Occurrence of Hyp3-bradykinin in methanol extracts of the skin of the South African leptodactylid frogHeleophryne purcelli

Summary Methanol extracts of the skin of the South African amphibians belonging to the genusHeleophryne (H. purcelli purcelli, H. purcelli depressa, H. purcelli orientalis, H. natalensis) contain large amounts (20–500 g/g fresh tissue) of Hyp³-bradykinin.Supported by grants from the Consiglio Nazionale delle Ricerche, Italy, and from the Ministry of Education, Japan.     

Identification of low-frequency variants associated with gout and serum uric acid levels

We tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. We identified a low-frequency missense variant (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5 × 10(-16), at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5 × 10(-21)). We confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. We also found a second variant on chromosome 1 associated with gout (OR = 1.92, P = 0.046, at-risk allele frequency = 0.986) and serum uric acid levels (effect = 0.48 s.d., P = 4.5 × 10(-16)). This variant is close to a common variant previously associated with serum uric acid levels. This work illustrates how whole-genome sequencing data allow the detection of associations between low-frequency variants and complex traits.     

Identical point mutations of PMP-22 in Trembler-J mouse and Charcot-Marie-Tooth disease type 1A.

We have investigated the peripheral myelin protein gene, PMP-22, in a family with Charcot-Marie-Tooth disease type 1A (CMT1A). The DNA duplication commonly found in CMT1A was absent in this family, but strong linkage existed between the disease and the CMT1A marker VAW409R3 on chromosome 17p11.2. We found a point mutation in PMP-22 which was completely linked with the disease. The mutation, a proline for leucine substitution in the first putative transmembrane domain, is identical to that recently found in the Trembler-J mouse. The presence of this PMP-22 defect in this CMT1A family and the location of PMP-22 within the DNA duplication associated with CMT1A suggest that both structural alteration and overexpression of PMP-22 may lead to the disease.     

Extrusion Freeforming of Millimeter-Wave Electromagnetic Bandgap (EBG) Photonic Crystals

Extrusion freeforming can be used for the rapid prototyping of millimeter-wave electromagnetic bandgap (EBG) structures. In this work, an alumina-polymer paste with a relatively high volatility solvent (propanol) was used and the characteristics of the ceramic paste, particularly the rheological features are described. The advantage of high volatility solvent is that the viscosity and elastic modulus of the paste are increased sharply as the solvent evaporates. Thus, the rigidity of the extruded filament is quickly increased as a small amount of solvent evaporates. Finally, by employing this procedure, different EBG structures such as 2-D, 3-D woodpile and aperiodic structures were fabricated and their bandgaps were measured. The experimental results show that extrusion freeforming is a relatively simple and easy method to fabricate these woodpile structures with a bandgap in the 90–110 GHz region.     

Solid Freeforming and Combinatorial Research

A view of manufacturing processes is presented in which five distinct categories are defined as casting, deformation, machining, joining, and solid freeforming. Solid freeforming is essentially biomimetic and shares problems of morphogenesis with natural processes. Our team in University of London has been exploring three mechanisms of solid freeforming. In dry powder deposition and direct ink-jet printing, the emphasis has turned to the problem of delivering a complex shape in which the three dimensional spatial arrangement of composition is delivered from the design file. In extrusion freeforming, the aim is to control microstructure at hierarchical levels also from the design file. The quest for 3-D functional gradients is satisfied by acoustic and ultrasonic dispensing and mixing of powders so that each layer can be patterned. These methods could be extended to deliver the complex patterns demanded by left-handed microwave metamaterials. Dry powder deposition and direct ink-jet printing are turning towards combinatorial methods in which multiple sample libraries are used to accelerate discovery. In turn, this paves the way for ‘autonomous research machines’ which steer their own search refinements in response to our requests for new materials. In this way, solid freeforming used for sample preparation can give an ‘arm’ to an intelligent machine so that it can conduct its own experimentation and learning; an idea that originated with Alan Turing in the late 1940s.     

Subunits of the translation initiation factor eIF2B are mutant in leukoencephalopathy with vanishing white matter.

Leukoencephalopathy with vanishing white matter (VWM) is an inherited brain disease that occurs mainly in children. The course is chronic-progressive with additional episodes of rapid deterioration following febrile infection or minor head trauma. We have identified mutations in EIF2B5 and EIF2B2, encoding the epsilon- and beta-subunits of the translation initiation factor eIF2B and located on chromosomes 3q27 and 14q24, respectively, as causing VWM. We found 16 different mutations in EIF2B5 in 29 patients from 23 families. We also found two distantly related individuals who were homozygous with respect to a missense mutation in EIF2B2, affecting a conserved amino acid. Three other patients also had mutations in EIF2B2. As eIF2B has an essential role in the regulation of translation under different conditions, including stress, this may explain the rapid deterioration of people with VWM under stress. Mutant translation initiation factors have not previously been implicated in disease.     

Climate change and population declines in a long-distance migratory bird

Phenological responses to climate change differ across trophic levels, which may lead to birds failing to breed at the time of maximal food abundance. Here we investigate the population consequences of such mistiming in the migratory pied flycatcher, Ficedula hypoleuca. In a comparison of nine Dutch populations, we find that populations have declined by about 90% over the past two decades in areas where the food for provisioning nestlings peaks early in the season and the birds are currently mistimed. In areas with a late food peak, early-breeding birds still breed at the right time, and there is, at most, a weak population decline. If food phenology advances further, we also predict population declines in areas with a late food peak, as in these areas adjustment to an advanced food peak is insufficient. Mistiming as a result of climate change is probably a widespread phenomenon, and here we provide evidence that it can lead to population declines.     

Environmental biosafety and transgenic potato in a centre of diversity for this crop

The Nuffield Council on Bioethics suggests that introgression of genetic material into related species in centres of crop biodiversity is an insufficient justification to bar the use of genetically modified crops in the developing world. They consider that a precautionary approach to forgo the possible benefits invokes the fallacy of thinking that doing nothing is itself without risk to the poor. Here we report findings relevant to this and other aspects of environmental biosafety for genetically modified potato in its main centre of biodiversity, the central Andes. We studied genetically modified potato clones that provide resistance to nematodes, principal pests of Andean potato crops. We show that there is no harm to many non-target organisms, but gene flow occurs to wild relatives growing near potato crops. If stable introgression were to result, the fitness of these wild species could be altered. We therefore transformed the male sterile cultivar Revolucion to provide a genetically modified nematode-resistant potato to evaluate the benefits that this provides until the possibility of stable introgression to wild relatives is determined. Thus, scientific progress is possible without compromise to the precautionary principle.     

Generation time and temporal scaling of bird population dynamics

Theoretical studies have shown that variation in density regulation strongly influences population dynamics, yet our understanding of factors influencing the strength of density dependence in natural populations still is limited. Consequently, few general hypotheses have been advanced to explain the large differences between species in the magnitude of population fluctuations. One reason for this is that the detection of density regulation in population time series is complicated by time lags induced by the life history of species that make it difficult to separate the relative contributions of intrinsic and extrinsic factors to the population dynamics. Here we use population time series for 23 bird species to estimate parameters of a stochastic density-dependent age-structured model. We show that both the strength of total density dependence in the life history and the magnitude of environmental stochasticity, including transient fluctuations in age structure, increase with generation time. These results indicate that the relationships between demographic and life-history traits in birds translate into distinct population dynamical patterns that are apparent only on a scale of generations.