Structural plasticity and associative memory in balanced neural networks with spike-time dependent inhibitory plasticity

Peer reviewe

Reptielen in de heide : verslag veldwerkplaats Droog zandlandschap Hoge Veluwe, 23 juni 2009

Reptielen staan in Nederland onder druk. Een belangrijk habitat wordt gevormd door heide. Slangen en hagedissen stellen echter specifieke eisen aan hun leefgebied. Voor zes van de zeven hagedissen soorten die in Nederland voorkomen, is heide een belangrijk of het belangrijkste habitat. Wat maakt een heideveld wel geschikt als habitat? “ We maaien, branden, plaggen, zorgen voor paarse heide. Dat kan bij ons, doordat we zo’n grote oppervlakte hebben. Wel gaan we nu naar wat kleinschaliger beheer. Maar bovenal voeren we een consistent beheer, niet afhankelijk van waar toevallig subsidie voor is. Ik denk dat we het daarom zo goed doen wat reptielen betreft.” aldus Leidekker, hoofdbeheerder bij de Hoge Veluw

Ethyl 6-methyl-4-[2-(4,4,5,5-tetra­methyl-1,3,2-dioxaborolan-2-yl)thio­phen-3-yl]-2-thioxo-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

A new Biginelli compound, C18H25BN2O4S2, containing a boronate ester group was synthesized from a lithium bromide-catalysed reaction. The compound crystallizes with two independent mol­ecules in the asymmetric unit that differ mainly in the conformation of the ester functionality. The crystal structure is stabilized by inter­molecular N—H⋯O and N—H⋯S hydrogen bonds involving the 3,4-dihydro­pyrimidine-2(1H)-thione NH groups as donors and the carbonyl O and thio­phene S atoms as acceptors

Training deep neural density estimators to identify mechanistic models of neural dynamics

Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators-- trained using model simulations-- to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features, and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin-Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics

Inflammatory cytokines in an experimental model for the multiple organ dysfunction syndrome

Contains fulltext : 4834.pdf (publisher's version ) (Open Access

Percutaneous reduction and fixation of intraarticular calcaneal fractures

Objective: Percutaneous reduction by distraction and subsequent percutaneous screw fixation to restore calcaneal and posterior talocalcaneal facet anatomy. The aim of this technique is to improve functional outcome and to diminish the rate of secondary posttraumatic arthrosis compared to conservative treatment and, secondly, to reduce infectious complications compared to open reduction and internal fixation (ORIF). Indications: Sanders type II-IV displaced intraarticular calcaneal fractures. Contraindications: Isolated centrally depressed fragment. Contraindications: Patients who are expected to be noncompliant. Surgical Technique: Four distractors (Synthes™) are positioned, two on each side of the foot, between the tuberosity of the calcaneus and talus and between the tuberosity and cuboid. A distracting force is given over all four distractors. A blunt drifter is then introduced from the plantar side to unlock and push up any remaining depressed parts of the subtalar joint surface of the calcaneus. The reduction is fixated with two or three screws inserted percutaneously. Postoperative Management: Directly postoperatively, full active range of motion exercises of the ankle joint can start, with the foot elevated in the 1st postoperative week. Stitches are removed after 14 days. Implant removal is necessary in 50-60% of patients. Results: Between 1999 and 2004, 59 patients with 71 fractures were treated by percutaneous skeletal triangular distraction and percutaneous fixation. A total of 50 patients with 61 fractures and a minimum follow-up of 1 year were available for follow-up. According to the American Orthopaedic Foot and Ankle Society Hindfoot Score, 72% had a good to excellent result. A secondary subtalar arthrodesis was performed in five patients and planned in four (total 15%). Böhler's angle increased by about 20° postoperatively. Sagittal motion was 90% andsubtalar motion 70% compared to the healthy foot

Bispecific Tau Antibodies with Additional Binding to C1q or Alpha-Synuclein

BACKGROUND: Alzheimer’s disease (AD) and other tauopathies are neurodegenerative disorders characterized by cellular accumulation of aggregated tau protein. Tau pathology within these disorders is accompanied by chronic neuroinflammation, such as activation of the classical complement pathway by complement initiation factor C1q. Additionally, about half of the AD cases present with inclusions composed of aggregated alpha-synuclein called Lewy bodies. Lewy bodies in disorders such as Parkinson’s disease and Lewy body dementia also frequently occur together with tau pathology. OBJECTIVE: Immunotherapy is currently the most promising treatment strategy for tauopathies. However, the presence of multiple pathological processes within tauopathies makes it desirable to simultaneously target more than one disease pathway. METHODS: Herein, we have developed three bispecific antibodies based on published antibody binding region sequences. One bispecific antibody binds to tau plus alpha-synuclein and two bispecific antibodies bind to tau plus C1q. RESULTS: Affinity of the bispecific antibodies to their targets compared to their monospecific counterparts ranged from nearly identical to one order of magnitude lower. All bispecific antibodies retained binding to aggregated protein in patient-derived brain sections. The bispecific antibodies also retained their ability to inhibit aggregation of recombinant tau, regardless of whether the tau binding sites were in IgG or scFv format. Mono- and bispecific antibodies inhibited cellular seeding induced by AD-derived pathological tau with similar efficacy. Finally, both Tau-C1q bispecific antibodies completely inhibited the classical complement pathway. CONCLUSIONS: Bispecific antibodies that bind to multiple pathological targets may therefore present a promising approach to treat tauopathies and other neurodegenerative disorders