Human Rap1 modulates TRF2 attraction to telomeric DNA

More than two decades of genetic research have identified and assigned main biological functions of shelterin proteins that safeguard telomeres. However, a molecular mechanism of how each protein subunit contributes to the protecting function of the whole shelterin complex remains elusive. Human Repressor activator protein 1 (Rap1) forms a multifunctional complex with Telomeric Repeat binding Factor 2 (TRF2). Rap1–TRF2 complex is a critical part of shelterin as it suppresses homology-directed repair in Ku 70/80 heterodimer absence. To understand how Rap1 affects key functions of TRF2, we investigated full-length Rap1 binding to TRF2 and Rap1–TRF2 complex interactions with double-stranded DNA by quantitative biochemical approaches. We observed that Rap1 reduces the overall DNA duplex binding affinity of TRF2 but increases the selectivity of TRF2 to telomeric DNA. Additionally, we observed that Rap1 induces a partial release of TRF2 from DNA duplex. The improved TRF2 selectivity to telomeric DNA is caused by less pronounced electrostatic attractions between TRF2 and DNA in Rap1 presence. Thus, Rap1 prompts more accurate and selective TRF2 recognition of telomeric DNA and TRF2 localization on single/double-strand DNA junctions. These quantitative functional studies contribute to the understanding of the selective recognition of telomeric DNA by the whole shelterin complex.     

Into the light: diurnality has evolved multiple times in geckos

Geckos are the only major lizard group consisting mostly of nocturnal species. Nocturnality is presumed to have evolved early in gecko evolution and geckos possess numerous adaptations to functioning in low light and at low temperatures. However, not all gecko species are nocturnal and most diurnal geckos have their own distinct adaptations to living in warmer, sunlit environments. We reconstructed the evolution of gecko activity patterns using a newly generated time‐calibrated phylogeny. Our results provide the first phylogenetic analysis of temporal activity patterns in geckos and confirm an ancient origin of nocturnality at the root of the gecko tree. We identify multiple transitions to diurnality at a variety of evolutionary time scales and transitions back to nocturnality occur in several predominantly diurnal clades. The scenario presented here will be useful in reinterpreting existing hypotheses of how geckos have adapted to varying thermal and light environments. These results can also inform future research of gecko ecology, physiology, morphology and vision as it relates to changes in temporal activity patterns. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, ●●, ●●–●●.     

Diagnosis, clinical features, and self-reported morbidity of Strongyloides stercoralis and hookworm infection in a Co-endemic setting

Background

Infections with Strongyloides stercoralis and other helminths represent important, yet often neglected issues in developing countries. Indeed, strongyloidiasis can be fatal, but only a few studies provide information regarding its health relevance in Africa. Moreover, clinical data on symptomatology and typical recognition patterns mainly originate from Western travel clinics.

Methodology

A cross-sectional epidemiological survey was carried out in a rural part of south-central Côte d''Ivoire. Stool samples from 292 randomly selected individuals were examined for intestinal helminths, using a suite of diagnostic techniques (i.e., Kato-Katz, Baermann funnel, and Koga agar plate). Participants were interviewed with a pre-tested questionnaire and clinically examined. Multivariate logistic regression analysis was done to relate perceived morbidity and clinical findings to helminth infection status.

Principal Findings

The prevalence of hookworm and S. stercoralis was 51.0% and 12.7%, respectively. Both infections were strongly associated with each other (adjusted odds ratio, 6.73; P<0.001) and higher prevalences were observed with age. S. stercoralis-infected individuals expressed self-reported morbidity considerably more often than those with hookworm infection. Clinical examination identified high prevalences of various pathologies and detected tendencies to worse health conditions in helminth-infected subjects.

Conclusions/Significance

The use of multiple diagnostic tools showed that S. stercoralis and hookworm are co-endemic in rural Côte d''Ivoire and that each infection causes clinical symptoms and sequelae. Our findings are important for (re-)estimating the burden of helminth infections, and highlight the need for integrating epidemiological surveys, rigorous diagnostic approaches, and clinical assessments in the developing world.     

Autosomal-Recessive Hypophosphatemic Rickets Is Associated with an Inactivation Mutation in the ENPP1 Gene

Human disorders of phosphate (Pi) handling and hypophosphatemic rickets have been shown to result from mutations in PHEX, FGF23, and DMP1, presenting as X-linked recessive, autosomal-dominant, and autosomal-recessive patterns, respectively. We present the identification of an inactivating mutation in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene causing autosomal-recessive hypophosphatemic rickets (ARHR) with phosphaturia by positional cloning. ENPP1 generates inorganic pyrophosphate (PPi), an essential physiologic inhibitor of calcification, and previously described inactivating mutations in this gene were shown to cause aberrant ectopic calcification disorders, whereas no aberrant calcifications were present in our patients. Our surprising result suggests a different pathway involved in the generation of ARHR and possible additional functions for ENPP1.     

A perfusion-independent role of blood vessels in determining branching stereotypy of lung airways

Blood vessels have been shown to play perfusion-independent roles in organogenesis. Here, we examined whether blood vessels determine branching stereotypy of the mouse lung airways in which coordinated branching of epithelial and vascular tubes culminates in their co-alignment. Using different ablative strategies to eliminate the lung vasculature, both in vivo and in lung explants, we show that proximity to the vasculature is indeed essential for patterning airway branching. Remarkably, although epithelial branching per se proceeded at a nearly normal rate, branching stereotypy was dramatically perturbed following vascular ablation. Specifically, branching events requiring a rotation to change the branching plane were selectively affected. This was evidenced by either the complete absence or the shallow angle of their projections, with both events contributing to an overall flat lung morphology. Vascular ablation also led to a high frequency of ectopic branching. Regain of vascularization fully rescued arrested airway branching and restored normal lung size and its three-dimensional architecture. This role of the vasculature is independent of perfusion, flow or blood-borne substances. Inhibition of normal branching resulting from vascular loss could be explained in part by perturbing the unique spatial expression pattern of the key branching mediator FGF10 and by misregulated expression of the branching regulators Shh and sprouty2. Together, these findings uncovered a novel role of the vasculature in organogenesis, namely, determining stereotypy of epithelial branching morphogenesis.     

Genomic and phenomic analysis of island ant community assembly

Island biodiversity has long fascinated biologists as it typically presents tractable systems for unpicking the eco‐evolutionary processes driving community assembly. In general, two recurring themes are of central theoretical interest. First, immigration, diversification, and extinction typically depend on island geographical properties (e.g., area, isolation, and age). Second, predictable ecological and evolutionary trajectories readily occur after colonization, such as the evolution of adaptive trait syndromes, trends toward specialization, adaptive radiation, and eventual ecological decline. Hypotheses such as the taxon cycle draw on several of these themes to posit particular constraints on colonization and subsequent eco‐evolutionary dynamics. However, it has been challenging to examine these integrated dynamics with traditional methods. Here, we combine phylogenomics, population genomics and phenomics, to unravel community assembly dynamics among Pheidole (Hymenoptera, Formicidae) ants in the isolated Fijian archipelago. We uphold basic island biogeographic predictions that isolated islands accumulate diversity primarily through in situ evolution rather than dispersal, and population genomic support for taxon cycle predictions that endemic species have decreased dispersal ability and demography relative to regionally widespread taxa. However, rather than trending toward island syndromes, ecomorphological diversification in Fiji was intense, filling much of the genus‐level global morphospace. Furthermore, while most endemic species exhibit demographic decline and reduced dispersal, we show that the archipelago is not an evolutionary dead‐end. Rather, several endemic species show signatures of population and range expansion, including a successful colonization to the Cook islands. These results shed light on the processes shaping island biotas and refine our understanding of island biogeographic theory.     

Genetics,Morphology, Advertisement Calls,and Historical Records Distinguish Six New Polyploid Species of African Clawed Frog (Xenopus,Pipidae) from West and Central Africa

African clawed frogs, genus Xenopus, are extraordinary among vertebrates in the diversity of their polyploid species and the high number of independent polyploidization events that occurred during their diversification. Here we update current understanding of the evolutionary history of this group and describe six new species from west and central sub-Saharan Africa, including four tetraploids and two dodecaploids. We provide information on molecular variation, morphology, karyotypes, vocalizations, and estimated geographic ranges, which support the distinctiveness of these new species. We resurrect Xenopus calcaratus from synonymy of Xenopus tropicalis and refer populations from Bioko Island and coastal Cameroon (near Mt. Cameroon) to this species. To facilitate comparisons to the new species, we also provide comments on the type specimens, morphology, and distributions of X. epitropicalis, X. tropicalis, and X. fraseri. This includes significantly restricted application of the names X. fraseri and X. epitropicalis, the first of which we argue is known definitively only from type specimens and possibly one other specimen. Inferring the evolutionary histories of these new species allows refinement of species groups within Xenopus and leads to our recognition of two subgenera (Xenopus and Silurana) and three species groups within the subgenus Xenopus (amieti, laevis, and muelleri species groups).     

High Molecular Weight Forms of Mammalian Respiratory Chain Complex II

Mitochondrial respiratory chain is organised into supramolecular structures that can be preserved in mild detergent solubilisates and resolved by native electrophoretic systems. Supercomplexes of respiratory complexes I, III and IV as well as multimeric forms of ATP synthase are well established. However, the involvement of complex II, linking respiratory chain with tricarboxylic acid cycle, in mitochondrial supercomplexes is questionable. Here we show that digitonin-solubilised complex II quantitatively forms high molecular weight structures (CII_hmw) that can be resolved by clear native electrophoresis. CII_hmw structures are enzymatically active and differ in electrophoretic mobility between tissues (500 – over 1000 kDa) and cultured cells (400–670 kDa). While their formation is unaffected by isolated defects in other respiratory chain complexes, they are destabilised in mtDNA-depleted, rho0 cells. Molecular interactions responsible for the assembly of CII_hmw are rather weak with the complexes being more stable in tissues than in cultured cells. While electrophoretic studies and immunoprecipitation experiments of CII_hmw do not indicate specific interactions with the respiratory chain complexes I, III or IV or enzymes of the tricarboxylic acid cycle, they point out to a specific interaction between CII and ATP synthase.