The phylogenetic range of bacterial and viral pathogens of vertebrates

Many major human pathogens are multihost pathogens, able to infect other vertebrate species. Describing the general patterns of host–pathogen associations across pathogen taxa is therefore important to understand risk factors for human disease emergence. However, there is a lack of comprehensive curated databases for this purpose, with most previous efforts focusing on viruses. Here, we report the largest manually compiled host–pathogen association database, covering 2,595 bacteria and viruses infecting 2,656 vertebrate hosts. We also build a tree for host species using nine mitochondrial genes, giving a quantitative measure of the phylogenetic similarity of hosts. We find that the majority of bacteria and viruses are specialists infecting only a single host species, with bacteria having a significantly higher proportion of specialists compared to viruses. Conversely, multihost viruses have a more restricted host range than multihost bacteria. We perform multiple analyses of factors associated with pathogen richness per host species and the pathogen traits associated with greater host range and zoonotic potential. We show that factors previously identified as important for zoonotic potential in viruses—such as phylogenetic range, research effort, and being vector‐borne—are also predictive in bacteria. We find that the fraction of pathogens shared between two hosts decreases with the phylogenetic distance between them. Our results suggest that host phylogenetic similarity is the primary factor for host‐switching in pathogens.     

Rapid generation of ecologically relevant behavioral novelty in experimental cichlid hybrids

The East African cichlid radiations are characterized by repeated and rapid diversification into many distinct species with different ecological specializations and by a history of hybridization events between nonsister species. Such hybridization might provide important fuel for adaptive radiation. Interspecific hybrids can have extreme trait values or novel trait combinations and such transgressive phenotypes may allow some hybrids to explore ecological niches neither of the parental species could tap into. Here, we investigate the potential of second‐generation (F2) hybrids between two generalist cichlid species from Lake Malawi to exploit a resource neither parental species is specialized on: feeding by sifting sand. Some of the F2 hybrids phenotypically resembled fish of species that are specialized on sand sifting. We combined experimental behavioral and morphometric approaches to test whether the F2 hybrids are transgressive in both morphology and behavior related to sand sifting. We then performed a quantitative trait loci (QTL) analysis using RADseq markers to investigate the genetic architecture of morphological and behavioral traits. We show that transgression is present in several morphological traits, that novel trait combinations occur, and we observe transgressive trait values in sand sifting behavior in some of the F2 hybrids. Moreover, we find QTLs for morphology and for sand sifting behavior, suggesting the existence of some loci with moderate to large effects. We demonstrate that hybridization has the potential to rapidly generate novel and ecologically relevant phenotypes that may be suited to a niche neither of the parental species occupies. Interspecific hybridization may thereby contribute to the rapid generation of ecological diversity in cichlid radiations.     

Cyclo-saligenyl-5-fluoro-2′-deoxyuridinemonophosphate (cycloSal-FdUMP) — A New Prodrug Approach for FdUMP

Abstract

The synthesis of cycloSal-FdUMP 3a-d as a new prodrug approach for FdU 1 is described. Phosphotriesters 3 release the FdUMP 2 selectively by a controlled, chemically induced tandem reaction in hydrolysis studies. The biological activity (IC₅₀) of cycloSal-phosphotriesters 3 was evaluated in FM3A/O cells and FM3A/TK^? cells.     

Altered expression of the PTR/NRT1 homologue OsPTR9 affects nitrogen utilization efficiency,growth and grain yield in rice

The plant PTR/NRT1 (peptide transporter/nitrate transporter 1) gene family comprises di/tripeptide and low‐affinity nitrate transporters; some members also recognize other substrates such as carboxylates, phytohormones (auxin and abscisic acid), or defence compounds (glucosinolates). Little is known about the members of this gene family in rice (Oryza sativa L.). Here, we report the influence of altered OsPTR9 expression on nitrogen utilization efficiency, growth, and grain yield. OsPTR9 expression is regulated by exogenous nitrogen and by the day‐night cycle. Elevated expression of OsPTR9 in transgenic rice plants resulted in enhanced ammonium uptake, promotion of lateral root formation and increased grain yield. On the other hand, down‐regulation of OsPTR9 in a T‐DNA insertion line (osptr9) and in OsPTR9‐RNAi rice plants had the opposite effect. These results suggest that OsPTR9 might hold potential for improving nitrogen utilization efficiency and grain yield in rice breeding.     

Inhibitor of Apoptosis (IAP) Proteins–Modulators of Cell Death and Inflammation

Misregulated innate immune signaling and cell death form the basis of much human disease pathogenesis. Inhibitor of apoptosis (IAP) protein family members are frequently overexpressed in cancer and contribute to tumor cell survival, chemo-resistance, disease progression, and poor prognosis. Although best known for their ability to regulate caspases, IAPs also influence ubiquitin (Ub)-dependent pathways that modulate innate immune signaling via activation of nuclear factor κB (NF-κB). Recent research into IAP biology has unearthed unexpected roles for this group of proteins. In addition, the advances in our understanding of the molecular mechanisms that IAPs use to regulate cell death and innate immune responses have provided new insights into disease states and suggested novel intervention strategies. Here we review the functions assigned to those IAP proteins that act at the intersection of cell death regulation and inflammatory signaling.Apoptosis represents a fundamental biological process that relies on the activation of caspases. Inhibitor of apoptosis (IAP) proteins represent a group of negative regulators of both caspases and cell death. Although best known for their ability to regulate caspases and cell death, it is now clear that they function as arbiters of diverse biological processes (Gyrd-Hansen and Meier 2010). Most prominently, IAPs control ubiquitin (Ub)-dependent signaling events that regulate activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways that in turn drive expression of genes important for inflammation, immunity, cell migration, and cell survival. IAPs thereby function as E3 Ub ligases, mediating the transfer of Ub from E2s to target substrates. This in turn modulates the signaling process through regulating protein stability as well as via nondegradative means (see below for details). Many of the cellular processes controlled by IAPs are frequently deregulated in cancer and, directly or indirectly, contribute to disease initiation, tumor maintenance, and/or progression, making IAPs obvious targets for anticancer therapy (LaCasse et al. 2008). Accordingly, small pharmacological inhibitors of IAPs, frequently referred to as Smac-mimetics (SM), were developed and are currently undergoing clinical trials for the treatment of cancer (LaCasse et al. 2008). The use of SMs in preclinical tumor models and clinical trials has provided compelling evidence for the therapeutic benefit of IAP inhibition.