Deletion of the Na-K-2Cl cotransporter NKCC1 results in a more severe epileptic phenotype in the intrahippocampal kainate mouse model of temporal lobe epilepsy

Increased neuronal expression of the Na-K-2Cl cotransporter NKCC1 has been implicated in the generation of seizures and epilepsy. However, conclusions from studies on the NKCC1-specific inhibitor, bumetanide, are equivocal, which is a consequence of the multiple potential cellular targets and poor brain penetration of this drug. Here, we used Nkcc1 knockout (KO) and wildtype (WT) littermate control mice to study the ictogenic and epileptogenic effects of intrahippocampal injection of kainate. Kainate (0.23 ?g in 50 nl) induced limbic status epilepticus (SE) in both KO and WT mice with similar incidence, latency to SE onset, and SE duration, but the number of intermittent generalized convulsive seizures during SE was significantly higher in Nkcc1 KO mice, indicating increased SE severity. Following SE, spontaneous recurrent seizures (SRS) were recorded by continuous (24/7) video/EEG monitoring at 0-1, 4-5, and 12-13 weeks after kainate, using depth electrodes in the ipsilateral hippocampus. Latency to onset of electrographic SRS and the incidence of electrographic SRS were similar in WT and KO mice. However, the frequency of electrographic seizures was lower whereas the frequency of electroclinical seizures was higher in Nkcc1 KO mice, indicating a facilitated progression from electrographic to electroclinical seizures during chronic epilepsy, and a more severe epileptic phenotype, in the absence of NKCC1. The present findings suggest that NKCC1 is dispensable for the induction, progression and manifestation of epilepsy, and they do not support the widely held notion that inhibition of NKCC1 in the brain is a useful strategy for preventing or modifying epilepsy.Peer reviewe

Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood

Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in -1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.Peer reviewe

Zur Morphologie des Huehnerknochenmarkes unter normalen Bedingungen und bei verschiedenen anaemischen Zustaenden

Available from: Zentralstelle fuer Agrardokumentation und -information (ZADI), Villichgasse 17, D-53177 Bonn / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

The Comparative Advantage of X-Teams

Traditional teams are not faring well in today's rapidly changing business environment. Even when they establish clear roles and responsibilities, build trust among members and define goals according to the book, their projects often fail or get axed. Three MIT Sloan School researchers think they have found the reason: Traditional teams are too inwardly focused and lack flexibility. Traditional team-building activities are still important, they contend, but only when combined with a greater awareness of external stakeholders and information sources. Fortunately, a new, externally focused team has arisen: the X-team. The authors detail the high levels of performance that X-teams are seeing. And they explain how managers in a wide variety of industries and functions can establish the organizational structures that support such teams. The researchers outline the five components of X-teams they have studied: external activity, extensive ties both inside the larger organization and outside the company, expandable tiers or kinds of responsibility, flexible membership (switching roles, moving in and out of the team as needed) and execution mechanisms that facilitate getting the job done. The results are impressive. One observed X-team greatly improved the dispersal of innovation throughout its organization. X-teams in sales were seen to bring in more revenue. Drug-development teams were more adept at drawing in external technology. Product-development teams were more innovative than traditional teams ¿ and more often on time and on budget. Managers that recognize their own company in the new, flatter organizational structures, the increasing interdependence of tasks and teams, the constant updating of information and the overall complexity of work should consider creating an environment for successful X-teams

Behandelte Kunststoffoberflaeche, Verfahren zu ihrer Herstellung und Anwendung

Mit der Erfindung wird eine verbundfreundliche Kunststoffoberflaeche und ein Verfahren zu deren Herstellung zur Verfuegung gestellt. Die verbundfreundliche Kunststoffoberflaeche zeichnet sich dadurch aus, dass sie eine zerfranste Oberflaechenstruktur hat, und sie ist in der Weise herstellbar, dass aus einer unzerfransten Kunststoffoberflaeche im viskoelastischen oder plastischen Zustand dieser Kunststoffoberflaeche Kunststoffanteile herausgezogen werden, indem die viskoelastische oder plastische Kunststoffoberflaeche mit einer haftenden Matrize in Kontakt gebracht und die haftende Matrize von der Kunststoffoberflaeche weggezogen wird. Hierbei ergibt sich eine profilografische Kunststoffoberflaeche, die durch ihre Zerfransung eine formschluessige Verbindung mit Klebstoffen, Lacken oder sonstigen Beschichtungsmitteln bildet, welche ausserordentlich fest ist. Ausserdem umfasst die Erfindung die Anwendung einer solchen verbundfreundlichen Kunststoffoberflaeche

Aufbereitung und Verwertung von sortenreinen Kunststoffen aus Kunststoffverpackungen bekannt als Kunststoff-Recycling-Test Berlin Diskussionsunterlage zur Bewertung der Ergebnisse und zur Festlegung von Folgerungen

SIGLEAvailable from TIB Hannover: FR 5155+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Analysing the SEDs of protoplanetary disks with machine learning

Context. The analysis of spectral energy distributions (SEDs) of protoplanetary disks to determine their physical properties is known to be highly degenerate. Hence, a full Bayesian analysis is required to obtain parameter uncertainties and degeneracies. The main challenge here is computational speed, as one proper full radiative transfer model requires at least a couple of CPU minutes to compute. Aims. We performed a full Bayesian analysis for 30 well-known protoplanetary disks to determine their physical disk properties, including uncertainties and degeneracies. To circumvent the computational cost problem, we created neural networks (NNs) to emulate the SED generation process. Methods. We created two sets of MCFOST Monte Carlo radiative transfer disk models to train and test two NNs that predict SEDs for continuous and discontinuous disks, with 18 and 26 free model parameters, respectively. A Bayesian analysis was then performed on 30 protoplanetary disks with SED data collected by the FP7-Space DIANA project to determine the posterior distributions of all parameters. We ran this analysis twice, (i) with old distances and additional parameter constraints as used in a previous study, to compare results, and (ii) with updated distances and free choice of parameters to obtain homogeneous and unbiased model parameters. We evaluated the uncertainties in the determination of physical disk parameters from SED analysis, and detected and quantified the strongest degeneracies. Results. The NNs are able to predict SEDs within ∼1 ms with uncertainties of about 5% compared to the true SEDs obtained by the radiative transfer code. We find parameter values and uncertainties that are significantly different from previous values obtained by χ 2 fitting. Comparing the global evidence for continuous and discontinuous disks, we find that 26 out of 30 objects are better described by disks that have two distinct radial zones. The analysed sample shows a significant trend for massive disks to have small scale heights, which is consistent with lower midplane temperatures in massive disks. We find that the frequently used analytic relationship between disk dust mass and millimetre-flux systematically underestimates the dust mass for high-mass disks (dust mass ≥10-4 M⊙). We determine how well the dust mass can be determined with our method for different numbers of flux measurements. As a byproduct, we created an interactive graphical tool that instantly returns the SED predicted by our NNs for any parameter combination.</p