The cys-loop ligand-gated ion channel gene superfamily of the nematode, Caenorhabditis elegans

The nematode, Caenorhabditis elegans, possesses the most extensive known superfamily of cys-loop ligand-gated ion channels (cys-loop LGICs) consisting of 102 subunit-encoding genes. Less than half of these genes have been functionally characterised which include cation-permeable channels gated by acetylcholine (ACh) and γ-aminobutyric acid (GABA) as well as anion-selective channels gated by ACh, GABA, glutamate and serotonin. Following the guidelines set for genetic nomenclature for C. elegans, we have designated unnamed subunits as lgc genes (ligand-gated ion channels of the cys-loop superfamily). Phylogenetic analysis shows that several of these lgc subunits form distinct groups which may represent novel cys-loop LGIC subtypes

A comparative analysis of predictive models of morbidity in intensive care unit after cardiac surgery – Part I: model planning

<p>Abstract</p> <p>Background</p> <p>Different methods have recently been proposed for predicting morbidity in intensive care units (ICU). The aim of the present study was to critically review a number of approaches for developing models capable of estimating the probability of morbidity in ICU after heart surgery. The study is divided into two parts. In this first part, popular models used to estimate the probability of class membership are grouped into distinct categories according to their underlying mathematical principles. Modelling techniques and intrinsic strengths and weaknesses of each model are analysed and discussed from a theoretical point of view, in consideration of clinical applications.</p> <p>Methods</p> <p>Models based on Bayes rule, <it>k-</it>nearest neighbour algorithm, logistic regression, scoring systems and artificial neural networks are investigated. Key issues for model design are described. The mathematical treatment of some aspects of model structure is also included for readers interested in developing models, though a full understanding of mathematical relationships is not necessary if the reader is only interested in perceiving the practical meaning of model assumptions, weaknesses and strengths from a user point of view.</p> <p>Results</p> <p>Scoring systems are very attractive due to their simplicity of use, although this may undermine their predictive capacity. Logistic regression models are trustworthy tools, although they suffer from the principal limitations of most regression procedures. Bayesian models seem to be a good compromise between complexity and predictive performance, but model recalibration is generally necessary. <it>k</it>-nearest neighbour may be a valid non parametric technique, though computational cost and the need for large data storage are major weaknesses of this approach. Artificial neural networks have intrinsic advantages with respect to common statistical models, though the training process may be problematical.</p> <p>Conclusion</p> <p>Knowledge of model assumptions and the theoretical strengths and weaknesses of different approaches are fundamental for designing models for estimating the probability of morbidity after heart surgery. However, a rational choice also requires evaluation and comparison of actual performances of locally-developed competitive models in the clinical scenario to obtain satisfactory agreement between local needs and model response. In the second part of this study the above predictive models will therefore be tested on real data acquired in a specialized ICU.</p

On the interpretation of removable interactions: A survey of the field 33 years after Loftus

In a classic 1978 Memory &Cognition article, Geoff Loftus explained why noncrossover interactions are removable. These removable interactions are tied to the scale of measurement for the dependent variable and therefore do not allow unambiguous conclusions about latent psychological processes. In the present article, we present concrete examples of how this insight helps prevent experimental psychologists from drawing incorrect conclusions about the effects of forgetting and aging. In addition, we extend the Loftus classification scheme for interactions to include those on the cusp between removable and nonremovable. Finally, we use various methods (i.e., a study of citation histories, a questionnaire for psychology students and faculty members, an analysis of statistical textbooks, and a review of articles published in the 2008 issue of Psychology andAging) to show that experimental psychologists have remained generally unaware of the concept of removable interactions. We conclude that there is more to interactions in a 2 × 2 design than meets the eye

Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively

An overview of tissue engineering approaches for management of spinal cord injuries

Severe spinal cord injury (SCI) leads to devastating neurological deficits and disabilities, which necessitates spending a great deal of health budget for psychological and healthcare problems of these patients and their relatives. This justifies the cost of research into the new modalities for treatment of spinal cord injuries, even in developing countries. Apart from surgical management and nerve grafting, several other approaches have been adopted for management of this condition including pharmacologic and gene therapy, cell therapy, and use of different cell-free or cell-seeded bioscaffolds. In current paper, the recent developments for therapeutic delivery of stem and non-stem cells to the site of injury, and application of cell-free and cell-seeded natural and synthetic scaffolds have been reviewed

MtDNA-maintenance defects: syndromes and genes

A large group of mitochondrial disorders, ranging from early-onset pediatric encephalopathic syndromes to late-onset myopathy with chronic progressive external ophthalmoplegia (CPEOs), are inherited as Mendelian disorders characterized by disturbed mitochondrial DNA (mtDNA) maintenance. These errors of nuclear-mitochondrial intergenomic signaling may lead to mtDNA depletion, accumulation of mtDNA multiple deletions, or both, in critical tissues. The genes involved encode proteins belonging to at least three pathways: mtDNA replication and maintenance, nucleotide supply and balance, and mitochondrial dynamics and quality control. In most cases, allelic mutations in these genes may lead to profoundly different phenotypes associated with either mtDNA depletion or multiple deletions. Communicated by: Shamima Rahman Presented at the Annual Symposium of the Society for the Study of Inborn Errors of Metabolism, Rome, Italy, September 6–9, 2016This work was supported by: ERC FP7-322424 grant (to MZ), CoEN grant 3038 (to MZ and CV) and the MRC core grant to the Mitochondrial Biology Unit

Attitude determination through image registration model and test-case for novel attitude system in low earth orbit

The mass and cost requirements of high-accuracy satellite pointing systems often inhibit the potential application of smaller and more affordable satellites. There is therefore an increasing need to develop high accuracy attitude systems that do not breach small satellite mass and cost constraints. This paper proposes a novel method of attitude determination using imagery from two canted, Earth pointing, push-broom sensors. The effects of attitude on inter-imager shifts are modelled, with model inversions proving the techniques potential, given an adequate registration scheme, for determining attitude over 3-axes. Simulated results are presented alongside real data from the Surrey Satellite Technology Ltd (SSTL) Disaster Monitoring Constellation (DMC), confirming the viability of using Earth observational cameras to measure attitude, rotation rates or onboard vibrations to a high degree of accuracy. Since the technique Is capable of working with conventional onboard imaging sensors, the implementation costs and additional payload mass of such a system are deemed negligible. Copyright © 2006 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved