R. Sullivan

ATCG nucleotide fluctuation of Deinococcus radiodurans radiation genes

The radiation resistance-repair genes in Deinococcus radiodurans (DR) and E-coli were analyzed in terms of the A, T, C, G nucleotide fluctuations. The studied genes were Rec-A, Rec-Q, and the unique DR PprA gene. In an ATCG sequence, each base was assigned a number equal to its atomic number. The resulting numerical sequence was the basis of the statistical analysis. Fractal analysis using the Higuchi method gave a fractal dimension increase of the Deinococcus radiodurans genes as compared to E-coli, which is comparable to the enhancement observed in the human HAR1 region (HAR1F gene) over that of the chimpanzee. Near neighbor fluctuation was also studied via the Black-Scholes model where the increment sequence was treated as a random walk series. The Deinococcus radiodurans radiation gene standard deviations were consistently higher than that of the E-coli deviations, and agree with the fractal analysis results. The sequence stacking interaction was studied using the published nucleotide-pair melting free energy values and Deinococcus radiodurans radiation genes were shown to possess larger negative free energies. The high sensitivity of the fractal dimension as a biomarker was tested with correlation analysis of the gamma ray dose versus fractal dimension, and the R square values were found to be above 0.9 (N=5). When compared with other nucleotide sequences such as the rRNA sequences, HAR1 and its chimpanzee counterpart, the higher fluctuation (correlated randomness) and larger negative free energy of a DR radiation gene suggested that a radiation resistance-repair sequence exhibited higher complexity. As the HAR1 nucleotide sequence complexity and its transcription activity of co-expressing cortex protein reelin supported a positive selection event in humans, a similar inference of positive selection of coding genes could be drawn for Deinococcus radiodurans when compared to E-coli. The origin of such a positive selection would be consistent with that of a Martian environment.

Marfan Syndrome Exon CpG Percentage and Fractal Dimension

The CpG di-nucleotide percentage and exon fractal dimension fluctuation were investigated with respect to the recently identified Marfan syndrome exons in the FBN1 gene. The CpG di-nucleotide percentage was found to rank high in exon 1 (9%), exon 44 (6.5%), exon 24 (5.3%) and exon 27 (4.8%). The most significant Marfan exon group was reported to be exon 24- 32. An exon nucleotide sequence can be expressed as a numerical sequence when each nucleotide is assigned its proton number. The resulting exon nucleotide numerical sequence could be investigated for its fractal dimension. The fractal dimension exhibited fluctuation across the 65 FBN1 exons and the values formed a Gaussian-like distribution (N = 65). The moving average fractal dimension was found to exhibit a broad peak around exons 24 to 32, consistent with the reported Marfan syndrome exon group.

Nucleotide fluctuation of RecA repair gene in Siberian permafrost Psychrobacter cryohalolentis K5

A nucleotide sequence can be expressed as a numerical sequence when each nucleotide is assigned its proton number. A resulting gene numerical sequence can be investigated for its fractal dimension in terms of evolution and chemical properties for comparative studies. We have investigated such nucleotide fluctuation in the RecA repair gene of Psychrobacter cryohalolentis K5, Psychrobacter arcticus 273-4, and Psychrobacter sp. PRwf-1. The fractal dimension was found to correlate with the genes operating temperature with the highest fractal dimension associated with P. cryohalolentis K5 living at the low temperatures found in Siberian permafrost. The CpG dinucleotide content was found to be about 5% for the three species of Psychrobacters, which is substantially lower than that of Deinococcus radiodurans at about 12%. The average nucleotide pair-wise free energy was found to be lowest for Psychrobacter sp. PRwf-1, the species with the lowest fractal dimension of the three, consistent with the recent finding that Psychrobacter sp. PRw-f1 has a temperature growth maximum of 15-20°C higher than P. arcticus 273-4 and P. cryohaloentis K5. The results suggest that microbial vitality in extreme environments is associated with fractal dimension as well as high CpG dinucleotide content, while the average nucleotide pair-wise free energy is related to the operating environment. Evidence that extreme temperature operation would impose constraints measurable by Shannon entropy is also discussed. A quantitative estimate of an entropy-based measure having the characteristics of a mechanical pressure shows that the Psychrobacter RecA sequence experiences lower pressure than that of the human HAR1 sequence.

Fractal Analysis of Filamentous Actin Fluorescent Speckle Microscope Patterns in Cell Migration

The fluorescent speckle microscope pattern of newt lung epithelial cell filamentous actin during migration was analyzed using the Higuchi fractal method. The public domain datasets of 2004 PNAS Vallotton et al. were studied. The time series data from time lapsed images exhibited similar fractal dimensions (about 1.68 to 1.82) for various cell regions. Computer simulation of random time series data suggested an average fractal dimension of about 2 with a standard deviation of about 0.027. Speckle trend removals revealed pulsation features which were further studied using a sinusoidal signal model commonly used in gene regulatory studies. Gaussian noise models mixed with sinusoidal signal were used to simulate the observed fractal dimensions. The extracted constraints could be interpreted as polymerization and control pathway related. The administration of contractility promotion drug calyculin-A resulted in an increase of the overall image fractal dimension, which is consistent with the loss of correlation due to random direction contractions. It appears that high fractal dimension could be interpreted as being due to further randomization. Two doses of 20 nM calyculin-A increased cell noise by about 45%. Extension of this proof-of-concept fractal analysis to clinical treatment was also discussed.

DNA sequence-based comparative studies between non-extremophile and extremophile organisms with implications in exobiology

We have characterized function related DNA sequences of various organisms using informatics techniques, including fractal dimension calculation, nucleotide and multi-nucleotide statistics, and sequence fluctuation analysis. Our analysis shows trends which differentiate extremophile from non-extremophile organisms, which could be reproduced in extraterrestrial life. Among the systems studied are radiation repair genes, genes involved in thermal shocks, and genes involved in drug resistance. We also evaluate sequence level changes that have occurred during short term evolution (several thousand generations) under extreme conditions.

Assessment of high-school engineering education outreach program employing project-based learning in astronomy and bio-optics within a college setting

A college outreach engineering education program designed for high school students was implemented in a community college using the three principles of K-12 engineering education, namely, product design, science knowledge, and mindset development. The means of transforming a science question into a design driven one was illustrated using examples and projects from the fields of astronomy and bio-optics. The relevant scientific principles were presented by introducing various iterated designs in an interactive learning environment. A high school level research component using astronomy and bio-optics-related public data was also implemented to enrich the students’ exposure to numerical processing techniques accessible in Microsoft Excel. Examples including solar events driven by magnetic field topology, cosmological images generated by IllustrisTNG Project, muon flux data, Killer T-cell motion, and wound assay cell migration are used in the teaching of iterated designs. A Path Diagram assessment model based on a LISREL computation scheme with learning intent and engineering mindset as latent variables was used to gauge the effectiveness of an implementation, the results of which would be used in the subsequent semester’s implementation of the research component. The materials developed in a College Now course, where high school students take a research course at a community college, would be readily adaptable to other four-year college programs. The possible future incorporation of an introductory engineering course for high school student education, using the MIT low-cost

Bioinformatics comparison of sulfate-reducing metabolism nucleotide sequences

100 muon detector and Fermi Lab QuarkNet muon scintillation detector, is discussed.

Complexity of genetic sequences modified by horizontal gene transfer and degraded-DNA uptake

The sulfate-reducing bacteria can be traced back to 3.5 billion years ago. The thermodynamics details of the sulfur cycle have been well documented. A recent sulfate-reducing bacteria report (Robator, Jungbluth, et al , 2015 Jan, Front. Microbiol) with Genbank nucleotide data has been analyzed in terms of the sulfite reductase (dsrAB) via fractal dimension and entropy values. Comparison to oil field sulfate-reducing sequences was included. The AUCG translational mass fractal dimension versus ATCG transcriptional mass fractal dimension for the low temperature dsrB and dsrA sequences reported in Reference Thirteen shows correlation R-sq ~ 0.79 , with a probably of about 3% in simulation. A recent report of using Cystathionine gamma-lyase sequence to produce CdS quantum dot in a biological method, where the sulfur is reduced just like in the H2S production process, was included for comparison. The AUCG mass fractal dimension versus ATCG mass fractal dimension for the Cystathionine gamma-lyase sequences was found to have R-sq of 0.72, similar to the low temperature dissimilatory sulfite reductase dsr group with 3% probability, in contrary to the oil field group having R-sq ~ 0.94, a high probable outcome in the simulation. The other two simulation histograms, namely, fractal dimension versus entropy R-sq outcome values, and di-nucleotide entropy versus mono-nucleotide entropy R-sq outcome values are also discussed in the data analysis focusing on low probability outcomes.

The bioinformatics of nucleotide sequence coding for proteins requiring metal coenzymes and proteins embedded with metals

Horizontal gene transfer has been a major vehicle for efficient transfer of genetic materials among living species and could be one of the sources for noncoding DNA incorporation into a genome. Our previous study of lnc- RNA sequence complexity in terms of fractal dimension and information entropy shows a tight regulation among the studied genes in numerous diseases. The role of sequence complexity in horizontal transferred genes was investigated with Mealybug in symbiotic relation with a 139K genome microbe and Deinococcus radiodurans as examples. The fractal dimension and entropy showed correlation R-sq of 0.82 (N = 6) for the studied Deinococcus radiodurans sequences. For comparison the Deinococcus radiodurans oxidative stress tolerant catalase and superoxide dismutase genes under extracellular dGMP growth condition showed R-sq ~ 0.42 (N = 6); and the studied arsenate reductase horizontal transferred genes for toxicity survival in several microorganisms showed no correlation. Simulation results showed that R-sq < 0.4 would be improbable at less than one percent chance, suggestive of additional selection pressure when compared to the R-sq ~ 0.29 (N = 21) in the studied transferred genes in Mealybug. The mild correlation of R-sq ~ 0.5 for fractal dimension versus transcription level in the studied Deinococcus radiodurans sequences upon extracellular dGMP growth condition would suggest that lower fractal dimension with less electron density fluctuation favors higher transcription level.

Effect of non-homogenous thermal stress during sub-lethal photodynamic antimicrobial chemotherapy

All metallo-proteins need post-translation metal incorporation. In fact, the isotope ratio of Fe, Cu, and Zn in physiology and oncology have emerged as an important tool. The nickel containing F430 is the prosthetic group of the enzyme methyl coenzyme M reductase which catalyzes the release of methane in the final step of methano-genesis, a prime energy metabolism candidate for life exploration space mission in the solar system. The 3.5 Gyr early life sulfite reductase as a life switch energy metabolism had Fe-Mo clusters. The nitrogenase for nitrogen fixation 3 billion years ago had Mo. The early life arsenite oxidase needed for anoxygenic photosynthesis energy metabolism 2.8 billion years ago had Mo and Fe. The selection pressure in metal incorporation inside a protein would be quantifiable in terms of the related nucleotide sequence complexity with fractal dimension and entropy values. Simulation model showed that the studied metal-required energy metabolism sequences had at least ten times more selection pressure relatively in comparison to the horizontal transferred sequences in Mealybug, guided by the outcome histogram of the correlation R-sq values. The metal energy metabolism sequence group was compared to the circadian clock KaiC sequence group using magnesium atomic level bond shifting mechanism in the protein, and the simulation model would suggest a much higher selection pressure for the energy life switch sequence group. The possibility of using Kepler 444 as an example of ancient life in Galaxy with the associated exoplanets has been proposed and is further discussed in this report. Examples of arsenic metal bonding shift probed by Synchrotron-based X-ray spectroscopy data and Zn controlled FOXP2 regulated pathways in human and chimp brain studied tissue samples are studied in relationship to the sequence bioinformatics. The analysis results suggest that relatively large metal bonding shift amount is associated with low probability correlation R-sq outcome in the bioinformatics simulation.