Theory of mind and cognitive processes in aging and Alzheimer type dementia: a systematic review.

OBJECTIVES: Theory of mind (ToM) performance in aging and dementia of the Alzheimer type (DAT) has been a growing interest of researchers and recently, theoretical trends in ToM development have led to a focus on determining the cognitive skills involved in ToM performance. The aim of the present review is to answer three main questions: How is ToM assessed in aging and DAT? How does ToM performance evolve in aging and DAT? Do cognitive processes influence ToM performance in aging and DAT? METHOD: A systematic review was conducted to provide a targeted overview of recent studies relating ToM performance with cognitive processes in aging and DAT. RESULTS: RESULTS suggest a decrease in ToM performance, more pronounced in complex ToM tasks. Moreover, the review points up the strong involvement of executive functions, especially inhibition, and reasoning skills in ToM task achievement. CONCLUSION: Current data suggest that the structure of ToM tasks itself could lead to poor performance, especially in populations with reduced cognitive abilities.

Genetic consequences of the ice ages on nurseries of the bat Myotis myotis: a mitochondrial and nuclear survey.

Analyses of mitochondrial DNA (mtDNA) control region polymorphism and of variation at 10 nuclear microsatellite loci were used to investigate the mechanisms and genetic consequences of postglacial expansion of Myotis myotis in Europe. Initial sampling consisted of 480 bats genotyped in 24 nursery colonies arranged along a transect of approximately 3000 km. The phylogeographical survey based on mtDNA sequences revealed the existence of major genetic subdivisions across this area, with several suture zones between haplogroups. Such zones of secondary contact were found in the Alps and Rhodopes, whereas other potential barriers to gene flow, like the Pyrenees, did not coincide with genetic discontinuities. Areas of population admixture increased locally the genetic diversity of colonies, which confounded the northward decrease in nucleotide diversity predicted using classical models of postglacial range expansion. However, when analyses were restricted to a subset of 15 nurseries originating from a single presumed glacial refugium, mtDNA polymorphism did indeed support a northwards decrease in diversity. Populations were also highly structured (PhiST = 0.384). Conversely, the same subset of colonies showed no significant latitudinal decrease in microsatellite diversity and much less population structure (FST = 0.010), but pairwise genetic differentiation at these nuclear markers was strongly correlated with increasing geographical distance. Together, this evidence suggests that alleles carried via male bats have maintained enough nuclear gene flow to counteract the effects of recurrent bottlenecks generally associated with recolonization processes. As females are highly philopatric, we argue that the maternally transmitted mtDNA marker better reflects the situation of past, historical gene flow, whereas current levels of gene flow are better reflected by microsatellite markers.

Polymorphism at a sex-linked transcription cofactor in European tree frogs (Hyla arborea): Sex-antagonistic selection or neutral processes?

Nascent sex chromosomes offer a unique opportunity to investigate the evolutionary fate of genesrecently trapped in non-recombining segments. A housekeeping gene (MED15) was recently shown to lie on the nascent sex-chromosomes of the European tree frog (Hyla arborea), with different alleles fixed on the X and the Y chromosomes. Here we document a polymorphism (glutamine deletion) in the X copy of the gene, and use population surveys and experimental crosses to test whether this polymorphism is neutral or maintained by sex-antagonistic selection. Tadpoles from parents of known genotypes revealed significant discrepancies from Mendelian inheritance, suggesting possible sex-antagonistic effects under laboratory conditions. Quantitatively, however, these effects did not meet the conditions for polymorphism maintenance. Furthermore, field estimates of female genotypic frequencies did not differ from Hardy-Weinberg equilibrium and allelic frequencies on the X chromosome did not differ between sexes. In conclusion, although sex antagonistic effects cannot be excluded given the laboratory conditions, the X-linked polymorphism under study appears neutral in the wild. Alternatively, sex-antagonistic selection might still account for the fixation of a male specific allele on the Y chromosome.

Consensus paper: the role of the cerebellum in perceptual processes.

Various lines of evidence accumulated over the past 30 years indicate that the cerebellum, long recognized as essential for motor control, also has considerable influence on perceptual processes. In this paper, we bring together experts from psychology and neuroscience, with the aim of providing a succinct but comprehensive overview of key findings related to the involvement of the cerebellum in sensory perception. The contributions cover such topics as anatomical and functional connectivity, evolutionary and comparative perspectives, visual and auditory processing, biological motion perception, nociception, self-motion, timing, predictive processing, and perceptual sequencing. While no single explanation has yet emerged concerning the role of the cerebellum in perceptual processes, this consensus paper summarizes the impressive empirical evidence on this problem and highlights diversities as well as commonalities between existing hypotheses. In addition to work with healthy individuals and patients with cerebellar disorders, it is also apparent that several neurological conditions in which perceptual disturbances occur, including autism and schizophrenia, are associated with cerebellar pathology. A better understanding of the involvement of the cerebellum in perceptual processes will thus likely be important for identifying and treating perceptual deficits that may at present go unnoticed and untreated. This paper provides a useful framework for further debate and empirical investigations into the influence of the cerebellum on sensory perception.

Rethinking the triggering inflammatory processes of chronic periaortitis.

Chronic periaortitis (CP) is an uncommon inflammatory disease which primarily involves the infrarenal portion of the abdominal aorta. However, CP should be regarded as a generalized disease with three different pathophysiological entities, namely idiopathic retroperitoneal fibrosis (RPF), inflammatory abdominal aortic aneurysm and perianeurysmal RPF. These entities share similar histopathological characteristics and finally will lead to fibrosis of the retroperitoneal space. Beside fibrosis, an infiltrate with variable chronic inflammatory cell is present. The majority of these cells are lymphocytes and macrophages as well as vascular endothelial cells, most of which are HLA-DR-positive. B and T cells are present with a majority of T cells of the T-helper phenotype. Cytokine gene expression analysis shows the presence of interleukin (IL)-1alpha, IL-2, IL-4, interferon-gamma and IL-2 receptors. Adhesion molecules such as E-selectin, intercellular adhesion molecule-1 and the vascular cell adhesion molecule-1 were also found in aortic tissue, and may play a significant role in CP pathophysiology. Although CP pathogenesis remains unknown, an exaggerated inflammatory response to advanced atherosclerosis (ATS) has been postulated to be the main process. Autoimmunity has also been proposed as a contributing factor based on immunohistochemical studies. The suspected allergen may be a component of ceroid, which is elaborated within the atheroma. We review the pathogenesis and the pathophysiology of CP, and its potential links with ATS. Clinically relevant issues are summarized in each section with regard to the current working hypothesis of this complex inflammatory disease.

Evolutionary history of almond tree domestication in the Mediterranean basin.

Genetic diversity of contemporary domesticated species is shaped by both natural and human-driven processes. However, until now, little is known about how domestication has imprinted the variation of fruit tree species. In this study, we reconstruct the recent evolutionary history of the domesticated almond tree, Prunus dulcis, around the Mediterranean basin, using a combination of nuclear and chloroplast microsatellites [i.e. simple sequence repeat (SSRs)] to investigate patterns of genetic diversity. Whereas conservative chloroplast SSRs show a widespread haplotype and rare locally distributed variants, nuclear SSRs show a pattern of isolation by distance with clines of diversity from the East to the West of the Mediterranean basin, while Bayesian genetic clustering reveals a substantial longitudinal genetic structure. Both kinds of markers thus support a single domestication event, in the eastern side of the Mediterranean basin. In addition, model-based estimation of the timing of genetic divergence among those clusters is estimated sometime during the Holocene, a result that is compatible with human-mediated dispersal of almond tree out of its centre of origin. Still, the detection of region-specific alleles suggests that gene flow from relictual wild preglacial populations (in North Africa) or from wild counterparts (in the Near East) could account for a fraction of the diversity observed.

Fine-scale genetic structure and marginal processes in an expanding population of Biscutella laevigata L. (Brassicaceae).

Evolutionary processes acting at the expanding margins of a species' range are still poorly understood. Genetic drift is considered prevalent in marginal populations, and the maintenance of genetic diversity during recolonization might seem puzzling. To investigate such processes, a fine-scale investigation of 219 individuals was performed within a population of Biscutella laevigata (Brassicaceae), located at the leading edge of its range. The survey used amplified fragment length polymorphisms (AFLPs). As commonly reported across the whole species distribution range, individual density and genetic diversity decreased along the local axis of recolonization of this expanding population, highlighting the enduring effect of the historical colonization on present-day diversity. The self-incompatibility system of the plant may have prevented local inbreeding in newly found patches and sustained genetic diversity by ensuring gene flow from established populations. Within the more continuously populated region, spatial analysis of genetic structure revealed restricted gene flow among individuals. The distribution of genotypes formed a mosaic of relatively homogenous patches within the continuous population. This pattern could be explained by a history of expansion by long-distance dispersal followed by fine-scale diffusion (that is, a stratified dispersal combination). The secondary contact among expanding patches apparently led to admixture among differentiated genotypes where they met (that is, a reshuffling effect). This type of dynamics could explain the maintenance of genetic diversity during recolonization.

Prospective analysis of KRAS, BRAF, and PIK3CA mutations and EGFR copy number in patients (pts) with locally advanced rectal cancer: A translational substudy of a clinical trial (SAKK 41/07) evaluating the effect of neoadjuvant chemoradiation (CRT) with or without panitumumab

Background: Prognostic and predictive markers are of great importance for future study designs and essential for the interpretation of clinical trials incorporating an EGFR-inhibitor. The current study prospectively assessed and validated KRAS, BRAF and PIK3CA mutations in rectal cancer patients screened for the trial SAKK41/07 of concomitant preoperative radio-chemotherapy with or without panitumumab.Methods: Macrodissection was performed on pretreatment formalin fixed paraffin embedded biopsy tissue sections to arrive at a minimum of 50% of tumor cells. DNA was extracted with the Maxwell 16 FFPE Tissue LEV DNA purification kit. After PCR amplification, mutations were identified by pyrosequencing. We prospectively analysed pretreatment biopsy material from 149 rectal cancer pts biopsies for KRAS (exon 2 codon 12 [2-12] and 13 [2-13], exon 3 codon 59 [3-59]) and 61 [3-61], exon 4 codon 117 [4-117] and 146 [4-146]). Sixty-eight pts (KRASwt exon 2, 3 only) were further analysed for BRAF (exon 15 codon 600) and PIK3CA (exon 9 codon 542, 545 and 546, exon 20 codon 1043 [20-1043] and 1047 [20-1047]) mutations, and EGFR copy number by qPCR. For the calculation of the EGFR copy number, we used KRAS copy number as internal reference standard. The calculation was done on the basis of the two standard curves relative quantification method.Results: In 149 screened pts with rectal cancer, the prevalence of KRAS mutations was 36%. Among the 68 pts enrolled in SAKK 41/07 based on initially presumed KRASwt status (exon 2/codons 12+13), 18 pts (26%) had a total of 23 mutations in the RAS/PIK3CA-pathways upon validation analysis. Twelve pts had a KRAS mutation, 7 pts had a PIK3CA mutation, 3 pts had a NRAS mutation, 1 patient a BRAF mutation. Surprisingly, five of these pts had double- mutations, including 4 pts with KRAS plus PIK3CA mutations, and 1 pt with NRAS plus PIK3CA mutations. The median normalized EGFR copy number was 1. Neither mutations of KRAS, BRAF, and PIK3CA, nor EGFR copy number were statistically associated with the primary study endpoint pCR (pathological complete regression).Conclusions: The prevalence of KRAS mutations in rectal and in colon cancer appears to be similar. BRAF mutations are rare; PIK3CA mutations are more common (10%). EGFR copy number is not increased in rectal cancer. A considerable number or KRAS exon 2 wt tumors harbored KRAS exon 3+4 mutations. Further study is needed to determine if KRAS testing should include exons 2-4.

Low dispersing species : population genetic processes in space and time : the genus "Trochulus" (Gastropoda: Hygromiidae) as a case study

RÉSUMÉ Une espèce est rarement composée d'une population unique. Parce que les individus ont des capacités de dispersion limitées et que les paysages sont des mosaïques d'habitats, la plupart des espèces sont plutôt composées de sous-populations connectées par la migration. Cette variation spatiale influence directement la distribution de la variabilité génétique dans et entre les populations. Durant ce travail, nous avons abordé certains des processus populationnels qui ont joué un rôle supposé dans l'apparition de nouvelles espèces au sein du genre Trochulus. Plus précisément, nous avons tenté d'évaluer les impacts respectifs de l'isolement passé (facteurs historiques) et présent (facteurs locaux). Nous avons d'abord pu montrer que les faibles capacités de dispersion des escargots terrestres ont directement influencé leur histoire évolutive à toutes les échelles spatiales et temporelles. En réduisant l'effet homogénéisant de la migration, une faible dispersion maintient dans les populations les traces génétiques d'évènements passés. A l'échelle de la distribution globale de Trochulus villosus, ces traces ont permis de reconstruire une histoire faite d'isolements et d'expansions de populations. En combinant des données génétiques avec une modélisation de la niche climatique passée, il a été possible de proposer un scénario significativement meilleur que toutes les hypothèses alternatives que nous avons testées. A l'échelle locale par contre, l'héritage historique est difficile à distinguer de la dynamique actuelle. Ce fut le cas des lignées mitochondriales du complexe sericeus-hispidus : les deux principales lignées étaient phylogénétiquement éloignées, avaient eu des démographies passées différentes et corrélaient avec des différences morphologiques. D'un autre côté, le flux de gène nucléaire était fort, contredisant l'idée de deux espèces cryptiques isolées reproductivement. Pour pouvoir conclure à la présence ou non de deux espèces, il nous a manqué des informations locales sur la dynamique des populations et les conditions écologiques que l'on trouve dans la région d'étude. Enfin, nous avons pu souligner que la connectivité entre populations d'escargots est soumise à la qualité des habitats et à leur organisation spatiale. Les escargots sont dépendants d'un habitat et s'y adaptent, comme l'indiquent la présence de «poils » uniquement sur la coquille d'espèces vivant dans des habitats humides ou la corrélation entre morphologie et habitat au sein du complexe sericeus-hispidus. Logiquement donc, les escargots migrent préférentiellement au travers d'habitats favorables comme l'a montré la réduction de flux de gènes au travers des prairies chez T. villosus (une espèce forestière). De ces données, nous pouvons supposer que les populations d'escargots en particulier, et des espèces à faible dispersion en général, ont de fortes chances d'être affectées par les changements climatiques, avec de probables implications pour leurs histoires évolutives. SUMMARY : Species rarely consists in a single population. Because individuals have limited dispersal abilities, because landscapes are habitat patchworks, most species are made of several subpopulations connected by migration. This spatial variation has consequences on the distribution of genetic diversity within and between populations, creating a structure among the populations. During the present work, we investigated some of the population processes assumed to have played an important role on the speciation within the genus Trochulus. More specifically, we questioned the respective impacts of past (historical factors) or present (local factors) population isolations. We first could show that the poor dispersal abilities of land snails have had profound impacts on their evolutionary histories at all spatial and temporal scales. Low dispersal maintains a strong signature of past events in the populations by minimising the homogenising effects of geneflow. At the scale of Trochulus villosus global distribution, they allowed to retrieve the detailed history of this species population isolations and expansions. Combining a large genetic dataset with paleo-climatic niche modelling ended up with a historical scenario significantly better than all traditional alternatives we tested. At local scale on the contrary, past events become difficult to tease apart from ongoing processes. This was the case for the divergent mitochondria) lineages within the sericeus-hispidus complex: the two principal lineages appeared to be phylogenetically distant, to have experienced different demographic histories and to correlate with morphological differences. On the other hand, nuclear (present day) geneflow was high, contradicting the idea of two reproductively isolated cryptic species. Information on the local population dynamics and environmental conditions are lacking to be able to decide whether past isolation has indeed resulted here in new species. Finally, we emphasised the importance of the habitat types present in a landscape as well as their spatial organisation for the population connectivity of land snails. These species are tightly dependent on a habitat and adapt to it as shown by thé occurrence of hair-like structures only in species living in humid environments or by the correlation between shell morphology and habitat in the sericeus-hispidus complex. As a result, land snails preferentially migrate through favourable habitats: Trochulus villosus, a forest species, had its geneflow significantly reduced across meadows. From these data, we can hypothesise that the populations of land snails in particular and of low dispersing species in general are likely to be strongly affected by the ongoing climate changes, with potential major consequences on their evolutionary histories.

Seismic attenuation and velocity dispersion in heterogeneous partially saturated porous rocks

Using a numerical approach, we explore wave-induced fluid flow effects in partially saturated porous rocks in which the gas-water saturation patterns are governed by mesoscopic heterogeneities associated with the dry frame properties. The link between the dry frame properties and the gas saturation is defined by the assumption of capillary pressure equilibrium, which in the presence of heterogeneity implies that neighbouring regions can exhibit different levels of saturation. To determine the equivalent attenuation and phase velocity of the synthetic rock samples considered in this study, we apply a numerical upscaling procedure, which permits to take into account mesoscopic heterogeneities associated with the dry frame properties as well as spatially continuous variations of the pore fluid properties. The multiscale nature of the fluid saturation is taken into account by locally computing the physical properties of an effective fluid, which are then used for the larger-scale simulations. We consider two sets of numerical experiments to analyse such effects in heterogeneous partially saturated porous media, where the saturation field is determined by variations in porosity and clay content, respectively. In both cases we also evaluate the seismic responses of corresponding binary, patchy-type saturation patterns. Our results indicate that significant attenuation and modest velocity dispersion effects take place in this kind of media for both binary patchy-type and spatially continuous gas saturation patterns and in particular in the presence of relatively small amounts of gas. The numerical experiments also show that the nature of the gas distribution patterns is a critical parameter controlling the seismic responses of these environments, since attenuation and velocity dispersion effects are much more significant and occur over a broader saturation range for binary patchy-type gas-water distributions. This analysis therefore suggests that the physical mechanisms governing partial saturation should be accounted for when analysing seismic data in a poroelastic framework. In this context, heterogeneities associated with the dry frame properties, which do not play important roles in wave-induced fluid flow processes per se, should be taken into account since they may determine the kind of gas distribution pattern taking place in the porous rock.