Molecular Genetics of Cystinuria: Identification of Four New Mutations and Seven Polymorphisms, and Evidence for Genetic Heterogeneity

A cystinuria disease gene (rBAT) has been recently identified, and some mutations causing the disease have been described. The frequency of these mutations has been investigated in a large sample of 51 Italian and Spanish cystinuric patients. In addition, to identify new mutated alleles, genomic DNA has been analyzed by an accurate and sensitive method able to detect nucleotide changes. Because of the lack of information available on the genomic structure of rBAT gene, the study was carried out using the sequence data so far obtained by us. More than 70% of the entire coding sequence and 8 intron-exon boundaries have been analyzed. Four new mutations and seven intragenic polymorphisms have been detected. All mutations so far identified in rBAT belong only to cystinuria type I alleles, accounting for ~44% of all type I cystinuric chromosomes. Mutation M467T is the most common mutated allele in the Italian and Spanish populations. After analysis of 70% of the rBAT coding region, we have detected normal sequences in cystinuria type II and type III chromosomes. The presence of rBAT mutated alleles only in type I chromosomes of homozygous (type I/I) and heterozygous (type I/III) patients provides evidence for genetic heterogeneity where rBAT would be responsible only for type I cystinuria and suggests a complementation mechanism to explain the intermediate type I/type III phenotype.     

Chronic anthropogenic disturbance causes homogenization of plant and ant communities in the Brazilian Caatinga

Although chronic anthropogenic disturbance (CAD) represents a significant threat to the integrity of tropical biotas, few efforts have been made to understand its impacts. We address the effects of CAD on plant and ant communities in the Caatinga, a seasonally dry tropical forest in northeast Brazil. Both taxa were recorded across 25 0.1-ha plots within a 220-km² landscape dominated by old-growth vegetation exposed to human activities. CAD was measured indirectly via a disturbance index, which was calculated from proxies of human disturbance such as plot distance to roads and villages, and density of people and livestock. Plant and ant abundance was not correlated to the CAD index. However, CAD had negative, positive or neutral effects on species diversity, depending upon diversity measure, taxa and soil type; e.g. plants were more negatively affected than ants. Furthermore, several plant and ant species exhibited higher abundance in the most disturbed vegetation patches while some exhibited lower abundance. Species-level responses resulted in taxonomic responses at the community level and increments in cross-plot species similarity as CAD increased. Our results indicate that: (1) CAD affects several community-level attributes, but with differing intensities; (2) community-level effects can be either positive or negative, and effects are soil dependent; (3) plants are more negatively affected than ants; (4) some species benefit, while others are negatively affected by CAD; and (5) by affecting the abundance and occurrence of particular species, CAD causes biotic homogenization towards the higher end of the disturbance gradient.     

Domain 3 of NS5A protein from the hepatitis C virus has intrinsic alpha-helical propensity and is a substrate of cyclophilin A

Nonstructural protein 5A (NS5A) is essential for hepatitis C virus (HCV) replication and constitutes an attractive target for antiviral drug development. Although structural data for its in-plane membrane anchor and domain D1 are available, the structure of domains 2 (D2) and 3 (D3) remain poorly defined. We report here a comparative molecular characterization of the NS5A-D3 domains of the HCV JFH-1 (genotype 2a) and Con1 (genotype 1b) strains. Combining gel filtration, CD, and NMR spectroscopy analyses, we show that NS5A-D3 is natively unfolded. However, NS5A-D3 domains from both JFH-1 and Con1 strains exhibit a propensity to partially fold into an α-helix. NMR analysis identifies two putative α-helices, for which a molecular model could be obtained. The amphipathic nature of the first helix and its conservation in all genotypes suggest that it might correspond to a molecular recognition element and, as such, promote the interaction with relevant biological partner(s). Because mutations conferring resistance to cyclophilin inhibitors have been mapped into NS5A-D3, we also investigated the functional interaction between NS5A-D3 and cyclophilin A (CypA). CypA indeed interacts with NS5A-D3, and this interaction is completely abolished by cyclosporin A. NMR heteronuclear exchange experiments demonstrate that CypA has in vitro peptidyl-prolyl cis/trans-isomerase activity toward some, but not all, of the peptidyl-prolyl bonds in NS5A-D3. These studies lead to novel insights into the structural features of NS5A-D3 and its relationships with CypA.     

Biological diversity and cultural heritage

In this paper some examples of the development of communities of microorganisms and plants on historic buildings and montiments are shown. When the building stones differ from the surrounding natural substrata, an increase in the biological diversity of the area is produced. In some cases, monuments can come to constitute a true refuge for a few species when the natural habitat is threatened. It is suggested that biological diversity, when it does not represent a threat for the cultural heritage, should be considered worthy of preservation.     

Biogeochemical mass-balances (C, N, P, Si) in three large reservoirs of the Seine Basin (France)

Three major reservoirs (Marne, Seine and Aube), situated in the upstream basin of the river Seine represent a storage capacity of 800 10⁶ m³. In order to quantify the possible role of these reservoirs as a sink or source of nutrients and organic matter for the river system, an input/output mass-balance of suspended matter, organic carbon, inorganic nitrogen forms, phosphorus and reactive silica was established, providing reliable estimates of their retention/elimination and export. The study was carried out over 3 years (1993, 1994 and 1995) in differing hydrological conditions. The retention times varied from 0.3 to 0.8 year, depending on the reservoir and the year, but was longer in 1993 that was a drier year than 1994 and 1995, hydrologically quite similar.Regarding retention (or elimination) and export, the behaviour of the three studied reservoirs was similar. A clear loss or retention of nitrogen, phosphorus and silica was observed in the reservoirs and represented about 40% of the incoming flux of nitrate, 50% of silica, and 60% of phosphate. The retention was lower for total phosphorus than for phosphate. The reservoirs are also sites of suspended matter deposition except during the decennial drawdown, when suspended matter is exported. For inorganic nitrogen, the average amount of nitrate retained in the Seine basin reservoirs upstream from Paris is 5000 tonnes y^–1 that is almost equal to the estimated retention by deposition or denitrification in river channel sediments for the whole drainage network. The retention in the reservoirs represents about 12% of the total flux of nitrate at the outlet of the basin upstream from Paris, and 5% at the mouth of the Seine River.We also calculated inlake C, N, P, Si budgets on the basis of direct process measurements. Measurements of planktonic primary and bacterial activity production led to annual net production of 4200 and 580 tonnes of carbon, respectively. A reasonable value (450 tonnes of carbon) of grazing was calculated. Corresponding N, P, Si fluxes were drawn from appropriate C:N:P:Si ratios. Benthic fluxes were measured with bell jars. The retention of P and Si represents a small fraction of important internal fluxes of phytoplanktonic uptake and recycling, while inorganic nitrogen retention depends mostly on benthic denitrification. The behaviour of P and Si differs in that P is mainly recycled in the water column, while Si dissolution occurs at the sediment interface. Nitrogen is recycled in both the planktonic and the benthic phase.     

Size‐based interactions and trophic transfer efficiency are modified by fish predation and cyanobacteria blooms in Lake Mývatn,Iceland

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Understanding the role of DNA methylation in successful biological invasions: a review

Biological invasions provide a unique opportunity to investigate rapid adaptation and evolution as the introduced taxa adapt to biogeographic contexts or habitats in which they have not evolved. The capacity of populations to evolve is generally thought to be constrained by their existing heritable genetic variation, which is usually associated with variation in genomic DNA nucleotide sequences. However, there is increasing acceptance that a range of mechanisms—collectively termed ‘epigenetics’ can alter gene function and affect ecologically important traits. Epigenetic processes may mediate adaptive phenotypic plasticity and provide heritable variation on a finer timescale than DNA sequence-based mutations. This review focuses on DNA methylation, a well-studied epigenetic mechanism known to be associated with biological adaptation to environmental stress. We explore the role of DNA methylation in characterising the adaptive potential of invasive species. We also provide an overview of studies focused on DNA methylation and invasive species to date, and identify knowledge gaps and potential ways to advance understanding of epigenetic-based adaptation. A summary of the literature suggests that DNA methylation could play a key role in the success of invasive species. Introduced populations with reduced genetic diversity often display increased DNA methylation variation in comparison with native populations, which could create phenotypic diversity when it is most required. Recent data show that DNA methylation could contribute to adaptation through both phenotypic plasticity and heritable variation, particularly through clonal reproduction. From a methodological perspective, recent advances in molecular techniques provide an exciting opportunity to explore the functional relevance of DNA methylation to successful biological invasions. Gaining a greater understanding of the adaptive and evolutionary processes that contribute to invasion success is critical for preventing and managing the future introduction, establishment and spread of invasive species.     

The inositol phosphatase SHIP-1 inhibits NOD2-induced NF-κB activation by disturbing the interaction of XIAP with RIP2

SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling. NOD2 is a crucial cytoplasmic bacterial sensor that activates proinflammatory and antimicrobial responses upon bacterial invasion. We observed that SHIP-1 decreases NOD2-induced NF-κB activation in macrophages. This negative regulation relies on its interaction with XIAP. Indeed, we observed that XIAP is an essential mediator of the NOD2 signaling pathway that enables proper NF-κB activation in macrophages. Upon NOD2 activation, SHIP-1 C-terminal proline rich domain (PRD) interacts with XIAP, thereby disturbing the interaction between XIAP and RIP2 in order to decrease NF-κB signaling.