Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed

Evaluation of a group based cognitive behavioural therapy programme for menstrual pain management in young women with intellectual disabilities: protocol for a mixed methods controlled clinical trial

BACKGROUND: Menstrual pain which is severe enough to impact on daily activities is very common amongst menstruating females. Research suggests that menstrual pain which impacts on daily functioning may be even more prevalent amongst those with intellectual disabilities. Despite this, little research attention has focused on pain management programmes for those with intellectual disabilities. The aims of this pilot study were to develop and evaluate a theory-based cognitive behavioural therapy (CBT) programme for menstrual pain management in young women with intellectual disabilities. METHODS/DESIGN: The study utilised a mixed methods controlled clinical trial to evaluate elements from a CBT programme called Feeling Better (McGuire & McManus, 2010). The Feeling Better programme is a modular, manualised intervention designed for people with an intellectual disability and their carers. The programme was delivered to 36 young women aged 12 – 30 years who have a Mild - Moderate Intellectual Disability, split between two conditions. The treatment group received the Feeling Better intervention and the control group received treatment as usual. To evaluate the effectiveness of the programme, measures were taken of key pain variables including impact, knowledge, self-efficacy and coping. Process evaluation was conducted to examine which elements of the programme were most successful in promoting change. DISCUSSION: Participants in the intervention group were expected to report the use of a greater number of coping strategies and have greater knowledge of pain management strategies following participation in the intervention and at three month follow-up, when compared to control group participants. A significant advantage of the study was the use of mixed methods and inclusion of process evaluation to determine which elements of a cognitive behavioural therapy programme work best for individuals with intellectual disabilities. TRIAL REGISTRATION: Current Controlled Trials ISRCTN7556775

Caveolin-1 enhances resveratrol-mediated cytotoxicity and transport in a hepatocellular carcinoma model

<p>Abstract</p> <p>Background</p> <p>Resveratrol (RES), an estrogen analog, is considered as a potential cancer chemo-preventive agent. However, it remains unclear how RES is transported into cells. In this study, we observed that Caveolin-1(CAV1) expression can increase the cytotoxic and pro-apoptotic activity of RES in a dose- and time-dependent manner both <it>in vitro </it>and <it>in vivo </it>in a Hepatocellular Carcinoma animal model.</p> <p>Methods</p> <p>High performance liquid chromatography (HPLC) demonstrated that RES intra-cellular concentration is increased about 2-fold in cells stably expressing CAV1 or CAVM1 (a scaffolding domain (81-101AA)-defective CAV1 mutant) compared to the untransduced human Hepatoblastoma cell line (HepG2) or after transduction with the green fluorescent protein (GFP) control vector. The increased intra-cellular transport of RES was abolished in cells stably expressing CAVM2 (a cholesterol shuttle domain (143-156AA)-defective CAV1 mutant) or CAVRNAi. In order to further characterize CAV1-dependent RES transport, we synthesized RES-dansyl chloride derivatives as fluorescent probes to visualize the transport process, which demonstrated a distribution consistent with that of CAV1 in HepG2 cells.</p> <p>Results</p> <p>In addition, RES endocytosis was not mediated by estrogen receptor (ER) α and β, as suggested by lack of competitive inhibition by estrogen or Tamoxifen. Pathway analysis showed that RES can up-regulate the expression of endogenous CAV1; this activates further the MAPK pathway and caspase-3 expression.</p> <p>Discussion</p> <p>This study provides novel insights about the role played by CAV1 in modulating cellular sensitivity to RES through enhancement of its internalization and trafficking.</p

Computational modeling with spiking neural networks

This chapter reviews recent developments in the area of spiking neural networks (SNN) and summarizes the main contributions to this research field. We give background information about the functioning of biological neurons, discuss the most important mathematical neural models along with neural encoding techniques, learning algorithms, and applications of spiking neurons. As a specific application, the functioning of the evolving spiking neural network (eSNN) classification method is presented in detail and the principles of numerous eSNN based applications are highlighted and discussed

Balancing Feed-Forward Excitation and Inhibition via Hebbian Inhibitory Synaptic Plasticity

It has been suggested that excitatory and inhibitory inputs to cortical cells are balanced, and that this balance is important for the highly irregular firing observed in the cortex. There are two hypotheses as to the origin of this balance. One assumes that it results from a stable solution of the recurrent neuronal dynamics. This model can account for a balance of steady state excitation and inhibition without fine tuning of parameters, but not for transient inputs. The second hypothesis suggests that the feed forward excitatory and inhibitory inputs to a postsynaptic cell are already balanced. This latter hypothesis thus does account for the balance of transient inputs. However, it remains unclear what mechanism underlies the fine tuning required for balancing feed forward excitatory and inhibitory inputs. Here we investigated whether inhibitory synaptic plasticity is responsible for the balance of transient feed forward excitation and inhibition. We address this issue in the framework of a model characterizing the stochastic dynamics of temporally anti-symmetric Hebbian spike timing dependent plasticity of feed forward excitatory and inhibitory synaptic inputs to a single post-synaptic cell. Our analysis shows that inhibitory Hebbian plasticity generates ‘negative feedback’ that balances excitation and inhibition, which contrasts with the ‘positive feedback’ of excitatory Hebbian synaptic plasticity. As a result, this balance may increase the sensitivity of the learning dynamics to the correlation structure of the excitatory inputs

Gray zones around diffuse large B cell lymphoma. Conclusions based on the workshop of the XIV meeting of the European Association for Hematopathology and the Society of Hematopathology in Bordeaux, France

The term “gray-zone” lymphoma has been used to denote a group of lymphomas with overlapping histological, biological, and clinical features between various types of lymphomas. It has been used in the context of Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL), including classical HL (CHL), and primary mediastinal large B cell lymphoma, cases with overlapping features between nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B cell lymphoma, CHL, and Epstein–Barr-virus-positive lymphoproliferative disorders, and peripheral T cell lymphomas simulating CHL. A second group of gray-zone lymphomas includes B cell NHL with intermediate features between diffuse large B cell lymphoma and classical Burkitt lymphoma. In order to review controversial issues in gray-zone lymphomas, a joint Workshop of the European Association for Hematopathology and the Society for Hematopathology was held in Bordeaux, France, in September 2008. The panel members reviewed and discussed 145 submitted cases and reached consensus diagnoses. This Workshop summary is focused on the most controversial aspects of gray-zone lymphomas and describes the panel’s proposals regarding diagnostic criteria, terminology, and new prognostic and diagnostic parameters

An overview of the recent developments on fructooligosaccharide production and applications

Over the past years, many researchers have suggested that deficiencies in the diet can lead to disease states and that some diseases can be avoided through an adequate intake of relevant dietary components. Recently, a great interest in dietary modulation of the human gut has been registered. Prebiotics, such as fructooligosaccharides (FOS), play a key role in the improvement of gut microbiota balance and in individual health. FOS are generally used as components of functional foods, are generally regarded as safe (generally recognized as safe status—from the Food and Drug Administration, USA), and worth about 150€ per kilogram. Due to their nutrition- and health-relevant properties, such as moderate sweetness, low carcinogenicity, low calorimetric value, and low glycemic index, FOS have been increasingly used by the food industry. Conventionally, FOS are produced through a two-stage process that requires an enzyme production and purification step in order to proceed with the chemical reaction itself. Several studies have been conducted on the production of FOS, aiming its optimization toward the development of more efficient production processes and their potential as food ingredients. The improvement of FOS yield and productivity can be achieved by the use of different fermentative methods and different microbial sources of FOS producing enzymes and the optimization of nutritional and culture parameter; therefore, this review focuses on the latest progresses in FOS research such as its production, functional properties, and market data.Agencia de Inovacao (AdI)-Project BIOLIFE reference PRIME 03/347. Ana Dominguez acknowledges Fundacao para a Ciencia e a Tecnologia, Portugal, for her PhD grant reference SFRH/BD/23083/2005

25th Annual Computational Neuroscience Meeting: CNS-2016

Abstracts of the 25th Annual Computational Neuroscience Meeting: CNS-2016 Seogwipo City, Jeju-do, South Korea. 2–7 July 201