned their attention to development. In recent years, the combination of technologies from developmental biology and abundant genomic resources for a multitude of model and nonmodel organisms has greatly enriched our understanding of the genetic and developmental processes underlying organogenesis. This broad set of tools provides a new framework for testing hypotheses derived from paleontological findings, thereby forming an interdisciplinary research program with comparative genomics as well as genetic manipulation of embryonic development (12–15).Here, we use the evolution and diversification of the vertebrate limb as an exemplar to reveal how discoveries in paleontology can leverage experimental and comparative work in molecular biology, genomics, and embryology. First, we review how fossil analyses of early gnathostomes, coupled with embryological studies, offer the foundation for hypotheses on the origin of paired appendages. Then, we discuss current research on model and nonmodel species that shed light on the origin of digits by comparing gene expression and regulatory mechanisms underlying fin and limb development. Next, we examine recent studies that identify the genetic and developmental basis for digit reduction in tetrapods. Finally, we highlight novel technologies that are enabling biologists to solve century-old evolutionary puzzles with state-of-the-art molecular approaches. The synthesis of modern technology with paleontological findings has been an ongoing topic of interest (16–18). Continued advances in technology now give morphologists an ever-expanding toolkit to test genome function and, ultimately, manipulate genomes in a phylogenetic framework. When these new technologies are coupled with paleontological discovery, new insights into classical questions in evolutionary morphology lie in the offing.     

MiR-200b/200c/429 subfamily negatively regulates Rho/ROCK signaling pathway to suppress hepatocellular carcinoma metastasis

MiR-200 family is an important regulator of epithelial-mesenchymal transition and has been implicated in human carcinogenesis. However, their expression and functions in human cancers remain controversial. In the work presented here, we showed that miR-200 family members were frequently down-regulated in hepatocellular carcinoma (HCC). Although all five members of miR-200 family inhibited ZEB1/2 expression in HCC cell lines, we showed that overexpression only of the miR-200b/200c/429 subfamily, but not the miR-200a/141 subfamily, resulted in impeded HCC cell migration. Further investigations led to the identification of RhoA and ROCK2 as specific down-stream targets of the miR-200b/200c/429 subfamily. We demonstrated that the miR-200b/200c/429 subfamily inhibited HCC cell migration through modulating Rho/ROCK mediated cell cytoskeletal reorganization and cell-substratum adhesion. Re-expression of miR-200b significantly suppressed lung metastasis of HCC cells in an orthotopic liver implantation model in vivo. In conclusion, our findings identified the miR-200b/200c/429 subfamily as metastasis suppressor microRNAs in human HCC and highlighted the functional discrepancy among miR-200 family members.     

Evaluation of a robotic technique for transrectal MRI-guided prostate biopsies

Objectives  

To evaluate the accuracy and speed of a novel robotic technique as an aid to perform magnetic resonance image (MRI)-guided prostate biopsies on patients with cancer suspicious regions.