A study on transduction an transmission in catfish ampullary electroreceptor organs

Electroreception is the ability of animal species to detect weak electric fields. It is mediated by a sensory system that occurs in some aquatic vertebrates. Electroreception is useful for prey- and predator detection, orientation in space, electrolocation and communication. This thesis deals with the transduction mechanism of catfish ampullary electroreceptor organs. In the first two chapters, patch clamp and FURA-2 experiments are described that are designed to get find out which ion channels are involved in the transduction of the sensory signal. The experiments show that an electrical stimulus induces a calcium-influx into the cells. This stimulus evoked calcium influx can be manipulated by application of calcium channel blockers, as well as sodium and potassium channel blockers. This leads to the conclusion that sodium and potassium channels provide the apical membrane conductance that allows depolarisation of the membrane and activation of the presynaptic calcium channels. In the last two chapters, the issue of spontaneous activity of the afferent nerve fibre is addressed. It is studied whether this spontaneous spike activity arises from continuous neurotransmitter release of the electroreceptor cells, or if it is a property of the nerve itself. The transmission of the receptor cells and the afferent nerve is blocked by application of the neurotoxin tetanus toxin. The results show disappearance of stimulus evoked activity, while the spontaneous activity continues. The conclusion is that the spontaneous activity is generated by the nerve fibre itself. The occurrence of the spontaneous activity is implemented in a mathematical model of the afferent nerve fibre. The model is based on the extensive branching pattern of the afferent fibre. The branching pattern is revealed by an immunocytochemical staining and shows extensive converging. Multiple synapses are present between the single nerve afferent and each of the approximately 20 electroreceptor cells of the organ. The model predicts that the convergence within each organ leads to increased sensitivity

Human immunodeficiency virus continuum of care in 11 european union countries at the end of 2016 overall and by key population: Have we made progress?

Background. High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods. A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results. We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions. The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control

A highly virulent variant of HIV-1 circulating in the Netherlands.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log <sub>10</sub> increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence