Intracisternal delivery of NFκB-inducible scAAV2/9 reveals locoregional neuroinflammation induced by systemic kainic acid treatment.

We have previously demonstrated disease-dependent gene delivery in the brain using an AAV vector responding to NFκB activation as a probe for inflammatory responses. This vector, injected focally in the parenchyma prior to a systemic kainic acid (KA) injection mediated inducible transgene expression in the hippocampus but not in the cerebellum, regions, respectively, known to be affected or not by the pathology. However, such a focal approach relies on previous knowledge of the model parameters and does not allow to predict the whole brain response to the disease. Global brain gene delivery would allow to predict the regional distribution of the pathology as well as to deliver therapeutic factors in all affected brain regions. We show that self-complementary AAV2/9 (scAAV2/9) delivery in the adult rat cisterna magna allows a widespread but not homogenous transduction of the brain. Indeed, superficial regions, i.e., cortex, hippocampus, and cerebellum were more efficiently transduced than deeper regions, such as striatum, and substantia nigra. These data suggest that viral particles penetration from the cerebrospinal fluid (CSF) into the brain is a limiting factor. Interestingly, AAV2/9-2YF a rationally designed capsid mutant (affecting surface tyrosines) increased gene transfer efficiency approximately fivefold. Neurons, astrocytes, and oligodendrocytes, but not microglia, were transduced in varying proportions depending on the brain region and the type of capsid. Finally, after a single intracisternal injection of scAAV2/9-2YF using the NFκB-inducible promoter, KA treatment induced transgene expression in the hippocampus and cortex but not in the cerebellum, corresponding to the expression of the CD11b marker of microglial activation. These data support the use of disease-inducible vectors administered in the cisterna magna as a tool to characterize the brain pathology in systemic drug-induced or transgenic disease models. However, further improvements are required to enhance viral particles penetration into the brain

A novel approach to model 4 decades of marine chemical data

The awareness of the negative effects of chemical pollution in the sixties has led to an increased concern on the chemical status of the marine environment in the following decades. International regulation in Europe started with the Oslo and Paris convention in the seventies, later on leading to the OSPAR commission. At national level, extended research on chemical pollutants in marine sediments and marine biota was done within the “Project Mer/Projekt Zee” from 1970 to 1976. Since then, a long series of research and monitoring projects was conducted, reporting on the chemical status of the Belgian Part of the North&nbsp;Sea. &nbsp; Within the 4demon project, a major work package focused on the collection, quality control and intercalibration of more than 40 years of data on heavy metals and polychlorinated biphenyls. In this presentation, the modelling approach and results on sediment data will be&nbsp;presented. &nbsp; Within current OSPAR and MSFD monitoring on chemical pollution, variability in location, seasonality, grain size, etc. is reduced thanks to standardized OSPAR guidelines. This facilitates comparability of data within and between regions and assessments based on 5-15 year timetrends are frequently made. Within more than 40 years of pollution data, variability is much larger, and multiple issues should be tackled to intercalibrate the data: changes in sampling locations and analyses methods over time, missing essential metadata, sample analysis on different grain size fractions,… Therefore, existing time trend modelling approaches could not be applied within the 4Demon project. An alternative approach, focused on cluster analysis and different normalisation procedures was proposed. A parametric linear mixed effect model was used to integrate all data into consistent long term time lines which give a view on PCB and heavy metal pollution on a large time&nbsp;frame. &nbsp; Acknowledgement We want to thank the Belgian Science Policy Office (BELSPO) for the financial support of the 4Demon&nbsp;project.</p

Diffractive shear interferometry for extreme ultraviolet high-resolution lensless imaging

We demonstrate a novel imaging approach and associated reconstruction algorithm for far-field coherent diffractive imaging, based on the measurement of a pair of laterally sheared diffraction patterns. The differential phase profile retrieved from such a measurement leads to improved reconstruction accuracy, increased robustness against noise, and faster convergence compared to traditional coherent diffractive imaging methods. We measure laterally sheared diffraction patterns using Fourier-transform spectroscopy with two phase-locked pulse pairs from a high harmonic source. Using this approach, we demonstrate spectrally resolved imaging at extreme ultraviolet wavelengths between 28 and 35 nm

Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is a rare disease caused by mutations in the TSC1 or TSC2 genes and is characterized by widespread tumour growth, intractable epilepsy, cognitive deficits and autistic behaviour. CBD has been reported to decrease seizures and inhibit tumour cell progression, therefore we sought to determine the influence of CBD on TSC pathology in zebrafish carrying a nonsense mutation in the tsc2 gene. CBD treatment from 6 to 7 days post-fertilization (dpf) induced significant anxiolytic actions without causing sedation. Furthermore, CBD treatment from 3 dpf had no impact on tsc2-/- larvae motility nor their survival. CBD treatment did, however, reduce the number of phosphorylated rpS6 positive cells, and their cross-sectional cell size. This suggests a CBD mediated suppression of mechanistic target of rapamycin (mTOR) activity in the tsc2-/- larval brain. Taken together, these data suggest that CBD selectively modulates levels of phosphorylated rpS6 in the brain and additionally provides an anxiolytic effect. This is pertinent given the alterations in mTOR signalling in experimental models of TSC. Additional work is necessary to identify upstream signal modulation and to further justify the use of CBD as a possible therapeutic strategy to manage TSC

Short-range oscillators in power-series picture

A class of short-range potentials on the line is considered as an asymptotically vanishing phenomenological alternative to the popular confining polynomials. We propose a method which parallels the analytic Hill-Taylor description of anharmonic oscillators and represents all our Jost solutions non-numerically, in terms of certain infinite hypergeometric-like series. In this way the well known solvable Rosen-Morse and scarf models are generalized.Comment: 23 pages, latex, submitted to J. Phys. A: Math. Ge

Complement component 4A protein levels are negatively related to frontal volumes in patients with schizophrenia spectrum disorders

Background: Excessive C4A-gene expression may result in increased microglia-mediated synaptic pruning. As C4A overexpression is observed in schizophrenia spectrum disorders (SSD), this mechanism may account for the altered brain morphology (i.e. reduced volume and cortical thickness) and cognitive symptoms that characterize SSD. Therefore, this study investigates the association of C4A serum protein levels with brain morphology and cognition, and in particular whether this association differs between recent-onset SSD (n = 69) and HC (n = 40). Methods: Serum C4A protein levels were compared between groups. Main outcomes included total gray matter volume, mean cortical thickness and cognitive performance. Regression analysis on these outcomes included C4A level, group (SSD vs. HC), and C4A*Group interactions. All statistical tests were corrected for age, sex, BMI, and antipsychotic medication dose. Follow-up analyses were performed on separate brain regions and scores on cognitive sub-tasks. Results: The group difference in C4A levels was not statistically significant (p = 0.86). The main outcomes did not show a significant interaction effect (p &gt; 0.13) or a C4A main effect (p &gt; 0.27). Follow-up analyses revealed significant interaction effects for the left medial orbitofrontal and left frontal pole volumes (p &lt; 0.001): C4A was negatively related to these volumes in SSD, but positively in HC. Conclusion: This study demonstrated that C4A was negatively related to – specifically – frontal brain volumes in SSD, but this relation was inverse for HC. The results support the hypothesis of complement-mediated brain volume reduction in SSD. The results also suggest that C4A has a differential association with brain morphology in SSD compared to HC.</p

Public rules about using and owning real estate in Cuba

The discussion on urban land continues to be absent in most of the specialized Cuban literature about planning and economic policies, despite its relevance. In very thorough essays about the present challenges and future development of the Cuban economy, nothing is said about the need for adequate public land policies and the implementation of public value capture mechanisms as part of the economic development of the country. The issue is complex, there is a void of almost half a century of not dealing with land value, but these reasons are not sufficient to justify the continued lack of vision in this direction, all the more when the Cuban cities are in desperate need to reverse the deterioration and stagnation that affects them. The Cuban state determines the general rules under which citizens and organisations may own and use real estate. These are rules about property rights and about the limitations - in compliance with aspects such as state security, environmental and heritage protection, economic development, social equity and human and civil rights – on exercising those rights. In doing this, the Cuban state is no different from other states: most states make such rules and enforce them when necessary. What is particular to Cuba is the content of those rules. In particular, the Cuban state has the monopoly to perform land development and management. There are public institutions to plan and deal with all of these aspects, and there are no recognised real estate markets in the country. Another important aspect is the utmost importance given to planning. But in spite of this, Cuban urban planners have rarely been certain of what will be built and where. The main reason for this may be that, despite the numerous master plans to study and anticipate development trends, most of the decisions ultimately involve top officials who envision the projects and establish the investment priorities according to the public interests or needs and the historical moment, irrespective of the plans. This article intends to give a clear picture of how things are done in the public sector, how the administration works, and under which legal framework. I will look at the physical planning system and its importance in the location and implementation of land use, investment projects and housing programs, and at the legal procedures that include licenses for construction, demolition, habitat and other licenses for heritage conservation and redevelopment. I will analyze the difficulties faced by the Cuban planning and legal system with respect to land and urban development, in the attempt to understand the limits imposed by the government on land and urban development, and I will explore to what extent those limits are to blame for the increasing irregularities and violations at all levels of the formal procedures for land and property. I will also introduce the public and personal rights concerning housing, buying and selling, permutes, donations and other tenure alternatives; and clarify the civil responsibilities, namely types of ownership, properties, property registers and so forth in order to expose the opportunities and accessibility of the system but also its limitations