2,353 research outputs found
Pulmonary intravascular macrophages: Prime suspects as cellular mediators of porcine CARPA
Pigs provide a highly sensitive and quantitative in vivo model for complement (C) activation-related pseudoallergy (CARPA), a hypersensitivity reaction caused by some state-of-art nanomedicines. In an effort to understand the mechanism of the pigs' unique sensitivity for CARPA, this review focuses on pulmonary intravascular macrophages (PIMs), which are abundantly present in the lung of pigs. These cells represent a macrophage subpopulation whose unique qualities explain the characteristic symptoms of CARPA in this species, most importantly the rapidly (within minutes) developing pulmonary vasoconstriction, leading to elevation of pulmonary arterial pressure. The unique qualities of PIM cells include the following; 1) they are strongly adhered to the capillary walls via desmosome-like intercellular adhesion plaques, which secure stable and lasting direct exposition of the bulk of these cells to the blood stream; 2) their ruffled surface engaged in intense phagocytic activity ensures efficient binding and phagocytosis of nanoparticles; 3) PIM cells express anaphylatoxin receptors, this way C activation can trigger these cells, 4) they also express pattern recognition molecules on their surface, whose engagement with certain coated nanoparticles may also activate these cells or act in synergy with anaphylatoxins and, finally 5) their high metabolic activity and capability for immediate secretion of vasoactive mediators upon stimulation explain the circulatory blockage and other robust physiological effects that their stimulation may cause. These qualities taken together with reports on liposome uptake by PIM cells during CARPA and the possible presence of these cells in human lung suggests that PIM cells may be a potential therapeutic target against CARPA. © 2015 by De Gruyter
Dynamic clamp with StdpC software
Dynamic clamp is a powerful method that allows the introduction of artificial electrical components into target cells to simulate ionic conductances and synaptic inputs. This method is based on a fast cycle of measuring the membrane potential of a cell, calculating the current of a desired simulated component using an appropriate model and injecting this current into the cell. Here we present a dynamic clamp protocol using free, fully integrated, open-source software (StdpC, for spike timing-dependent plasticity clamp). Use of this protocol does not require specialist hardware, costly commercial software, experience in real-time operating systems or a strong programming background. The software enables the configuration and operation of a wide range of complex and fully automated dynamic clamp experiments through an intuitive and powerful interface with a minimal initial lead time of a few hours. After initial configuration, experimental results can be generated within minutes of establishing cell recording
Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells
Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization
A Mathematical model for Astrocytes mediated LTP at Single Hippocampal Synapses
Many contemporary studies have shown that astrocytes play a significant role
in modulating both short and long form of synaptic plasticity. There are very
few experimental models which elucidate the role of astrocyte over Long-term
Potentiation (LTP). Recently, Perea & Araque (2007) demonstrated a role of
astrocytes in induction of LTP at single hippocampal synapses. They suggested a
purely pre-synaptic basis for induction of this N-methyl-D- Aspartate (NMDA)
Receptor-independent LTP. Also, the mechanisms underlying this pre-synaptic
induction were not investigated. Here, in this article, we propose a
mathematical model for astrocyte modulated LTP which successfully emulates the
experimental findings of Perea & Araque (2007). Our study suggests the role of
retrograde messengers, possibly Nitric Oxide (NO), for this pre-synaptically
modulated LTP.Comment: 51 pages, 15 figures, Journal of Computational Neuroscience (to
appear
Study of ZÎł events and limits on anomalous ZZÎł and Zγγ couplings in ppÌ collisions at s=1.96TeV
We present a measurement of the ZÎł production cross section and limits on anomalous ZZÎł and Zγγ couplings for form-factor scales of Î=750 and 1000 GeV. The measurement is based on 138 (152) candidates in the eeÎł (ÎŒÎŒÎł) final state using 320(290)pb-1 of ppÌ collisions at s=1.96TeV. The 95% C.L. limits on real and imaginary parts of individual anomalous couplings are |h10,30Z|<0.23, |h20,40Z|<0.020, |h10,30Îł|<0.23, and |h20,40Îł|<0.019 for Î=1000GeV. © 2005 The American Physical Society
Investigating the Role of Islet Cytoarchitecture in Its Oscillation Using a New ÎČ-Cell Cluster Model
The oscillatory insulin release is fundamental to normal glycemic control. The basis of the oscillation is the intercellular coupling and bursting synchronization of ÎČ cells in each islet. The functional role of islet ÎČ cell mass organization with respect to its oscillatory bursting is not well understood. This is of special interest in view of the recent finding of islet cytoarchitectural differences between human and animal models. In this study we developed a new hexagonal closest packing (HCP) cell cluster model. The model captures more accurately the real islet cell organization than the simple cubic packing (SCP) cluster that is conventionally used. Using our new model we investigated the functional characteristics of ÎČ-cell clusters, including the fraction of cells able to burst fb, the synchronization index λ of the bursting ÎČ cells, the bursting period Tb, the plateau fraction pf, and the amplitude of intracellular calcium oscillation [Ca]. We determined their dependence on cluster architectural parameters including number of cells nÎČ, number of inter-ÎČ cell couplings of each ÎČ cell nc, and the coupling strength gc. We found that at low values of nÎČ, nc and gc, the oscillation regularity improves with their increasing values. This functional gain plateaus around their physiological values in real islets, at nÎČâŒ100, ncâŒ6 and gcâŒ200 pS. In addition, normal ÎČ-cell clusters are robust against significant perturbation to their architecture, including the presence of non-ÎČ cells or dead ÎČ cells. In clusters with nÎČ>âŒ100, coordinated ÎČ-cell bursting can be maintained at up to 70% of ÎČ-cell loss, which is consistent with laboratory and clinical findings of islets. Our results suggest that the bursting characteristics of a ÎČ-cell cluster depend quantitatively on its architecture in a non-linear fashion. These findings are important to understand the islet bursting phenomenon and the regulation of insulin secretion, under both physiological and pathological conditions
Three-Dimensional Geometric Analysis of Felid Limb Bone Allometry
Studies of bone allometry typically use simple measurements taken in a small number of locations per bone; often the midshaft diameter or joint surface area is compared to body mass or bone length. However, bones must fulfil multiple roles simultaneously with minimum cost to the animal while meeting the structural requirements imposed by behaviour and locomotion, and not exceeding its capacity for adaptation and repair. We use entire bone volumes from the forelimbs and hindlimbs of Felidae (cats) to investigate regional complexities in bone allometry.Computed tomographic (CT) images (16435 slices in 116 stacks) were made of 9 limb bones from each of 13 individuals of 9 feline species ranging in size from domestic cat (Felis catus) to tiger (Panthera tigris). Eleven geometric parameters were calculated for every CT slice and scaling exponents calculated at 5% increments along the entire length of each bone. Three-dimensional moments of inertia were calculated for each bone volume, and spherical radii were measured in the glenoid cavity, humeral head and femoral head. Allometry of the midshaft, moments of inertia and joint radii were determined. Allometry was highly variable and related to local bone function, with joint surfaces and muscle attachment sites generally showing stronger positive allometry than the midshaft.Examining whole bones revealed that bone allometry is strongly affected by regional variations in bone function, presumably through mechanical effects on bone modelling. Bone's phenotypic plasticity may be an advantage during rapid evolutionary divergence by allowing exploitation of the full size range that a morphotype can occupy. Felids show bone allometry rather than postural change across their size range, unlike similar-sized animals
A biophysical model of endocannabinoid-mediated short term depression in hippocampal inhibition
Memories are believed to be represented in the synaptic pathways of vastly interconnected networks of neurons. The
plasticity of synapses, that is, their strengthening and weakening depending on neuronal activity, is believed to be the basis
of learning and establishing memories. An increasing number of studies indicate that endocannabinoids have a widespread
action on brain function through modulation of synapâtic transmission and plasticity. Recent experimental studies have
characterised the role of endocannabinoids in mediating both short- and long-term synaptic plasticity in various brain
regions including the hippocampus, a brain region strongly associated with cognitive functions, such as learning and
memory. Here, we present a biophysically plausible model of cannabinoid retrograde signalling at the synaptic level and
investigate how this signalling mediates depolarisation induced suppression of inhibition (DSI), a prominent form of shortterm
synaptic depression in inhibitory transmission in hippocampus. The model successfully captures many of the key
characteristics of DSI in the hippocampus, as observed experimentally, with a minimal yet sufficient mathematical
description of the major signalling molecules and cascades involved. More specifically, this model serves as a framework to
test hypotheses on the factors determining the variability of DSI and investigate under which conditions it can be evoked.
The model reveals the frequency and duration bands in which the post-synaptic cell can be sufficiently stimulated to elicit
DSI. Moreover, the model provides key insights on how the state of the inhibitory cell modulates DSI according to its firing
rate and relative timing to the post-synaptic activation. Thus, it provides concrete suggestions to further investigate
experimentally how DSI modulates and is modulated by neuronal activity in the brain. Importantly, this model serves as a
stepping stone for future deciphering of the role of endocannabinoids in synaptic transmission as a feedback mechanism
both at synaptic and network level
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at â s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fbâ1 of â s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
Comparing the efficacy of metronome beeps and stepping stones to adjust gait: steps to follow!
Acoustic metronomes and visual targets have been used in rehabilitation practice to improve pathological gait. In addition, they may be instrumental in evaluating and training instantaneous gait adjustments. The aim of this study was to compare the efficacy of two cue types in inducing gait adjustments, viz. acoustic temporal cues in the form of metronome beeps and visual spatial cues in the form of projected stepping stones. Twenty healthy elderly (aged 63.2 ± 3.6 years) were recruited to walk on an instrumented treadmill at preferred speed and cadence, paced by either metronome beeps or projected stepping stones. Gait adaptations were induced using two manipulations: by perturbing the sequence of cues and by imposing switches from one cueing type to the other. Responses to these manipulations were quantified in terms of step-length and step-time adjustments, the percentage correction achieved over subsequent steps, and the number of steps required to restore the relation between gait and the beeps or stepping stones. The results showed that perturbations in a sequence of stepping stones were overcome faster than those in a sequence of metronome beeps. In switching trials, switching from metronome beeps to stepping stones was achieved faster than vice versa, indicating that gait was influenced more strongly by the stepping stones than the metronome beeps. Together these results revealed that, in healthy elderly, the stepping stones induced gait adjustments more effectively than did the metronome beeps. Potential implications for the use of metronome beeps and stepping stones in gait rehabilitation practice are discussed
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