No supernovae associated with two long-duration gamma-ray bursts

It is now accepted that long-duration gamma-ray bursts (GRBs) are produced during the collapse of a massive star. The standard 'collapsar' model predicts that a broad-lined and luminous type Ic core-collapse supernova accompanies every long-duration GRB. This association has been confirmed in observations of several nearby GRBs. Here we report that GRB 060505 (ref. 10) and GRB 060614 (ref. 11) were not accompanied by supernova emission down to limits hundreds of times fainter than the archetypal supernova SN 1998bw that accompanied GRB 980425, and fainter than any type Ic supernova ever observed. Multi-band observations of the early afterglows, as well as spectroscopy of the host galaxies, exclude the possibility of significant dust obscuration and show that the bursts originated in actively star-forming regions. The absence of a supernova to such deep limits is qualitatively different from all previous nearby long-duration GRBs and suggests a new phenomenological type of massive stellar death.     

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.     

Sintering study of Ti6Al4V powders with different particle sizes and their mechanical properties

Ti6Al4V powders with three different particle size distributions (0-20, 20-45, and 45-75 μm) were used to evaluate the effect of the particle size distribution on the solid-state sintering and their mechanical properties. The sintering kinetics was determined by dilatometry at temperatures from 900 to 1260℃. The mechanical properties of the sintered samples were evaluated by microhardness and compression tests. The sintering kinetics indicated that the predominant mechanism depends on the relative density irrespective of the particle size used. The mechanical properties of the sintered samples are adversely affected by increasing pore volume fraction. The elastic Young's modulus and yield stress follow a power law function of the relative density. The fracture behavior after compression is linked to the neck size developed during sintering, exhibiting two different mechanisms of failure:interparticle neck breaking and intergranular cracking in samples with relative densities below and above of 90%, respectively. The main conclusion is that relative density is responsible for the kinetics, mechanical properties, and failure behavior of Ti6Al4V powders.     

Target mimicry provides a new mechanism for regulation of microRNA activity

MicroRNAs (miRNA) regulate key aspects of development and physiology in animals and plants. These regulatory RNAs act as guides of effector complexes to recognize specific mRNA sequences based on sequence complementarity, resulting in translational repression or site-specific cleavage. In plants, most miRNA targets are cleaved and show almost perfect complementarity with the miRNAs around the cleavage site. Here, we examined the non-protein coding gene IPS1 (INDUCED BY PHOSPHATE STARVATION 1) from Arabidopsis thaliana. IPS1 contains a motif with sequence complementarity to the phosphate (Pi) starvation-induced miRNA miR-399, but the pairing is interrupted by a mismatched loop at the expected miRNA cleavage site. We show that IPS1 RNA is not cleaved but instead sequesters miR-399. Thus, IPS1 overexpression results in increased accumulation of the miR-399 target PHO2 mRNA and, concomitantly, in reduced shoot Pi content. Engineering of IPS1 to be cleavable abolishes its inhibitory activity on miR-399. We coin the term 'target mimicry' to define this mechanism of inhibition of miRNA activity. Target mimicry can be generalized beyond the control of Pi homeostasis, as demonstrated using artificial target mimics.     

Characterization of the role of metallothionein-3 in an animal model of Alzheimer’s disease

Among the dementias, Alzheimer’s disease (AD) is the most commonly diagnosed, but there are still no effective drugs available for its treatment. It has been suggested that metallothionein-3 (MT-3) could be somehow involved in the etiology of AD, and in fact very promising results have been found in in vitro studies, but the role of MT-3 in vivo needs further analysis. In this study, we analyzed the role of MT-3 in a mouse model of AD, Tg2576 mice, which overexpress human Amyloid Precursor Protein (hAPP) with the Swedish mutation. MT-3 deficiency partially rescued the APP-induced mortality of females, and mildly affected APP-induced changes in behavior assessed in the hole-board and plus-maze tests in a gender-dependent manner. Amyloid plaque burden and/or hAPP expression were decreased in the cortex and hippocampus of MT-3-deficient females. Interestingly, exogenously administered Zn₇MT-3 increased soluble Aβ40 and Aβ42 and amyloid plaques and gliosis, particularly in the cortex, and changed several behavioral traits (increased deambulation and exploration and decreased anxiety). These results highlight that the control of the endogenous production and/or action of MT-3 could represent a powerful therapeutic target in AD.     

Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus

Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.     

Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase

A functional immune system depends on the production of a wide range of immunoglobulin molecules. Immunoglobulin variable region (IgV) genes are diversified after gene rearrangement by hypermutation. In the DNA deamination model, we have proposed that deamination of dC residues to dU by activation-induced deaminase (AID) triggers this diversification. In hypermutating chicken DT40 B cells, most IgV mutations are dC --> dG/dA or dG --> dC/dT transversions, which are proposed to result from replication over sites of base loss produced by the excision activity of uracil-DNA glycosylase. Blocking the activity of uracil-DNA glycosylase should instead lead to replication over the dU lesion, resulting in dC --> dT (and dG --> dA) transitions. Here we show that expression in DT40 cells of a bacteriophage-encoded protein that inhibits uracil-DNA glycosylase shifts the pattern of IgV gene mutations from transversion dominance to transition dominance. This is good evidence that antibody diversification involves dC --> dU deamination within the immunoglobulin locus itself.     

The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome

Sterile inflammation is a cornerstone of immune activation in obesity and type 2 Diabetes Mellitus. The molecular underpinnings of this inflammation include nutrient excess-mediated activation of the innate immune NLRP3 inflammasome. At the same time, disruption of mitochondrial integrity is emerging as an integral control node in NLRP3 inflammasome activation and is also associated with caloric overload conditions including obesity and diabetes. Conversely, caloric restriction and fasting mimetic interventions alleviate these caloric excess-linked diseases and reduce inflammation and the NLRP3 inflammasome. The objective of this review is to integrate the findings linking mitochondrial integrity to the activation of the NLRP3 inflammasome and to evaluate how caloric restriction or caloric restriction mimetic compounds may play a role in attenuating the NLRP3 inflammasome and sterile inflammation.     

Nonparametric Quantile Regression‐Based Classifiers for Bankruptcy Forecasting

An improved classification device for bankruptcy forecasting is proposed. The proposed approach relies on mainstream classifiers whose inputs are obtained from a so‐called multinorm analysis, instead of traditional indicators such as the ROA ratio and other accounting ratios. A battery of industry norms (computed by using nonparametric quantile regressions) is obtained, and the deviations of each firm from this multinorm system are used as inputs for the classifiers. The approach is applied to predict bankruptcy on a representative sample of Spanish manufacturing firms. Results indicate that our proposal may significantly enhance predictive accuracy, both in linear and nonlinear classifiers. Copyright © 2013 John Wiley & Sons, Ltd.