Geographical variation in predictors of mammalian extinction risk: big is bad, but only in the tropics

Whereas previous studies have investigated correlates of extinction risk either at global or regional scales, our study explicitly models regional effects of anthropogenic threats and biological traits across the globe. Using phylogenetic comparative methods with a newly-updated supertree of 5020 extant mammals, we investigate the impact of species traits on extinction risk within each WWF ecoregion. Our analyses reveal strong geographical variation in the influence of traits on risk: notably, larger species are at higher risk only in tropical regions. We then relate these patterns to current and recent-historical human impacts across ecoregions using spatial modelling. The body–mass results apparently reflect historical declines of large species outside the tropics due to large-scale land conversion. Narrow-ranged and rare species tend to be at high risk in areas of high current human impacts. The interactions we describe between biological traits and anthropogenic threats increase understanding of the processes determining extinction risk.     

Phylogenetic diversity does not capture body size variation at risk in the world's mammals

Mammals contribute to important ecosystem processes and services, but many mammalian species are threatened with extinction. We compare how global patterns in three measures of mammalian diversity—species richness, phylogenetic diversity (PD) and body mass variance (BMV)—would change if all currently threatened species were lost. Given that many facets of species'' ecology and life history scale predictably with body mass, the BMV in a region roughly reflects the diversity of species'' roles within ecosystems and so is a simple proxy for functional diversity (FD). PD is also often considered to be a proxy for FD, but our results suggest that BMV losses within ecoregions would be much more severe than losses of PD or species richness, and that its congruence with the latter two measures is low. Because of the disproportionate loss of large mammals, 65 per cent of ecoregions would lose significantly more BMV than under random extinction, while only 11 per cent would lose significantly more PD. Ecosystem consequences of these selective losses may be profound, especially throughout the tropics, but are not captured by PD. This low surrogacy stresses a need for conservation prioritization based on threatened trait diversity, and for conservation efforts to take an ecosystem perspective.     

Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

Introduction

The human monoclonal antibody adalimumab is known to induce an anti-globulin response in some adalimumab-treated patients. Antibodies against adalimumab (AAA) are associated with non-response to treatment. Immunoglobulins, such as adalimumab, carry allotypes which represent slight differences in the amino acid sequences of the constant chains of an IgG molecule. Immunoglobulins with particular IgG (Gm) allotypes are racially distributed and could be immunogenic for individuals who do not express these allotypes. Therefore, we investigated whether a mismatch in IgG allotypes between adalimumab and IgG in adalimumab-treated patients is associated with the development of AAA.

Methods

This cohort study consisted of 250 adalimumab-treated rheumatoid arthritis (RA) patients. IgG allotypes were determined for adalimumab and for all patients. Anti-idiotype antibodies against adalimumab were measured with a regular radio immunoassay (RIA), and a newly developed bridging enzyme linked immunosorbent assay (ELISA) was used to measure anti-allotype antibodies against adalimumab. The association between AAA and the G1m3 and the G1m17 allotypes was determined. For differences between groups we used the independent or paired samples t-test, Mann-Whitney test or Chi square/Fisher's exact test as appropriate. To investigate the influence of confounders on the presence or absence of AAA a multiple logistic regression-analysis was used.

Results

Adalimumab carries the G1m17 allotype. No anti-allotype antibodies against adalimumab were detected. Thirty-nine out of 249 patients had anti-idiotype antibodies against adalimumab (16%). IgG allotypes of RA patients were associated with the frequency of AAA: patients homozygous for G1m17 had the highest frequency of AAA (41%), patients homozygous for G1m3 the lowest frequency (10%), and heterozygous patients' AAA frequency was 14% (P = 0.0001).

Conclusions

An allotype mismatch between adalimumab and IgG in adalimumab-treated patients did not lead to a higher frequency of AAA. On the contrary, patients who carried the same IgG allotype as present on the adalimumab IgG molecule, had the highest frequency of anti-adalimumab antibodies compared to patients whose IgG allotype differed from adalimumab. This suggests that the allotype of adalimumab may not be highly immunogenic. Furthermore, patients carrying the G1m17-allotype might be more prone to antibody responses.     

Exploiting the full power of temporal gene expression profiling through a new statistical test: Application to the analysis of muscular dystrophy data

Background  

The identification of biologically interesting genes in a temporal expression profiling dataset is challenging and complicated by high levels of experimental noise. Most statistical methods used in the literature do not fully exploit the temporal ordering in the dataset and are not suited to the case where temporal profiles are measured for a number of different biological conditions. We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T ²-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other.     

A covalent oxidoreductase intermediate in propeptide-dependent von Willebrand factor multimerization

The assembly of von Willebrand factor multimers in the Golgi apparatus requires D1D2 domains of the von Willebrand factor propeptide, which may act as an oxidoreductase to promote disulfide bond formation or rearrangement between two D3 domains in the mature subunit. This mechanism predicts that the propeptide should form a transient intrachain disulfide bond with the D3 domain before multimerization. Such an intermediate was detected using truncated subunits that simplify the analysis of the multimerization process. When only the D1D2D'D3 region of von Willebrand factor was expressed in baby hamster kidney cells, the propeptide and D'D3 formed an intrachain disulfide-linked species in the endoplasmic reticulum that could be identified by two-dimensional gel electrophoresis after cleavage with thrombin or furin. This intermediate rearranged in the Golgi to form free propeptide and D'D3 dimers that were secreted. A similar intracellular disulfide-linked species was identified in cells expressing the propeptide and D'D3 as separate proteins and in cells expressing full-length von Willebrand factor. These results support a model in which the propeptide acts as an oxidoreductase to promote von Willebrand factor multimerization in the Golgi apparatus.     

Power of eight tree shape statistics to detect nonrandom diversification: a comparison by simulation of two models of cladogenesis

We used simulations to compare the relative power of eight statistical tests to detect imbalance in phylogenies that is too great to be ascribed to an equal-rates Markov null model. Three of these tests have never had their power assessed before. Our simulations are the first to assess performance under scenarios in which the speciation rates of various lineages can evolve independently. In one of the scenarios explored, rates depend upon the value of an evolving trait, whereas in the other the probability that a species will speciate declines with the time since it last did so. The results indicate that the relative performance of the methods depends upon how the imbalance is generated. Different types of processes lead to different imbalance signatures, i.e., different patterns of imbalance at different depths in the phylogeny, and the measures of tree shape differ in the depth of phylogeny at which they are most sensitive. Relative performance is also affected by tree size but does not appear to depend greatly upon the degree of speciation rate variation among lineages. Two of the indices (Colless's index I(c) and Shao and Sokal's Nmacr;) show reasonable performance throughout, but another (Shao and Sokal's B(2)) is never indicated to be a preferred method. Two tests that do not require completely resolved phylogenies, mean I' and mean I'(10), have reasonable power.     

Taxonomic selectivity in amphibians: ignorance, geography or biology?

Many taxa, including amphibians, have been shown to have a taxonomically non-random distribution of threatened species. There are three possible non-exclusive reasons for this selectivity: non-random knowledge of species conservation status, clades endemic to different regions experiencing different intensities of threatening process and the effects of clade-specific biological attributes on the susceptibility of species to these processes. This paper tests the sufficiency of the first two explanations using extinction risk evaluations from the 2004 Global Amphibian Assessment. Our results indicate that they cannot alone account for the degree of non-randomness in extinction risk among amphibian families. The overall distribution of threatened amphibians remained taxonomically non-random when species of unknown conservation status were omitted, and significant selectivity was detected not only at a global geographic scale but also in country- and site-specific data sets. Furthermore, the same families tend to be over- or underthreatened within different countries. Together, these results suggest that biological differences among amphibian families play an important role in determining species' susceptibility to anthropogenic threatening processes.     

Body size and species-richness in carnivores and primates.

We use complete species-level phylogenies of extant Carnivora and Primates to perform the first thorough phylogenetic tests, in mammals, of the hypothesis that small body size is associated with species-richness. Our overall results, based on comparisons between sister clades, indicate a weak tendency for lineages with smaller bodies to contain more species. The tendency is much stronger within caniform carnivores (canids, procyonids, pinnipeds, ursids and mustelids), perhaps relating to the dietary flexibility and hence lower extinction rates in small, meat-eating species. We find significant heterogeneity in the size-diversity relationship within and among carnivore families. There is no significant association between body mass and species-richness in primates or feliform carnivores. Although body size is implicated as a correlate of species-richness in mammals, much of the variation in diversity cannot be attributed to size differences.     

Genetic and biochemical heterogeneity in patients with the rhizomelic form of chondrodysplasia punctata — a complementation study

Summary The genetic relationship between 10 patients with clinical manifestations of rhizomelic chondrodysplasia punctata (RCDP) was studied by complementation analysis after somatic cell fusion. Biochemically, 9 out of the 10 patients were characterized by a partial deficiency of acyl-CoA: dihydroxyacetone phosphate acyltransferase (DHAP-AT) and an impairment of plasmalogen biosynthesis, phytanate catabolism and the maturation of peroxisomal 3-oxoacyl-CoA thiolase; 3-oxoacyl-CoA thiolase was strongly reduced in the peroxisomes of these patients. Fusion of fibroblasts from these 9 patients with Zellweger fibroblasts resulted in complementation as indicated by the restoration of DHAP-AT activity, plasmalogen biosynthesis, and punctate fluorescence after staining with a monoclonal antibody to peroxisomal thiolase. No complementation was observed after fusion of different combinations of the 9 RCDP cell lines, suggesting that they belong to a single complementation group. The tenth patient was characterized biochemically by a deficiency of DHAP-AT and an impairment of plasmalogen biosynthesis. However, maturation and localization of peroxisomal thiolase were normal. Fusion of fibroblasts from this patient with fibroblasts from the other 9 patients resulted in complementation as indicated by the restoration of plasmalogen biosynthesis. We conclude that mutations in at least two different genes can lead to the clinical phenotype of RCDP.     

Lichen biomonitoring near Karabash smelter town, ural mountains, Russia, one of the most polluted areas in the world

Biogeochemical signatures were investigated in transplanted and native lichens near a major pollution source using sensitive multi-element chemical analysis. Transplants were established across a 60 km transect centred on the smelter town of Karabash, Ural Mountains, Russia. Statistically significant trends in element concentrations were recorded, some below one part per million. Fine metal particles are accumulated from pollution aerosols. Prolonged exposure may lead to cellular damage and enhanced accumulation or element loss. 206Pb: 207Pb isotope ratios are similar to those associated with airborne particles in Europe and Russia; an outlier near Kyshtym with a lower ratio indicates a source with a higher 235U : 238U ratio. The method is discrete, sensitive, able to detect short-term pollution episodes and useful for understanding element cycling, which is of critical importance for human and environmental health.