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Occurrence of Fibonacci numbers in development and structure of animal forms: Phylogenetic observations and epigenetic significance

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Natural Science 2012年第4期4卷 216-232页

作者： john j. wille Bioderm Technologies Inc. Chesterfield UK

A survey of zoological literature affirmed the wide occurrence of Fibonacci numbers in the organization of acellular and prokaryotic life forms as well as in some eukaryotic protistans and in the embryonic development and adult forms of many living and fossil remains of metazoan animals. A detailed comparative analysis of the axial skeleton of a fossil fish and humans revealed a new rule of the “nested triad” of bones organized along the proximal to distal axis of limb appendages. This growth pattern and its ubiquity among living vertebrates appear to underlie a profound rule of pattern formation that is dictated in part by the genetics and epigenetic mechanisms of stem cell clonal development.

关键词： Animal Body Plan Fibonacci Numbers (n) Hox Genes Nested Triads Phylogeny Recursive Transition Networks Segmentation

Induced Differentiation of Epithelioid Carcinoma Cell Lines: Evidence for Tumor Cell Quantal Mitosis

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j.urnal of Cancer Therapy 2016年第11期7卷 794-811页

作者： john j. wille j.ng Y. Park Department of Cell Biology Southern Research Institute Birmingham AL USA

The effects of growth factors and calcium concentrations present in different culture media on induction of terminal differentiation were investigated for four different epidermoid carcinoma cell lines, Hela, KB, A431, and SCC-25, and their responses determined relative to those elicited by normal human keratinocytes subj.cted to these culture conditions. Differentiation status was determined cyto-chemically by a validated keratin protein staining method, and by autoradiographic analyses. Growth and differentiation promoting factors that influenced the direction of integrated control of growth and differentiation in normal human keratinocytes were found to be effective for some cell lines but not others. The factors examined were 1) high density arrest in serum-free and serum-containing media, 2) media shifts from high density culture in serum-containing media to low density growth factor-depleted or supplemented serum-free medium, and 3) the concentration of calcium in the media. The extent and degree of differentiation achieved varied among different cell lines depend on the presence or absence of serum, EGF and insulin protein growth factors. Certain growth media appear to sponsor keratin protein, cyto-chemically-detected differentiation, and evidence of quantal mitotic division in low density HeLa cell and SCC25 cell cultures. Epidermoid carcinoma cell lines retain limited capacity to commit to early stages of cell differentiation.

关键词： Cell Differentiation Epidermoid Carcinoma Cell Lines A431 Hela Kb SCC-25 Keratinocytes Cytochemical Staining Methods Quantal Mitosis

Retinoid and Ethanol-Sensitive Benzo(<i>α</i>)Pyrene Induction of Cytochrome P450 in Human Keratinocytes

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j.urnal of Cancer Therapy 2012年第6期3卷 1080-1085页

作者： john j. wille j.ng Y. Park Bioderm Technologies Inc. Chesterfield USA Division of Cancer Prevention and Control Moffitt Cancer Center Tampa USA.

Polycyclic aromatic hydrocarbons (PAHs) induce cytochrome P-450 monoxygenase enzymes that catalyze the formation of DNA adducts. We investigated the effects benzo(α)pyrene (B[α]P) alone or in combination with ethanol on normal human keratinocyte (NHK) growth, induction of cytochrome P-4501A1 (CYP1A1), and modulation of these treatments by retinoic acid (RA) in a serum-free culture medium. Growth-arrested confluent NHK serum-free cultures were treated with B[α]P alone or in combination with ethanol and RA. The effects on CYP1A1 enzyme activity were investigated. B[α]P treatment alone was not toxic to post-confluent cells;sub-toxic ethanol stimulated cell growth regardless B[α]P treatment. No CYP1A1 activity was detected in control or ethanol-treated NHK cell cultures. B[α]P alone induced CYP1A1 activity, and B[α]P plus ethanol treatment further enhanced B[α]P-induced CYP1A1 activity. Pretreatment with all-trans-RA (t-RA) abolished ethanol enhancement of CYP1A1 activity. There is a synergistic action of ethanol in combination with PAH on induction of P-450 cytochrome enzymes. By contrast, RA reverses ethanol enhancement implying a role for retinoid therapy in counteracting the risk posed by combined alcohol and PAH exposure on epidermal cell carcinogenesis.

关键词： CYP1A1 Aryl Hydrocarbon Hydroxylase Benzo(α)Pyrene Ethanol Keratinocytes Retinoids

Cell Cycle Arrest Mediates Global DNA Methylation Patterns in Normal Human Keratinocytes, Epidermoid Carcinoma Cells and Murine Embryonic Fibroblasts

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j.urnal of Cancer Therapy 2013年第1期4卷 199-207页

作者： john j. wille j.ng Y. Park Bioderm Technologies Inc Trenton USA Division of Cancer Prevention and Control Moffitt Cancer Center Tampa USA

The 5-methylationcytosine (5-MC) DNA content of murine embryonic fibroblasts arrested in G1 by four growth conditions (Gc, Gn, Gd, and Gs) were hypermethylated relative to rapidly growing (RG) fibroblasts. Normal human keratinocytes (NHK) arrested in G1 by suspension were hypermethylated relative to RG cultures. Four RG cultures of epidermoid carcinoma cells (ECC) were hypomethylated relative to RG NHK cultures, and two cultures (SCC25 and A431) were further hypomethylated by SUS-induced arrest. Linear regression analyses established a positive linear correlation between growth rate and 5-MC content for three murine fibroblasts lines, and a negative correlation for both NHK and ECC lines.

关键词： Anoikis Epitheliod Carcinoma Cells Cell Cycle DNA Methylation G1 Phase Restriction Points

Effects of Okadaic Acid, Retinoic Acid, and Phorbol Myristate Acetate Tumor Promoter on Oncogene Expression

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j.urnal of Cancer Therapy 2014年第6期5卷 591-604页

作者： john j. wille j.ng Y. Park Bioderm Technologies Inc. Trenton USA Department of Cancer Epidemiology Moffitt Cancer Center Tampa USA

The effect of okadaic acid (OA) on proto-oncogene protein expression of c-neu, c-myc, v-rasH, EGFR, and phosphotyrosine-containing phosphoproteins (P-Tyr) was investigated in rapidly growing (RG) normal human keratinocytes (NHK) and in SV-40 virally-transformed keratinocytes (SVK) cultured in a growth factor supplemented serum-free medium as assessed by indirect immunofluorescence microscopy. P-Tyr positively stains cell surface antigens (cytoplasm) diffusely at monopolar sites in RG NHK cultures. OA-treatment intensifies cytoplasmic P-Tyr staining at localized monopolar intercellular focal adhesion (IFA) sites with reduced cytoplasmic staining. P-Tyr expression was predominate at IFA sites with little cytoplasmic staining in RG SVK cultures. OA-treatment increased monopolar P-Tyr staining and cytoplasmic staining. OA-treatment in RG NHK cultures intensified cytoplasmic staining of c-myc and EGFR (epidermal growth factor receptor) expression. OA-treatment in RG NHK and SVK cultures intensified c-neu staining at monopolar IFA sites and intensified c-neu staining at both cytoplasmic and bipolar IFA sites in RG SVK cells. OA was especially cytotoxic for SVK cells. RA treatment decreased c-neu expression in RG NHK cultures while TPA treatment has a lesser effect on both cytoplasmic and IFA sites. RA treatment also decreased P-Tyr staining in both NHK and SVK cells. Again, TPA had a lesser inhibitory effect on P-Tyr staining pattern. RA-treatment had a similar effect on P-Tyr staining of RG cultures of a mouse fibroblast cell line. These results confirm the generality of OA, RA and TPA on the regulation of oncogene expression in both normal and malignantly transformed keratinocytes.

关键词： Epidermal Keratinocytes Indirect Immunofluorescence Microscopy Oncogene Protein Antibodies Okadaic Acid Phosphotyrosine Antibody Retinoic Acid SV-40 Transformed Keratinocytes TPA Tumor Promoter

Differential Anticancer Effect of an Apple Extract (Applephenon<sup>&reg</sup>), Polyphenols and Isoflavones on Normal Human Keratinocytes and Epidermoid Cancer Cells

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j.urnal of Cancer Therapy 2019年第6期10卷 476-493页

作者： john j. wille Mark A. Berhow j.ng Y. Park Bioplast Medical LLC Chesterfield NJ USA ARS USDA Peoria IL USA Moffitt Cancer Center Tampa FL USA

Applephenon®, a purified extract prepared from green apples, was examined for its cytotoxicity and inhibitory effects on the proliferation of cultures of normal human keratinocytes and several epidermoid cancer cell lines. Our HPLC studies demonstrated a high content of phenolic compounds (>65%), including catechin, epicatechin, caffeic acid and phloretin as well as polyphenols such as proanthocyanidins. Applephenon® demonstrated a greater cytotoxic effect against HeLa, A431 cancer cell lines and HaCaT, an immortalized keratinocyte cell line than serum-free cultures of proliferating normal human keratinocytes (NHK). Proliferation of NHK was inhibited at concentrations above 0.0013% while concentrations above 0.005% were cytotoxic. By contrast, Applephenon® solutions above 0.00025% killed each of the cancer cell lines. Treated cells displayed increased intercellular separation and evidence of keratinizing stratification. We also tested the effect of epicatechin, and two isoflavonoids, genistein and daidzein, on cancer cell lines. Hela cells were more sensitive to epicatechin and genistein inhibition of cell growth and cytotoxicity than were NHK. Daidzein at these concentrations had little effect on cancer cells. These results indicate that Applephenon® and some of its phenolic components have selective anticancer activity.

关键词： ApplephenonTM (AP-SH Grade) Cytotoxicity Epicatechin Epidermal Keratinocytes Epidermoid Cancer Cell Lines (A431 HaCaT HeLa) Genistein Polyphenols

Cancer Chemopreventive Retinoids: Validation and Analysis of in Vivo and in Vitro Bioassay Results

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j.urnal of Cancer Therapy 2016年第13期7卷 1008-1033页

作者： john j. wille j.ng Y. Park Y. Fulmer Shealy Department of Biochemistry Southern Research Institute Birmingham AL USA Department of Cell Biology Bioplast Medical LLC Chesterfield NJ USA Department of Cancer Epidemiology Moffitt Cancer Center Tampa FL USA

Several natural and synthetic retinoids (vitamin-A derived analogies) were examined for their potential anti-cancer activity in both in vivo animal models and a novel in vitro human keratinocyte clonal growth bioassay system. The natural retinoids included all-trans-retinoic (RA), 13-cis-retinoic acid, 4-oxoretinoic acid, and retinol. Among the synthetic retinoids tested were all trans N-(4-hydroxy(phenyl)retinamide, 3-substituted oxoretinoic acids, and 13 cis-N-ethylretinamide. The animal models employed were: 1) vitamin A-deficient hamster tracheal organ assay (HTOC);2) the benzo(α)pyrene-induced squamous metaplasia in a hamster tracheal organ system (BP-HTOC);3) the mouse skin tumor promoter (TPA)-induced ornithine decarboxylase enzyme assay(ODC);4) the mouse skin papilloma (MPA) assay;and 5) a novel retinoid bioassay in which retinoids display IC50 values to inhibit clonal growth of NHK. All-trans-RA, 4-oxoretinoic acid and retinol were consistently more active than any of the synthetic derivatives in all bioassays tested. A statistical model was developed and significant positive correlations were found between: 1) ED50 values in the HTOC system and reduction in TPA-induced ODC enzyme activity;2) tumors per animal in the MPA bioassay and suppression of TPA-induced ODC activity;and 3) a positive correlation between suppression of tumors per animal in the MPA assay, and retinoid inhibition of keratinocyte clonal growth. Test retinoids, were tested for their capacity to inhibit the clonal growth of a squamous carcinoma cell line (SCC-25), which were found to be 2 - 3 logs less sensitive for each tested retinoid than the corresponding activity against NHK cells. Antineoplastic retinoid drugs were reviewed.

关键词： Cancer Chemoprevention in Vivo Bioassays in Vitro Bioassays Retinoids

What diameter?What height?Influence of measures of average tree size on area-based allometric volume relationships

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Forest Ecosystems 2024年第1期11卷 100-109页

作者： Yilin Wang john A.Kershaw Mark j.Ducey Yuan Sun j.mes B.McCarter Integrated Forest Mensuration and Systems Analysis Laboratory Faculty of Forestry and Environmental ManagementUniversity of New BrunswickFrederictonNBCanada Department of Natural Resources and the Environment University of New HampshireDurhamNHUSA College of Forestry Nanjing Forestry UniversityNanjing210037China Scientific Programmer RayonierYuleeFLUSA

Volume is an important attribute used in many forest management *** from 83 fixed-area plots located in central New Brunswick,Canada,are used to examine how different measures of stand-level diameter and height influence volume prediction using a stand-level variant of Honer's(1967)volume *** density was included in the models(Volume=f(Diameter,Height,Density))choice of diameter measure was more important than choice of height *** density was not included(Volume=f(Diameter,Height)),the opposite was *** models with density included,moment-based estimators of stand diameter and height performed better than all other *** models without density,largest tree estimators of stand diameter and height performed better than other *** overall best equation used quadratic mean diameter,Lorey's height,and density(root mean square error=5.26 m^3·ha^(-1);1.9%relative error).The best equation without density used mean diameter of the largest trees needed to calculate a stand density index of 400 and the mean height of the tallest 400 trees per ha(root mean square error=32.08 m^(3)·ha^(-1);11.8%relative error).The results of this study have some important implications for height subsampling and LiDAR-derived forest inventory analyses.

关键词： Allometric relationships Stand structure Volume estimation Stand-level attributes

Rodent management in Aotearoa New Zealand: approaches and challenges to landscape-scale control

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Integrative Zoology 2024年第1期19卷 8-26页

作者： john G.INNES Grant NORBURY Araceli SAMANIEGO Susan WALKER Deborah j.WILSON Manaaki Whenua-Landcare Research HamiltonNew Zealand Manaaki Whenua-Landcare Research AlexandraNew Zealand Manaaki Whenua-Landcare Research AucklandNew Zealand Manaaki Whenua-Landcare Research DunedinNew Zealand

Aotearoa—New Zealand has only four rodent species,all *** order of arrival,they are Pacific rat Rattus exulans,brown rat ***,house mouse Mus musculus,and black rat *** management in New Zealand aims mainly to conserve indigenous biodiversity rather than to protect crops or manage diseases,as is usual *** describe four maj.r“regimes”and one maj.r vision for rodent control in New Zealand to meet ecological restoration *** challenges for island eradications are for large islands that are remote or populated by *** 1080 is the only large-scale(tens of thousands of hectares)option for black rat control,but its application requires adj.stment to counter subsequent rapid black rat ***“ecosanctuaries”(mean 720 ha)use ground-based traps and poisons to target mainly black rats and face constant *** with mammal-resistant fences(up to 3500 ha)limit reinvasion and target more pest species and have enabled the return of previously extirpated taxa to the main *** Free 2050 aims to eradicate the rat species(but not mice)plus some other introduced mammals from New Zealand by *** vision is not attainable with current tools,but research and experimental management is exploring techniques and *** large scale(to 100000 ha)at which black rats are now targeted for control to extremely low abundance seems to be unique to New Zealand.

关键词： black rat brown rat eradication house mouse rodent control