Genetic Code: A New Understanding of Codon - Amino Acid Assignment

In this work it is shown that 20 canonical amino acids (AAs) within genetic code appear to be a whole system with strict AAs positions; more exactly, with AAs ordinal number in three variants; first variant 00-19, second 00-21 and third 00-20. The ordinal number follows from the positions of belonging codons, i.e. their digrams (or doublets). The reading itself is a reading in quaternary numbering system if four bases possess the values within a specific logical square: A = 0, C = 1, G = 2, U = 3. By this, all splittings, distinctions and classifications of AAs appear to be in accordance to atom and nucleon number balance as well as to the other physico-chemical properties, such as hydrophobicity and polarity.Comment: 25 Pages, 8 Tables, 5 Figures and 5 Surveys. The paper is submitting to GLASNIK of Montenegrin Academy of Science and Arts as a extended version of paper published in Ann. N.Y. Acad. Sci. 1048: 517-523 (2005

Prenatal Serum Concentrations of Brominated Flame Retardants and Autism Spectrum Disorder and Intellectual Disability in the Early Markers of Autism Study: A Population-Based Case-Control Study in California.

BackgroundPrior studies suggest neurodevelopmental impacts of polybrominated diphenyl ethers (PBDEs), but few have examined diagnosed developmental disorders.ObjectivesOur aim was to determine whether prenatal exposure to brominated flame retardants (BFRs) is associated with autism spectrum disorder (ASD) or intellectual disability without autism (ID).MethodsWe conducted a population-based case-control study including children with ASD (n=545) and ID (n=181) identified from the California Department of Developmental Services and general population (GP) controls (n=418) from state birth certificates. ASD cases were matched to controls by sex, birth month, and birth year. Concentrations of 10 BFRs were measured in maternal second trimester serum samples stored from routine screening. Logistic regression was used to calculate crude and adjusted odds ratios (AOR) for associations with ASD, and separately for ID, compared with GP controls, by quartiles of analyte concentrations in primary analyses.ResultsGeometric mean concentrations of five of the six congeners with ≥55% of samples above the limit of detection were lower in mothers of children with ASD or ID than in controls. In adjusted analyses, inverse associations with several congeners were found for ASD relative to GP (e.g., quartile 4 vs. 1, BDE-153: AOR=0.56, 95% CI: 0.38, 0.84). When stratified by child sex (including 99 females with ASD, 77 with ID, and 73 with GP), estimates were consistent with overall analyses in boys, but in the opposite direction among girls, particularly for BDE-28 and -47 (AOR=2.58, 95% CI: 0.86, 7.79 and AOR=2.64, 95% CI: 0.97, 7.19, respectively). Similar patterns overall and by sex were observed for ID.ConclusionsContrary to expectation, higher PBDE concentrations were associated with decreased odds of ASD and ID, though not in girls. These findings require confirmation but suggest potential sexual dimorphism in associations with prenatal exposure to BFRs. https://doi.org/10.1289/EHP1079

MCMC Methods for Multi-Response Generalized Linear Mixed Models: The MCMCglmm R Package

Generalized linear mixed models provide a flexible framework for modeling a range of data, although with non-Gaussian response variables the likelihood cannot be obtained in closed form. Markov chain Monte Carlo methods solve this problem by sampling from a series of simpler conditional distributions that can be evaluated. The R package MCMCglmm implements such an algorithm for a range of model fitting problems. More than one response variable can be analyzed simultaneously, and these variables are allowed to follow Gaussian, Poisson, multi(bi)nominal, exponential, zero-inflated and censored distributions. A range of variance structures are permitted for the random effects, including interactions with categorical or continuous variables (i.e., random regression), and more complicated variance structures that arise through shared ancestry, either through a pedigree or through a phylogeny. Missing values are permitted in the response variable(s) and data can be known up to some level of measurement error as in meta-analysis. All simu- lation is done in C/ C++ using the CSparse library for sparse linear systems.

The role of language in mathematical development: Evidence from children with specific language impairments

A sample (n=48) of eight year olds with Specific Language Impairments is compared with age-matched (n=55) and language matched controls (n=55) on a range of tasks designed to test the interdependence of language and mathematical development. Performance across tasks varies substantially in the SLI group, showing profound deficits in production of the count word sequence and basic calculation and significant deficits in understanding of the place-value principle in Hindu-Arabic notation. Only in understanding of arithmetic principles does SLI performance approximate that of age-matched-controls, indicating that principled understanding can develop even where number sequence production and other aspects of number processing are severely compromised

Neural Network and Bioinformatic Methods for Predicting HIV-1 Protease Inhibitor Resistance

This article presents a new method for predicting viral resistance to seven protease inhibitors from the HIV-1 genotype, and for identifying the positions in the protease gene at which the specific nature of the mutation affects resistance. The neural network Analog ARTMAP predicts protease inhibitor resistance from viral genotypes. A feature selection method detects genetic positions that contribute to resistance both alone and through interactions with other positions. This method has identified positions 35, 37, 62, and 77, where traditional feature selection methods have not detected a contribution to resistance. At several positions in the protease gene, mutations confer differing degress of resistance, depending on the specific amino acid to which the sequence has mutated. To find these positions, an Amino Acid Space is introduced to represent genes in a vector space that captures the functional similarity between amino acid pairs. Feature selection identifies several new positions, including 36, 37, and 43, with amino acid-specific contributions to resistance. Analog ARTMAP networks applied to inputs that represent specific amino acids at these positions perform better than networks that use only mutation locations.Air Force Office of Scientific Research (F49620-01-1-0423); National Geospatial-Intelligence Agency (NMA 201-01-1-2016); National Science Foundation (SBE-0354378); Office of Naval Research (N00014-01-1-0624

Assessing Potential Cognitive Precursors to Math Anxiety: Non-Symbolic Operations and Symbolic Ordinality in Adults

Math anxiety, or a sense of dread related to performing mathematics, affects a wide population of students and adults, but we do not fully understand how math anxiety comes into being. One possibility is the Reduced Capacities Theory, which suggests that natural variations in numeric/spatial capacities are a causal factor in math anxiety. To understand how these numeric capacities relate to math anxiety in adults, this work focuses on three areas that remain underexplored. Chapter 2 focuses on performing operations on nonsymbolic quantities, which has not yet been tested in relation to math anxiety. We tested the hypothesis that performing addition and subtraction with dots using the Approximate Number System would relate to math anxiety. We asked participants to complete a math anxiety survey, two measures of working memory, a timed symbolic arithmetic test, and a non-symbolic “approximate arithmetic” task, in which participants performed addition and subtraction on dot arrays. Using Bayesian analysis and multiple regression, we found evidence for there being no relation between approximate arithmetic performance and math anxiety, suggesting that difficulties performing operations does not constitute a basic number ability linked to math anxiety. In chapter 3, we measured the relation between number and letter ordinal processing and math anxiety. In separate blocks, we asked participants to determine if triads of numbers and letters were in order (e.g., 4 5 6) or out of order (e.g., C E A) to measure response time and accuracy. Participants also completed a timed arithmetic test to understand the relation between ordinality, arithmetic, and math anxiety. Several hypotheses were assessed including the specificity of math anxiety to numbers (comparing number ordinal trials to letter trials. We found that there was no relation between math anxiety on any measure except that high math anxiety related to slower responses to number ordinal judgement, and that math anxiety mediated the relation between ordinal judgement performance and arithmetic. Together, these data suggest that ordinal processes are unlikely to be a causal factor for math anxiety, despite being critical for early mathematics learning. In chapter 4, we assessed responses to counting sequences and inhibitory control in relation to math anxiety. We developed a modified Go/No-Go task in which we manipulated trial length, whether they responded to completed vs “violated” (e.g., 21 22 23 vs 21 22 24, respectively) sequences, and distance (violated being +1 or +4, between subjects). Participants also completed a math anxiety survey. We assessed response time, and accuracy to understand counting sequence representation’s relation to MA, and false alarm rates to understand inhibition’s relation to MA. We found that the high MA group was significantly slower to respond when number to respond to was not consecutive. There were no relations between MA and any other measure. When viewed together, these data suggest that the Reduced Capacities theory may not be a viable framework for understanding the origin of math anxiety, as all results can be more easily explained by the effects of anxiety on performance. However, because these data were all collected with adults, it remains plausible that children who go on to develop MA may struggle with these capacities during early schooling and see equal gains as their low MA peers. We end by suggesting several potential avenues of research related to MA, focusing on students’ and adults’ emotional interpretation of their math experiences

A generalization of partial least squares regression and correspondence analysis for categorical and mixed data: An application with the ADNI data

The present and future of large scale studies of human brain and behaviorin typical and disease populationsis mutli-omics, deep-phenotyping, or other types of multi-source and multi-domain data collection initiatives. These massive studies rely on highly interdisciplinary teams that collect extremely diverse types of data across numerous systems and scales of measurement (e.g., genetics, brain structure, behavior, and demographics). Such large, complex, and heterogeneous data requires relatively simple methods that allow for exibility in analyses without the loss of the inherent properties of various data types. Here we introduce a method designed * Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimag-ing Initiative (ADNI) database (http://adni.loni.usc.edu/). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found a