Effects of Host Interspecific Interaction in the <Emphasis Type="Italic">Maculinea</Emphasis>–<Emphasis Type="Italic">Myrmica</Emphasis> Parasite–Host System

A model of interspecific host competition in a system with one parasite (butterfly—Maculinea) and multiple potential hosts (ants—Myrmica) is presented. Results indicate that host interspecific competition increases the occurrence of multiple host behaviour in Maculinea natural populations but decreases the ability of the parasite populations to adapt to the most abundant host species. These qualitative predictions were compared with data on host specificity, with good agreement. Analysis of the data also indicates that Maculinea teleius and Maculinea arion respond differently to changes in relative host abundances. Maculinea teleius shows a larger fraction of sites where it displays multiple host behaviour and a larger fraction of sites where the niches of the hosts overlap. In some instances, Maculinea teleius is adapted to Myrmica hosts that are present in lower frequencies. Maculinea arion is locally more host-specific and occurs at sites where host interspecific competition is unlikely and is more frequently adapted to the most abundant host species.     

Herbarium specimens show patterns of fruiting phenology in native and invasive plant species across New England

Premise of the Study

Patterns of fruiting phenology in temperate ecosystems are poorly understood, despite the ecological importance of fruiting for animal nutrition and seed dispersal. Herbarium specimens represent an under‐utilized resource for investigating geographical and climatic factors affecting fruiting times within species, patterns in fruiting times among species, and differences between native and non‐native invasive species.

Methods

We examined over 15,000 herbarium specimens, collected and housed across New England, and found 3159 specimens with ripe fruits, collected from 1849–2013. We examined patterns in fruiting phenology among 37 native and 18 invasive woody plant species common to New England. We compared fruiting dates between native and invasive species, and analyzed how fruiting phenology varies with temperature, space, and time.

Key Results

Spring temperature and year explained a small but significant amount of the variation in fruiting dates. Accounting for the moderate phylogenetic signal in fruiting phenology, invasive species fruited 26 days later on average than native species, with significantly greater standard deviations.

Conclusions

Herbarium specimens can be used to detect patterns in fruiting times among species. However, the amount of intraspecific variation in fruiting times explained by temporal, geographic, and climatic predictors is small, due to a combination of low temporal resolution of fruiting specimens and the protracted nature of fruiting. Later fruiting times in invasive species, combined with delays in autumn bird migrations in New England, may increase the likelihood that migratory birds will consume and disperse invasive seeds in New England later into the year.     

Animal models of biliary injury and altered bile acid metabolism

In the last 25 years, a number of animal models, mainly rodents, have been generated with the goal to mimic cholestatic liver injuries and, thus, to provide in vivo tools to investigate the mechanisms of biliary repair and, eventually, to test the efficacy of innovative treatments. Despite fundamental limitations applying to these models, such as the distinct immune system and the different metabolism regulating liver homeostasis in rodents when compared to humans, multiple approaches, such as surgery (bile duct ligation), chemical-induced (3,5-diethoxycarbonyl-1,4-dihydrocollidine, DDC, α-naphthylisothiocyanate, ANIT), viral infections (Rhesus rotavirustype A, RRV-A), and genetic manipulation (Mdr2, Cftr, Pkd1, Pkd2, Prkcsh, Sec63, Pkhd1) have been developed. Overall, they have led to a range of liver phenotypes recapitulating the main features of biliary injury and altered bile acid metabolisms, such as ductular reaction, peribiliary inflammation and fibrosis, obstructive cholestasis and biliary dysgenesis. Although with a limited translability to the human setting, these mouse models have provided us with the ability to probe over time the fundamental mechanisms promoting cholestatic disease progression. Moreover, recent studies from genetically engineered mice have unveiled ‘core’ pathways that make the cholangiocyte a pivotal player in liver repair. In this review, we will highlight the main phenotypic features, the more interesting peculiarities and the different drawbacks of these mouse models. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.     

Optimising the clinical strategy for autoimmune liver diseases: Principles of value-based medicine

Background

Autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis represent the three major autoimmune liver diseases (AILDs). Their management is highly specialized, requires a multidisciplinary approach and often relies on expensive, orphan drugs. Unfortunately, their treatment is often unsatisfactory, and the care pathway heterogeneous across different centers. Disease-specific clinical outcome indicators (COIs) able to evaluate the whole cycle of care are needed to assist both clinicians and administrators in improving quality and value of care. Aim of our study was to generate a set of COIs for the three AILDs. We then prospectively validated these indicators based on a series of consecutive patients recruited at three tertiary clinical centers in Lombardy, Italy.

Targeting plant DIHYDROFOLATE REDUCTASE with antifolates and mechanisms for genetic resistance

The folate biosynthetic pathway and its key enzyme dihydrofolate reductase (DHFR) is a popular target for drug development due to its essential role in the synthesis of DNA precursors and some amino acids. Despite its importance, little is known about plant DHFRs, which, like the enzymes from the malarial parasite Plasmodium, are bifunctional, possessing DHFR and thymidylate synthase (TS) domains. Here using genetic knockout lines we confirmed that either DHFR‐TS1 or DHFR‐TS2 (but not DHFR‐TS3) was essential for seed development. Screening mutated Arabidopsis thaliana seeds for resistance to antimalarial DHFR‐inhibitor drugs pyrimethamine and cycloguanil identified causal lesions in DHFR‐TS1 and DHFR‐TS2, respectively, near the predicted substrate‐binding site. The different drug resistance profiles for the plants, enabled by the G137D mutation in DHFR‐TS1 and the A71V mutation in DHFR‐TS2, were consistent with biochemical studies using recombinant proteins and could be explained by structural models. These findings provide a great improvement in our understanding of plant DHFR‐TS and suggest how plant‐specific inhibitors might be developed, as DHFR is not currently targeted by commercial herbicides.