Forecasting Longevity Gains Using a Seemingly Unrelated Time Series Model

In this paper a multivariate time series model using the seemingly unrelated time series equation (SUTSE) framework is proposed to forecast longevity gains. The proposed model is represented in state space form and uses Kalman filtering to estimate the unobservable components and fixed parameters. We apply the model both to male mortality rates in Portugal and the USA. Our results compare favorably, in terms of mean absolute percentage error, in‐sample and out‐of‐sample, to those obtained by the Lee–Carter method and some of its extensions. Copyright © 2015 John Wiley & Sons, Ltd.     

Common variants at 12q14 and 12q24 are associated with hippocampal volume

Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7). In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10(-11)) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10(-11)). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10(-7)) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10(-7)); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.     

Mutations in SEC63 cause autosomal dominant polycystic liver disease

Mutations in PRKCSH, encoding the beta-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that mutations in SEC63, encoding a component of the protein translocation machinery in the ER, also cause this disease. These findings are suggestive of a role for cotranslational protein-processing pathways in maintaining epithelial luminal structure and implicate noncilial ER proteins in human polycystic disease.     

Active genes are tri-methylated at K4 of histone H3

Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl. Histone H3 has been found to be di-methylated at lysine 4 (K4) in active euchromatic regions but not in silent heterochromatic sites. Here we show that the Saccharomyces cerevisiae Set1 protein can catalyse di- and tri-methylation of K4 and stimulate the activity of many genes. Using antibodies that discriminate between the di- and tri-methylated state of K4 we show that di-methylation occurs at both inactive and active euchromatic genes, whereas tri-methylation is present exclusively at active genes. It is therefore the presence of a tri-methylated K4 that defines an active state of gene expression. These findings establish the concept of methyl status as a determinant for gene activity and thus extend considerably the complexity of histone modifications.     

Technology and the Myth of ‘Natural Man’

The main suggestions and objections raised by Don Ihde and Charles Lenay to my ‘Technology and the body: the (im)possibilities of re-embodiment’ are summarized and discussed. On the one hand, I agree that we should pay more attention to whole body experience and to further resisting Cartesian assumptions in the field of cognitive neuroscience and philosophy of cognition. On the other hand, I explain that my account in no way presupposes the myth of ‘natural man’ or of a natural, delineated body from before the fall into technology.     

Forecasting value‐at‐risk with a parsimonious portfolio spillover GARCH (PS‐GARCH) model

Accurate modelling of volatility (or risk) is important in finance, particularly as it relates to the modelling and forecasting of value‐at‐risk (VaR) thresholds. As financial applications typically deal with a portfolio of assets and risk, there are several multivariate GARCH models which specify the risk of one asset as depending on its own past as well as the past behaviour of other assets. Multivariate effects, whereby the risk of a given asset depends on the previous risk of any other asset, are termed spillover effects. In this paper we analyse the importance of considering spillover effects when forecasting financial volatility. The forecasting performance of the VARMA‐GARCH model of Ling and McAleer (2003), which includes spillover effects from all assets, the CCC model of Bollerslev (1990), which includes no spillovers, and a new Portfolio Spillover GARCH (PS‐GARCH) model, which accommodates aggregate spillovers parsimoniously and hence avoids the so‐called curse of dimensionality, are compared using a VaR example for a portfolio containing four international stock market indices. The empirical results suggest that spillover effects are statistically significant. However, the VaR threshold forecasts are generally found to be insensitive to the inclusion of spillover effects in any of the multivariate models considered. Copyright © 2008 John Wiley & Sons, Ltd.     

Ultrastructure of a mucous gland cell found in the tube feet of the starfishAsterina stellifera

Resumen Es describida la ultraestrutura de un segundo tipo de célula glandular mucosa que es encontrada en el pié ambulacrario de la estrella del marAsterina stellifera. Los gránulos secretores de esta célula tienen en su interior una ultraestrutura en forma de pequeños puntos densos y delicadas fibrillas, mas faltando una organizatión, principalmente comparada con la organizatión del otro tipo de granulo mucoso, también encontrado en el mismo pié ambulacrario.     

Electron diffraction and electron microscopy studies on the crystalline component of enamel of theOdontaspis (selachii)

Résumé L'auteur constate que dans la dent du Requin du genreOdontaspis l'ultrastucture de la substance qui recouvre la dentine est morphologiquement très semblable à celle de l'émail de la dent humaine. Par diffraction électronique le composant cristallin de l'émail du Requin a été déterminé comme étant del'apatite. Ces résultats montrent que le revêtement externe de la dent d'Odontaspis peut être considéré comme un véritable émail.     

Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites

Inhibitory neurotransmission mediated by GABA(A) receptors can be modulated by the endogenous neurosteroids, allopregnanolone and tetrahydro-deoxycorticosterone. Neurosteroids are synthesized de novo in the brain during stress, pregnancyand after ethanol consumption, and disrupted steroid regulation of GABAergic transmission is strongly implicated in several debilitating conditions such as panic disorder, major depression, schizophrenia, alcohol dependence and catamenial epilepsy. Determining how neurosteroids interact with the GABA(A) receptor is a prerequisite for understanding their physiological and pathophysiological roles in the brain. Here we identify two discrete binding sites in the receptor's transmembrane domains that mediate the potentiating and direct activation effects of neurosteroids. They potentiate GABA responses from a cavity formed by the alpha-subunit transmembrane domains, whereas direct receptor activation is initiated by interfacial residues between alpha and beta subunits and is enhanced by steroid binding to the potentiation site. Thus, significant receptor activation by neurosteroids relies on occupancy of both the activation and potentiation sites. These sites are highly conserved throughout the GABA(A )receptor family, and their identification provides a unique opportunity for the development of new therapeutic, neurosteroid-based ligands and transgenic disease models of neurosteroid dysfunction.