Immunotronics - novel finite-state-machine architectures with built-in self-test using self-nonself differentiation

A novel approach to hardware fault tolerance is demonstrated that takes inspiration from the human immune system as a method of fault detection. The human immune system is a remarkable system of interacting cells and organs that protect the body from invasion and maintains reliable operation even in the presence of invading bacteria or viruses. This paper seeks to address the field of electronic hardware fault tolerance from an immunological perspective with the aim of showing how novel methods based upon the operation of the immune system can both complement and create new approaches to the development of fault detection mechanisms for reliable hardware systems. In particular, it is shown that by use of partial matching, as prevalent in biological systems, high fault coverage can be achieved with the added advantage of reducing memory requirements. The development of a generic finite-state-machine immunization procedure is discussed that allows any system that can be represented in such a manner to be "immunized" against the occurrence of faulty operation. This is demonstrated by the creation of an immunized decade counter that can detect the presence of faults in real tim

Embryonics: A path to artificial life?

Electronic systems, no matter how clever and intelligent they are, cannot yet demonstrate the reliability that biological systems can. Perhaps we can learn from these processes, which have developed through millions of years of evolution, in our pursuit of highly reliable systems. This article discusses how such systems, inspired by biological principles, might be built using simple embryonic cells. We illustrate how they can monitor their own functional integrity in order to protect themselves from internal failure or from hostile environmental effects and how faults caused by DNA mutation or cell death can be repaired and thus full system functionality restored. ©2006 Massachusetts Institute of Technology

A splice variant in KRT71 is associated with curly coat phenotype of Selkirk Rex cats.

One of the salient features of the domestic cat is the aesthetics of its fur. The Selkirk Rex breed is defined by an autosomal dominant woolly rexoid hair (ADWH) abnormality that is characterized by tightly curled hair shafts. A genome-wide case - control association study was conducted using 9 curly coated Selkirk Rex and 29 controls, including straight-coated Selkirk Rex, British Shorthair and Persian, to localize the Selkirk autosomal dominant rexoid locus (SADRE). Although the control cats were from different breed lineages, they share recent breeding histories and were validated as controls by Bayesian clustering, multi-dimensional scaling and genomic inflation. A significant association was found on cat chromosome B4 (Praw = 2.87 × 10(-11)), and a unique haplotype spanning ~600 Kb was found in all the curly coated cats. Direct sequencing of four candidate genes revealed a splice site variant within the KRT71 gene associated with the hair abnormality in Selkirk Rex

Construction of 3D in vitro models by bioprinting human pluripotent stem cells: Challenges and opportunities

Three-dimensional (3D) printing of biological material, or 3D bioprinting, is a rapidly expanding field with interesting applications in tissue engineering and regenerative medicine. Bioprinters use cells and biocompatible materials as an ink (bioink) to build 3D structures representative of organs and tissues, in a controlled manner and with micrometric resolution. Human embryonic (hESCs) and induced (hiPSCs) pluripotent stem cells are ideally able to provide all cell types found in the human body. A limited, but growing, number of recent reports suggest that cells derived by differentiation of hESCs and hiPSCs can be used as building blocks in bioprinted human 3D models, reproducing the cellular variety and cytoarchitecture of real tissues. In this review we will illustrate these examples, which include hepatic, cardiac, vascular, corneal and cartilage tissues, and discuss challenges and opportunities of bioprinting more demanding cell types, such as neurons, obtained from human pluripotent stem cells

Accelerated Evolution of the ASPM Gene Controlling Brain Size Begins Prior to Human Brain Expansion

Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size

ModHMM: A Modular Supra-Bayesian Genome Segmentation Method

Genome segmentation methods are powerful tools to obtain cell type or tissue-specific genome-wide annotations and are frequently used to discover regulatory elements. However, traditional segmentation methods show low predictive accuracy and their data-driven annotations have some undesirable properties. As an alternative, we developed ModHMM, a highly modular genome segmentation method. Inspired by the supra-Bayesian approach, it incorporates predictions from a set of classifiers. This allows to compute genome segmentations by utilizing state-of-the-art methodology. We demonstrate the method on ENCODE data and show that it outperforms traditional segmentation methods not only in terms of predictive performance, but also in qualitative aspects. Therefore, ModHMM is a valuable alternative to study the epigenetic and regulatory landscape across and within cell types or tissues

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

Fibronectin Contributes To Notochord Intercalation In The Invertebrate Chordate, Ciona Intestinalis

Background: Genomic analysis has upended chordate phylogeny, placing the tunicates as the sister group to the vertebrates. This taxonomic rearrangement raises questions about the emergence of a tunicate/vertebrate ancestor. Results: Characterization of developmental genes uniquely shared by tunicates and vertebrates is one promising approach for deciphering developmental shifts underlying acquisition of novel, ancestral traits. The matrix glycoprotein Fibronectin (FN) has long been considered a vertebrate-specific gene, playing a major instructive role in vertebrate embryonic development. However, the recent computational prediction of an orthologous “vertebrate-like” Fn gene in the genome of a tunicate, Ciona savignyi, challenges this viewpoint suggesting that Fn may have arisen in the shared tunicate/vertebrate ancestor. Here we verify the presence of a tunicate Fn ortholog. Transgenic reporter analysis was used to characterize a Ciona Fn enhancer driving expression in the notochord. Targeted knockdown in the notochord lineage indicates that FN is required for proper convergent extension. Conclusions: These findings suggest that acquisition of Fn was associated with altered notochord morphogenesis in the vertebrate/tunicate ancestor