Clinical and molecular phenotype of Aicardi-Goutières syndrome

Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P = .001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified. © 2007 by The American Society of Human Genetics. All rights reserved.

Introducing the biogeographic species pool

The species pool concept has played a central role in the development of ecological theory for at least 60 yr. Surprisingly, there is little consensus as to how one should define the species pool, and consequently, no systematic approach exists. Because the definition of the species pool is essential to infer the processes that shape ecological communities, there is a strong incentive to develop an ecologically realistic definition of the species pool based on repeatable and transparent analytical approaches. Recently, several methodological tools have become available to summarize repeated patterns in the geographic distribution of species, phylogenetic clades and taxonomically broad lineages. Here, we present three analytical approaches that can be used to define what we term 'the biogeographic species pool': distance-based clustering analysis, network modularity analysis, and assemblage dispersion fields. The biogeographic species pool defines the pool of potential community members in a broad sense and represents a first step towards a standardized definition of the species pool for the purpose of comparative ecological, evolutionary and biogeographic studies. © 2013 The Authors.

The functional biogeography of species: Biogeographical species roles of birds in Wallacea and the West Indies

Biogeographical systems can be analyzed as networks of species and geographical units. Within such a biogeographical network, individual species may differ fundamentally in their linkage pattern, and therefore hold different topological roles. To advance our understanding of the relationship between species traits and large-scale species distribution patterns in archipelagos, we use a network approach to classify birds as one of four biogeographical species roles: peripherals, connectors, module hubs, and network hubs. These roles are based upon the position of species within the modular network of islands and species in Wallacea and the West Indies. We test whether species traits - including habitat requirements, altitudinal range-span, feeding guild, trophic level, and body length - correlate with species roles. In both archipelagos, habitat requirements, altitudinal range-span and body length show strong relations to species roles. In particular, species that occupy coastal- and open habitats, as well as habitat generalists, show higher proportions of connectors and network hubs and thus tend to span several biogeographical modules (i.e. subregions). Likewise, large body size and a wide altitudinal range-span are related to a wide distribution on many islands and across several biogeographical modules. On the other hand, species restricted to interior forest are mainly characterized as peripherals and, thus, have narrow and localized distributions within biogeographical modules rather than across the archipelago-wide network. These results suggest that the ecological amplitude of a species is highly related to its geographical distribution within and across bio geographical subregions and furthermore supports the idea that large-scale species distributions relate to distributions at the local community level. We finally discuss how our biogeographical species roles may correspond to the stages of the taxon cycle and other prominent theories of species assembly. © 2013 The Authors.

Live High-Train High increases hemoglobin mass in Olympic swimmers

This study tested whether 3-4 weeks of classical Live High-Train High (LHTH) altitude training increases swim-specific VO2max through increased hemoglobin mass (Hb(mass)).Ten swimmers lived and trained for more than 3 weeks between 2,130 and 3,094 m of altitude, and a control group of ten swimmers followed the same training at sea-level (SL). Body composition was examined using dual X-ray absorptiometry. Hb(mass) was determined by carbon monoxide rebreathing. Swimming VO2peak was determined and swimming trials of 4 x 50, 200 and 3,000 m were performed before and after the intervention.Hb(mass) (n = 10) was increased (P < 0.05)after altitude training by 6.2 +/- A 3.9 % in the LHTH group, whereas no changes were apparent in the SL group (n = 10). Swimming VO2peak was similar before and after training camps in both groups (LHTH: n = 7, SL: n = 6). Performance of 4 x 50 m at race pace was improved to a similar degree in both groups (LHTH: n = 10, SL: n = 10). Maximal speed reached in an incremental swimming step test (P = 0.051), and time to complete 3,000 m tended (P = 0.09) to be more improved after LHTH (n = 10) than SL training (n = 10).In conclusion, 3-4 weeks of classical LHTH is sufficient to increase Hb(mass) but exerts no effect on swimming-specific VO2peak. LHTH may improve performance more than SL training.

Vitamin B6-Dependent Enzymes in the Human Malaria Parasite Plasmodium falciparum: A Druggable Target?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Determinants of bird species richness, endemism, and island network roles in Wallacea and the West Indies: is geography sufficient or does current and historical climate matter?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)