Taxonomic distinctness and species richness as measures of functional structure in bird assemblages

Most traditional "biodiversity" indices have an uncertain ecological interpretation, unfavourable sampling properties, and excessive data requirements. A new index of taxonomic distinctness (the average evolutionary distance between species in an assemblage) has many advantages over traditional measures, but its ecological interpretation remains unclear. We used published behavioural species data in conjunction with bird atlas data to quantify simple functional metrics (the fraction of species engaged in non-competitive interactions, and the average between-species disparity in habitat preferences) for breeding-bird assemblages in Europe and North America. We then analysed correlations of functional metrics with taxonomic distinctness and species richness, respectively. All functional metrics had weak, positive correlations with species richness. In contrast, correlations between functional metrics and taxonomic distinctness ranged from slightly negative to strongly positive, depending on the relative habitat heterogeneity, and on the resource involved in the between-species interaction. Strong positive correlations between taxonomic distinctness and the fraction of interactive species occurred for resources with few producer species per consumer species, and we suggest that taxonomic distinctness is consistently correlated with conservation worth. With its favourable sampling properties and data requirements, this taxonomic distinctness measure is a promising tool for biodiversity research and for environmental monitoring and management.     

Trophic specialisation in a predatory group: the case of prey‐specialised spiders (Araneae)

Predators appear to be less frequently specialised (i.e. adapted to restricted diet) on their prey than herbivores, parasites or parasitoids. Here, we critically evaluate contemporary evolutionary hypotheses that might be used to explain the evolution of specialised foraging in predators. We propose a unifying concept within which we define four types of trophic categories using ecological (diet breadth) and evolutionary (degree of adaptations) contexts. We use data on spiders (Araneae), the most diversified order of terrestrial predators, to assess applicability of frameworks and evolutionary concepts related to trophic specialisation. The majority of spider species are euryphagous but a few have a restricted prey range, i.e. they are stenophagous. We provide a detailed overview of specialisation on different prey types, namely spiders, crustaceans, moths, dipterans, ants, and termites. We also review the available evidence for trophic adaptations, classified into four categories: behavioural, morphological, venomic and metabolic. Finally, we discuss the ecological and evolutionary implications of trophic specialisation and propose avenues for future research.     

Extending Serum Half-life of Albumin by Engineering Neonatal Fc Receptor (FcRn) Binding

A major challenge for the therapeutic use of many peptides and proteins is their short circulatory half-life. Albumin has an extended serum half-life of 3 weeks because of its size and FcRn-mediated recycling that prevents intracellular degradation, properties shared with IgG antibodies. Engineering the strictly pH-dependent IgG-FcRn interaction is known to extend IgG half-life. However, this principle has not been extensively explored for albumin. We have engineered human albumin by introducing single point mutations in the C-terminal end that generated a panel of variants with greatly improved affinities for FcRn. One variant (K573P) with 12-fold improved affinity showed extended serum half-life in normal mice, mice transgenic for human FcRn, and cynomolgus monkeys. Importantly, favorable binding to FcRn was maintained when a single-chain fragment variable antibody was genetically fused to either the N- or the C-terminal end. The engineered albumin variants may be attractive for improving the serum half-life of biopharmaceuticals.     

The Fibrin Matrix Regulates Angiogenic Responses within the Hemostatic Microenvironment through Biochemical Control

Conceptually, premature initiation of post-wound angiogenesis could interfere with hemostasis, as it relies on fibrinolysis. The mechanisms facilitating orchestration of these events remain poorly understood, however, likely due to limitations in discerning the individual contribution of cells and extracellular matrix. Here, we designed an in vitro Hemostatic-Components-Model (HCM) to investigate the role of the fibrin matrix as protein factor-carrier, independent of its cell-scaffold function. After characterizing the proteomic profile of HCM-harvested matrix releasates, we demonstrate that the key pro-/anti-angiogenic factors, VEGF and PF4, are differentially bound by the matrix. Changing matrix fibrin mass consequently alters the balance of releasate factor concentrations, with differential effects on basic endothelial cell (EC) behaviors. While increasing mass, and releasate VEGF levels, promoted EC chemotactic migration, it progressively inhibited tube formation, a response that was dependent on PF4. These results indicate that the clot’s matrix component initially serves as biochemical anti-angiogenic barrier, suggesting that post-hemostatic angiogenesis follows fibrinolysis-mediated angiogenic disinhibition. Beyond their significance towards understanding the spatiotemporal regulation of wound healing, our findings could inform the study of other pathophysiological processes in which coagulation and angiogenesis are prominent features, such as cardiovascular and malignant disease.     

Criteria Used in Clinical Practice to Guide Immunosuppressive Treatment in Patients with Primary Sclerosing Cholangitis

Background & Aims

Current guidelines recommend immunosuppressive treatment (IT) in patients with primary sclerosing cholangitis (PSC) and elevated aminotransferase levels more than five times the upper limit of normal and elevated serum IgG-levels above twice the upper limit of normal. Since there is no evidence to support this recommendation, we aimed to assess the criteria that guided clinicians in clinical practice to initiate IT in patients with previously diagnosed PSC.

Methods

This is a retrospective analysis of 196 PSC patients from seven German hepatology centers, of whom 36 patients had received IT solely for their liver disease during the course of PSC. Analyses were carried out using methods for competing risks.

Results

A simplified autoimmune hepatitis (AIH) score >5 (HR of 36, p<0.0001) and a modified histological activity index (mHAI) greater than 3/18 points (HR 3.6, p = 0.0274) were associated with the initiation of IT during the course of PSC. Of note, PSC patients who subsequently received IT differed already at the time of PSC diagnosis from those patients, who did not receive IT during follow-up: they presented with increased levels of IgG (p = 0.004) and more frequently had clinical signs of cirrhosis (p = 0.0002).

Conclusions

This is the first study which investigates the parameters associated with IT in patients with PSC in clinical practice. A simplified AIH score >5 and a mHAI score >3, suggesting concomitant features of AIH, influenced the decision to introduce IT during the course of PSC. In German clinical practice, the cutoffs used to guide IT may be lower than recommended by current guidelines.     

Close linkage between X-linked ectodermal dysplasia and a cloned DNA sequence detecting a two allele restriction fragment length polymorphism in the region Xp11-q12

Summary EDA (ectodermal dysplasia, anhidrotic) is an X-linked recessive disorder characterized by hypohidrosis, hypoor anodontia, and hypotrichosis. A possible linkage between the gene for EDA and a number of restriction fragment length polymorphisms (RFLPs) spread over the X chromosome was investigated in two Danish families segregating EDA. No recombination between the gene for EDA and our probe pTAK8, which detects a two allele polymorphism in the region Xp11-q12, was found in nine informative meiotic events (seven of which are phase known), giving a maximal lod score of 2.41 at a recombination fraction of 0.00. This juxtacentromeric location of the gene for EDA agrees well with the linkage data obtained with the other markers used in this study.