Concomitant Fractional Anisotropy and Volumetric Abnormalities in Temporal Lobe Epilepsy: Cross-Sectional Evidence for Progressive Neurologic Injury

Background

In patients with temporal lobe epilepsy and associated hippocampal sclerosis (TLEhs) there are brain abnormalities extending beyond the presumed epileptogenic zone as revealed separately in conventional magnetic resonance imaging (MRI) and MR diffusion tensor imaging (DTI) studies. However, little is known about the relation between macroscopic atrophy (revealed by volumetric MRI) and microstructural degeneration (inferred by DTI).

Methodology/Principal Findings

For 62 patients with unilateral TLEhs and 68 healthy controls, we determined volumes and mean fractional anisotropy (FA) of ipsilateral and contralateral brain structures from T1-weighted and DTI data, respectively. We report significant volume atrophy and FA alterations of temporal lobe, subcortical and callosal regions, which were more diffuse and bilateral in patients with left TLEhs relative to right TLEhs. We observed significant relationships between volume loss and mean FA, particularly of the thalamus and putamen bilaterally. When corrected for age, duration of epilepsy was significantly correlated with FA loss of an anatomically plausible route - including ipsilateral parahippocampal gyrus and temporal lobe white matter, the thalamus bilaterally, and posterior regions of the corpus callosum that contain temporal lobe fibres - that may be suggestive of progressive brain degeneration in response to recurrent seizures.

Conclusions/Significance

Chronic TLEhs is associated with interrelated DTI-derived and volume-derived brain degenerative abnormalities that are influenced by the duration of the disorder and the side of seizure onset. This work confirms previously contradictory findings by employing multi-modal imaging techniques in parallel in a large sample of patients.     

The art of cellular communication: tunneling nanotubes bridge the divide

The ability of cells to receive, process, and respond to information is essential for a variety of biological processes. This is true for the simplest single cell entity as it is for the highly specialized cells of multicellular organisms. In the latter, most cells do not exist as independent units, but are organized into specialized tissues. Within these functional assemblies, cells communicate with each other in different ways to coordinate physiological processes. Recently, a new type of cell-to-cell communication was discovered, based on de novo formation of membranous nanotubes between cells. These F-actin-rich structures, referred to as tunneling nanotubes (TNT), were shown to mediate membrane continuity between connected cells and facilitate the intercellular transport of various cellular components. The subsequent identification of TNT-like structures in numerous cell types revealed some structural diversity. At the same time it emerged that the direct transfer of cargo between cells is a common functional property, suggesting a general role of TNT-like structures in selective, long-range cell-to-cell communication. Due to the growing number of documented thin and long cell protrusions in tissue implicated in cell-to-cell signaling, it is intriguing to speculate that TNT-like structures also exist in vivo and participate in important physiological processes.     

Intercellular transfer mediated by tunneling nanotubes

Animal cells have evolved different mechanisms to communicate with one another. In 2004, a new route of cell-to-cell communication mediated by tunneling nanotubes (TNT) was reported. These membranous cell bridges form de novo between cells and mediate the intercellular transfer of organelles, plasma membrane components and cytoplasmic molecules. The characterization of TNT-like bridges from several cell types revealed variations in the cytoskeletal composition as well as in the modality by which they interconnect cells, suggesting that different subclasses may exist. Furthermore, the growing number of cell types for which TNT-like structures were detected, supports the view that they represent a general mechanism for functional connectivity between cells, which could have important implications under physiological conditions.     

Growth aspects of Flustra foliacea(Bryozoa, Cheilostomata) in laboratory culture

Flustra foliacea is a cheilostome marine bryozoan which, after initial horizontal growth during the first year, changes to erect growth thereafter. Appraising this slow-growing species for biotechnological use, required the development of cultivation methods for economical biomass production. Vegetative reproduction via cuttings, as employed in the horticulture of various plants, was tested. Fronds of F. foliacea were cut into pieces (10–150 mg fresh weight) and fixed in longitudinally cut silicon tubes. Bryozoa were fed with a mixture of Isochrysis galbana, Dunaliella tertiolecta and Cryptomonas sp. yielding growth rates of 0.3% ± 0.02 day^?1of the initial fresh weight. Growth of the colony occurred firstly at the original growth margin, but later also at the transections, including the side fixed in the silicon tube, opposite to the growth margin. After three months of growth, the two layers of zooids split at the growth margin, forming two monolayers. This growth feature, not described previously for Flustra foliacea,was observed under experimental and natural conditions, and is interpreted as the beginning of one type of ramification. According to our findings, vegetative reproduction of F. foliacea under laboratory conditions is possible and might be an alternative to natural resources regarding biomass of this species.     

Unspecific labeling of pancreatic islets by antisera against fibroblast growth factors and their receptors.

Six distinct fibroblast growth factors (FGFs) have been detected in pancreatic islets by immunohistochemistry (IHC) using commercially available antisera. We show here that these antisera are useful for Western blotting but that only two are suited for IHC. By Western blotting, these antisera detect recombinant FGFs. Detection can be eliminated by preabsorption with immunizing peptide but not with irrelevant peptide. By IHC we find specific labeling of islets with anti-FGF1 and anti-FGF2 antisera. Labeling can be abolished by preabsorption with the immunizing peptides. In contrast, prominent staining of islets by anti-FGF4, -FGF5, -FGF7, and -FGF10 antisera is unspecific because the staining cannot be competed by preabsorption with the immunizing peptides.     

Competing ParA Structures Space Bacterial Plasmids Equally over the Nucleoid

Low copy number plasmids in bacteria require segregation for stable inheritance through cell division. This is often achieved by a parABC locus, comprising an ATPase ParA, DNA-binding protein ParB and a parC region, encoding ParB-binding sites. These minimal components space plasmids equally over the nucleoid, yet the underlying mechanism is not understood. Here we investigate a model where ParA-ATP can dynamically associate to the nucleoid and is hydrolyzed by plasmid-associated ParB, thereby creating nucleoid-bound, self-organizing ParA concentration gradients. We show mathematically that differences between competing ParA concentrations on either side of a plasmid can specify regular plasmid positioning. Such positioning can be achieved regardless of the exact mechanism of plasmid movement, including plasmid diffusion with ParA-mediated immobilization or directed plasmid motion induced by ParB/parC-stimulated ParA structure disassembly. However, we find experimentally that parABC from Escherichia coli plasmid pB171 increases plasmid mobility, inconsistent with diffusion/immobilization. Instead our observations favor directed plasmid motion. Our model predicts less oscillatory ParA dynamics than previously believed, a prediction we verify experimentally. We also show that ParA localization and plasmid positioning depend on the underlying nucleoid morphology, indicating that the chromosomal architecture constrains ParA structure formation. Our directed motion model unifies previously contradictory models for plasmid segregation and provides a robust mechanistic basis for self-organized plasmid spacing that may be widely applicable.     

Biphenyls as potent vitronectin receptor antagonists.

Vitronectin receptor (alpha(V)beta(3)) antagonism has been implicated as a mechanism for the treatment of restenosis following balloon angioplasty. In this work we present results from screening of a focused combinatorial library based on a biphenyl moiety. Our SAR studies led to the identification of compounds with subnanomolar activity, selectivity towards the related GPIIbIIIa receptor and functional activity on human smooth muscle cell migration.     

18F-FET MicroPET and MicroMRI for Anti-VEGF and Anti-PlGF Response Assessment in an Orthotopic Murine Model of Human Glioblastoma

BackgroundConflicting data exist for anti-cancer effects of anti-placental growth factor (anti-PlGF) in combination with anti-VEGF. Still, this treatment combination has not been evaluated in intracranial glioblastoma (GBM) xenografts. In clinical studies, position emission tomography (PET) using the radiolabeled amino acid O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) and magnetic resonance imaging (MRI) add complementary but distinct information about glioma growth; however, the value of ¹⁸F-FET MicroPET combined with MicroMRI has not been investigated preclinically. Here we examined the use of ¹⁸F-FET MicroPET and MicroMRI for evaluation of anti-VEGF and anti-PlGF treatment response in GBM xenografts.MethodsMice with intracranial GBM were treated with anti-VEGF, anti-PlGF + anti-VEGF or saline. Bioluminescence imaging (BLI), ¹⁸F-FET MicroPET and T2-weighted (T2w)-MRI were used to follow tumour development. Primary end-point was survival, and tumours were subsequently analysed for Ki67 proliferation index and micro-vessel density (MVD). Further, PlGF and VEGFR-1 expression were examined in a subset of the xenograft tumours and in 13 GBM patient tumours.ResultsAnti-VEGF monotherapy increased survival and decreased ¹⁸F-FET uptake, BLI and MVD, while no additive effect of anti-PlGF was observed. ¹⁸F-FET SUV_max tumour-to-brain (T/B) ratio was significantly lower after one week (114±6%, n = 11 vs. 143±8%, n = 13; p = 0.02) and two weeks of treatment (116±12%, n = 8 vs. 190±24%, n = 5; p = 0.02) in the anti-VEGF group as compared with the control group. In contrast, T2w-MRI volume was unaffected by anti-VEGF. Gene expression of PlGF and VEGFR-1 in xenografts was significantly lower than in patient tumours.Conclusion¹⁸F-FET PET was feasible for anti-angiogenic response evaluation and superior to T2w-MRI; however, no additive anti-cancer effect of anti-PlGF and anti-VEGF was observed. Thus, this study supports use of ¹⁸F-FET PET for response evaluation in future studies.     

Male reproductive health statement (XIIIth international symposium on Spermatology,may 9th–12th 2018, Stockholm,Sweden

On the occasion of the XIIIth International Symposium on Spermatology held from 9 to 13 May 2018 in Stockholm (Sweden), participants (guest speakers and audience) collectively felt the need to make a public statement on the general issue of male reproductive health. Our intention is to raise awareness of what we believe is a neglected area of research despite alarming situations around the world. The disclosure strategy desired by the co-authors is to bring it to the attention of the greatest number partly by considering co-publication in the various periodicals dealing with Reproductive Biology and Andrology. BaCA’s editorial office accepted this mission and found it natural that our periodical, the official journal of the French Andrology Society (SALF), should carry this message.