343 research outputs found
Gap junctions, dendrites and resonances : a recipe for tuning network dynamics
Get PDFGap junctions, also referred to as electrical synapses, are expressed along the entire central nervous system and are important in mediating various brain rhythms in both normal and pathological states. These connections can form between the dendritic trees of individual cells. Many dendrites express membrane channels that confer on them a form of sub-threshold resonant dynamics. To obtain insight into the modulatory role of gap junctions in tuning networks of resonant dendritic trees, we generalise the “sum-over-trips” formalism for calculating the response function of a single branching dendrite to a gap junctionally coupled network. Each cell in the network is modelled by a soma connected to an arbitrary structure of dendrites with resonant membrane. The network is treated as a single extended tree structure with dendro-dendritic gap junction coupling. We present the generalised “sum-over-trips” rules for constructing the network response function in terms of a set of coefficients defined at special branching, somatic and gap-junctional nodes. Applying this framework to a two-cell network, we construct compact closed form solutions for the network response function in the Laplace (frequency) domain and study how a preferred frequency in each soma depends on the location and strength of the gap junction
Editorial for special issue on neurodynamics
Get PDF“Neurodynamics” is an interdisciplinary area of mathematics where dynamical systems theory (deterministic and stochastic) is the primary tool for elucidating the fundamental mechanisms responsible for the behaviour of neural systems (whether biological or synthetic). A meeting on this topic was held at the International Centre for Mathematical Sciences in Edinburgh from March 5–7 in 2012. In this special issue, we have invited seven of the main contributors to this event to expand on their presentations and highlight the use of mathematics in understanding the dynamics of neural systems
Computational convergence of the path integral for real dendritic morphologies
Get PDFNeurons are characterised by a morphological structure unique amongst biological cells, the core of which is the dendritic tree. The vast number of dendritic geometries, combined with heterogeneous properties of the cell membrane, continue to challenge scientists in predicting neuronal input-output relationships, even in the case of sub-threshold dendritic currents. The Green’s function obtained for a given dendritic geometry provides this functional relationship for passive or quasi-active dendrites and can be constructed by a sum-over-trips approach based on a path integral formalism. In this paper, we introduce a number of efficient algorithms for realisation of the sum-over-trips framework and investigate the convergence of these algorithms on different dendritic geometries. We demonstrate that the convergence of the trip sampling methods strongly depends on dendritic morphology as well as the biophysical properties of the cell membrane. For real morphologies, the number of trips to guarantee a small convergence error might become very large and strongly affect computational efficiency. As an alternative, we introduce a highly-efficient matrix method which can be applied to arbitrary branching structures
Monocationic μ-diborolyl triple-decker complexes [CpCo(μ-1,3-C 3B2Me5)M(ring)]+: Synthesis, structures, and electrochemistry
No full textCationic triple-decker complexes with a bridging diborolyl ligand, [CpCo(μ-1,3-C3B2Me5)M(ring)]+ (M(ring) = CoCp (2a), CoCp* (2b), RhCp (3a), RhCp* (3b), IrCp (4a), IrCp* (4b), Ru(C6H6) (5a), Ru(p-MeC 6H4Pri) (5b), Ru(C6Me6) (5c), Ru(η6-cycloheptatriene) (6)), were synthesized by reaction of CpCo(μ-1,3-C3B2Me5)Tl with [M(ring)Hal2]2. The structures of 2aBPh4, 2bPF6, 4aPF6, 5aOTf, and 5cPF6 were determined by X-ray diffraction. The electron-transfer ability of the complexes has been ascertained by electrochemical and spectroelectrochemical techniques. In general, they are able to shuttle reversibly in the sequence 2+/+/0/-, plausibly affording completely delocalized mixed-valence derivatives. DFT calculations revealed structural changes accompanying redox processes and satisfactorily predicted the potentials for the first reduction and first oxidation. © 2013 American Chemical Society
Are interleukin-16 and thrombopoietin new tolls for the in vitro generation of dendritic cells?
Get PDFThe effects of interleukin 16 (IL-16) on dendritic cell (DC) generation from human CD34+ progenitor cells are not known. Here, we show that IL-16 added to a basal cocktail comprised of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, Flt-3 ligand (Flt3L), and tumor necrosis factor α (TNF-α) does induce the CD34+ hematopoietic cells to proliferate in vitro and to differentiate into phenotypically and functionally mature DCs. IL-16 exerts this function more efficiently than stem cell factor (SCF) as a control, thrombopoietin (TPO), or IL-16 plus TPO. Moreover, we show that the combination of IL-16 plus TPO induces the generation of tolerogenic DCs, able to induce an anergic state in T cells that persists when T cells are rechallenged with immunogenic DCs. An altered pattern of cytokine production, a reduced expression of the C-type lectin DC-SIGN, and an increased surface expression of the inhibitory molecules immunoglobulin-like transcript 2 (ILT-2), ILT-3, and ILT-4 may all contribute to confer the tolerogenic properties of these DCs. Generation of tolerogenic DCs may aid the exploration of new therapeutic strategies to promote tolerance to autoantigens and prevent disease development. (Blood. 2004;104:4020-4028
Role of naïve-derived T memory stem cells in T cell reconstitution following allogeneic transplantation
No full textEarly T cell reconstitution following allogeneic transplantation depends on the persistence and function of T cells that are adoptively transferred with the graft. Post-transplant cyclophosphamide (pt-Cy) effectively prevents alloreactive responses from unmanipulated grafts, but its effect on subsequent immune reconstitution remains undetermined. Here we show that T memory stem cells (TSCM), which demonstrated superior reconstitution capacity in preclinical models, are the most abundant circulating T cell population in the early days following haploidentical transplantation combined with pt-Cy, and precede the expansion of effector cells. Transferred naïve, but not TSCM or conventional memory cells preferentially survive cyclophosphamide, thus suggesting that post-transplant TSCM cells originate from naïve precursors. Moreover, donor naïve T cells specific for exogenous and self/tumor antigens persist in the host and contribute to peripheral reconstitution by differentiating into effectors. Similarly, pathogen-specific memory T cells generated detectable recall responses but only in the presence of the cognate antigen. We thus define the cellular basis of T cell reconstitution following pt-Cy at the antigen-specific level and propose to explore naïve-derived TSCM cells in the clinical setting to overcome immunodeficiency
Desensitization with plasma exchange in a patient with human leukocyte antigen donor-specific antibodies before T-cell-replete haploidentical transplantation
No full textBACKGROUND The presence of human leukocyte antigen donor-specific antibodies (DSAs) increases the risk of graft failure in T-cell-replete haploidentical hematopoietic stem cell transplantation (haplo-HSCT) CASE REPORT A 49-year-old female with high-risk acute myeloid leukemia in first complete remission received a haplo-HSCT from her daughter. Pretransplant recipient screening examination showed high DSAs levels against unshared class I leukocyte antigens. RESULTS The patient underwent a desensitization program consisting of plasma exchange (PEX), polyvalent intravenous (IV) immunoglobulins, and IV tacrolimus and mycophenolate mofetil (MMF). This protocol resulted in the disappearance of the DSA anti HLA B41. Engraftment was prompt with stable full donor chimerism. CONCLUSIONS This case report suggests that the adopted scheme is safe for reducing DSA levels and facilitating donor engraftment in patients scheduled for haplo-HSCT
Branching dendrites with resonant membrane: a “sum-over-trips” approach
Get PDFDendrites form the major components of neurons. They are complex branching structures that receive and process thousands of synaptic inputs from other neurons. It is well known that dendritic morphology plays an important role in the function of dendrites. Another important contribution to the response characteristics of a single neuron comes from the intrinsic resonant properties of dendritic membrane. In this paper we combine the effects of dendritic branching and resonant membrane dynamics by generalising the “sum-over-trips” approach (Abbott et al. in Biol Cybernetics 66, 49–60 1991). To illustrate how this formalism can shed light on the role of architecture and resonances in determining neuronal output we consider dual recording and reconstruction data from a rat CA1 hippocampal pyramidal cell. Specifically we explore the way in which an Ih current contributes to a voltage overshoot at the soma
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