Progressive iron overload enhances chemically mediated tumor promotion in murine skin

Iron overload has been shown to enhance chemically mediated cutaneous tumor promotion in animals. However, the majority of these animal studies have used high concentrations of iron before initiating tumor development. The current study was designed to evaluate the effect of small doses of iron on the promotion stage of chemically mediated cutaneous carcinogenesis. We found an increased tumor response in mice initiated with dimethylbenz(a)anthracene (DMBA) when iron at the dose levels of 0.5, 1.0, and 1.5mg/mouse was injected (intramuscularly) once a week into mice at the promotion stage of skin carcinogenesis, employing 12-O-tetradecanoyl phorbol-13-acetate (TPA)/benzoyl peroxide (BPO) as tumor promoter. The appearance of first papilloma and the number of tumors/mouse were recorded weekly. When compared to the control (non-iron-treated) group, the iron-treated groups showed an augmented incidence of tumors and number of tumors/mouse. In iron-treated mice, tumors appeared earlier than in the control group. TPA/BPO treatment resulted in a significant decrease in the activities of antioxidant enzymes and depletion in the level of epidermal reduced glutathione (GSH). TPA treatment in non-iron-treated mice resulted in approximately 20-40% decrease in GSH level and in the activities of antioxidant enzymes, whereas 1.5-mg iron treatment along with TPA treatment resulted in about approximately 30-70% decrease in GSH level and in the activities of antioxidant enzymes. Similarly, treatment of iron along with BPO treatment resulted in a dose-dependent higher depletion of GSH and the antioxidant enzymes as compared to non-iron-treated animals treated with BPO. Further, TPA/BPO-mediated induction in ornithine decarboxylase activity and [3H]thymidine incorporation in cutaneous DNA was approx two- to threefold higher in mice treated with iron as compared to non-iron-treated mice. Cutaneous lipid peroxidation and iron levels were also higher in mice treated with iron as compared to non-iron-treated mice. These data suggest that progressive iron overload can enhance the tumor promotion ability of TPA/BPO in DMBA-initiated murine skin.     

Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy

Administration of replacement doses of testosterone to healthy hypogonadal men and supraphysiological doses to eugonadal men increases muscle size. To determine whether testosterone-induced increase in muscle size is due to muscle fiber hypertrophy, 61 healthy men, 18-35 yr of age, received monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist to suppress endogenous testosterone secretion and weekly injections of 25, 50, 125, 300, or 600 mg testosterone enanthate (TE) for 20 wk. Thigh muscle volume was measured by magnetic resonance imaging (MRI) scan, and muscle biopsies were obtained from vastus lateralis muscle in 39 men before and after 20 wk of combined treatment with GnRH agonist and testosterone. Administration of GnRH agonist plus TE resulted in mean nadir testosterone concentrations of 234, 289, 695, 1,344, and 2,435 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Graded doses of testosterone administration were associated with testosterone dose and concentration-dependent increase in muscle volume measured by MRI (changes in vastus lateralis volume, -4, +7, +15, +32, and +48 ml at 25-, 50-, 125-, 300-, and 600-mg doses, respectively). Changes in cross-sectional areas of both type I and II fibers were dependent on testosterone dose and significantly correlated with total (r = 0.35, and 0.44, P < 0.0001 for type I and II fibers, respectively) and free (r = 0.34 and 0.35, P < 0.005) testosterone concentrations during treatment. The men receiving 300 and 600 mg of TE weekly experienced significant increases from baseline in areas of type I (baseline vs. 20 wk, 3,176 +/- 186 vs. 4,201 +/- 252 microm(2), P < 0.05 at 300-mg dose, and 3,347 +/- 253 vs. 4,984 +/- 374 microm(2), P = 0.006 at 600-mg dose) muscle fibers; the men in the 600-mg group also had significant increments in cross-sectional area of type II (4,060 +/- 401 vs. 5,526 +/- 544 microm(2), P = 0.03) fibers. The relative proportions of type I and type II fibers did not change significantly after treatment in any group. The myonuclear number per fiber increased significantly in men receiving the 300- and 600-mg doses of TE and was significantly correlated with testosterone concentration and muscle fiber cross-sectional area. In conclusion, the increases in muscle volume in healthy eugonadal men treated with graded doses of testosterone are associated with concentration-dependent increases in cross-sectional areas of both type I and type II muscle fibers and myonuclear number. We conclude that the testosterone induced increase in muscle volume is due to muscle fiber hypertrophy.     

Molecular systematics and paleobiogeography of the South American sigmodontine rodents [published erratum appears in Mol Biol Evol 1998 Feb;15(2):224]

The murid rodent subfamily Sigmodontinae contains 79 genera which are distributed throughout the New World. The time of arrival of the first sigmodontines in South America and the estimated divergence time(s) of the different lineages of South American sigmodontines have been controversial due to the lack of a good fossil record and the immense number of extant species. The "early-arrival hypothesis" states that the sigmodontines must have arrived in South America no later than the early Miocene, at least 20 MYA, in order to account for their vast present-day diversity, whereas the "late-arrival hypothesis" includes the sigmodontines as part of the Plio-Pleistocene Great American Interchange, which occurred approximately 3.5 MYA. The phylogenetic relationships among 33 of these genera were reconstructed using mitochondrial DNA (mtDNA) sequence data from the ND3, ND4L, arginine tRNA, and ND4 genes, which we show to be evolving at the same rate. A molecular clock was calibrated for these genes using published fossil dates, and the genetic distances were estimated from the DNA sequences in this study. The molecular clock was used to estimate the dates of the South American sigmodontine origin and the main sigmodontine radiation in order to evaluate the "early-" and "late-arrival" scenarios. We estimate the time of the sigmodontine invasion of South America as between approximately 5 and 9 MYA, supporting neither of the scenarios but suggesting two possible models in which the invading lineage was either (1) ancestral to the oryzomyines, akodonts, and phyllotines or (2) ancestral to the akodonts and phyllotines and accompanied by the oryzomyines. The sigmodontine invasion of South America provides an example of the advantage afforded to a lineage by the fortuitous invasion of a previously unexploited habitat, in this case an entire continent.      

Anthropological studies among Pangwalas and Gaddis of Himachal Pradesh, North India

The present paper is based on the Research Project entitled "Impact of Technological and Economic Development Programme on Bio-Cultural Heritage of Gaddis and Pangwalas Population Groups of Himachal Pradesh". The project was framed after UNESCO/MAB Project Nos. 6 and 12 under UNESCO Programme on Man Biosphere (MAB) and supported by the Department of Science and Technology, Government of India. The population groups under investigation are: 1. Transhumant Gaddis of Bharmour Sub-Tehsil, Chamba District; 2. Settled Gaddis of Kangra District; and 3. Pangwalas of Pangi Tehsil, Chamba District, Himachal Pradesh. The carrying capacity has been calculated for Pangi and Bharmour Sub-Tehsil and it has been observed that in both the places the size of population is beyond the capacity of the land. The pattern of body growth and respiratory functions among Transhumant Gaddis of Bharmour Sub-Tehsil, Chamba District and Settled Gaddis of Kangra District have been studied. Statistically non-significant differences in most of the biological variables have been observed among these groups.     

Genetic diversity among the Newars of Nepal

Genetic diversity among the Newars of Nepal has been studied using Wright's FST and the ratio of observed variance to theoretical variance following Lewontin and Krakauer's 1973 method, based on six genetic characteristics. The gene differentiation among the Newars is only 1.7%. These observations are further corroborated by the results obtained through genetic distance analysis. The average heterozygosity per locus is high (ranging from 35 to 42%) for all the groups. About 95% of total gene diversity exists within the Newar groups, the intergroup components being only about 5%.     

Responses of the biting midge Culicoides impunctatus to acetone, CO2 and 1-octen-3-ol in a wind tunnel

Responses of host-seeking female Culicoides impunctatus (Goetghebuer) (Diptera: Ceratopogonidae) to acetone, carbon dioxide and 1-octen-3-ol were measured in a wind tunnel. Carbon dioxide, presented as a filamentous plume, increased upwind flight in a dose-dependent manner, up to 0.09% concentration. A homogenous CO2 plume elicited similar upwind responses at concentrations up to 0.09%, whereas higher plume concentrations (> 0.1%) induced erratic responses with a suppression of upwind flight. Bovine equivalent concentrations of acetone (1.5 x 10(-6)g/l) and 1-octen-3-ol (1.3 x 10(-8)g/) failed to induce any significant upwind response when tested alone. In the presence of CO2, however, 1-octen-3-ol showed highly significant increases in upwind responses at concentrations of 1.3 x 10(-1) - 10(-8)g/l. Mixtures of CO2+ acetone also enhanced upwind flight at 1.5 x 10(-9)g/l. High tunnel concentrations of both 1-octen-3-ol and acetone inhibited upwind responses. These findings are discussed in relation to host finding by C. impunctatus and known mechanisms by which upwind flight is initiated and arrested at high odour concentrations.     

Support vector machine-based method for subcellular localization of human proteins using amino acid compositions, their order, and similarity search

Here we report a systematic approach for predicting subcellular localization (cytoplasm, mitochondrial, nuclear, and plasma membrane) of human proteins. First, support vector machine (SVM)-based modules for predicting subcellular localization using traditional amino acid and dipeptide (i + 1) composition achieved overall accuracy of 76.6 and 77.8%, respectively. PSI-BLAST, when carried out using a similarity-based search against a nonredundant data base of experimentally annotated proteins, yielded 73.3% accuracy. To gain further insight, a hybrid module (hybrid1) was developed based on amino acid composition, dipeptide composition, and similarity information and attained better accuracy of 84.9%. In addition, SVM modules based on a different higher order dipeptide i.e. i + 2, i + 3, and i + 4 were also constructed for the prediction of subcellular localization of human proteins, and overall accuracy of 79.7, 77.5, and 77.1% was accomplished, respectively. Furthermore, another SVM module hybrid2 was developed using traditional dipeptide (i + 1) and higher order dipeptide (i + 2, i + 3, and i + 4) compositions, which gave an overall accuracy of 81.3%. We also developed SVM module hybrid3 based on amino acid composition, traditional and higher order dipeptide compositions, and PSI-BLAST output and achieved an overall accuracy of 84.4%. A Web server HSLPred (www.imtech.res.in/raghava/hslpred/ or bioinformatics.uams.edu/raghava/hslpred/) has been designed to predict subcellular localization of human proteins using the above approaches.     

Proliferating cell nuclear antigen (PCNA) as a proliferative marker during embryonic and adult zebrafish hematopoiesis

We investigated the expression of proliferative cell nuclear antigen (PCNA) in zebrafish to delineate the proliferative hematopoietic component during adult and embryonic hematopoiesis. Immunostaining for PCNA and enhanced green fluorescence protein (eGFP) was performed in wild-type and fli1-eGFP (endothelial marker) and gata1-eGFP (erythroid cell marker) transgenic fish. Expression of PCNA mRNA was examined in wild-type and chordin morphant embryos. In adult zebrafish kidney, the renal tubules are surrounded by endothelial cells and it is separated into hematopoietic and excretory compartments. PCNA was expressed in hematopoietic progenitor cells but not in mature neutrophils, eosinophils or erythroid cells. Some PCNA+ cells are scattered in the hematopoietic compartment of the kidney while others are closely associated with renal tubular cells. PCNA was also expressed in spermatogonial stem cells and intestine crypts, consistent with its role in cell proliferation and DNA synthesis. In embryos, PCNA is expressed in the brain, spinal cord and intermediate cell mass (ICM) at 24 h-post fertilization. In chordin morphants, PCNA is significantly upregulated in the expanded ICM. Therefore, PCNA can be used to mark cell proliferation in zebrafish hematopoietic tissues and to identify a population of progenitor cells whose significance would have to be further investigated.     

SVM based method for predicting HLA-DRB1*0401 binding peptides in an antigen sequence

Prediction of peptides binding with MHC class II allele HLA-DRB1(*)0401 can effectively reduce the number of experiments required for identifying helper T cell epitopes. This paper describes support vector machine (SVM) based method developed for identifying HLA-DRB1(*)0401 binding peptides in an antigenic sequence. SVM was trained and tested on large and clean data set consisting of 567 binders and equal number of non-binders. The accuracy of the method was 86% when evaluated through 5-fold cross-validation technique.