Ontogenetic De Novo Copy Number Variations (CNVs) as a Source of Genetic Individuality: Studies on Two Families with MZD Twins for Schizophrenia

Genetic individuality is the foundation of personalized medicine, yet its determinants are currently poorly understood. One issue is the difference between monozygotic twins that are assumed identical and have been extensively used in genetic studies for decades [1]. Here, we report genome-wide alterations in two nuclear families each with a pair of monozygotic twins discordant for schizophrenia evaluated by the Affymetrix 6.0 human SNP array. The data analysis includes characterization of copy number variations (CNVs) and single nucleotide polymorphism (SNPs). The results have identified genomic differences between twin pairs and a set of new provisional schizophrenia genes. Samples were found to have between 35 and 65 CNVs per individual. The majority of CNVs (∼80%) represented gains. In addition, ∼10% of the CNVs were de novo (not present in parents), of these, 30% arose during parental meiosis and 70% arose during developmental mitosis. We also observed SNPs in the twins that were absent from both parents. These constituted 0.12% of all SNPs seen in the twins. In 65% of cases these SNPs arose during meiosis compared to 35% during mitosis. The developmental mitotic origin of most CNVs that may lead to MZ twin discordance may also cause tissue differences within individuals during a single pregnancy and generate a high frequency of mosaics in the population. The results argue for enduring genome-wide changes during cellular transmission, often ignored in most genetic analyses

The Drosophila Gap Gene Network Is Composed of Two Parallel Toggle Switches

Drosophila “gap” genes provide the first response to maternal gradients in the early fly embryo. Gap genes are expressed in a series of broad bands across the embryo during first hours of development. The gene network controlling the gap gene expression patterns includes inputs from maternal gradients and mutual repression between the gap genes themselves. In this study we propose a modular design for the gap gene network, involving two relatively independent network domains. The core of each network domain includes a toggle switch corresponding to a pair of mutually repressive gap genes, operated in space by maternal inputs. The toggle switches present in the gap network are evocative of the phage lambda switch, but they are operated positionally (in space) by the maternal gradients, so the synthesis rates for the competing components change along the embryo anterior-posterior axis. Dynamic model, constructed based on the proposed principle, with elements of fractional site occupancy, required 5–7 parameters to fit quantitative spatial expression data for gap gradients. The identified model solutions (parameter combinations) reproduced major dynamic features of the gap gradient system and explained gap expression in a variety of segmentation mutants

Monotone and near-monotone biochemical networks

Monotone subsystems have appealing properties as components of larger networks, since they exhibit robust dynamical stability and predictability of responses to perturbations. This suggests that natural biological systems may have evolved to be, if not monotone, at least close to monotone in the sense of being decomposable into a “small” number of monotone components, In addition, recent research has shown that much insight can be attained from decomposing networks into monotone subsystems and the analysis of the resulting interconnections using tools from control theory. This paper provides an expository introduction to monotone systems and their interconnections, describing the basic concepts and some of the main mathematical results in a largely informal fashion

Community detection in graphs

The modern science of networks has brought significant advances to our understanding of complex systems. One of the most relevant features of graphs representing real systems is community structure, or clustering, i. e. the organization of vertices in clusters, with many edges joining vertices of the same cluster and comparatively few edges joining vertices of different clusters. Such clusters, or communities, can be considered as fairly independent compartments of a graph, playing a similar role like, e. g., the tissues or the organs in the human body. Detecting communities is of great importance in sociology, biology and computer science, disciplines where systems are often represented as graphs. This problem is very hard and not yet satisfactorily solved, despite the huge effort of a large interdisciplinary community of scientists working on it over the past few years. We will attempt a thorough exposition of the topic, from the definition of the main elements of the problem, to the presentation of most methods developed, with a special focus on techniques designed by statistical physicists, from the discussion of crucial issues like the significance of clustering and how methods should be tested and compared against each other, to the description of applications to real networks.Comment: Review article. 103 pages, 42 figures, 2 tables. Two sections expanded + minor modifications. Three figures + one table + references added. Final version published in Physics Report

Raw grain as human food

Citation: Hastings, Milo M. Raw grain as human food. Senior thesis, Kansas State Agricultural College, 1906.Morse Department of Special CollectionsIntroduction: The determination of the best diet for man has been attempted by analogous reasoning from the diets of lower animals, but for reasons clear to a biologist such conclusions avail nothing. Likewise the attempt to determine the proper diet from a study of prevailing diets will, for obvious reasons, not correct prevailing faults. With this latter source of information has been combined the results of the physiological chemist. Of this class of knowledge there is not much fault to find save its incompleteness. The development of this science must add greatly to the understanding of nutrition and the determination of the best diets but the chemist must admit that the subtler organic changes that constitute the vital processes and determine the intensity and length of life are at present beyond his reach. If all these methods fall short of solving the problem of the optimum diet of man, by what method, it may be asked, is the problem to be solved. There is, it seems to me, one final test to which any theory of diet must submit and that is the test of careful experimental study of the effect of the diet upon men. The opinion of the mass of men in regard to food is not to be accepted as it is based upon immediate pleasures; neither the rapidity nor completeness of digestion nor the results of an isolated experiment are to be accepted as conclusive, for these may be only incidental. The worth of a diet for man is to be determined by the effect of that diet upon his fitness for living and, as with the dairy cow, this must first be determined for the race by combined experiment and then adapted in the details to each individual

Ironclad C++ A Library-Augmented Type-Safe Subset of C++

C++ remains a widely used programming language, despite retaining many unsafe features from C. These unsafe features often lead to violations of type and memory safety, which manifest as buffer overflows, use-after-free vulnerabilities, or abstraction violations. Malicious attackers are able to exploit such violations to compromise application and system security. This paper introduces Ironclad C++, an approach to bring the benefits of type and memory safety to C++. Ironclad C++ is, in essence, a library-augmented type-safe subset of C++. All Ironclad C++ programs are valid C++ programs, and thus Ironclad C++ programs can be compiled using standard, off-the-shelf C++ compilers. However, not all valid C++ programs are valid Ironclad C++ programs. To determine whether or not a C++ program is a valid Ironclad C++ program, Ironclad C++ uses a syntactic source code validator that statically prevents the use of unsafe C++ features. For properties that are difficult to check statically Ironclad C++ applies dynamic checking to enforce memory safety using templated smart pointer classes. Drawing from years of research on enforcing memory safety, Ironclad C++ utilizes and improves upon prior techniques to significantly reduce the overhead of enforcing memory safety in C++. To demonstrate the effectiveness of this approach, we translate (with the assistance of a semi-automatic refactoring tool) and test a set of performance benchmarks, multiple bug-detection suites, and the open-source database leveldb. These benchmarks incur a performance overhead of 12 % on average as compared to the unsafe original C++ code, which is small compared to prior approaches for providing comprehensive memory safety in C and C++. 1