Generation of an Fsp1 (fibroblast‐specific protein 1)‐Flpo transgenic mouse strain

Recombination systems represent a major breakthrough in the field of genetic model engineering. The Flp recombinases (Flp, Flpe, and Flpo) bind and cleave DNA Frt sites. We created a transgenic mouse strain ([Fsp1‐Flpo]) expressing the Flpo recombinase in fibroblasts. This strain was obtained by random insertion inside mouse zygotes after pronuclear injection. Flpo expression was placed under the control of the promoter of Fsp1 (fibroblast‐specific protein 1) gene, whose expression starts after gastrulation at Day 8.5 in cells of mesenchymal origin. We verified the correct expression and function of the Flpo enzyme by several ex vivo and in vivo approaches. The [Fsp1‐Flpo] strain represents a genuine tool to further target the recombination of transgenes with Frt sites specifically in cells of mesenchymal origin or with a fibroblastic phenotype.     

Über die Determination der sekundären Geschlechtsmerkmale (Brutsackbildung) der weiblichen Wasserassel durch das Ovar

Ohne Zusammenfassung     

Eveningness and poor sleep quality contribute to depressive residual symptoms and behavioral inhibition in patients with bipolar disorder

ABSTRACT

Eveningness and sleep disturbances are considered as markers of Bipolar Disorder (BD) and influence mood and emotional or behavioral states. This study investigates the associations between circadian markers and sleep quality on residual depressive symptoms and inhibition/activation dimensions during the euthymic phase. A sample of 89 euthymic adult individuals with BD was assessed for circadian preference and typology using the Composite Scale of Morningness (CSM) and the Circadian Type Inventory (CTI) and for sleep quality using the Pittsburgh Sleep Quality Index (PSQI). The Montgomery and Asberg Depression Rating Scale (MADRS) and the Multidimensional Assessment of Thymic States (MAThyS) were used to measure residual depressive symptoms and the inhibition/activation dimensions. We examined any associations between these parameters using correlations and path analyses. We identified significant associations between eveningness and poorer sleep quality that correlated to higher depressive residual symptoms and a global inhibition. The use of path analyses led us to conclude that poor sleep quality mediated the relationship between eveningness and either residual mood symptoms or behavioral inhibition (motivation, sensory perception, interpersonal interaction, and cognition). These factors should be considered in the clinical evaluation of individuals with BD, with a specific attention during the euthymic phase, in order to achieve the best functional outcome possible.     

Improvement of Ratio-Type Estimators

This paper proposes a method for using multi-auxiliary information at both the design and the estimation stages of a sample survey. The proposed method is an extension of the classical multivariate method of Olkin (1958). The results of Agarwal and Kumar (1978) come out as a special case.     

S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) influences cytotoxicity, translocating to the nucleus during apoptosis. Here we report a signalling pathway in which nitric oxide (NO) generation that follows apoptotic stimulation elicits S-nitrosylation of GAPDH, which triggers binding to Siah1 (an E3 ubiquitin ligase), nuclear translocation and apoptosis. S-nitrosylation of GAPDH augments its binding to Siah1, whose nuclear localization signal mediates translocation of GAPDH. GAPDH stabilizes Siah1, facilitating its degradation of nuclear proteins. Activation of macrophages by endotoxin and of neurons by glutamate elicits GAPDH-Siah1 binding, nuclear translocation and apoptosis, which are prevented by NO deletion. The NO-S-nitrosylation-GAPDH-Siah1 cascade may represent an important molecular mechanism of cytotoxicity.     

Gene Disruption in <Emphasis Type="Italic">Scedosporium aurantiacum</Emphasis>: Proof of Concept with the Disruption of <Emphasis Type="Italic">SODC</Emphasis> Gene Encoding a Cytosolic Cu,Zn-Superoxide Dismutase

Scedosporium species are opportunistic pathogens responsible for a large variety of infections in humans. An increasing occurrence was observed in patients with underlying conditions such as immunosuppression or cystic fibrosis. Indeed, the genus Scedosporium ranks the second among the filamentous fungi colonizing the respiratory tracts of the CF patients. To date, there is very scarce information on the pathogenic mechanisms, at least in part because of the limited genetic tools available. In the present study, we successfully developed an efficient transformation and targeted gene disruption approach on the species Scedosporium aurantiacum. The disruption cassette was constructed using double-joint PCR procedure, and resistance to hygromycin B as the selection marker. This proof of concept was performed on the functional gene SODC encoding the Cu,Zn-superoxide dismutase. Disruption of the SODC gene improved susceptibility of the fungus to oxidative stress. This technical advance should open new research areas and help to better understand the biology of Scedosporium species.     

Variation in plant biodiversity across sacred groves and fallows in Western Highlands of Cameroon

The study was conducted to compare species richness and diversity in different ecosystems and abiotic factors. The results showed that the sacred groves had a plant genetic diversity composed of a total of 42, 65 and 82 ethno‐botanical species of herbs, shrubs and trees, respectively, with varied qualities. There were six herbaceous species common in the fallow ecosystem and the sacred groves, 35 herbaceous species found in the sacred grove and absent in the fallow vegetation and 70 herbaceous species in the fallow vegetation and absent in the ground layer of the sacred groves. Thirty‐two regenerated species and 49 nonregenerated tree species were found in the sacred groves. The herbaceous α‐diversity was significantly higher in the fallows than the sacred groves at the low altitude. The tree species richness was higher at the low altitude compared to the high altitude with tree β‐diversity increasing with altitude. Varying combinations of soil pH, total P, total K, CEC and slope per cent were related to some of the parameters evaluated. Biodiversity changes in the sacred groves may be governed by biophysical drivers, while a combination of human and biophysical explained the variation in rotational fallow vegetation.     

Association between coffee,tobacco, and alcohol daily consumption and sleep/wake cycle: an actigraphy study in euthymic patients with bipolar disorders

ABSTRACT

Individuals with bipolar disorder (BD) have higher than average rates of coffee, tobacco and alcohol use. These substances may have deleterious effects on sleep quality and quantity, which may destabilize sleep/wake cycles and negatively impact the clinical course and prognosis of BD. The use of these substances may also be perceived as a self-medication attempt, for example, to induce sleep or to increase vigilance during the day. The objective of the current study was to investigate associations between the self-reported daily use of coffee, tobacco, and alcohol, and objective measures of sleep and activity patterns in adult individuals with BD. A sample of 147 euthymic individuals with BD were assessed for daily coffee, tobacco and alcohol consumption and 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and daytime activity were compared between groups classified as coffee+/coffee-, tobacco+/tobacco- and alcohol+/alcohol-, defined according to their current daily use. Then, we examined potential correlations between sleep/wake cycle parameters and the amount of daily consumption of each substance. Multivariable analyses identified associations between the use of coffee, tobacco, and alcohol and several sleep and activity parameters, such as between coffee, alcohol, and the relative amplitude of activity (respectively, p = .003 and p = .005), between alcohol and M10 onset (onset time of the 10 most active hours during the 24-h cycle) (p = .003), and between coffee and sleep duration (p = .047). This study supports the hypothesis that there is a relationship, whose direction would be bidirectional, between the daily use of these substances and the sleep/wake cycle in euthymic individuals with BD. These preliminary results require replications in other retrospective and prospective samples. They may have a clinical impact on psycho-education strategies to be proposed to individuals with BD.     

Genome wide association study of Escherichia coli bloodstream infection isolates identifies genetic determinants for the portal of entry but not fatal outcome

Escherichia coli is an important cause of bloodstream infections (BSI), which is of concern given its high mortality and increasing worldwide prevalence. Finding bacterial genetic variants that might contribute to patient death is of interest to better understand infection progression and implement diagnostic methods that specifically look for those factors. E. coli samples isolated from patients with BSI are an ideal dataset to systematically search for those variants, as long as the influence of host factors such as comorbidities are taken into account. Here we performed a genome-wide association study (GWAS) using data from 912 patients with E. coli BSI from hospitals in Paris, France. We looked for associations between bacterial genetic variants and three patient outcomes (death at 28 days, septic shock and admission to intensive care unit), as well as two portals of entry (urinary and digestive tract), using various clinical variables from each patient to account for host factors. We did not find any association between genetic variants and patient outcomes, potentially confirming the strong influence of host factors in influencing the course of BSI; we however found a strong association between the papGII operon and entrance of E. coli through the urinary tract, which demonstrates the power of bacterial GWAS when applied to actual clinical data. Despite the lack of associations between E. coli genetic variants and patient outcomes, we estimate that increasing the sample size by one order of magnitude could lead to the discovery of some putative causal variants. Given the wide adoption of bacterial genome sequencing of clinical isolates, such sample sizes may be soon available.