Functional and structural properties of dentate granule cells with hilar basal dendrites in mouse entorhino-hippocampal slice cultures

During postnatal development hippocampal dentate granule cells (GCs) often extend dendrites from the basal pole of their cell bodies into the hilar region. These so-called hilar basal dendrites (hBD) usually regress with maturation. However, hBDs may persist in a subset of mature GCs under certain conditions (both physiological and pathological). The functional role of these hBD-GCs remains not well understood. Here, we have studied hBD-GCs in mature (≥18 days in vitro) mouse entorhino-hippocampal slice cultures under control conditions and have compared their basic functional properties (basic intrinsic and synaptic properties) and structural properties (dendritic arborisation and spine densities) to those of neighboring GCs without hBDs in the same set of cultures. Except for the presence of hBDs, we did not detect major differences between the two GC populations. Furthermore, paired recordings of neighboring GCs with and without hBDs did not reveal evidence for a heavy aberrant GC-to-GC connectivity. Taken together, our data suggest that in control cultures the presence of hBDs on GCs is neither sufficient to predict alterations in the basic functional and structural properties of these GCs nor indicative of a heavy GC-to-GC connectivity between neighboring GCs

IL28B SNP screening and distribution in the French Canadian population using a rapid PCR-based test

Single nucleotide polymorphisms (SNPs) in the proximity of the interleukin-28B (IL28B) gene can predict spontaneous resolution of hepatitis C virus (HCV) infection and response to interferon therapy. Screening for this polymorphism has become part of the standard criteria for the management of HCV-infected patients, hence the need for a rapid, cost-effective screening method. Here, we describe a rapid PCR-based test to screen for two IL28B SNPs (rs12979860 and rs8099917). We used this test to investigate IL28B polymorphism and prevalence in a cohort of French Canadian injection drug users who are part of a unique population known to have a strong genetic founder effect. This population had lower linkage disequilibrium between the two tested SNPs as compared to other cohorts (|d′| = 0.68, r = 0.59). The special genetic makeup should be considered in the management of HCV-infected patients within that population

Prognostic Factors Associated with Ocriplasmin Efficacy for the Treatment of Symptomatic Vitreomacular Adhesion and Full-thickness Macular Hole: Analysis from Four Studies

Purpose: To assess the effect of patient baseline characteristics on the efficacy of ocriplasmin treatment for symptomatic vitreomacular adhesion (VMA) with full-thickness macular hole (FTMH) from phase 3/4 studies. Methods: Patients with symptomatic VMA and FTMH at baseline and receiving ocriplasmin treatment 12

Cupiennin 1a exhibits a remarkably broad, non-stereospecific cytolytic activity on bacteria, protozoan parasites, insects, and human cancer cells

Cupiennin 1a, a cytolytic peptide isolated from the venom of the spider Cupiennius salei, exhibits broad membranolytic activity towards bacteria, trypanosomes, and plasmodia, as well as human blood and cancer cells. In analysing the cytolytic activity of synthesised all-d- and all-l-cupiennin 1a towards pro- and eukaryotic cells, a stereospecific mode of membrane destruction could be excluded. The importance of negatively charged sialic acids on the outer leaflet of erythrocytes for the binding and haemolytic activity of l-cupiennin 1a was demonstrated. Reducing the overall negative charges of erythrocytes by partially removing their sialic acids or by protecting them with tri- or pentalysine results in reduced haemolytic activity of the peptid

Synthesis and Characterization of Oxidized Polysaccharides for In Situ Forming Hydrogels

[EN] Polysaccharides are widely used as building blocks of scaffolds and hydrogels in tissue engineering, which may require their chemical modification to permit crosslinking. The goal of this study was to generate a library of oxidized alginate (oALG) and oxidized hyaluronic acid (oHA) that can be used for in situ gelling hydrogels by covalent reaction between aldehyde groups of the oxidized polysaccharides (oPS) and amino groups of carboxymethyl chitosan (CMC) through imine bond formation. Here, we studied the effect of sodium periodate concentration and reaction time on aldehyde content, molecular weight of derivatives and cytotoxicity of oPS towards 3T3-L1 fibroblasts. It was found that the molecular weights of all oPs decreased with oxidation and that the degree of oxidation was generally higher in oHA than in oALG. Studies showed that only oPs with an oxidation degree above 25% were cytotoxic. Initial studies were also done on the crosslinking of oPs with CMC showing with rheometry that rather soft gels were formed from higher oxidized oPs possessing a moderate cytotoxicity. The results of this study indicate the potential of oALG and oHA for use as in situ gelling hydrogels or inks in bioprinting for application in tissue engineering and controlled release.This work was supported by the Deutscher Akademischer Austauschdienst DAAD (grant No. 91605199 to MM) and Deutsche Forschungsgemeinschaft (grant Gr1290/11-1 to TG). The kind support by Spanish State Research Agency (AEI) through the PID2019-106000RB-C21/AEI/10.13039/501100011033 project (including the FEDER financial support) to GGF is acknowledged. We acknowledge the financial support within the funding programme "Open Access Publishing" by the German Research Foundation (DFG).We are very thankful to Andrea Liedmann for her guidance during the cell experiments and Alexandros Repanas for his help during the synthesis and characterization of oPs and data analyses. Furthermore, Marie-Luise Trutschel is acknowledged for her guidance during the rheological measurements.Muhammad, M.; Willems, C.; Rodríguez-Fernández, J.; Gallego Ferrer, G.; Groth, T. (2020). Synthesis and Characterization of Oxidized Polysaccharides for In Situ Forming Hydrogels. Biomolecules. 10(8):1-18. https://doi.org/10.3390/biom10081185S118108Ratner, B. D. (2019). Biomaterials: Been There, Done That, and Evolving into the Future. Annual Review of Biomedical Engineering, 21(1), 171-191. doi:10.1146/annurev-bioeng-062117-120940Morais, J. M., Papadimitrakopoulos, F., & Burgess, D. J. (2010). 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Full immersion TRIZ in education

Within the University of Twente, the Netherlands, TRIZ is seen as a powerful methodology that stimulates students in investigating innovative solutions during the product development process. The TRIZ methodology has been part of the Twente curriculum for many years, mainly as small parts of courses and projects. In 2009, TRIZ was presented as an 84 or 140 hour master course for the first time. The course organisation differs from regular university courses both by subject, timing and intensity. The course was offered during the summer break within two weeks, with a workload reaching 10+ hours a day. This paper describes the course itself, course results and the student evaluation of the course

Alkaloids from marine fungi : promising antimicrobials

Resistance of pathogenic microorganisms against antimicrobials is a major threat to contemporary human society. It necessitates a perpetual influx of novel antimicrobial compounds. More specifically, Gram(-)pathogens emerged as the most exigent danger. In our continuing quest to search for novel antimicrobial molecules, alkaloids from marine fungi show great promise. However, current reports of such newly discovered alkaloids are often limited to cytotoxicity studies and, moreover, neglect to discuss the enigma of their biosynthesis. Yet, the latter is often a prerequisite to make them available through sufficiently efficient processes. This review aims to summarize novel alkaloids with promising antimicrobial properties discovered in the past five years and produced by marine fungi. Several discovery strategies are summarized, and knowledge gaps in biochemical production routes are identified. Finally, links between the structure of the newly discovered molecules and their activity are proposed. Since 2015, a total of 35 new antimicrobial alkaloids from marine fungi were identified, of which 22 showed an antibacterial activity against Gram(-)microorganisms. Eight of them can be classified as narrow-spectrum Gram(-)antibiotics. Despite this promising ratio of novel alkaloids active against Gram(-)microorganisms, the number of newly discovered antimicrobial alkaloids is low, due to the narrow spectrum of discovery protocols that are used and the fact that antimicrobial properties of newly discovered alkaloids are barely characterized. Alternatives are proposed in this review. In conclusion, this review summarizes novel findings on antimicrobial alkaloids from marine fungi, shows their potential as promising therapeutic candidates, and hints on how to further improve this potential

Effect of GTP and Ca2+ on inositol 1,4,5-trisphosphate induced Ca2+ release from permeabilized rat exocrine pancreatic acinar cells

The effects of Ca2+ and GTP on the release of Ca2+ from the inositol 1,4,5-trisphosphate (IP3) sensitive Ca2+ compartment were investigated with digitonin permeabilized rat pancreatic acinar cells. The amount of Ca2+ released due to IP3 directly correlated with the amount of stored Ca2+ and was found to be inversely proportional to the medium free Ca2+ concentration. Ca2+ release induced by 0.18 μM IP3 was half maximally inhibited at 0.5 μM free Ca2+, i.e. at concentrations observed in the cytosol of pancreatic acinar cells. GTP did not cause Ca2+ release on its own, but a single addition of GTP (20 μM) abolished the apparent desensitization of the Ca2+ release which was observed during repeated IP3 applications. This effect of GTP was reversible. GTPγS could not replace GTP. Desensitization still occurred when GTPγS was added prior to GTP. The reported data indicate that GTP, stored Ca2+ and cytosolic free Ca2+ modulate the IP3 induced Ca2+ release. EGTA, Ethylene-glycol-bis (2-aminoethylether)-N,N,N′,N′- tetra acetic acid; GTPγS, Guanosine 5′-O-[3-thio]triphosphate; GDPβS, Guanosine 5′-O-[2-thio]diphosphate; IP3, Inositol 1,4,5-trisphosphate; IP2, Inositol 1,4-bisphosphate; IP4, Inositol 1,3,4,5-tetrakisphosphate; MOPS, Morpholinopropane sulfonic acid; HEPES, 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid; pHMB, Parahydroxymercuribenzoat

Array Configuration Effect on the Spatial Correlation of MU-MIMO Channels in NLoS Environments

In this paper, three different base-station antenna (BSA) configurations are compared in terms of inter-user spatial correlation in a two dimensional (2D) non-line-of-sight (NLoS) environment. The three configurations are: (i) a regular uniform linear array (ULA); (ii) a periodic sparse array; and (iii) an aperiodic sparse array. Electromagnetic modeling of the NLoS channel is proposed where scatterers are considered as resonant dipoles confined in clusters of scatterers (CoSs). While the probability of facing highly correlated user-equipments (UEs) in a multi-user multiple-input multiple-output (MU-MIMO) system is decreasing as the richness of mutipath increases, the sparsity (increased inter-element spacing) is seen to be capable of reducing this probability as well. This is due to the larger spatial variations experienced by the sparse array. Moreover, the results show that further improvement can be achieved by deploying an aperiodic distribution of antenna elements into the sparse antenna aperture