Systematic and biogeographic relationships of the Japanese white-toothed shrew (Crocidura dsinezumi)

To assess the zoogeographic and phylogenetic relationships of C. dsinezumi, its systematic position has been investigated through electrophoretic comparisons. These comparisons comprise typical Indomalayan and Palaearctic species, including C. russula, the supposed sister taxon of the Japanese white-toothed shrew. The range of measured genetic distances that separate dsinezumi from the other shrews (Nei's D = 0.232-0.406) is typical for interspecific comparisons among Crocidura taxa. Our results reinforce morphologic considerations that suggest C. dsinezumi be treated as a valid species. Phylogenetic relationships deduced from a cladistic treatment of allozyme data refute the possibility that the western Palaearctic C. russula is the sister taxon of C. dsinezumi. Zoogeographic interpretation of the genetic results indicates that the Southeast Asian representatives constitute a clade distinct from one that includes the Palaearctic species. However, C. dsinezumi is difficult to assign to either clade due to many intermediate or plesiomorphic electrophoretic characters. Unlike the major karyologic and biochemical separation that divides Afrotropical and Palaearctic species, the subdivision between Palaearctic and Indomalayan Crocidura is not correlated with any trend in karyotypic evolution. It also is shown that the Eurasiatic species of Crocidura possessing 2n = 40 chromosomes (including C. dsinezumi) do not represent a particular clade, but probably share a plesiomorphic character. Further analysis of other Indian or Asiatic species is needed to test whether the Palaearctic versus Indomalayan separation is due to real zoogeographic barriers or whether it is the result of limited samples.

Geographic variation of the greater white-toothed shrew (Crocidura russula Hermann, 1780 Mammalia, Soricidae)

A multivariate morphometric study of the Greater white-toothed shrew (C. russula) throughout its Palearctic range was carried out to search for patterns of geographic variation within the species boundary. Burnaby's and multiple group principal component analysis allowed the adjustment of raw data with respect to within-sample allometric variation. Multivariate 'size-free' results show a stepped dine with the phenotypical trait reduction and shape change from the eastern to the western Maghreb. Pleistocene fossil mandibles proved to have low phenetic distances with eastern populations (Tunisia, east Algeria) and it is argued that their character set is the primitive condition. The ancestral Mid-Pleistocene shrews lived in a relatively more humid climate. Gee-climatic changes in the north African range during the Quaternary provoked phenetic variation of C. russula and, it can be argued, evolution of the modern western C.r. yebalensis. A historical process can thus be assumed as the main cause of this categorical variation, by segmentation of the species range due to gee-climatic events. Morphometric discontinuity within the C. russula Maghreb range is shown to be congruent with karyological and biochemical studies. Moroccan and Tunisian shrews differ, for example, in NFa chromosomes and electrophoretical traits. A stasipatric process should be invoked to explain categorical variation in the Maghreb range. Colonization and divergence of insular populations results in more or less differentiated geographic races. The populations of Ibiza and Pantelleria are close to the species threshold (Nei's D greater than or equal to 0.1). The process of speciation undergone by the Greater white-toothed shrew results in a complex pattern of geographic variation, including both allopatric and non-allopatric modes.

Fecundity versus offspring size in the greater white-toothed shrew Crocidura russula

1. The relationships between female body mass (WWal)i, tter size (m), juvenile growth rate (G) and mass at weaning (W20) were examined by monitoring natural litters in 29 greater white-toothed shrews, Crocidura russula (Hermann 1780). The trade-offs between m and G or W20 were further investigated by manipulating litter sizes: each of seven females reared four litters of 2, 4, 6 and 8 offspring. 2. Offspring mass at weaning (W20) exhibited a large variance, most of which could be attributed (ANCOVA on manipulated litters) to two effects: a litter-size effect, and a female individual effect, referred to as 'female quality'. 3. Litter size explained 68% of the variance in W20 among manipulated litters (linear regression). The limited milk supply was probably responsible for this effect, because litter size depressed growth rate during the first half of the lactation period (G1), but not during the weaning stage (G2). 4. Among non-manipulated litters, litter size correlated positively with maternal body mass (Wa), so that large females tended to produce small juveniles. This correlation between m and Wa is seen as the result of a body-mass dependence in the cost of raising a litter of a given size, during either pregnancy or lactation. 5. Differences in 'female quality' explained 16% of the variance in W20 among manipulated litters. This factor did not affect GI and may thus relate to differences among offspring of different females in their rates of processing milk and/or external food during late lactation. 6. 'Female quality' was independent of both body mass and litter size: larger females did not produce larger offspring when controlled for litter size, while higher-quality females did not produce larger litters. 7. Our results support the hypothesis that most variance in adult and juvenile body masses is non-genetic, and stems from the trade-off between litter size and offspring size.

Epidemiology of Masked and White-Coat Hypertension: The Family-Based SKIPOGH Study.

OBJECTIVE: We investigated factors associated with masked and white-coat hypertension in a Swiss population-based sample. METHODS: The Swiss Kidney Project on Genes in Hypertension is a family-based cross-sectional study. Office and 24-hour ambulatory blood pressure were measured using validated devices. Masked hypertension was defined as office blood pressure<140/90 mmHg and daytime ambulatory blood pressure≥135/85 mmHg. White-coat hypertension was defined as office blood pressure≥140/90 mmHg and daytime ambulatory blood pressure<135/85 mmHg. Mixed-effect logistic regression was used to examine the relationship of masked and white-coat hypertension with associated factors, while taking familial correlations into account. High-normal office blood pressure was defined as systolic/diastolic blood pressure within the 130-139/85-89 mmHg range. RESULTS: Among the 652 participants included in this analysis, 51% were female. Mean age (±SD) was 48 (±18) years. The proportion of participants with masked and white coat hypertension was respectively 15.8% and 2.6%. Masked hypertension was associated with age (odds ratio (OR) = 1.02, p = 0.012), high-normal office blood pressure (OR = 6.68, p<0.001), and obesity (OR = 3.63, p = 0.001). White-coat hypertension was significantly associated with age (OR = 1.07, p<0.001) but not with education, family history of hypertension, or physical activity. CONCLUSIONS: Our findings suggest that physicians should consider ambulatory blood pressure monitoring for older individuals with high-normal office blood pressure and/or who are obese.

Colonisation capacity of the Greater white-toothed shrew Crocidura russula : an experimental study

greater white toothed shrew; Crocidura russula; colonisation capacity

Peroxisome proliferator-activated receptor gamma is required in mature white and brown adipocytes for their survival in the mouse.

The peroxisome proliferator-activated receptor gamma (PPARgamma) mediates the activity of the insulin-sensitizing thiazolidinediones and plays an important role in adipocyte differentiation and fat accretion. The analysis of PPARgamma functions in mature adipocytes is precluded by lethality of PPARgamma(-/-) fetuses and tetraploid-rescued pups. Therefore we have selectively ablated PPARgamma in adipocytes of adult mice by using the tamoxifen-dependent Cre-ER(T2) recombination system. We show that mature PPARgamma-null white and brown adipocytes die within a few days and are replaced by newly formed PPARgamma-positive adipocytes, demonstrating that PPARgamma is essential for the in vivo survival of mature adipocytes, in addition to its well established requirement for their differentiation. Our data suggest that potent PPARgamma antagonists could be used to acutely reduce obesity.

Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial.

BACKGROUND: Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy. METHODS: Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470. FINDINGS: 1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17-6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10-8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40-3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38-5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29-6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45-27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7. INTERPRETATION: The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.

Habitat fragmentation, ecology and sexual selection in forest bird species in Monteverde, Costa Rica

Abstract Forest fragmentation is often associated with local extinction and changes in species abundance patterns. The main topic of this thesis is the effect of forest fragmentation on birds in Monteverde, Costa Rica. This thesis also studies aspects of sexual selection and ecology of Long-tailed Manakins, Chiroxiphia Linearis. Chapter 1 investigates bird species assemblages in two degrees of forest fragmentation. It is shown that the distribution, abundance and diversity of forest bird species are strongly influenced by the amount of forest in the landscape matrix. Presence of cattle within the forest influences the presence of some bird species. The prevalence and intensity of ticks and blood parasites on birds in relation to fragmentation is described in Chapter 2. Overall tick prevalence is 3%. Understory birds are significantly more infested with ticks than species at intermediate heights. Tick prevalence on birds does not differ significantly between two degrees of forest fragmentation and individual tick loads tend to be higher in High- than in Low-fragmentation sites. Infestations by the blood parasites Haemoproteus sp. was low except in white-eared ground sparrow, Melozone leucotis, that is 28% and is significantly higher in High- than in Low-fragmentation sites. In chapter 3 results on the ecology and habitat movements of the Bare-necked Umbrellabird, Cephalopterus glabricollis, are presented. The abundance of umbrellabirds at high elevations during the breeding season coincides with the highest peak of fruit abundance. Birds leave the protected area during the non-breeding season moving to unprotected forest fragments. In chapter 4 ontogenetic changes in feather morphology through sexual maturity in Long-tailed Manakins are described. In adult males, rectrices length is positively correlated to testis volume. Changes in male morphology during ontogeny in the long-tailed manakin appear to be associated with their specific-display behaviours. Significant interpopulation differences in the morphology of Long-tailed Manakins are shown in chapter 5. These differences are more accentuated in morphological traits related to flight displays. A field experiment demonstrates that long rectrices impose flying costs for males and females. A reduction in flying ability was found to be strongest in males from a population presenting the highest degree of sexual dimorphism. Résumé La fragmentation des forêts est souvent associée avec des modifications dans l'abondance des espèces et des extinctions locales. Le thème principale de cette thèse est l'étude de l'effet de la fragmentation des forêts sur les oiseaux de Monteverde, Costa Rica. Elle décrit par ailleurs certains aspects de la sélection sexuelle et l'écologie du manakin à longue queue, Chiroxiphia linearis. Dans le Chapitre 1 je montre que la distribution, l'abondance et la diversité des assemblages d'oiseaux vivant dans la forêt sont fortement influencées pas le degré de fragmentation de celle ci. Par ailleurs, la présence ou l'absence de bétail dans les forêts influence la présence de certaines espèces d'oiseaux. Dans le chapitre 2 j'ai étudié la prévalence et l'intensité d'infestation par des tiques ainsi que la présence de parasites sanguins chez les oiseaux en relation avec la fragmentation des forêts. La prévalence globale de tiques est de 3 %, les oiseaux vivant au niveau du sol étaient plus souvent infectés par des tiques que les espèces se déplaçant à un niveau plus élevé. La prévalence de tiques sur les oiseaux n'était pas significativement différente entre les paysages avec différentes fragmentations. Les parasites sanguins du genre Haemoproteus sp. étaient présents à très basse fréquence à l'exception chez Melozone leucotis ou la prevalence était de 28% et significativement plus élevée chez les oiseaux vivant dans les forêts à forte fragmentation. Dans le Chapitre 3 je présente des résultats sur l'écologie et les mouvements entre habitats chez le "Bare-necked umbrellabird", Cephalopterus glabricollis. Cette espèce endémique du Costa Rica niche à haute altitude durant la période d'abondance des fruits et réalise une migration altitudinale vers des zones basses durant la saison de non reproduction. Dans le chapitre 4 je présente les changements ontogénétiques dans la morphologie du plumage des manakins à longue queue. Chez les mâles, les changements de morphologie semblent être associés avec leurs comportements de parade spécifiques. Dans le chapitre 5 je présente des différences morphologiques significative entre deux populations chez le manakin à longue queue et je montre que la capacité de vols chez les mâles est plus fortement influencée dans la population avec le degré de dimorphisme sexuel le plus prononcé.

Plac8 is required for white adipocyte differentiation in vitro and cell number control in vivo.

Plac8 belongs to an evolutionary conserved family of proteins, mostly abundant in plants where they control fruit weight through regulation of cell number. In mice, Plac8 is expressed both in white and brown adipose tissues and we previously showed that Plac8(-/-) mice develop late-onset obesity, with abnormal brown fat differentiation and reduced thermogenic capacity. We also showed that in brown adipocytes, Plac8 is an upstream regulator of C/EBPβ expression. Here, we first assessed the role of Plac8 in white adipogenesis in vitro. We show that Plac8 is induced early after induction of 3T3-L1 adipocytes differentiation, a process that is prevented by Plac8 knockdown; similarly, embryonic fibroblasts obtained from Plac8 knockout mice failed to form adipocytes upon stimulation of differentiation. Knockdown of Plac8 in 3T3-L1 was associated with reduced expression of C/EBPβ, Krox20, and Klf4, early regulators of the white adipogenic program, and we show that Plac8 could transactivate the C/EBPβ promoter. In vivo, we show that absence of Plac8 led to increased white fat mass with enlarged adipocytes but reduced total number of adipocytes. Finally, even though Plac8(-/-) mice showed impaired thermogenesis due to brown fat dysfunction, this was not associated with changes in glycemia or plasma free fatty acid and triglyceride levels. Collectively, these data indicate that Plac8 is an upstream regulator of C/EBPβ required for adipogenesis in vitro. However, in vivo, Plac8 is dispensable for the differentiation of white adipocytes with preserved fat storage capacity but is required for normal fat cell number regulation.

New pool of cortical interneuron precursors in the early postnatal dorsal white matter.

The migration of cortical γ-aminobutyric acidergic interneurons has been extensively studied in rodent embryos, whereas few studies have documented their postnatal migration. Combining in vivo analysis together with time-lapse imaging on cortical slices, we explored the origin and migration of cortical interneurons during the first weeks of postnatal life. Strikingly, we observed that a large pool of GAD65-GFP-positive cells accumulate in the dorsal white matter region during the first postnatal week. Part of these cells divides and expresses the transcription factor paired box 6 indicating the presence of local transient amplifying precursors. The vast majority of these cells are immature interneurons expressing the neuronal marker doublecortin and partly the calcium-binding protein calretinin. Time-lapse imaging reveals that GAD65-GFP-positive neurons migrate from the white matter pool into the overlying anterior cingulate cortex (aCC). Some interneurons in the postnatal aCC express the same immature neuronal markers suggesting ongoing migration of calretinin-positive interneurons. Finally, bromodeoxyuridine incorporation experiments confirm that a small fraction of interneurons located in the aCC are generated during the early postnatal period. These results altogether reveal that at postnatal ages, the dorsal white matter contains a pool of interneuron precursors that divide and migrate into the aCC.

Multimodal MRI analysis of structural and functional networks in the human brain : application to two clinical studies : driving abilities under THC intoxication and early white matter changes in FXTAS

Les approches multimodales dans l'imagerie cérébrale non invasive sont de plus en plus considérées comme un outil indispensable pour la compréhension des différents aspects de la structure et de la fonction cérébrale. Grâce aux progrès des techniques d'acquisition des images de Resonance Magnetique et aux nouveaux outils pour le traitement des données, il est désormais possible de mesurer plusieurs paramètres sensibles aux différentes caractéristiques des tissues cérébraux. Ces progrès permettent, par exemple, d'étudier les substrats anatomiques qui sont à la base des processus cognitifs ou de discerner au niveau purement structurel les phénomènes dégénératifs et développementaux. Cette thèse met en évidence l'importance de l'utilisation d'une approche multimodale pour étudier les différents aspects de la dynamique cérébrale grâce à l'application de cette approche à deux études cliniques: l'évaluation structurelle et fonctionnelle des effets aigus du cannabis fumé chez des consommateurs réguliers et occasionnels, et l'évaluation de l'intégrité de la substance grise et blanche chez des jeunes porteurs de la prémutations du gène FMR1 à risque de développer le FXTAS (Fragile-X Tremor Ataxia Syndrome). Nous avons montré que chez les fumeurs occasionnels de cannabis, même à faible concentration du principal composant psychoactif (THC) dans le sang, la performance lors d'une tâche visuo-motrice est fortement diminuée, et qu'il y a des changements dans l'activité des trois réseaux cérébraux impliqués dans les processus cognitifs: le réseau de saillance, le réseau du contrôle exécutif, et le réseau actif par défaut (Default Mode). Les sujets ne sont pas en mesure de saisir les saillances dans l'environnement et de focaliser leur attention sur la tâche. L'augmentation de la réponse hémodynamique dans le cortex cingulaire antérieur suggère une augmentation de l'activité introspective. Une investigation des ef¬fets au niveau cérébral d'une exposition prolongée au cannabis, montre des changements persistants de la substance grise dans les régions associées à la mémoire et au traitement des émotions. Le niveau d'atrophie dans ces structures corrèle avec la consommation de cannabis au cours des trois mois précédant l'étude. Dans la deuxième étude, nous démontrons des altérations structurelles des décennies avant l'apparition du syndrome FXTAS chez des sujets jeunes, asymptomatiques, et porteurs de la prémutation du gène FMR1. Les modifications trouvées peuvent être liées à deux mécanismes différents. Les altérations dans le réseau moteur du cervelet et dans la fimbria de l'hippocampe, suggèrent un effet développemental de la prémutation. Elles incluent aussi une atrophie de la substance grise du lobule VI du cervelet et l'altération des propriétés tissulaires de la substance blanche des projections afférentes correspondantes aux pédoncules cérébelleux moyens. Les lésions diffuses de la substance blanche cérébrale peu¬vent être un marquer précoce du développement de la maladie, car elles sont liées à un phénomène dégénératif qui précède l'apparition des symptômes du FXTAS. - Multimodal brain imaging is becoming a leading tool for understanding different aspects of brain structure and function. Thanks to the advances in Magnetic Resonance imaging (MRI) acquisition schemes and data processing techniques, it is now possible to measure different parameters sensitive to different tissue characteristics. This allows for example to investigate anatomical substrates underlying cognitive processing, or to disentangle, at a pure structural level degeneration and developmental processes. This thesis highlights the importance of using a multimodal approach for investigating different aspects of brain dynamics by applying this approach to two clinical studies: functional and structural assessment of the acute effects of cannabis smoking in regular and occasional users, and grey and white matter assessment in young FMR1 premutation carriers at risk of developing FXTAS. We demonstrate that in occasional smokers cannabis smoking, even at low concentration of the main psychoactive component (THC) in the blood, strongly decrease subjects' performance on a visuo-motor tracking task, and globally alters the activity of the three brain networks involved in cognitive processing: the Salience, the Control Executive, and the Default Mode networks. Subjects are unable to capture saliences in the environment and to orient attention to the task; the increase in Hemodynamic Response in the Anterior Cingulate Cortex suggests an increase in self-oriented mental activity. A further investigation on long term exposure to cannabis, shows a persistent grey matter modification in brain regions associated with memory and affective processing. The degree of atrophy in these structures also correlates with the estimation of drug use in the three months prior the participation to the study. In the second study we demonstrate structural changes in young asymptomatic premutation carriers decades before the onset of FXTAS that might be related to two different mechanisms. Alteration of the cerebellar motor network and of the hippocampal fimbria/ fornix, may reflect a potential neurodevelopmental effect of the premutation. These include grey matter atrophy in lobule VI and modification of white matter tissue property in the corresponding afferent projections through the Middle Cerebellar Peduncles. Diffuse hemispheric white matter lesions that seem to appear closer to the onset of FXTAS and be related to a neurodegenerative phenomenon may mark the imminent onset of FXTAS.