Testing advances in molecular discrimination among Chinook salmon life histories: evidence from a blind test.

The application of DNA-based markers toward the task of discriminating among alternate salmon runs has evolved in accordance with ongoing genomic developments and increasingly has enabled resolution of which genetic markers associate with important life-history differences. Accurate and efficient identification of the most likely origin for salmon encountered during ocean fisheries, or at salvage from fresh water diversion and monitoring facilities, has far-reaching consequences for improving measures for management, restoration and conservation. Near-real-time provision of high-resolution identity information enables prompt response to changes in encounter rates. We thus continue to develop new tools to provide the greatest statistical power for run identification. As a proof of concept for genetic identification improvements, we conducted simulation and blind tests for 623 known-origin Chinook salmon (Oncorhynchus tshawytscha) to compare and contrast the accuracy of different population sampling baselines and microsatellite loci panels. This test included 35 microsatellite loci (1266 alleles), some known to be associated with specific coding regions of functional significance, such as the circadian rhythm cryptochrome genes, and others not known to be associated with any functional importance. The identification of fall run with unprecedented accuracy was demonstrated. Overall, the top performing panel and baseline (HMSC21) were predicted to have a success rate of 98%, but the blind-test success rate was 84%. Findings for bias or non-bias are discussed to target primary areas for further research and resolution.

Health-related quality of life and functioning in bipolar disorder: the impact of pharmacotherapy.

Bipolar disorder has a major deleterious impact on many aspects of a patient's functioning and health-related quality of life. Although the formal measurement of these deficits has been neglected until recently, many well-designed trials now include an assessment of functioning and health-related quality of life using one or more rating scales. This review describes recent developments in the measurement of functioning and health-related quality of life in bipolar disorder, and discusses the evidence that medications that improve symptoms in bipolar disorder also offer clinically relevant benefits in functioning and health-related quality of life. Direct comparisons of the benefits of medications including atypical antipsychotics are problematic due to differences in trial populations, study durations and rating scales. Data from quetiapine trials indicate that this medication offers prompt and sustained improvement of functioning in patients with mania and enhancement of health-related quality of life in patients with bipolar depression, to accompany the significant improvements in mood episodes.

The impact of vascular burden on late-life depression.

Small vessel pathology and microvascular lesions are no longer considered as minor players in the fields of cognitive impairment and mood regulation. Although frequently found in cognitively intact elders, both neuroimaging and neuropathological data revealed the negative impact on cognitive performances of their presence within neocortical association areas, thalamus and basal ganglia. Unlike cognition, the relationship between these lesions and mood dysregulation is still a matter of intense debate. Early studies focusing on the role of macroinfarct location in the occurrence of post-stroke depression (PSD) led to conflicting data. Later on, the concept of vascular depression proposed a deleterious effect of subcortical lacunes and deep white matter demyelination on mood regulation in elders who experienced the first depressive episode. More recently, the chronic accumulation of lacunes in thalamus, basal ganglia and deep white matter has been considered as a strong correlate of PSD. We provide here a critical overview of neuroimaging and neuropathological sets of evidence regarding the affective repercussions of vascular burden in the aging brain and discuss their conceptual and methodological limitations. Based on these observations, we propose that the accumulation of small vascular and microvascular lesions constitutes a common neuropathological platform for both cognitive decline and depressive episodes in old age.

Pluralized life courses? An exploration of the life trajectories of individuals with psychiatric disorders.

BACKGROUND: : Most of the existing research relating to the life courses of people with psychiatric symptoms focuses on the occurrence and the impact of non-normative events on the onsets of crises; it usually disregards the more regular dimensions of life, such as work, family and intimate partnerships that may be related to the timing and seriousness of psychiatric problems. An additional reason for empirically addressing life trajectories of individuals with psychiatric problems relates to recent changes of family and occupational trajectories in relation to societal trends such as individualization and pluralization of life courses.¦AIM: : This paper explores the life trajectories of 86 individuals under clinical supervision and proposes a typology of their occupational, co-residence and intimacy trajectories. The results are discussed in light of the life-course paradigm.¦METHOD: : A multidimensional optimal matching analysis was performed on a sample of 86 individuals under clinical supervision to create a typology of trajectories. The influence of these trajectories on psychiatric disorders, evaluated using a SCL-90-R questionnaire, was then assessed using linear regression modelling.¦RESULTS: : The typologies of trajectories showed that the patients developed a diversity of life trajectories. Individuals who have developed a standard life course with few institutionalization periods reported more symptoms and distress than individuals with an institutionalized life trajectory.¦CONCLUSION: : The results of this study stress that psychiatric patients are social actors who are influenced by society at large and its ongoing process of change. Therefore, it is essential to take into account the diversity of occupational and family trajectories when dealing with individuals in therapeutic settings.

Detecting nanoscale vibrations as signature of life.

The existence of life in extreme conditions, in particular in extraterrestrial environments, is certainly one of the most intriguing scientific questions of our time. In this report, we demonstrate the use of an innovative nanoscale motion sensor in life-searching experiments in Earth-bound and interplanetary missions. This technique exploits the sensitivity of nanomechanical oscillators to transduce the small fluctuations that characterize living systems. The intensity of such movements is an indication of the viability of living specimens and conveys information related to their metabolic activity. Here, we show that the nanomotion detector can assess the viability of a vast range of biological specimens and that it could be the perfect complement to conventional chemical life-detection assays. Indeed, by combining chemical and dynamical measurements, we could achieve an unprecedented depth in the characterization of life in extreme and extraterrestrial environments.

Life history analysis of integrative and conjugative element activation in growing microcolonies of Pseudomonas.

Integrative and conjugative elements (ICE) are in some ways parasitic mobile DNA that propagate vertically through replication with the bacterial host chromosome but at low frequencies can excise and invade new recipient cells through conjugation and reintegration (horizontal propagation). The factors that contribute to successful horizontal propagation are not very well understood. Here, we study the influence of host cell life history on the initiation of transfer of a model ICE named ICEclc in bacteria of the genus Pseudomonas. We use time-lapse microscopy of growing and stationary-phase microcolonies of ICEclc bearing cells in combination with physiological staining and gene reporter analysis in stationary-phase suspended cells. We provide evidence that cell age and cell lineage are unlikely to play a role in the decision to initiate the ICEclc transfer program. In contrast, cells activating ICEclc show more often increased levels of reactive oxygen species and membrane damage than nonactivating cells, suggesting that some form of biochemical damage may make cells more prone to ICEclc induction. Finally, we find that ICEclc active cells appear spatially at random in a microcolony, which may have been a selective advantage for maximizing ICEclc horizontal transmission to new recipient species.

Biological embedding of early life exposures and disease risk in humans: a role for DNA methylation.

BACKGROUND: Following wider acceptance of "the thrifty phenotype" hypothesis and the convincing evidence that early life exposures can influence adult health even decades after the exposure, much interest has been placed on the mechanisms through which early life exposures become biologically embedded. METHODS: In this review, we summarize the current literature regarding biological embedding of early life experiences. To this end we conducted a literature search to identify studies investigating early life exposures in relation to DNA methylation changes. In addition, we summarize the challenges faced in investigations of epigenetic effects, stemming from the peculiarities of this emergent and complex field. A proper systematic review and meta-analyses were not feasible given the nature of the evidence. RESULTS: We identified 7 studies on early life socioeconomic circumstances, 10 studies on childhood obesity, and 6 studies on early life nutrition all relating to DNA methylation changes that met the stipulated inclusion criteria. The pool of evidence gathered, albeit small, favours a role of epigenetics and DNA methylation in biological embedding, but replication of findings, multiple comparison corrections, publication bias, and causality are concerns remaining to be addressed in future investigations. CONCLUSIONS: Based on these results, we hypothesize that epigenetics, in particular DNA methylation, is a plausible mechanism through which early life exposures are biologically embedded. This review describes the current status of the field and acts as a stepping stone for future, better designed investigations on how early life exposures might become biologically embedded through epigenetic effects. This article is protected by copyright. All rights reserved.

An analysis of the components of pain, function, and health-related quality of life in patients with failed back surgery syndrome treated with spinal cord stimulation or conventional medical management

Objectives: Failed back surgery syndrome (FBSS) patients experience pain, functional disability, and reduced health-related quality of life (HRQoL) despite anatomically successful surgery. Examining sub-dimensions of health outcomes measures provides insight into patient well-being. Materials and Methods: The international multicenter PROCESS trial collected detailed HRQoL (EuroQol-5D; Short-Form 36) and function (Oswestry Disability Index) information on 100 FBSS patients. Results: At baseline, patients reported moderate-to-severe leg and back pain adversely affecting all dimensions of function and HRQoL. Compared with conventional medical management alone, patients also receiving spinal cord stimulation (SCS) reported superior pain relief, function, and HRQoL at six months on overall and most sub-component scores. The majority of these improvements with SCS were sustained at 24 months. Nonetheless, 36-40% of patients experienced ongoing marked disability (standing, lifting) and HRQoL problems (pain/discomfort). Conclusions: Longer-term patient management and research must focus on these refractory FBSS patients with persisting poor function and HRQoL outcomes.

Evolution of life history traits in a natural population of the shrew Crocidura russula

Abstract Life history traits encompass all the decisions concerning fitness an individual is faced with during his life. The study of these traits is crucial to understand the factors shaping the biology of living organisms. Up until now, most of the information on the evolution of life history traits comes from laboratory studies. While these studies are interesting to test the effect of specific parameters, their conclusions are difficult to extrapolate to natural populations. Investigating the evolution of life history traits in natural populations is of great interest. This may be tricky because it requires information on reproduction, survival and morphology of individuals. Mark-recapture methods allow most of this information to be obtained. However, when direct observations of a species are not possible due to its ecology, indirect methods must be used to infer lifetime reproductive success. In this case, molecular markers are particularly helpful in assessing the genetic relationships between individuals and allow the construction of a pedigree. This thesis focuses on a natural population of a small insectivorous mammal, the greater white-toothed shrew, Crocidura russula. Because of its hidden lifestyle, the two complementary techniques mentioned above were combined to gather information on this population. The data were used to explore diverse aspects of evolutionary biology. We demonstrated that the high genetic variance displayed by the species was not maintained by its mating system because this shrew was less monogamous than previously thought. The large genetic diversity was most likely promoted by gene flow from the neighborhood. Dispersal was thus a central topic in this thesis. We showed that dispersal was not driven by inbreeding avoidance. In addition, we did not find any inbreeding depression in the population. Dispersal was promoted by a high number of vacant territories in the population for both sexes, meaning that territory acquisition played an important role in driving dispersal. Moreover, dispersal propensity was shown to have a genetic basis and, once achieved, to have no effect on individual fitness. Body mass was found to be a life history trait strongly influenced by sexual and viability selection in both sexes. Larger individuals had higher access to reproduction through territory acquisition and defense than lighter ones. By contrast, intermediate size individuals were favored by viability selection presumably because of ecological constraints and metabolic costs. Finally, we demonstrated that the majority of the life history traits in our shrew population has the potential to evolve because they maintained substantial amounts of additive genetic variance. Nonetheless, life history traits had no significant heritability due to their high level of nonadditive or environmental variance. Résumé Les traits d'histoire de vie comprennent toutes les décisions auxquelles un individu est confronté au cours de sa vie et qui concernent sa valeur adaptative. L'étude de ces traits est cruciale pour comprendre les facteurs qui façonnent la biologie des êtres vivants. Jusqu'à ce jour, la majorité des informations sur l'évolution des traits d'histoire de vie provient d'études réalisées en laboratoire. Alors que ces études sont intéressantes pour tester l'effet de paramètres spécifiques, leurs conclusions sont difficilement extrapolables aux populations naturelles. Il est particulièrement intéressant d'étudier l'évolution des traits d'histoire de vie dans des populations naturelles. Toutefois, ces études peuvent se révéler difficiles parce qu'elles requièrent des informations sur la reproduction, la survie et la morphologie des individus. Des méthodes de marquage-recapture permettent d'obtenir ces informations. Cependant, lorsque l'écologie de l'espèce rend les obervations directes impossibles, des méthodes indirectes doivent être utilisées pour obtenir le succès reproducteur des individus. Dans ce cas, les marqueurs moléculaires sont particulièrement utiles pour évaluer les relations génétiques entre individus et permettre la construction d'un pedigree. Cette thèse porte sur une population naturelle d'un petit mammifère insectivore, la musaraigne musette, Crocidura russula. Parce que cette espèce présente un mode de vie souterrain, les deux techniques complémentaires mentionnées ci-dessus ont été combinées pour acquérir les informations nécessaires. Les données ont été utilisées pour explorer divers aspects de biologie evolutive. Nous avons montré que la grande quantité de variance génétique trouvée chez cette espèce n'est pas maintenue par son système d'appariement. Celle-ci s'est en effet avérée être moins monogame que ce qui était admis jusqu'ici. Sa grande diversité génétique est plutôt entretenue par le flux de gènes provenant du voisinage. La dispersion a donc été un sujet phare dans cette thèse. Nous avons montré qu'elle n'est pas provoquée par un évitement de la consanguinité et nous n'avons pas trouvé de dépression de consanguité dans notre population. L'acquisition d'un territoire joue par contre un rôle important dans la dispersion. En outre, la dispersion possède une base génétique chez cette espèce. De plus, une fois qu'ils ont dispersé, les individus n'ont pas une valeur adaptative differente d'individus philopatriques. Le poids s'est avéré être un trait d'histoire de vie fortement influencé par la sélection sexuelle et de viabilité chez les deux sexes. Les gros individus ont accès à la reproduction parce qu'ils acquièrent et défendent un territoire plus facilement que les plus légers. Au contraire, les individus de taille intermédiaire sont favorisés par la sélection de viabilité, certainement à cause de contraintes écologiques et de coûts métaboliques. Finalement, nous avons montré que la majorité des traits d'histoire de vie dans notre population a le potentiel d'évoluer parce qu'elle maintient des quantités considérables de variance génétique additive. Néanmoins, l'héritabilité de ces traits d'histoire de vie n'est pas significative à cause de la grande quantité de variance non-additive ou environmentale associée à ces traits.

Malaise du nourrisson pensez à une intoxication à l'anis étoil [Apparent life-threatening event in infants: think about star anise intoxication!].

In previous years, several publications have reported cases of infants presenting neurological and gastrointestinal symptoms after ingestion of star anise tea. Such teas are sometimes given in various cultures for the treatment of infant colic pains. In most cases, the cause of intoxication was contamination of Chinese star anise (Illicium verum) by Japanese star anise (Illicium anisatum). Indeed, the toxicity of Illicium anisatum, also known as Shikimi, is caused by its content in potent neurotoxins (anisatin, neoanisatin, and pseudoanisatin), due to their activity as non-competitive antagonists of GABA receptors. The main reasons explaining the frequent contaminations are the strong macroscopic resemblance of the 2 substances, as well as the fact that the fruits are often sold partially broken or in ground form. Therefore, in most cases, chemical analysis is required to determine the possible adulterations. CASE REPORT: A 2-month-old infant, in good general health, was brought to the emergency unit after 3 consecutive episodes of central cyanosis and tetany of the limbs with spontaneous recovery the same afternoon. The child was also very irritable, regurgitated a lot, and positioned himself in opisthotonos. Between these episodes, the neurological exam showed some perturbations (horizontal nystagmus and Bell's phenomenon, hypertony of the extensor muscles, and mild hypotony of the axial flexor muscles) with slow improvement over the following hours. The remaining clinical exam, the laboratory work (complete blood count, renal, hepatic, and muscular tests, capillary blood gas, plasmatic amino acids, and urinary organic acids), and the electroencephalogram findings were all normal. In the course of a detailed interview, the parents reported having given 3 bottles to their child, each one containing 200 mL of an infusion with 4 to 5 fruits of star anise, in the hours preceding the symptoms to relieve colic pains. The last seizure-like event took place approximately 8h after the last ingestion. We could prove the ingestion of anisatin, the toxic substance found in Japanese star anise, and the contamination of Chinese star anise by the Japanese species. Indeed, the anisatin analysis by liquid chromatography and mass spectroscopy (LC-MS) in a urine sample taken 22 h after the last infusion ingestion showed trace amounts of the substance. In another urine sample taken 33 h after ingestion, no anisatin could be detected. Furthermore, the analysis of the fruit sample gave an anisatin concentration of 7800 μg/kg while the maximum tolerance value in Switzerland is 1000 μg/kg. CONCLUSION: The evaluation of ALTE in infants should always include the possibility of intoxication. Star anise is generally considered a harmless medicine. Nevertheless, it can sometimes cause a severe intoxication resulting in various neurological and gastrointestinal symptoms. To prevent such events, not only the parents, but also the care personnel and pharmacists must be informed about the possible adverse effects caused either by the overdose of Chinese star anise or by the eventual contamination of herbal teas with Japanese star anise. A better control of the substances by the health authorities is also necessary.

Microvascular pathology in late-life depression.

Since the era of Gaupp who introduced the concept of atheroscletic depressive disorder, the concept of late-life depression has been correlated with cerebrovascular comorbidities, microvascular lesions, frontal cortical and subcortical gray and white matter hyperintensities. The predominant neuropsychological deficits concern the domains of planning, organization and abstraction, with executive dysfunction being the predominant finding. MRI studies reveal a higher prevalence of white matter lesions in elderly patients with depression. Molecular mechanisms underlying the disease still remain unclear. Hyperhomocysteinemia has been associated with depression through its toxicity to neurons and blood vessels. Endothelial dysfunction is another possible mechanism referring to the loss of vasodilatation capacity. Inflammatory phenomena, such as increased peripheral leucocytes, elevated CRP and cytokine levels, could play a role in endothelial dysfunction. In this review we will briefly combine findings from neurobiological, epidemiological, structural and post-mortem data. A more complex model in late-life depression combining different modalities could be an elucidating approach to the disease's etiopathogeny in the future.