Triphenyltin and intra-axonal Ca2+ mobilization

Triphenyltin (TPT) is an organotin compound causing environmental hazard to many wild creatures. Our previous findings show that TPT increases of the frequency of spontaneous glycinergic inhibitory postsynaptic currents (sIPSCs) in rat spinal neurons without changing the amplitude and 1/e decay time. In our study, the effects of 2-aminoethoxydiphenyl borate (2-APB), dantrolene sodium, and thapsigargin on sIPSC frequency were examined to reveal the contribution of intra-axonal Ca2+ mobilization by adding TPT. 2-APB considerably attenuated the TPT-induced facilitation of sIPSC frequency while dantrolene almost completely masked the TPT effects, suggesting that the TPT-induced synaptic facilitation results from the activation of both IP3 and ryanodine receptors on endoplasmic reticulum (ER) membrane, though inositol triphosphate (IP3) receptor is less sensitive to TPT. Thapsigargin itself significantly increased the sIPSC frequency without affecting the current amplitude and decay time. Successive addition of TPT could not further increase the sIPSC frequency in the presence of thapsigargin, indicating that thapsigargin completely masked the facilitatory action of TPT. Results suggest that TPT activates the IP3 and ryanodine receptors while TPT inhibits the Ca2+-pump of ER membranes, resulting in the elevation of intra-axonal Ca2+ levels, leading to the increase of spontaneous glycine release from synaptic vesicles

Triphenyltin and glycinergic transmission

Glycine is a fast inhibitory transmitter like γ-aminobutyric acid in the mammalian spinal cord and brainstem, and it is involved in motor reflex, nociception, and neuronal development. Triphenyltin (TPT) is an organometallic compound causing environmental hazard to many wild creatures. Our previous findings show that TPT ultimately induces a drain and/or exhaustion of glutamate in excitatory presynaptic nerve terminals, resulted in blockage of neurotransmission as well as methylmercury. Therefore, we have investigated the neurotoxic mechanism how TPT modulates inhibitory glycinergic transmission in the synaptic bouton preparation of rat isolated spinal neurons using a patch clamp technique. TPT at environmentally relevant concentrations (3–300 nM) significantly increased the number of frequency of glycinergic spontaneous and miniature inhibitory postsynaptic currents (sIPSC and mIPSC) without affecting the current amplitude and decay time. The TPT effects were also observed in external Ca2+-free solution containing tetrodotoxin (TTX) but removed in Ca2+-free solution with both TTX and BAPTA-AM (Ca2+ chelator). On the other hand, the amplitude of glycinergic evoked inhibitory postsynaptic currents (eIPSCs) increased with decreasing failure rate (Rf) and paired pulse ratio (PPR) in the presence of 300 nM TPT. At a high concentration (1 μM), TPT completely blocked eIPSCs after a transient facilitation. Overall, these results suggest that TPT directly acts transmitter-releasing machinery in glycinergic nerve terminals. Effects of TPT on the nerve terminals releasing fast transmitters were greater in the order of glycinergic > glutamatergic > GABAergic ones. Thus, TPT is supposed to cause a strong synaptic modulations on glycinergic neurotransmission in wild creatures

Neutrophil and lymphocyte responses to oral Streptococcus in Adamantiades-Behcet's disease

Immune reactions against microorganisms play an important pathogenic role in Adamantiades-Behçet’s disease (ABD). We had previously obtained Streptococcus sanguinis (strain BD113-20) isolated from the oral cavity of patients with ABD. To investigate the pathogenesis of this isolate, we examined neutrophil 5 reactions and level of cytokine production by lymphocytes after stimulation with the strain. The reactions of neutrophils were examined by chemiluminescence assay using whole blood. The amounts of interferon gamma (IFN-g) and interleukin (IL)-4, IL-8, IL-10, and IL-12 produced by peripheral blood mononuclear cells (PBMCs) were measured by ELISA. 10 Strain BD113-20 activated neutrophils from patients with ABD and healthy volunteers, and, in addition it increased IFN-g production by lymphocytes. Lymphocyte from the patients with ABD showed a dominant T helper 1 (Th-1) immune response. Results indicated that both bacterial stimulation and host hypersensitivity might be involved in the symptoms and pathogenesis of ABD

Involvement of (pro)renin receptor in the glomerular filtration barrier

(Pro)renin receptor-bound prorenin not only causes the generation of angiotensin II via the nonproteolytic activation of prorenin, it also activates the receptor’s own intracellular signaling pathways independent of the generated angiotensin II. Within the kidneys, the (pro)renin receptor is not only present in the glomerular mesangium, it is also abundant in podocytes, which play an important role in the maintenance of the glomerular filtration barrier. Recent in vivo studies have demonstrated that the overexpression of the (pro)renin receptor to a degree similar to that observed in hypertensive rat kidneys leads to slowly progressive nephropathy with proteinuria. In addition, the handle region peptide, which acts as a decoy peptide and competitively inhibits the binding of prorenin to the receptor, is more beneficial than an angiotensin-converting enzyme inhibitor with regard to alleviating proteinuria and glomerulosclerosis in experimental animal models of diabetes and essential hypertension. Thus, the (pro)renin receptor may be upregulated in podocytes under hypertensive conditions and may contribute to the breakdown of the glomerular filtration barrier

Generation and calibration of transit hyperpaths

This paper introduces a new discrete choice model aimed at describing behaviour of public transport passengers at stops. We assume that passengers choose a set of buses from which they take the first arriving. This leads to a nested model formulation in which the upper level (choice set formation) is based on utility maximisation. The lower level choice of a specific bus from the choice set is given by the frequency distribution of the bus arrivals. We further consider hyperpath characteristics in the choice set formulation which means that the utility of the choice set in general increases with the addition of further options due to a reduction in the reduced waiting time. We discuss model properties and apply our model to some selected OD pairs of the bus network of a local city in Japan where we could observe passenger behaviour due to the availability of smart card data. We find that choice sets vary fairly significantly between some passenger groups and discuss implications for transit assignment models

Using Bus Probe Data for Analysis of Travel Time Variability

The rapid progress of information technology (IT) may provide us with new insights into understanding traffic phenomena, and could help mitigate traffic problems. One of the key applications of IT to traffic and transport analysis is the identification of the location of moving objects using the Global Positioning System (GPS). It is expected that detailed traffic analysis could be carried out using these data. In this article, we first summarize the various applications of probe data in transport analysis. GPS data are merely a sequence of locations, and further data transformation such as map-matching, data-reduction, processing, and reporting is needed to use them effectively. We then discuss the application of bus probe data to evaluating travel time variability and the level of service (LOS) of roads. A methodology for evaluating the road network from the viewpoint of travel time stability and reliability using bus probe data is proposed. Travel time distributions of arbitrary routes are estimated by statistically summing up directly observed multiple travel time distributions. Based on the development of methodologies to estimate travel time distributions of arbitrary routes covered by the bus probe survey, this study proposes an approach to evaluate the LOS of road networks based on the concept of travel time reliability

Using Bus Probe Data for Analysis of Travel Time Variability

The rapid progress of information technology (IT) may provide us with new insights into understanding traffic phenomena, and could help mitigate traffic problems. One of the key applications of IT to traffic and transport analysis is the identification of the location of moving objects using the Global Positioning System (GPS). It is expected that detailed traffic analysis could be carried out using these data. In this article, we first summarize the various applications of probe data in transport analysis. GPS data are merely a sequence of locations, and further data transformation such as map-matching, data-reduction, processing, and reporting is needed to use them effectively. We then discuss the application of bus probe data to evaluating travel time variability and the level of service (LOS) of roads. A methodology for evaluating the road network from the viewpoint of travel time stability and reliability using bus probe data is proposed. Travel time distributions of arbitrary routes are estimated by statistically summing up directly observed multiple travel time distributions. Based on the development of methodologies to estimate travel time distributions of arbitrary routes covered by the bus probe survey, this study proposes an approach to evaluate the LOS of road networks based on the concept of travel time reliability