Multiscale Computations on Neural Networks: From the Individual Neuron Interactions to the Macroscopic-Level Analysis

We show how the Equation-Free approach for multi-scale computations can be exploited to systematically study the dynamics of neural interactions on a random regular connected graph under a pairwise representation perspective. Using an individual-based microscopic simulator as a black box coarse-grained timestepper and with the aid of simulated annealing we compute the coarse-grained equilibrium bifurcation diagram and analyze the stability of the stationary states sidestepping the necessity of obtaining explicit closures at the macroscopic level. We also exploit the scheme to perform a rare-events analysis by estimating an effective Fokker-Planck describing the evolving probability density function of the corresponding coarse-grained observables

Addressing Corporate Ties to Slavery: Corporate Apologia in a Discourse of Reconciliation

Pressured by activists to take responsibility, American corporations recently found themselves in the spotlight for their past ties to slavery. Responding to the issue, they stepped into a complex discourse of reconciliation. Taking a rhetorical approach, this article analyzes the response of Aetna Inc. It explores how corporate rhetoric functions within present discourses about historical injustices and illustrates that Aetna\u27s response informed by common strategies of corporate apologia inhibited meaningful reconciliation. The article thus furthers criticisms of (corporate) apologia in the context of historical injustice and raises questions about the potentialities and limitations of corporate rhetoric for reconciliation

Excretory/Secretory-Products of Echinococcus multilocularis Larvae Induce Apoptosis and Tolerogenic Properties in Dendritic Cells In Vitro

Parasitic helminths are inducers of chronic diseases and have evolved mechanisms to suppress the host immune response. Mostly from studies on roundworms, a picture is currently emerging that helminths secrete factors (E/S-products) that directly act on sentinels of the immune system, dendritic cells, in order to achieve an expansion of immunosuppressive, regulatory T cells (T-reg). Parasitic helminths are currently also intensely studied as therapeutic agents against autoimmune diseases and allergies, which is directly linked to their immunosuppressive activities. The immunomodulatory products of parasitic helminths are therefore of high interest for understanding immunopathology during infections and for the treatment of allergies. The present work was conducted on larvae of the tapeworm E. multilocularis, which grow like a tumor into surrounding host tissue and thus cause the lethal disease alveolar echinococcosis. The authors found that E/S-products from early infective larvae are strong inducers of tolerogenic DC in vitro and show that E/S-products of larvae of the chronic stage lead to an in vitro expansion of Foxp3+ T cells, suggesting that both the expansion of these T cells and poorly responsive DC are important for the establishment and persistence of E. multilocularis larvae within the host

Inverse Fusion PCR Cloning

Inverse fusion PCR cloning (IFPC) is an easy, PCR based three-step cloning method that allows the seamless and directional insertion of PCR products into virtually all plasmids, this with a free choice of the insertion site. The PCR-derived inserts contain a vector-complementary 5′-end that allows a fusion with the vector by an overlap extension PCR, and the resulting amplified insert-vector fusions are then circularized by ligation prior transformation. A minimal amount of starting material is needed and experimental steps are reduced. Untreated circular plasmid, or alternatively bacteria containing the plasmid, can be used as templates for the insertion, and clean-up of the insert fragment is not urgently required. The whole cloning procedure can be performed within a minimal hands-on time and results in the generation of hundreds to ten-thousands of positive colonies, with a minimal background

Description of Hymenolepis microstoma (Nottingham strain): a classical tapeworm model for research in the genomic era

<p>Abstract</p> <p>Background</p> <p><it>Hymenolepis microstoma </it>(Dujardin, 1845) Blanchard, 1891, the mouse bile duct tapeworm, is a rodent/beetle-hosted laboratory model that has been used in research and teaching since its domestication in the 1950s. Recent characterization of its genome has prompted us to describe the specific strain that underpins these data, anchoring its identity and bringing the 150+ year-old original description up-to-date.</p> <p>Results</p> <p>Morphometric and ultrastructural analyses were carried out on laboratory-reared specimens of the 'Nottingham' strain of <it>Hymenolepis microstoma </it>used for genome characterization. A contemporary description of the species is provided including detailed illustration of adult anatomy and elucidation of its taxonomy and the history of the specific laboratory isolate.</p> <p>Conclusions</p> <p>Our work acts to anchor the specific strain from which the <it>H. microstoma </it>genome has been characterized and provides an anatomical reference for researchers needing to employ a model tapeworm system that enables easy access to all stages of the life cycle. We review its classification, life history and development, and briefly discuss the genome and other model systems being employed at the beginning of a genomic era in cestodology.</p

Loss of ZnT8 function protects against diabetes by enhanced insulin secretion.

A rare loss-of-function allele p.Arg138* in SLC30A8 encoding the zinc transporter 8 (ZnT8), which is enriched in Western Finland, protects against type 2 diabetes (T2D). We recruited relatives of the identified carriers and showed that protection was associated with better insulin secretion due to enhanced glucose responsiveness and proinsulin conversion, particularly when compared with individuals matched for the genotype of a common T2D-risk allele in SLC30A8, p.Arg325. In genome-edited human induced pluripotent stem cell (iPSC)-derived β-like cells, we establish that the p.Arg138* allele results in reduced SLC30A8 expression due to haploinsufficiency. In human β cells, loss of SLC30A8 leads to increased glucose responsiveness and reduced KATP channel function similar to isolated islets from carriers of the T2D-protective allele p.Trp325. These data position ZnT8 as an appealing target for treatment aimed at maintaining insulin secretion capacity in T2D

Macroscopic coherent structures in a stochastic neural network: from interface dynamics to coarse-grained bifurcation analysis

We study coarse pattern formation in a cellular automaton modelling a spatially-extended stochastic neural network. The model, originally proposed by Gong and Robinson (Phys Rev E 85(5):055,101(R), 2012), is known to support stationary and travelling bumps of localised activity. We pose the model on a ring and study the existence and stability of these patterns in various limits using a combination of analytical and numerical techniques. In a purely deterministic version of the model, posed on a continuum, we construct bumps and travelling waves analytically using standard interface methods from neural field theory. In a stochastic version with Heaviside firing rate, we construct approximate analytical probability mass functions associated with bumps and travelling waves. In the full stochastic model posed on a discrete lattice, where a coarse analytic description is unavailable, we compute patterns and their linear stability using equation-free methods. The lifting procedure used in the coarse time-stepper is informed by the analysis in the deterministic and stochastic limits. In all settings, we identify the synaptic profile as a mesoscopic variable, and the width of the corresponding activity set as a macroscopic variable. Stationary and travelling bumps have similar meso- and macroscopic profiles, but different microscopic structure, hence we propose lifting operators which use microscopic motifs to disambiguate them. We provide numerical evidence that waves are supported by a combination of high synaptic gain and long refractory times, while meandering bumps are elicited by short refractory times

Single Molecule Imaging Reveals Differences in Microtubule Track Selection Between Kinesin Motors

Molecular motors differentially recognize and move cargo along discrete microtubule subpopulations in cells, resulting in preferential transport and targeting of subcellular cargoes