982 resultados para Logical Clocks


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The first steps in leishmaniasis are critical in determining the evolution of the disease. Major advances have recently been done in understanding this crucial moment. Fundamental research in parasite-vector interaction, parasite biology, insect saliva, and vertebrate host response have shed new light and uncovered a most fascinating and complex moment in leishmaniasis. We review here some of these aspects and we try to connect them in a logical framework.

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Gifted children develop asynchronously, often advanced for their age cognitively, but at or between their chronological and mental ages socially and emotionally (Robinson, 2008). In order to help gifted children and adolescents develop and practice social and emotional self-regulation skills, we investigated the use of an Adlerian play therapy approach during pen-and-paper role-playing games. Additionally, we used Goffman's (1961, 1974) social role identification and distance to encourage participants to experiment with new identities. Herein, we propose a psychosocial model of interactions during role-playing games based on Goffman's theory and Adlerian play therapy techniques, and suggest that role-playing games are an effective way of intervening with gifted children and adolescents to improve their intra- and interpersonal skills. We specifically targeted intrapersonal skills of exercising creativity, becoming self-aware, and setting individual goals by raising participants' awareness of their privately logical reasons for making decisions and their levels of social interest. We also targeted their needs and means of seeking significance in the group to promote collaboration and interaction skills with other gifted peers through role analysis, embracement, and distancing. We report results from a case study and conclude that role-playing games deserve more attention, both from researchers and clinical practitioners, because they encourage change while improving young clients' social and emotional development.

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The 1st International Symposium on Ostracoda (ISO) was held in Naples (1963). The philosophy behind this symposium and the logical outcome of what is now known as the International Research Group on Ostracoda (IRGO) is here reviewed, namely ostracodology over the last 50 years is sociologically analysed. Three different and important historic moments for the scientific achievements of this domain are recognised. The first one, between about 1963-1983, is related to applied research for the oil industry as well as to the great interest in the better description of the marine environment by both zoologists and palaeontologists. Another important aspect during this period was the work by researchers dealing with Palaeozoic ostracods, who had their own discussion group, IRGPO. Gradually, the merger of this latter group with those dealing with post-Palaeozoic ostracods at various meetings improved communication between the two groups of specialists. A second period was approximately delineated between 1983 and 2003. During this time-slice, more emphasis was addressed to environmental research with topics such as the study of global events and long-term climate change. Ostracodologists profited also from the research "politics" within national and international programmes. Large international research teams emerged using new research methods. During the third period (2003-2013), communication and collaborative research reached a global dimension. Amongst the topics of research we cite the reconstruction of palaeoclimate using transfer functions, the building of large datasets of ostracod distributions for regional and intercontinental studies, and the implementation of actions that should lead to taxonomic harmonisation. Projects within which molecular biological techniques are routinely used, combined with sophisticated morphological information, expanded now in their importance. The documentation of the ostracod description improved through new techniques to visualise morphological details, which stimulated also communication between ostracodologists. Efforts of making available ostracod information through newsletters and electronic media are evoked.

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Molecular trees of trypanosomes have confirmed conventionally accepted genera, but often produce topologies that are incongruent with knowledge of the evolution, systematics, and biogeography of hosts and vectors. These distorted topologies result largely from incorrect assumptions about molecular clocks. A host-based phylogenetic tree could serve as a broad outline against which the reasonability of molecular phylogenies could be evaluated. The host-based tree of trypanosomes presented here supports the " invertebrate first " hypothesis of trypansosome evolution, supports the monophyly of Trypanosomatidae, and indicates the digenetic lifestyle arose three times. An area cladogram of Leishmania supports origination in the Palaearctic during the Palaeocene.

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While the US jurisprudence of the 1993 Daubert requires judges to question not only the methodology behind, but also the principles governing, a body of knowledge to qualify it as scientific, can forensic science, based on Locard's and Kirk's Principles, pretend to this higher status in the courtroom ? Moving away from the disputable American legal debate, this historical and philosophical study will screen the relevance of the different logical epistemologies to recognize the scientific status of forensic science. As a consequence, the authors are supporting a call for its recognition as a science of its own, defined as the science of identifying and associating traces for investigative and security purposes, based o its fundamental principles and the case assesment and interpretation process that follows with its specific and relevant mode of inference.

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Many studies have provided evidence that prey adjust their behaviour to adaptively balance the fitness effects of reproduction and predation risk. Nocturnal terrestrial animals should deal with a range of environmental conditions during the reproductive season at the breeding sites, including a variable amount of natural ambient light. High degrees of illumination are expected to minimize those behaviours that might increase the animal detection by predators. Therefore, under habitat variable brightness conditions and in different ecosystems, the above mentioned behaviours are expected to depend on the variation in predation risk. Although moon effects on amphibian biology have been recognized, the direction of this influence is rather controversial with evidences of both increased and depressed activity under full moon. We tested in four nocturnal amphibian species (Hyla intermedia, Rana dalmatina, Rana italica, Salamandrina perspicillata) the effects of different (i) light conditions and (ii) habitats (open land vs. dense forest) on the reproductive phenology. Our results showed that the effects of the lunar cycle on the study species are associated with the change in luminosity, and there is no evidence of an endogenous rhythm controlled by biological clocks. The habitat type conditioned the amphibian reproductive strategy in relation to moon phases. Open habitat breeders (e. g., ponds with no canopy cover) strongly avoided conditions with high brightness, whereas forest habitat breeders were apparently unaffected by the different moon phases. Indeed, for all the studied species no effects of the moon phase itself on the considered metrics were found. Rather, the considered amphibian species seem to be conditioned mainly by moonlight irrespective of the moon phase. The two anurans spawning in open habitat apparently adjust their oviposition timing by balancing the fitness effects of the risk to be detected by predators and the reproduction.

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Cancer is the second leading cause of mortality worldwide. Cancer progression leads to metastasis formation, which accounts for more than ninety percent of cancer-related death. Metastases are more difficult to be surgically removed because of their invasive behavior and shape. In addition, during their transformation journey, they become more and more resistant to anticancer drugs. Significant improvements have been achieved in therapy against cancer in recent years but targeting the metastatic cascade remains the Achilles heel of the cure against cancer. A First step in the metastatic process is the escape of cancer cells from the primary tumor site. This involves an increase in cell motility and the concomitant ability to clear a path through the extracellular matrix. From a therapeutic point of view, inhibition of cell migration is a logical approach to develop anti-metastatic drugs. Our lab previously developed a cell permeable peptide derived from a caspase-3-generaied fragment of the RasGAP protein called TAT-RasGAP317-326. This peptide efficiently and specifically sensitizes cancer cells to chemotherapy- and radiotherapy-induced ceil death, which allows decreasing the anticancer drug doses and eventually their associated side- effects. In the present study we discovered that TAT-RasGAP317.326 also increases cell adhesion which was associated with inhibition of cell migration and invasion into the extracellular matrix. The ability of TAT-RasGAP317.326 to increase ceil adhesion involves the dramatic depolymerization of actin cytoskekton together with redistribution of focal adhesions. We found that the inhibitory effects on migration were mediated by a RhoGAP tumor and metastasis suppressor cailed DLC1 (Deleted in Liver Cancer 1). Moreover. DEC 1 was found to be a direct RasGAP-interacting protein and this interaction requires the RasGAP tryptophan 317 residue, the very first RasGAP residue of TAT-RasGAP317.326. We then evaluated the roie of RasGAP fragments in the in vivo metastatic cascade. We found that breast cancer cells overexpressing the parental RasGAP fragment, to which the TAT-RasGAP317.326 peptide belongs, have a markedly decreased ability to form lung metastases. Unfortunately, we were not able to recapitulate these an ti-metastatic effects when TAT-RasGAP317.326 was injected. However, we later understood that this was due to the fact that TAT-RasGAP317.326 was not properly delivered to the primary tumors. Further work, aimed at better understanding of how TAT-RasGAP317.326 functions, revealed that the ten amino acid TAT-RasGAP317.326 peptide could, be narrowed down to a three amino acid TAT-RasGAP317.329 peptide while keeping its sensitizer activity. In parallel, investigations on the RasGAP-DLCl binding indicated that the arginine linger of the DLC1 GAP domain is required for this interaction, which suggests that TAT-RasGAP317.326 modulates the GAP activity of DLC1. Additional work should be performed to fully elucidate its mechanism of action and render TAT-RasGAP317.326 usable as a tool to fight cancer on two fronts, by improving chemotherapy and preventing metastatic progression. - Le cancer est la deuxième cause de mortalité dans le monde. La formation de métastases est la dernière étape de la progression cancéreuse et représente plus du nonante pour cent des morts induites par le cancer. De par leur morphologie et comportement invasifs, ii est difficile d'avoir recours à la chirurgie pour exciser des métastases. De plus, les cellules cancéreuses en progression deviennent souvent de plus en plus résistantes aux drogues anticancéreuses. Ces dernières années, des avancements significatifs ont contribué à l'amélioration de la lutte contre le cancer. Néanmoins, pouvoir cibler spécifiquement la cascade métastatique demeure cependant le talon d'Achille des thérapies anticancéreuses. Une première étape dans ie processus métastatique est l'évasion des cellules cancéreuses du site de la tumeur primaire. Ceci requiert une augmentation de la motiliié cellulaire couplée à la capacité de se frayer un chemin au sein de la matrice extracelluiaire. D'un point de vue thérapeutique, inhiber la migration cellulaire est une approche attrayante. Notre laboratoire a développé un peptide, nommé TAT-RasGAP317.326 dérivé d'un fragment qui est lui-même le résultat du clivage de la protéine RasGAP par la caspase-3. Ce peptide est capable de pénétrer les cellules cancéreuses et de les sensibiliser spécifiquement à la mort induite par la radiothérapie et la chimiothérapie. La finalité des effets de ce peptide est de pouvoir diminuer les doses des traitements anti-cancéreux et donc des effets secondaires qu'ils engendrent. Dans cette étude, nous avons découvert que TAT-RasGAP317.326 augmente l'adhésion des cellules et inhibe la migration cellulaire ainsi que l'invasion des cellules à travers une matrice extracellulaire. La capacité de TAT-RasGAP317.326 à induire l'adhésion repose sur ia dépolymérisation du cytosquelette d'actine associée à une redistribution des points d'ancrage cellulaire. Nous avons découvert que l'inhibition de ia migration par TAT-RasGAP317.326 nécessitait la présence d'un suppresseur de tumeur et de métastases appelé DLC1 (Deleted in Liver Cancer l), qui par ailleurs s'avère aussi être une protéine RhoGAP. De plus, nous avons aussi trouvé que DLC1 était un partenaire d'interaction de RasGAP et que cette interaction s'effectuait via l'acide aminé tryptophane 317 de RasGAP. qui s'avère être le premier acide aminé du peptide TAT-RasGAP317.326. Nous avons ensuite évalué le rôle joué par certains fragments de RasGAP dans le processus de métastatisation. Dans ce contexte, des cellules de cancer du sein qui sur-expriment un fragment de RasGAP contenant la séquence TAT-RasGAP317.326 ont vu leur potentiel métastatique diminuer drastiquerment. Malheureusement, aucun effet anti-métastatique n'a été obtenu après injection de TAT-RasGAP317.326 dans les souris. Cependant, nous avons réalisé rétrospectivement que TAT-RasGAP317.326 n'était pas correctement délivré à la tumeur primaire, ce qui nous empêche de tirer des conclusions sur le rôle anti-métastatique de ce peptide. La suite de cette étude visant à mieux comprendre comment TAT-RasGAP317.326 agit, a mené à la découverte que les dix acides aminés de TAT-RasGAP317.326 pouvaient être réduits à trois acides aminés, TAT-RasGAP317.329, tout en gardant l'effet sensibilisateur à la chimiothérapie. En visant à élucider le mode d'interaction entre RasGAP et DLC1, nous avons découvert qu'un acide aminé nécessaire à l'activité GAP de DLC1 était requis pour lier RasGAP, ce qui laisse présager que TAT-RasGAp317.32c, module i'activité GAP de DLC1. Des travaux supplémentaires doivent encore être effectués pour complètement élucider les mécanismes d'action de TAT-RasGAP317.326 et afin de pouvoir l'utiliser comme un outil pour combattre le cancer sur deux fronts, en améliorant les chimiothérapies et en inhibant la formation de métastases.

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Recent evidence has emerged that peroxisome proliferator-activated receptor alpha (PPARalpha), which is largely involved in lipid metabolism, can play an important role in connecting circadian biology and metabolism. In the present study, we investigated the mechanisms by which PPARalpha influences the pacemakers acting in the central clock located in the suprachiasmatic nucleus and in the peripheral oscillator of the liver. We demonstrate that PPARalpha plays a specific role in the peripheral circadian control because it is required to maintain the circadian rhythm of the master clock gene brain and muscle Arnt-like protein 1 (bmal1) in vivo. This regulation occurs via a direct binding of PPARalpha on a potential PPARalpha response element located in the bmal1 promoter. Reversely, BMAL1 is an upstream regulator of PPARalpha gene expression. We further demonstrate that fenofibrate induces circadian rhythm of clock gene expression in cell culture and up-regulates hepatic bmal1 in vivo. Together, these results provide evidence for an additional regulatory feedback loop involving BMAL1 and PPARalpha in peripheral clocks.

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Résumé françaisLa majorité des organismes vivants sont soumis à l'alternance du jour et de la nuit, conséquence de la rotation de la terre autour de son axe. Ils ont développé un système interne de mesure du temps, appelé horloge circadienne, leur permettant de s'adapter et de synchroniser leur comportement et leur physiologie aux cycles de lumière. Cette dernière est considérée comme étant le signal majeur entraînant l'horloge interne et. par conséquent, les rythmes journaliers d'éveil et de sommeil. Outre sa régulation circadienne, le sommeil est contrôlé par un processus homéostatique qui détermine son besoin. La contribution de ces deux processus dans le fonctionnement cellulaire du cerveau n'a pas encore été investiguée. La mesure de l'amplitude ainsi que de la prévalence des ondes delta de l'EEG (activité delta) constitue un index très fiable du besoin de sommeil. Il a été démontré que cette activité est génétiquement déterminée et associée à un locus de trait quantitatif situé sur le chromosome 13 de la souris.Grâce à des expériences de privation de sommeil et d'analyses de transcriptome du cerveau dans trois souches de souris présentant diverses réponses à la privation de sommeil, nous avons trouvé que Homerla, localisé dans la région d'intérêt du chromosome 13, est le meilleur marqueur du besoin de sommeil. Homerla est impliqué dans la récupération de l'hyperactivité neuronale induite par le glutamate, grâce à son effet tampon sur le calcium intracellulaire. Une fonction fondamentale du sommeil pourrait donc être de protéger le cerveau et de lui permettre de récupérer après une hyperactivité neuronale imposée par une veille prolongée.De plus, nous avons montré que 2032 transcrits sont exprimés rythmiqueraent dans le cerveau de la souris, parmi lesquels seulement 391 le restent après que les animaux aient été privés de sommeil à différents moments au cours des 24 heures. Cette observation montre clairement que la plupart des changements rythmiques au niveau du transcriptome dépendent du sommeil et non de l'horloge circadienne et souligne ainsi l'importance du sommeil dans la physiologie des mammifères.La plupart des expériences concernant les rythmes circadiens ont été réalisées sur des individus isolés en négligeant l'effet du contexte social sur les comportements circadiens. Les espèces sociales, telles que les fourmis, se caractérisent par une division du travail où une répartition des tâches s'effectue entre ses membres. De plus, certaines d'entre elles doivent être pratiquées en continu comme les soins au couvain tandis que d'autres requièrent une activité rythmique comme le fourragement. Ainsi la fourmi est un excellent modèle pour l'étude de 1 influence du contexte social sur les rythmes circadiens.A ces fins, nous avons décidé d'étudier les rythmes circadiens chez une espèce de fourmi Camponotus fellah et de caractériser au niveau moléculaire son horloge circadienne. Nous avons ainsi développé un système vidéo permettant de suivre l'activité locomotrice de tous les individus d'une colonie. Nos résultats montrent que, bien que la plupart des fourmis soient arythmiques à l'intérieur de la colonie, elles développent d'amples rythmes d'activité en isolation. De plus, ces rythmes disparaissent presque aussitôt que la fourmi est réintroduite dans la colonie. Cette rythmicité observée en isolation semble être générée par l'horloge circadienne car elle persiste en condition constante (obscurité totale). Nous avons ensuite regardé si cette apparente arythmie observée dans la colonie résultait d'un effet masquant des interactions sociales sur les rythmes circadiens d'activité. Nos résultats suggèrent que l'horloge interne est fonctionnelle dans la colonie mais que l'expression de ses rythmes au niveau comportemental est inhibée par les interactions sociales. Les analyses moléculaires du statut de l'horloge dans différents contextes sociaux sont actuellement en cours. Le contexte social semble donc un déterminant majeur du comportement circadien chez la fourmi.AbstractAlmost all living organisms on earth are subjected to the alternance of day and night re-sulting from the rotation of the earth around its axis. They have evolved with an internal timing system, termed the circadian clock, enabling them to adapt and synchronize their behavior and physiology to the daily changes in light and related environmental parame¬ters. Light is thought to be the major cue entraining the circadian clock and consequently the rhythms of rest/activity. In addition to its circadian dependent timing, sleep is reg¬ulated by a homeostatic process that determines its need. The contribution of these two processes in the cellular functioning of the brain has not yet been considered. A highly reliable index of the homeostatic process of sleep is the measure of the amplitude and prevalence of the EEG delta waves (delta activity). It has been shown that sleep need, measured by delta activity, is genetically determined and associated with a Quantitative Trait Locus (QTL) located on the mouse chromosome 13. By using sleep deprivation and brain transcriptome profiling in three inbred mouse strains showing different responses to sleep loss, we found that Homerla, localized within this QTL region is the best transcrip¬tional marker of sleep need. Interestingly Homerla is primarily involved in the recovery from glutamate-induced neuronal hyperactivity by its buffering effect on intracellular cal¬cium. A fundamental function of sleep may therefore reside in the protection and recovery of the brain from a neuronal hyperactivity imposed by prolonged wakefulness.Moreover, time course gene expression experiments showed that 2032 brain tran¬scripts present a rhythmic variation, but only 391 of those remain rhythmic when mice are sleep deprived at four time points around the clock. This finding clearly suggests that most changes in gene transcription over the day are sleep-wake dependent rather than clock dependent and underlines the importance of sleep in mammalian physiology.In the second part of this PhD, I was interested in the social influence on circadian behavior. Most experiments done in the circadian field have been performed on isolated individuals and have therefore ignored the effect of the social context on circadian behav-ior. Eusocial insect species such as ants are characterized by a division of labor: colony tasks are distributed among individuals, some of them requiring continuous activity such as nursing or rhythmic ones such as foraging. Thus ants represent a suitable model to study the influence of the social context on the circadian clock and its output rhythms.The aim of this part was to address the effect of social context on circadian rhythms in the ant species Camponotus fellah and to characterize its circadian clock at the molecu¬lar level. We therefore developed a video tracking system to follow the locomotor activity of all individuals in a colony. Our results show that most ants are arrhythmic within the colony, but develop, when subjected to social isolation, strong rhythms of activity that intriguingly disappear when individuals are reintroduced into the colony. The rhythmicity observed in isolated ants seems to be driven by the circadian clock as it persists under constant conditions (complete darkness). We then tested whether the apparent arrhyth- micity in the colony stemmed from a masking effect of social interactions on circadian rhythms. Indeed, we found that circadian clocks of ants in the colony are functional but their expression at the behavioral level is inhibited by social interactions. The molecular assessment of the circadian clock functional state in the different social context is still under investigation. Our results suggest that social context is a major determinant of circadian behavior in ants.

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Today's approach to anti-doping is mostly centered on the judicial process, despite pursuing a further goal in the detection, reduction, solving and/or prevention of doping. Similarly to decision-making in the area of law enforcement feeding on Forensic Intelligence, anti-doping might significantly benefit from a more extensive gathering of knowledge. Forensic Intelligence might bring a broader logical dimension to the interpretation of data on doping activities for a more future-oriented and comprehensive approach instead of the traditional case-based and reactive process. Information coming from a variety of sources related to doping, whether directly or potentially, would feed an organized memory to provide real time intelligence on the size, seriousness and evolution of the phenomenon. Due to the complexity of doping, integrating analytical chemical results and longitudinal monitoring of biomarkers with physiological, epidemiological, sociological or circumstantial information might provide a logical framework enabling fit for purpose decision-making. Therefore, Anti-Doping Intelligence might prove efficient at providing a more proactive response to any potential or emerging doping phenomenon or to address existing problems with innovative actions or/and policies. This approach might prove useful to detect, neutralize, disrupt and/or prevent organized doping or the trafficking of doping agents, as well as helping to refine the targeting of athletes or teams. In addition, such an intelligence-led methodology would serve to address doping offenses in the absence of adverse analytical chemical evidence.

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BACKGROUND Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk. METHODS A case-control study design was used to test the association between prostate cancer risk and the polymorphisms TNF-A-308 A/G (rs 1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587) and MCP-1 2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area. RESULTS Diagnosis of prostate cancer was significantly associated with TNF-A GA + AA genotype (OR, 1.61; 95% CI, 1.09-2.64) and RANTES GA + AA genotype (OR, 1.44; 95% CI, 1.09-2.38). A alleles in TNF-A and RANTES influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and IL1-A or MCP-1 polymorphisms. CONCLUSION Our results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development.

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The purpose of resource management is the efficient and effective use of network resources, for instance bandwidth. In this article, a connection oriented network scenario is considered, where a certain amount of bandwidth is reserved for each label switch path (LSP), which is a logical path, in a MPLS or GMPLS environment. Assuming there is also some kind of admission control (explicit or implicit), these environments typically provide quality of service (QoS) guarantees. It could happen that some LSPs become busy, thus rejecting connections, while other LSPs may be under-utilised. We propose a distributed lightweight monitoring technique, based on threshold values, the objective of which is to detect congestion when it occurs in an LSP and activate the corresponding alarm which will trigger a dynamic bandwidth reallocation mechanism

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We present a system for dynamic network resource configuration in environments with bandwidth reservation and path restoration mechanisms. Our focus is on the dynamic bandwidth management results, although the main goal of the system is the integration of the different mechanisms that manage the reserved paths (bandwidth, restoration, and spare capacity planning). The objective is to avoid conflicts between these mechanisms. The system is able to dynamically manage a logical network such as a virtual path network in ATM or a label switch path network in MPLS. This system has been designed to be modular in the sense that in can be activated or deactivated, and it can be applied only in a sub-network. The system design and implementation is based on a multi-agent system (MAS). We also included details of its architecture and implementation

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The actual geographic distribution of the two sibling mouse-eared bat species Myotis myotis and Myotis blythii, which occur widely sympatrically in the western Palaearctic region, remains largely controversial. This concerns particularly the specific attribution of marginal populations from the Mediterranean islands and from adjacent areas of North Africa and Asia, which are morphologically intermediate between continental M. myotis and M. blythii from Europe. This study attempts to clarify this question by using four different approaches: cranial morphology, external morphology, genetics and trophic ecology. The three latter methods show unambiguously that North Africa, Malta, Sardinia and Corsica are presently inhabited by monospecific populations of M. myotis. In contrast, cranial morphometrics do not yield conclusive results. These results contradict all recent studies, which attribute North African and Maltese mouse-eared bats to M. blythii and consider that Sardinia and Corsica harbour sympatric populations of the two species. As concerns south-eastern populations, doubts are also expressed about the attribution of the subspecific taxon omari which may actually refer to M. myotis instead of M. blythii. Protein electrophoresis is presently the only absolute method available for determining M. myotis and M. blythii throughout their distribution ranges. However, species identification may be approached by relying on less sophisticated morphometrical methods as presented in this study. Species-specific habitat specializations are probably responsible for the differences observed between the geographic distributions of M. myotis and M. blythii, as they provide a logical groundwork for a coherent model of speciation for these two bat species.

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En aquest article intentarem donar una visió general del diferent programari que s'està utilitzant a les universitats de tot el món, ja sigui per a la gestió administrativa com per a la realització de les classes.