Anisotropic dispersion, space competition, and the slowdown of the Neolithic transition

The front speed of the Neolithic (farmer) spread in Europe decreased as it reached Northern latitudes, where the Mesolithic (huntergatherer) population density was higher. Here, we describe a reaction diffusion model with (i) an anisotropic dispersion kernel depending on the Mesolithicpopulation density gradient and (ii) a modified population growth equation. Both effects are related to the space available for the Neolithic population. The model is able to explain the slowdown of the Neolithic front as observed from archaeological data

Computational anatomy for studying use-dependant brain plasticity.

In this article we provide a comprehensive literature review on the in vivo assessment of use-dependant brain structure changes in humans using magnetic resonance imaging (MRI) and computational anatomy. We highlight the recent findings in this field that allow the uncovering of the basic principles behind brain plasticity in light of the existing theoretical models at various scales of observation. Given the current lack of in-depth understanding of the neurobiological basis of brain structure changes we emphasize the necessity of a paradigm shift in the investigation and interpretation of use-dependent brain plasticity. Novel quantitative MRI acquisition techniques provide access to brain tissue microstructural properties (e.g., myelin, iron, and water content) in-vivo, thereby allowing unprecedented specific insights into the mechanisms underlying brain plasticity. These quantitative MRI techniques require novel methods for image processing and analysis of longitudinal data allowing for straightforward interpretation and causality inferences.

Use of an in-house approach to study the three-dimensional structures of various outer membrane proteins: structure of the alcaligin outer membrane transporter FauA from Bordetella pertussis.

Bordetella pertussis is the bacterial agent of whooping cough in humans. Under iron-limiting conditions, it produces the siderophore alcaligin. Released to the extracellular environment, alcaligin chelates iron, which is then taken up as a ferric alcaligin complex via the FauA outer membrane transporter. FauA belongs to a family of TonB-dependent outer membrane transporters that function using energy derived from the proton motive force. Using an in-house protocol for membrane-protein expression, purification and crystallization, FauA was crystallized in its apo form together with three other TonB-dependent transporters from different organisms. Here, the protocol used to study FauA is described and its three-dimensional structure determined at 2.3 A resolution is discussed.

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.

Localization in sucrose gradients of the pyrophosphate-dependent proton transport of maize root membranes.

A maize (Zea mays L. cv LG 11) root homogenate was prepared and centrifuged to sediment the mitochondria. The pellet (6 KP) and the supernatant (6 KS) were collected and fractionated on linear sucrose density gradients. Marker enzymes were used to study the distribution of the different cell membranes in the gradients. The distribution of the ATP- and pyrophosphate-dependent proton pumping activities was similar after 3 hours of centrifugation of the 6 KS or the 6 KP fraction. The pumps were clearly separated from the mitochondrial marker cytochrome c oxidase and the plasmalemma marker UDP-glucose-sterolglucosyl-transferase. The pyrophosphate-dependent proton pump might be associated with the tonoplast, as the ATP-dependent pump, despite the lack of a specific marker for this membrane. However, under all the conditions tested, the two pumps overlapped the Golgi markers latent UDPase and glucan synthase I and the ER marker NADH-cytochrome c reductase. It is therefore not possible to exclude the presence of proton pumping activities on the Golgi or the ER of maize root cells. The two pumps (but especially the pyrophosphate-dependent one) were more active (or more abundant) in the tip than in the basal part of maize roots, indicating that these activities might be important in growth processes.

Integration of olfactory information in a spatial representation enabling accurate arm choice in the radial arm maze

The aim of the present study was to determine whether and how rats can use local olfactory cues for spatial orientation. Rats were trained in an eight-arm radial maze under different conditions as defined by the presence or absence of supplementary olfactory cues marking each arm, the availability of distant visuospatial information, and the illumination of the maze (light or darkness). The different visual conditions were designed to dissociate among the effects of light per se and those of visuospatial cues, on the use of olfactory cues for accurate arm choice. Different procedures with modifications of the arrangement of olfactory cues were used to determine if rats formed a representation of the spatial configuration of the olfactory cues and if they could rely on such a representation for accurate arm choice in the radial maze. The present study demonstrated that the use of olfactory cues to direct arm choice in the radial arm maze was critically dependent on the illumination conditions and implied two different modes of processing of olfactory information according to the presence or the absence of light. Olfactory cues were used in an explicit manner and enabled accurate arm choice only in the absence of light. Rats, however, had an implicit memory of the location of the olfactory cues and formed a representation of the spatial position of these cues, whatever the lighting conditions. They did not memorize the spatial configuration of the olfactory cues per se but needed these cues to be linked to the external spatial frame of reference.

Fracture Discrimination by Combined Bone Mineral Density (BMD) and Microarchitectural Texture Analysis.

The use of bone mineral density (BMD) for fracture discrimination may be improved by considering bone microarchitecture. Texture parameters such as trabecular bone score (TBS) or mean Hurst parameter (H) could help to find women who are at high risk of fracture in the non-osteoporotic group. The purpose of this study was to combine BMD and microarchitectural texture parameters (spine TBS and calcaneus H) for the detection of osteoporotic fractures. Two hundred and fifty five women had a lumbar spine (LS), total hip (TH), and femoral neck (FN) DXA. Additionally, texture analyses were performed with TBS on spine DXA and with H on calcaneus radiographs. Seventy-nine women had prevalent fragility fractures. The association with fracture was evaluated by multivariate logistic regressions. The diagnostic value of each parameter alone and together was evaluated by odds ratios (OR). The area under curve (AUC) of the receiver operating characteristics (ROC) were assessed in models including BMD, H, and TBS. Women were also classified above and under the lowest tertile of H or TBS according to their BMD status. Women with prevalent fracture were older and had lower TBS, H, LS-BMD, and TH-BMD than women without fracture. Age-adjusted ORs were 1.66, 1.70, and 1.93 for LS, FN, and TH-BMD, respectively. Both TBS and H remained significantly associated with fracture after adjustment for age and TH-BMD: OR 2.07 [1.43; 3.05] and 1.47 [1.04; 2.11], respectively. The addition of texture parameters in the multivariate models didn't show a significant improvement of the ROC-AUC. However, women with normal or osteopenic BMD in the lowest range of TBS or H had significantly more fractures than women above the TBS or the H threshold. We have shown the potential interest of texture parameters such as TBS and H in addition to BMD to discriminate patients with or without osteoporotic fractures. However, their clinical added values should be evaluated relative to other risk factors.

Prominent use of distal 5’ transcription start sites and discovery of a large number of additional exons in ENCODE regions

This report presents systematic empirical annotation of transcript products from 399 annotated protein-coding loci across the 1% of the human genome targeted by the Encyclopedia of DNA elements (ENCODE) pilot project using a combination of 5' rapid amplification of cDNA ends (RACE) and high-density resolution tiling arrays. We identified previously unannotated and often tissue- or cell-line-specific transcribed fragments (RACEfrags), both 5' distal to the annotated 5' terminus and internal to the annotated gene bounds for the vast majority (81.5%) of the tested genes. Half of the distal RACEfrags span large segments of genomic sequences away from the main portion of the coding transcript and often overlap with the upstream-annotated gene(s). Notably, at least 20% of the resultant novel transcripts have changes in their open reading frames (ORFs), most of them fusing ORFs of adjacent transcripts. A significant fraction of distal RACEfrags show expression levels comparable to those of known exons of the same locus, suggesting that they are not part of very minority splice forms. These results have significant implications concerning (1) our current understanding of the architecture of protein-coding genes; (2) our views on locations of regulatory regions in the genome; and (3) the interpretation of sequence polymorphisms mapping to regions hitherto considered to be "noncoding," ultimately relating to the identification of disease-related sequence alterations.

Use of a short hPDE6b promoter for rod gene transfer in a model of severe retinal cystrophy, the Rd10 mouse

Purpose: Gene therapy of severe retinal dystrophies directly affecting photoreceptor is still a challenge in terms of clinical application. One of the main hurdles is to generate high transgene expression specifically in rods or cones. In the present study, we are investigating the possibility to drive hPDE6b expression in the Rd10 mouse retina using a specific sequence of the human PDE6b promoter. Methods: Two 5' flanking fragments of the human PDE6b gene: (-93 to +53 (146 bp) and -297 to +53 (350 bp, see Di Polo and Farber, 1995) were cloned in different plasmids in order to check their expression in vitro and in vivo. These elements drove the activity of either luciferase (pGL3 plasmids) or EGFP (AAV2/8 backbone). Then, an AAV2/8 vector carrying the PDE6b cDNA was tested with subretinal injections at P9 in the Rd10 eyes. Eye fundus, OCT, ERG recordings and histological investigations were performed to assess the efficacy of the gene transfer. Results: The short PDE6b promoter containing 146bp (-93 to +53) showed the highest activity in the Y-79 cells, as described previously (Di Polo and Farber, 1995). Subretinal administrations of AAV2/8-PDE6bpromoter-EGFP allowed a rapid expression specifically in rods and not in cones. The expression is faster than a vector containing the CMV promoter. The AAV2/8-PDE6bpromoter-PDE6b and the control vector were injected at P9 in the Rd10 mouse retina and investigated 5 weeks post-injection. Out of 14 eyes, 6 presented an increased rod sensitivity of about 300 fold, and increased a- and b-wave responses in ERG recordings. Flicker stimulations revealed that cones are also functional. OCT images and histological analyses revealed an increased ONL size in the injected area. The retina treated with the therapeutic vector presented 4-6 rows of photoreceptors with outersegments containing PDE6b. In the control eyes, only 2-4 rows of photoreceptors with almost no OS were observed . Conclusions: The 146 bp promoter sequence (-93 to + 53) is the shortest regulatory element described to date which allows to obtain efficient rod-specific expression in the context of somatic gene transfer. This first result is of great interest for AAV vector design in general allowing more space for the accommodation of transgenes of interest and good expression in rods. Moreover we showed the proof of principle of the efficacy of AAV2/8-PDE6bp-PDE6b vector in the Rd10 mouse model of severe photoreceptor degeneration without using neither AAV mutated capsids, nor self-complementary vectors.

A longitudinal study of environmental tobacco smoke exposure in children: parental self reports versus age dependent biomarkers

Background: Awareness of the negative effects of smoking on children's health prompted a decrease in the self-reporting of parental tobacco use in periodic surveys from most industrialized countries. Our aim is to assess changes between ETS exposure at the end of pregnancy and at 4 years of age determined by the parents' self-report and measurement of cotinine in age related biological matrices.Methods: The prospective birth cohort included 487 infants from Barcelona city (Spain). Mothers were asked about maternal and household smoking habit. Cord serum and children's urinary cotinine were analyzed in duplicate using a double antibody radioimmunoassay. Results: At 4 years of age, the median urinary cotinine level in children increased 1.4 or 3.5 times when father or mother smoked, respectively. Cotinine levels in children's urine statistically differentiated children from smoking mothers (Geometric Mean (GM) 19.7 ng/ml; 95% CI 16.83–23.01) and exposed homes (GM 7.1 ng/ml; 95% CI 5.61–8.99) compared with non-exposed homes (GM 4.5 ng/ml; 95% CI 3.71–5.48). Maternal self-reported ETS exposure in homes declined in the four year span between the two time periods from 42.2% to 31.0% (p < 0.01). Nevertheless, most of the children considered non-exposed by their mothers had detectable levels of cotinine above 1 ng/mL in their urine.Conclusion: We concluded that cotinine levels determined in cord blood and urine, respectively, were useful for categorizing the children exposed to smoking and showed that a certain increase in ETS exposure during the 4-year follow-up period occurred.

On fast-decodable space-time block codes

We focus on full-rate, fast-decodable space–time block codes (STBCs) for 2 x 2 and 4 x 2 multiple-input multiple-output (MIMO) transmission. We first derive conditions and design criteria for reduced-complexity maximum-likelihood (ML) decodable 2 x 2 STBCs, and we apply them to two families of codes that were recently discovered. Next, we derive a novel reduced-complexity 4 x 2 STBC, and show that it outperforms all previously known codes with certain constellations.

On high-rate full-diversity 2x2 space-time codes with low-complexity optimum detection

The 2×2 MIMO profiles included in Mobile WiMAX specifications are Alamouti’s space-time code (STC) fortransmit diversity and spatial multiplexing (SM). The former hasfull diversity and the latter has full rate, but neither of them hasboth of these desired features. An alternative 2×2 STC, which is both full rate and full diversity, is the Golden code. It is the best known 2×2 STC, but it has a high decoding complexity. Recently, the attention was turned to the decoder complexity, this issue wasincluded in the STC design criteria, and different STCs wereproposed. In this paper, we first present a full-rate full-diversity2×2 STC design leading to substantially lower complexity ofthe optimum detector compared to the Golden code with only a slight performance loss. We provide the general optimized form of this STC and show that this scheme achieves the diversitymultiplexing frontier for square QAM signal constellations. Then, we present a variant of the proposed STC, which provides a further decrease in the detection complexity with a rate reduction of 25% and show that this provides an interesting trade-off between the Alamouti scheme and SM.

Low-density parity-check codes for nonergodic block-fading channels

We design powerful low-density parity-check (LDPC) codes with iterative decoding for the block-fading channel. We first study the case of maximum-likelihood decoding, and show that the design criterion is rather straightforward. Since optimal constructions for maximum-likelihood decoding do not performwell under iterative decoding, we introduce a new family of full-diversity LDPC codes that exhibit near-outage-limit performance under iterative decoding for all block-lengths. This family competes favorably with multiplexed parallel turbo codes for nonergodic channels.

Generalized low-density codes with BCH constituents for full-diversity near-outage performance

A new graph-based construction of generalized low density codes (GLD-Tanner) with binary BCH constituents is described. The proposed family of GLD codes is optimal on block erasure channels and quasi-optimal on block fading channels. Optimality is considered in the outage probability sense. Aclassical GLD code for ergodic channels (e.g., the AWGN channel,the i.i.d. Rayleigh fading channel, and the i.i.d. binary erasure channel) is built by connecting bitnodes and subcode nodes via a unique random edge permutation. In the proposed construction of full-diversity GLD codes (referred to as root GLD), bitnodes are divided into 4 classes, subcodes are divided into 2 classes, and finally both sides of the Tanner graph are linked via 4 random edge permutations. The study focuses on non-ergodic channels with two states and can be easily extended to channels with 3 states or more.

A comparison of full-rate full-diversity 2x2 space-time codes for WiMAX systems

Multiple-input multiple-output (MIMO) techniques have become an essential part of broadband wireless communications systems. For example, the recently developed IEEE 802.16e specifications for broadband wireless access include three MIMOprofiles employing 2×2 space-time codes (STCs), and two of these MIMO schemes are mandatory on the downlink of Mobile WiMAX systems. One of these has full rate, and the other has full diversity, but neither of them has both of the desired features. The third profile, namely, Matrix C, which is not mandatory, is both a full rate and a full diversity code, but it has a high decoder complexity. Recently, the attention was turned to the decodercomplexity issue and including this in the design criteria, several full-rate STCs were proposed as alternatives to Matrix C. In this paper, we review these different alternatives and compare them to Matrix C in terms of performances and the correspondingreceiver complexities.