Mammalian models of extended healthy lifespan

Over the last two centuries, there has been a significant increase in average lifespan expectancy in the developed world. One unambiguous clinical implication of getting older is the risk of experiencing age-related diseases including various cancers, dementia, type-2 diabetes, cataracts and osteoporosis. Historically, the ageing process and its consequences were thought to be intractable. However, over the last two decades or so, a wealth of empirical data has been generated which demonstrates that longevity in model organisms can be extended through the manipulation of individual genes. In particular, many pathological conditions associated with the ageing process in model organisms, and importantly conserved from nematodes to humans, are attenuated in long-lived genetic mutants. For example, several long-lived genetic mouse models show attenuation in age-related cognitive decline, adiposity, cancer and glucose intolerance. Therefore, these long-lived mice enjoy a longer period without suffering the various sequelae of ageing. The greatest challenge in the biology of ageing is to now identify the mechanisms underlying increased healthy lifespan in these model organisms. Given that the elderly are making up an increasingly greater proportion of society, this focused approach in model organisms should help identify tractable interventions that can ultimately be translated to humans

The assessment of vertebral fractures in elderly women with recent hip fractures: the BREAK Study

Summary This study aimed to evaluate the prevalence of vertebral fractures in elderly women with a recent hip fracture. The burden of vertebral fractures expressed by the Spinal Deformity Index (SDI) is more strictly associated with the trochanteric than the cervical localization of hip fracture and may influence short-term functional outcomes. Introduction This study aimed to determine the prevalence and severity of vertebral fractures in elderly women with recent hip fracture and to assess whether the burden of vertebral fractures may be differently associated with trochanteric hip fractures with respect to cervical hip fractures. Methods We studied 689 Italian women aged 60 years or over with a recent low trauma hip fracture and for whom an adequate X-ray evaluation of spine was available. All radiographs were examined centrally for the presence of any vertebral deformities and radiological morphometry was performed. The SDI, which integrates both the number and the severity of fractures, was also calculated. Results Prevalent vertebral fractures were present in 55.7 % of subjects and 95 women (13.7 %) had at least one severe fracture. The women with trochanteric hip fracture showed higher SDI and higher prevalence of diabetes with respect to those with cervical hip fracture, p00.017 and p00.001, respectively. SDI, surgical menopause, family history of fragility fracture, and type2 diabetes mellitus were independently associated with the risk of trochanteric hip fracture. Moreover, a higher SDI was associated with a higher percentage of postsurgery complications (p00.05) and slower recovery (p<0.05). Conclusions Our study suggests that the burden of prevalent vertebral fractures is more strictly associated with the trochanteric than the cervical localisation of hip fracture and that elevated values of SDI negatively influence short term functional outcomes in women with hip fracture

Masked suffix priming and morpheme positional constraints

Although masked stem priming (e.g., dealer\u2013DEAL) is one of the most established effects in visual word identification (e.g., Grainger et al., 1991), it is less clear whether primes and targets sharing a suffix (e.g., kindness\u2013WILDNESS) also yield facilitation (Giraudo & Grainger, 2003; Du\uf1abeitia et al., 2008). In a new take on this issue, we show that prime nonwords facilitate lexical decisions to target words ending with the same suffix (sheeter\uac\u2013TEACHER) compared to a condition where the critical suffix was substituted by another one (sheetal\u2013TEACHER) or by an unrelated non\u2013morphological ending (sheetub\u2013 TEACHER). We also show that this effect is genuinely morphological, as no priming emerged in non\u2013complex items with the same orthographic characteristics (sportel\u2013BROTHEL vs. sportic\u2013BROTHEL vs. sportur\u2013BROTHEL). In a further experiment, we took advantage of these results to assess whether suffixes are recognized in a position\u2013specific fashion. Masked suffix priming did not emerge when the relative order of stems and suffixes was reversed in the prime nonwords\u2014ersheet did not yield any time saving in the identification of teacher as compared to either alsheet or obsheet. We take these results to show that \u2013er was not identified as a morpheme in ersheet, thus indicating that suffix identification is position specific. This conclusion is in line with data on interference effects in nonword rejection (Crepaldi, Rastle, & Davis, 2010), and strongly constrains theoretical proposals on how complex words are identified. In particular, because these findings were reported in a masked priming paradigm, they suggest that positional constraints operate early, most likely at a pre\u2013lexical level of morpho\u2013orthographic analysi

The nature of semantic priming by subliminal spatial words: Embodied or disembodied?

Theories of embodied semantics (ES) suggest that a critical part of understanding what a word means consists of simulating the sensorimotor experience related to the word's referent. Some proponents of ES have suggested that sensorimotor activations are mandatory and highly automatic during semantic processing. Evidence supporting this claim comes from masked priming studies showing that unconsciously perceived spatial words (e.g., up, down) can directly modulate action performance on the basis of their meaning. However, a closer look reveals that such priming effects can be explained also in terms of symbolic (disembodied) semantic priming or nonsemantic mechanisms. In this study we sought to understand whether sensorimotor processing takes place during language understanding outside awareness. We used spatial words as a test bed and across 6 experiments we teased apart the possibility that action priming could be explained by: (a) nonsemantic mechanisms, (b) symbolic semantic priming, or (c) embodied semantic priming. The critical finding is that when symbolic and nonsemantic mechanisms were prevented, allowing only for a genuinely embodied semantic priming, no effect was found. Conversely, facilitation emerged in the same experimental paradigm when embodied priming was prevented and symbolic priming was allowed. Despite extensive testing, we found no evidence that unconsciously perceived words can activate sensorimotor processes, although these words are processed up to the semantic level. We thus conclude that sensorimotor activations might need conscious access to emerge during language understanding. (PsycINFO Database Recor

BOVITA: a first overview on genome-wide genetic diversity of Italian autochthonous cattle breeds

Analysis of genomic data is increasingly becoming part of the livestock industry and is an invaluable resource for effective management of breeding programs in small populations. The recent availability of genome-wide SNP panels allows providing background information concerning genome structure in domestic animals, opening new perspectives to livestock genetics. BOVITA was established to join local efforts and resources for the genomic characterization of Italian local cattle breeds. Despite the growing diffusion of some cosmopolite specialized breeds, several autochthonous breeds are still bred in Italy. The main aim of the BOVITA is to investigate the genomic structure of Italian local cattle breeds, to provide information on their genetic status that will be useful for the management of the genetic variability, as a contribution to biodiversity conservation and prioritization actions. A total of about 800 animals (20-32 per breed) belonging to thirty Italian cattle breeds (Agerolese, Bar\ue0-Pustertaler, Burlina, Cabannina, Calvana, Chianina, Cinisara, Garfagnina, Italian Brown, Italian Holstein, Italian Simmental, Marchigiana, Maremmana, Modenese, Modicana, Mucca Pisana, Pezzata Rossa d\u2019Oropa, Piedmontese, Pinzgau, Podolica, Pontremolese, Pustertaler, Reggiana, Rendena, Romagnola, Rossa Siciliana, Sarda, Sardo-Bruna, Sardo-Modicana and Ottonese-Varzese) and two cosmopolitan breeds (Charolaise and Limousine) genotyped with the Illumina BovineSNP50 v2 BeadChip array were collected for the analysis. The genotypes of several breeds were detected in the frame of the project, whereas for some breeds these data are derived by previous studies. The dataset will be analyzed to: study several aspects of population genetic diversity, multi-dimensional scaling plot, population structure, linkage disequilibrium, and runs of homozygosity. In addition, comparative analysis of conserved haplotypes will be conducted to identify genomic segments under selection pressure. Such information also provides important insights into the mechanisms of evolution and is useful for the annotation of significant functional genomics regions. Data analysis will also be useful to select SNPs suitable for parentage test and breed genetic traceability. The analysis of the data will pinpoint the genetic distinctiveness of Italian breeds. Moreover, the obtained results contribute to a better characterization of history and genetic structure of Italian cattle breeds

No fruits without color: Cross-modal priming and EEG reveal different roles for different features across semantic categories

Category-specific impairments witnessed in patients with semantic deficits have broadly dissociated into natural and artificial kinds. However, how the category of food (more specifically, fruits and vegetables) fits into this distinction has been difficult to interpret, given a pattern of deficit that has inconsistently mapped onto either kind, despite its intuitive membership to the natural domain. The present study explores the effects of a manipulation of a visual sensory (i.e., color) or functional (i.e., orientation) feature on the consequential semantic processing of fruits and vegetables (and tools, by comparison), first at the behavioral and then at the neural level. The categorization of natural (i.e., fruits/vegetables) and artificial (i.e., utensils) entities was investigated via cross-modal priming. Reaction time analysis indicated a reduction in priming for color-modified natural entities and orientationmodified artificial entities. Standard event-related potentials (ERP) analysis was performed, in addition to linear classification. For natural entities, a N400 effect at central channel sites was observed for the color-modified condition compared relative to normal and orientation conditions, with this difference confirmed by classification analysis. Conversely, there was no significant difference between conditions for the artificial category in either analysis. These findings provide strong evidence that color is an integral property to the categorization of fruits/vegetables, thus substantiating the claim that feature-based processing guides as a function of semantic category

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

Frequency-based neural discrimination in fast periodic visual stimulation

Humans capitalize on statistical cues to discriminate fundamental units of information within complex streams of sensory input. We sought neural evidence for this phenomenon by combining fast periodic visual stimulation (FPVS) and EEG recordings. Skilled readers were exposed to sequences of linguistic items with decreasing familiarity, presented at a fast rate and periodically interleaved with oddballs. Crucially, each sequence comprised stimuli of the same category, and the only distinction between base and oddball items was the frequency of occurrence of individual tokens within a stream. Frequency-domain analyses revealed robust neural responses at the oddball presentation rate in all conditions, reflecting the discrimination between two locally-emerged groups of items purely informed by token frequency. Results provide evidence for a fundamental frequency-tuned mechanism that operates under high temporal constraints and could underpin category bootstrapping. Concurrently, they showcase the potential of FPVS for providing a direct neural measure of implicit statistical learning