Rapid degradation of a large fraction of newly synthesized proteins by proteasomes

MHC class I molecules function to present peptides eight to ten residues long to the immune system. These peptides originate primarily from a cytosolic pool of proteins through the actions of proteasomes, and are transported into the endoplasmic reticulum, where they assemble with nascent class I molecules. Most peptides are generated from proteins that are apparently metabolically stable. To explain this, we previously proposed that peptides arise from proteasomal degradation of defective ribosomal products (DRiPs). DRiPs are polypeptides that never attain native structure owing to errors in translation or post-translational processes necessary for proper protein folding. Here we show, first, that DRiPs constitute upwards of 30% of newly synthesized proteins as determined in a variety of cell types; second, that at least some DRiPs represent ubiquitinated proteins; and last, that ubiquitinated DRiPs are formed from human immunodeficiency virus Gag polyprotein, a long-lived viral protein that serves as a source of antigenic peptides.     

Bootstrap Replacement to Validate the Influence of the Economic Cycle on the Structure and the Accuracy Level of Business Failure Prediction Models

The aim of this study was to answer the question of how the economic cycle affects the stability and efficiency of business failure prediction models, using bootstrap replacement method for validation. We analyse 2228 Spanish small and medium‐sized enterprises for the period 2001–2009, and divide it into three different phases of the economic cycle (growth, crisis, recession). We find that the structure and the ability of business failure prediction models are different according to the economic cycle. These findings are relevant for the debate on the most suitable financial ratios when developing business failure prediction models and to pose their accuracy level in these prediction models. Copyright © 2015 John Wiley & Sons, Ltd.     

Redescription of the Cephalaspidea gastropod Atys jeffreysi (Weinkauff, 1866) (Haminoeidae), with a discussion on the phylogenetic affinities of the Mediterranean species of the genus

Atys jeffreysi is a heterobranch Cephalaspidea gastropod belonging to the family Haminoeidae occurring in the Mediterranean Sea, Madeira and Canary archipelagos. Nearly nothing is known about the internal anatomical features of this species. In this paper we redescribe the species A. jeffreysi based on fine anatomical work and scanning electron microscopy. DNA barcodes are provided for the first time for A. jeffreysi and A. macandrewii, the only two species of the genus native in the Mediterranean Sea. The genetic distance (COI uncorrected p-distance) between them is estimate at 21.6%. A Bayesian molecular phylogeny based on the gene marker cytochrome c oxidase subunit I (COI) including all sequences available of the genera Aliculastrum, Liloa and Atys species did not support a sister relationship between the two Mediterranean species and suggests that they are more closely related to distinct Indo-West Pacific lineages. The complex systematics of the genus Atys is briefly discussed.     

Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration?

The low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies. Mesenchymal stem cells (MSCs) have been proposed as a possible therapeutic tool for CNS disorders. In addition to their differentiation potential, it is well accepted nowadays that their beneficial actions can also be mediated by their secretome. Indeed, it was already demonstrated, both in vitro and in vivo, that MSCs are able to secrete a broad range of neuroregulatory factors that promote an increase in neurogenesis, inhibition of apoptosis and glial scar formation, immunomodulation, angiogenesis, neuronal and glial cell survival, as well as relevant neuroprotective actions on different pathophysiological contexts. Considering their protective action in lesioned sites, MSCs’ secretome might also improve the integration of local progenitor cells in neuroregeneration processes, opening a door for their future use as therapeutical strategies in human clinical trials. Thus, in this review we analyze the current understanding of MSCs secretome as a new paradigm for the treatment of CNS neurodegenerative diseases.     

Calmodulin mediates melatonin cytoskeletal effects

In this article, we review the data concerning melatonin interactions with calmodulin. The kinetics of melatonin-calmodulin binding suggest that the hormone modulates cell activity through intracellular binding to the protein at physiological concentration ranges. Melatonin interaction with calmodulin may allow the hormone to modulate rhythmically many cellular functions. Melatonin's effect on tubulin polymerization, and cytoskeletal changes in MDCK and N1E-115 cells cultured with melatonin, suggest that at low concentrations (10^–9 M) cytoskeletal effects are mediated by its antagonism to Ca²⁺-calmodulin. At higher concentrations (10^–5 M), non-specific binding of melatonin to tubulin occurs thus overcoming the specific melatonin antagonism to Ca²⁺-calmodulin. Since the structures of melatonin and calmodulin are phylogenetically well preserved, calmodulin-melatonin interaction probably represents a major mechanism for regulation and synchronization of cell physiology.     

Phyllostomid bats flying in daylight: a case from the Neotropics

Bats (Chiroptera), one of the most diverse groups in terms of taxonomy, morphology and ecology, are known for their nocturnal behaviour of flight and feeding. Although there is no consensus on the evolution of nocturnality in bats, many authors mention risk of predation, overheating, competition and mobbing by non-competitor species as arguments to justify nocturnal instead of daytime flight in bats. Herein we describe the first records of three genera of phyllostomid bats flying, foraging and drinking water during daytime in the Brazilian Amazon. All taxa were recorded drinking water, and some Phyllostomus sp. individuals were recorded foraging on termites, alongside birds. Risk of dehydration and overheating in roosts, as well as low competition in daytime, may explain the emergence of phyllostomid bats before sunset.     

Forecasting using targeted diffusion indexes

The simplicity of the standard diffusion index model of Stock and Watson has certainly contributed to its success among practitioners, resulting in a growing body of literature on factor‐augmented forecasts. However, as pointed out by Bai and Ng, the ranked factors considered in the forecasting equation depend neither on the variable to be forecast nor on the forecasting horizon. We propose a refinement of the standard approach that retains the computational simplicity while coping with this limitation. Our approach consists of generating a weighted average of all the principal components, the weights depending both on the eigenvalues of the sample correlation matrix and on the covariance between the estimated factor and the targeted variable at the relevant horizon. This ‘targeted diffusion index’ approach is applied to US data and the results show that it outperforms considerably the standard approach in forecasting several major macroeconomic series. Moreover, the improvement is more significant in the final part of the forecasting evaluation period. Copyright © 2009 John Wiley & Sons, Ltd.     

Implications of new early Homo fossils from Ileret, east of Lake Turkana, Kenya

Sites in eastern Africa have shed light on the emergence and early evolution of the genus Homo. The best known early hominin species, H. habilis and H. erectus, have often been interpreted as time-successive segments of a single anagenetic evolutionary lineage. The case for this was strengthened by the discovery of small early Pleistocene hominin crania from Dmanisi in Georgia that apparently provide evidence of morphological continuity between the two taxa. Here we describe two new cranial fossils from the Koobi Fora Formation, east of Lake Turkana in Kenya, that have bearing on the relationship between species of early Homo. A partial maxilla assigned to H. habilis reliably demonstrates that this species survived until later than previously recognized, making an anagenetic relationship with H. erectus unlikely. The discovery of a particularly small calvaria of H. erectus indicates that this taxon overlapped in size with H. habilis, and may have shown marked sexual dimorphism. The new fossils confirm the distinctiveness of H. habilis and H. erectus, independently of overall cranial size, and suggest that these two early taxa were living broadly sympatrically in the same lake basin for almost half a million years.     

Magnitude and distribution of linkage disequilibrium in population isolates and implications for genome-wide association studies

The genome-wide distribution of linkage disequilibrium (LD) determines the strategy for selecting markers for association studies, but it varies between populations. We assayed LD in large samples (200 individuals) from each of 11 well-described population isolates and an outbred European-derived sample, using SNP markers spaced across chromosome 22. Most isolates show substantially higher levels of LD than the outbred sample and many fewer regions of very low LD (termed 'holes'). Young isolates known to have had relatively few founders show particularly extensive LD with very few holes; these populations offer substantial advantages for genome-wide association mapping.     

A wavelet approach for factor‐augmented forecasting

It has been acknowledged that wavelets can constitute a useful tool for forecasting in economics. Through a wavelet multi‐resolution analysis, a time series can be decomposed into different timescale components and a model can be fitted to each component to improve the forecast accuracy of the series as a whole. Up to now, the literature on forecasting with wavelets has mainly focused on univariate modelling. On the other hand, in a context of growing data availability, a line of research has emerged on forecasting with large datasets. In particular, the use of factor‐augmented models have become quite widespread in the literature and among practitioners. The aim of this paper is to bridge the two strands of the literature. A wavelet approach for factor‐augmented forecasting is proposed and put to test for forecasting GDP growth for the major euro area countries. The results show that the forecasting performance is enhanced when wavelets and factor‐augmented models are used together. Copyright © 2010 John Wiley & Sons, Ltd.