International Journal of Biological Sciences http://www.biolsci.org International Journal of Biological Sciences RSS feed -- Volume 4 en-us Sat, 10 May 2008 04:00:00 GMT Sat, 10 May 2008 04:00:00 GMT http://www.biolsci.org/v04p0143.htm Genetic Linkage Map of Olive Flounder, Paralichthys olivaceus http://www.biolsci.org/v04p0143.htm Olive flounder, Paralichthys olivaceus, is an important fish species in Asia, both for fisheries and aquaculture. As the first step for better understanding the genomic structure and functional analysis, we constructed a genetic linkage map for olive flounder based on 180 microsatellites and 31 expressed sequence tag (EST)-derived markers. Twenty-four linkage groups were identified, consistent with the 24 chromosomes of this species. The total map distance was 1,001.3 cM based on Kosambi sex-average mapping, and the average inter-locus distance was 4.7 cM. Linkage between the loci was identified by an LOD score of ≥3. This linkage map may be used to map quantitative trait loci associated with important traits of the species and may assist in breeding programs.

]]> Jung-Ha Kang, Woo-Jin Kim, Woo-Jai Lee Ivyspring International Publisher 4 3 143 149 2008-5-10 Research Paper http://www.biolsci.org/v04p0133.htm Identification and characterization of cancer initiating cells from BRCA1 related mammary tumors using markers for normal mammary stem cells http://www.biolsci.org/v04p0133.htm It is hypothesized that cancer stem cells arise either from normal stem cells or from progenitor cells that have gained the ability to self-renew. Here we determine whether mammary cancer stem cells can be isolated by using antibodies that have been used for the isolation of normal mammary stem cells. We show that BRCA1 mutant cancer cell lines contained a subpopulation of CD24+CD29+ or CD24+CD49f+ cells that exhibited increased proliferation and colony forming ability in vitro, and enhanced tumor-forming ability in vivo. The purified CD24+CD29+ cells could differentiate and reconstitute the heterogeneity found in parental cells when plated as a monolayer. Under low-attachment conditions, we detected “tumorspheres” only in the presence of double positive cells, which maintained their ability to self-renew. Furthermore, CD24+CD29+ cells could form tubular structures reminiscent of the mammary ductal tree when grown in three-dimensional cultures, implying that these cancer cells maintain some of the characteristics of the normal stem cells. Nevertheless, they could still drive tumor formation since as low as 500 double positive cells immediately after sorting from BRCA1 mutant primary tumors were able to form tumors with the same heterogeneity found in the original tumors. These data provide evidence that breast cancer stem cells originate from normal stem cells and advance our understanding of BRCA1-associated tumorigenesis with possible implications for future cancer treatment.

]]> Athanassios Vassilopoulos, Rui-Hong Wang, Constantinos Petrovas, David Ambrozak, Richard Koup, Chu-Xia Deng Ivyspring International Publisher 4 3 133 142 2008-5-4 Research Paper http://www.biolsci.org/v04p0126.htm Sex Hormones' Regulation of Rodent Physical Activity: A Review http://www.biolsci.org/v04p0126.htm There is a large body of emerging literature suggesting that physical activity is regulated to a varying extent by biological factors. Available animal data strongly suggests that there is a differential regulation of physical activity by sex and that the majority of this differential regulation is mediated by estrogen/testosterone pathways with females in many animal species having higher daily activity levels than males. The purpose of this manuscript is to review the mechanisms by which estrogen, progesterone, and testosterone affect the regulation of physical daily activity. This review lays the foundation for future investigations in humans as well as discussions about relative disease risk mediated by differential biological regulation of physical activity by sex.

]]> J. Timothy Lightfoot Ivyspring International Publisher 4 3 126 132 2008-4-29 Review http://www.biolsci.org/v04p0116.htm Relationship between calcium decoding elements and plant abiotic-stress resistance http://www.biolsci.org/v04p0116.htm Serving as an important second messenger, calcium ion has unique properties and universal ability to transmit diverse signals that trigger primary physiological actions in cells in response to hormones, pathogens, light, gravity, and stress factors. Being a second messenger of paramount significance, calcium is required at almost all stages of plant growth and development, playing a fundamental role in regulating polar growth of cells and tissues and participating in plant adaptation to various stress factors. Many researches showed that calcium signals decoding elements are involved in ABA-induced stomatal closure and plant adaptation to drought, cold, salt and other abiotic stresses. Calcium channel proteins like AtTPC1 and TaTPC1 can regulate stomatal closure. Recently some new studies show that Ca2+ is dissolved in water in the apoplast and transported primarily from root to shoot through the transpiration stream. The oscillating amplitudes of [Ca2+]o and [Ca2+]i are controlled by soil Ca2+ concentrations and transpiration rates. Because leaf water use efficiency (WUE) is determined by stomatal closure and transpiration rate, so there may be a close relationship between Ca2+ transporters and stomatal closure as well as WUE, which needs to be studied. The selection of varieties with better drought resistance and high WUE plays an increasing role in bio-watersaving in arid and semi-arid areas on the globe. The current paper reviews the relationship between calcium signals decoding elements and plant drought resistance as well as other abiotic stresses for further study.

]]> Wei-Yi Song, Zheng-Bin Zhang, Hong-Bo Shao, Xiu-Lin Guo, Hong-Xing Cao, Hong-Bin Zhao, Zheng-Yan Fu, Xiao-Jun Hu Ivyspring International Publisher 4 2 116 125 2008-4-26 Review http://www.biolsci.org/v04p0111.htm Association between the frequency of class II HLA antigens and the susceptibility to intrauterine infection of hepatitis B virus http://www.biolsci.org/v04p0111.htm Multiple factors determine the susceptibility to intrauterine hepatitis B virus (HBV) infection. These factors include the HBV structure, HBV mutation, HBV DNA level, placental barrier, the immune status of the mother, and the genetic make-ups of the newborn infants. Since HLA system is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes are the key determinants of intrauterine HBV infection. In this study, we selected newborn infants of HBsAg-positive mothers, and divided the infants into 2 groups: intrauterine infection group and non-intrauterine infection group according to the status whether or not they were infected at birth. Each infected infant was compared with 2 controls from the same birth cohort. HLA-DR allele typing was performed using a PCR-sequence specific primer (PCR-SSP) for 24 subjects with intrauterine infection and 48 controls without infection. We found that, among the fifteen (15) HLA-DR alleles assessed, HLA-DRB1*07 was the one, and the only one, significantly in excess (OR = 6.66, P = 0.004) in the intrauterine infection group compared to the non-intrauterine infection group. Our findings thus suggest that high frequency of HLA class II molecules, e.g. HLA-DRB1*07, is associated with the susceptibility of the infants to intrauterine HBV infection.

]]> Yuan-yong Xu, Ji-yun Yu, Yan-wei Zhong, Hong-bin Song, Hui-hui Liu, Lei-li Jia, Shen-long Li, Jian-qiu Xu, Qiao Li Ivyspring International Publisher 4 2 111 115 2008-4-25 Research Paper http://www.biolsci.org/v04p0103.htm Screening of Human Antibody Fab Fragment against HBsAg and the Construction of its dsFv Form http://www.biolsci.org/v04p0103.htm The objective of this study was to pursue the techniques involving the screening of the human antibody Fab fragment against hepatitis B virus surface antigen (HBsAg) and the construction of its disulfide-stabilized Fv fragment (dsFv). The phage antibody Fab fragments against HBsAg were screened from the human combinatorial immunoglobulin library. Sequence analysis revealed that its heavy chain gene was complete, but the light chain gene was lost. To improve the affinity of the antibody by chain shuffling, a human antibody light chain gene repertoire was generated by reverse transcriptase-polymerase chain reaction (RT-PCR) from the human peripheral blood lymphocytes. A phage antibody sub-library was then constructed by inserting the light chain gene repertoire into the phagmid that contained the Fd gene. Five clones with appreciably higher absorbance than that of the original clones were obtained, which indicated that the affinity of the light chain-shuffled phage antibodies was improved. Then, the mutated genes of dsFv against HBsAg were constructed by using PCR-based point mutagenesis method. Purified VH and VL proteins were folded into a 25-kDa protein, designated as anti-HBsAg dsFv. ELISA and competition ELISA revealed that the dsFv maintained the specificity of the Fab by binding to HBsAg, even through with a lower binding activity. These results have facilitated the undertaking of further functional analyses of the constructed dsFv, and may therefore provide an improved technique for the production and application of dsFvs against HBsAg.

]]> Leili Jia, Jiyun Yu, Hongbin Song, Xuelin Liu, Weina Ma, Yuanyong Xu, Chuanfu Zhang, Shicun Dong, Qiao Li Ivyspring International Publisher 4 2 103 110 2008-4-24 Research Paper http://www.biolsci.org/v04p0096.htm Comparative understanding of UTS2 and UTS2R genes for their involvement in type 2 diabetes mellitus http://www.biolsci.org/v04p0096.htm Several reports have shown that urotensin 2 (UTS2) and its receptor (UTS2R) are involved in glucose metabolism and insulin resistance, which lead to development of type 2 diabetes mellitus (T2DM) in humans. In the present study, we annotated both bovine UTS2 and UTS2R genes and identified 5 single nucleotide polymorphisms (SNPs) for the former gene and 14 mutations for the latter gene. Four mutations were genotyped on a Wagyu x Limousin reference population, including 6 F1 bulls, 113 F1 dams and ~250 F2 progeny. Among 12 phenotypes related to fat deposition and fatty acid composition, we observed that the UTS2 gene was significantly associated with the amount of skeletal saturated fatty acids, while its receptor (UTS2R) gene had significant effects on amounts of saturated and monounsaturated fatty acids, Δ9 desaturase activity for converting 16:0 into 16:1, muscle fat (marbling) score and Longissimus Dorsi muscle area. However, in this population, these markers were not associated with subcutaneous fat depth or percent kidney, pelvic and heart fat. We also found that mutations in the promoter regions altered the promoter activities in both genes and coding SNPs might affect the mRNA stability in the UTS2R gene. Overall, our present study provides the first evidence that both UTS2 and UTS2R genes regulate skeletal muscle fat accumulation and fatty acid metabolism, thus indicating their potential pathological functions related to obesity and T2DM in humans.

]]> Zhihua Jiang, Jennifer J. Michal, David J. Tobey, Zeping Wang, Michael D. MacNeil, Nancy S. Magnuson Ivyspring International Publisher 4 2 96 102 2008-4-23 Research Paper http://www.biolsci.org/v04p0087.htm Mutation at Tyrosine in AMLRY (GILRY Like) Motif of Yeast eRF1 on Nonsense Codons Suppression and Binding Affinity to eRF3 http://www.biolsci.org/v04p0087.htm Termination translation in Saccharomyces cerevisiae is controlled by two interacting polypeptide chain release factors, eRF1 and eRF3. Two regions in human eRF1, position at 281-305 and position at 411-415, were proposed to be involved on the interaction to eRF3. In this study we have constructed and characterized yeast eRF1 mutant at position 410 (correspond to 415 human eRF1) from tyrosine to serine residue resulting eRF1(Y410S). The mutations did not affect the viability and temperature sensitivity of the cell. The stop codons suppression of the mutant was analyzed in vivo using PGK-stop codon-LACZ gene fusion and showed that the suppression of the mutant was significantly increased in all of codon terminations. The suppression on UAG codon was the highest increased among the stop codons by comparing the suppression of the wild type respectively. In vitro interaction between eRF1 (mutant and wild type) to eRF3 were carried out using eRF1-(His)6 and eRF1(Y410S)-(His)6 expressed in Escherichia coli and indigenous Saccharomyces cerevisiae eRF3. The results showed that the binding affinity of eRF1(Y410S) to eRF3 was decreased up to 20% of the wild type binding affinity. Computer modeling analysis using Swiss-Prot and Amber version 9.0 programs revealed that the overall structure of eRF1(Y410S) has no significant different with the wild type. However, substitution of tyrosine to serine triggered the structural change on the other motif of C-terminal domain of eRF1. The data suggested that increasing stop codon suppression and decreasing of the binding affinity of eRF1(Y410S) were probably due to the slight modification on the structure of the C-terminal domain.

]]> Akhmaloka, Prima Endang Susilowati, Subandi, Fida Madayanti Ivyspring International Publisher 4 2 87 95 2008-4-21 Research Paper http://www.biolsci.org/v04p0081.htm Interactions between SNP Alleles at Multiple Loci Contribute to Skin Color Differences between Caucasoid and Mongoloid Subjects http://www.biolsci.org/v04p0081.htm This study aimed to identify single nucleotide polymorphism (SNP) alleles at multiple loci associated with racial differences in skin color using SNP genotyping. A total of 122 Caucasians in Toledo, Ohio and 100 Mongoloids in Japan were genotyped for 20 SNPs in 7 candidate genes, encoding the Agouti signaling protein (ASIP), tyrosinase-related protein 1 (TYRP1), tyrosinase (TYR), melanocortin 1 receptor (MC1R), oculocutaneous albinism II (OCA2), microphthalmia-associated transcription factor (MITF), and myosin VA (MYO5A). Data were used to analyze associations between the 20 SNP alleles using linkage disequilibrium (LD). Combinations of SNP alleles were jointly tested under LD for associations with racial groups by performing a χ2 test for independence. Results showed that SNP alleles at multiple loci can be considered the haplotype that contributes to significant differences between the two population groups and suggest a high probability of LD. Confirmation of these findings requires further study with other ethnic groups to analyze the associations between SNP alleles at multiple loci and skin color variation among races.

]]> Sumiko Anno, Takashi Abe, Takushi Yamamoto Ivyspring International Publisher 4 2 81 86 2008-3-31 Research Paper http://www.biolsci.org/v04p0071.htm Shedding Light on the Role of Vitreoscilla Hemoglobin on Cellular Catabolic Regulation by Proteomic Analysis http://www.biolsci.org/v04p0071.htm Heterologous expression of Vitreoscilla hemoglobin (VHb) has been reported to improve cell growth, protein synthesis, metabolite productivity and nitric oxide detoxification. Although it has been proposed that such phenomenon is attributed to the enhancement of respiration and energy metabolism by facilitating oxygen delivery, the mechanism of VHb action remains to be elucidated. In the present study, changes of protein expression profile in Escherichia coli as a consequence of VHb production was investigated by two-dimensional gel electrophoresis (2-DE) in conjunction with peptide mass fingerprinting. Total protein extracts derived from cells expressing native green fluorescent protein (GFPuv) and chimeric VHbGFPuv grown in Luria-Bertani broth were prepared by sonic disintegration. One hundred microgram of proteins was individually electrophoresed in IEF-agarose rod gels followed by gradient SDS-PAGE gels. Protein spots were excised from the gels, digested to peptide fragments by trypsin, and analyzed using matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry. Results revealed that expression of VHbGFPuv caused an entire disappearance of tryptophanase as well as down-regulated proteins involved in various metabolic pathways, e.g. glycerol kinase, isocitrate dehydrogenase, aldehyde dehydrogenase, and D-glucose-D-galactose binding protein. Phenotypic assay of cellular indole production confirmed the differentially expressed tryptophanase enzymes in which cells expressing chimeric VHbGFP demonstrated a complete indole-negative reaction. Supplementation of δ-aminolevulinic acid (ALA) to the culture medium enhanced expression of glyceraldehyde-3-phosphate dehydrogenase and glycerol kinase. Our findings herein shed light on the functional roles of VHb on cellular carbon and nitrogen consumptions as well as regulation of other metabolic pathway intermediates, possibly by autoregulation of the catabolite repressor regulons.

]]> Chartchalerm Isarankura-Na-Ayudhya, Patcharee Panpumthong, Teerawit Tangkosakul, Somchai Boonpangrak, Virapong Prachayasittikul Ivyspring International Publisher 4 2 71 80 2008-3-3 Research Paper http://www.biolsci.org/v04p0063.htm Effect of UVA Fluence Rate on Indicators of Oxidative Stress in Human Dermal Fibroblasts http://www.biolsci.org/v04p0063.htm During the course of a day human skin is exposed to solar UV radiation that fluctuates in fluence rate within the UVA (290-315 nm) and UVB (315-400 nm) spectrum. Variables affecting the fluence rate reaching skin cells include differences in UVA and UVB penetrating ability, presence or absence of sunscreens, atmospheric conditions, and season and geographical location where the exposure occurs. Our study determined the effect of UVA fluence rate in solar-simulated (SSR) and tanning-bed radiation (TBR) on four indicators of oxidative stress---protein oxidation, glutathione, heme oxygenase-1, and reactive oxygen species--in human dermal fibroblasts after receiving equivalent UVA and UVB doses. Our results show that the higher UVA fluence rate in TBR increases the level of all four indicators of oxidative stress. In sequential exposures when cells are exposed first to SSR, the lower UVA fluence rate in SSR induces a protective response that protects against oxidative stress following a second exposure to a higher UVA fluence rate. Our studies underscore the important role of UVA fluence rate in determining how human skin cells respond to a given dose of radiation containing both UVA and UVB radiation.

]]> James D. Hoerter, Christopher S. Ward, Kyle D. Bale, Admasu N. Gizachew, Rachelle Graham, Jaclyn Reynolds, Melanie E. Ward, Chesca Choi, Jean-Leonard Kagabo, Michael Sauer, Tara Kuipers, Timothy Hotchkiss, Nate Banner, Renee A. Chellson, Theresa Ohaeri, Langston Gant, Leah Vanderhill Ivyspring International Publisher 4 2 63 70 2008-2-19 Short Research Communication http://www.biolsci.org/v04p0058.htm Bioavailability of Heme Iron in Biscuit Filling Using Piglets as an Animal Model for Humans http://www.biolsci.org/v04p0058.htm The objective of this work was to evaluate the bioavailability of heme iron added to biscuit filling. It comprised two stages: first, the development of the heme iron enriched biscuit filling; second, the evaluation of the bioavailability of the mineral in fattening piglets. Two groups were selected randomly and fed: a) Low iron feed and biscuits with heme iron supplemented filling; b) Normal feed (with ferrous sulphate). Weight and blood parameters were measured every fifteen days. Averages were compared after duplicate analyses. The filling had a creamy appearance, chocolate taste and smell, appropriate spreadability, heme iron content of 2.6 mg per gram and a shelf-life of a month. The heme iron supplemented pigs registered a greater (P<0.05) weight gain (27.8% more than the control group). Mortality in the heme iron group was 10%, compared to 50% in the control group. The amount of iron measured in the different compartment was greater in the heme group (3315 mg) than in the control group (2792 mg). However, the amount of iron consumed in the latter was greater. We show that an acceptable product with high heme iron content can be formulated, suitable for use as biscuit filling. The heme iron supplement produced better weight increase and lesser mortality in fattening pigs. The bioavailability of heme iron was 23% greater (P<0.05) compared to ferrous sulphate.

]]> Adrián Guillermo Quintero-Gutiérrez, Guillermina González-Rosendo, Jonathan Sánchez-Muñoz, Javier Polo-Pozo, José Juan Rodríguez-Jerez Ivyspring International Publisher 4 1 58 62 2008-2-18 Research Paper http://www.biolsci.org/v04p0048.htm ParaHox genes in pancreatic cell cultures: effects on the insulin promoter regulation http://www.biolsci.org/v04p0048.htm The gene encoding PDX1 (pancreatic duodenum homeobox 1), the main transcription factor regulating the glucose-dependent transactivation of the insulin promoter in pancreatic β-cells, clusters with two closely related homeobox genes (Gsh1 and Cdx2/3), all of them belonging to the ParaHox gene family. The ParaHox gene evolutionary history in the vertebrate lineage involved duplications of the cluster and subsequent loss of some members, so that eventually, the human and murine genomes contain only 6 ParaHox genes. The crucial role of PDX1 in pancreas development, beta-cell formation and insulin transcription regulation has long been established. There is some data on CDX2/3 function in α-cells, but remarkably, nothing is known on the role of the other ParaHox genes, which are also expressed in the endocrine pancreas. Homeobox transcription factors that belong to the same family show high conservation of the homeodomain and share similar target sites and oligomeric partners, and thus may act redundantly, synergistically or antagonistically on the same promoters. Therefore, we explored the effects of the Parahox proteins (GSH1, GSH2, CDX1, CDX2/3 and CDX4) on the regulation of the insulin promoter in transfected α- and β- cultured cell lines at different glucose concentrations and compared them to those of PDX1. Noticeably, several ParaHox transcription factors are able to transactivate or inhibit the insulin promoter, depending on the cell type and glucose concentration, thus suggesting their possible participation in the regulation of similar target genes, such as insulin, either by silencing or activating them, in the absence of PDX1.

]]> Anna Rosanas-Urgell, Jordi Garcia-Fernàndez, Gemma Marfany Ivyspring International Publisher 4 1 48 57 2008-2-6 Research Paper http://www.biolsci.org/v04p0037.htm Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate http://www.biolsci.org/v04p0037.htm Inorganic polyphosphate [poly(P)] is a biopolymer existing in almost all cells and tissues, although its biological functions in higher eukaryotes have not been completely elucidated. We previously demonstrated that poly(P) enhances the function of fibroblast growth factors (FGFs) by stabilizing them and strengthening the affinity between FGFs and their cell surface receptors. Since FGFs play crucial roles in bone regeneration, we further investigated the effect of poly(P) on the cell differentiation of human stem cells via FGF signaling systems. Human dental pulp cells (HDPCs) isolated from human dental pulp show the characteristics of multipotent mesenchymal stem cells (MSCs). HDPCs secreted FGFs and the proliferation of HDPCs was shown to be enhanced by treatment with poly(P). Cell surface receptor-bound FGF-2 was stably maintained for more than 40 hours in the presence of poly(P). The phosphorylation of ERK1/2 was also enhanced by poly(P). The effect of poly(P) on the osteogenic differentiation of HDPCs and human MSCs (hMSCs) were also investigated. After 5 days of treatment with poly(P), type-I collagen expression of both cell types was enhanced. The C-terminal peptide of type-I collagen was also released at higher levels in poly(P)-treated HDPCs. Microarray analysis showed that expression of matrix metalloproteinase-1 (MMP1), osteopontin (OPN), osteocalcin (OC) and osteoprotegerin was induced in both cell types by poly(P). Furthermore, induced expression of MMP1, OPN and OC genes in both cells was confirmed by real-time PCR. Calcification of both cell types was clearly observed by alizarin red staining following treatment with poly(P). The results suggest that the activation of the FGF signaling pathway by poly(P) induces both proliferation and mineralization of stem cells.

]]> Yumi Kawazoe, Shinichi Katoh, Yuichiro Onodera, Takao Kohgo, Masanobu Shindoh, Toshikazu Shiba Ivyspring International Publisher 4 1 37 47 2008-2-3 Research Paper http://www.biolsci.org/v04p0029.htm Reduced white fat mass in adult mice bearing a truncated Patched 1 http://www.biolsci.org/v04p0029.htm Hedgehog (Hh) signaling emerges as a potential pathway contributing to fat formation during postnatal development. In this report, we found that Patched 1 (Ptc1), a negative regulator of Hh signaling, was expressed in the epididymal fat pad of adult mice. Reduced total white fat mass and epididymal adipocyte cell size were observed in naturally occurring spontaneous mesenchymal dysplasia (mes) adult mice (Ptc1mes/mes), which carry a deletion of Ptc1 at the carboxyl-terminal cytoplasmic region. Increased expression of truncated Ptc1, Ptc2 and Gli1, the indicators of ectopic activation of Hh signaling, was observed in epididymal fat pads of adult Ptc1mes/mes mice. In contrast, expression of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, adipocyte P2 and adipsin were reduced in epididymal fat pads of adult Ptc1mes/mes mice. Taken together, our results indicate that deletion of carboxyl-terminal tail of Ptc1 can lead to the reduction of white fat mass during postnatal development.

]]> Zili Li, Heng Zhang, Leslie A. Denhard, Lan-Hsin Liu, Huaxin Zhou, Zi-Jian Lan Ivyspring International Publisher 4 1 29 36 2008-1-26 Research Paper http://www.biolsci.org/v04p0023.htm Neurophysiologic Measurement of Continuity in the Sleep of Fetuses during the Last Week of Pregnancy and in Newborns http://www.biolsci.org/v04p0023.htm Our aim was to measure the correlation between fetal electrocardiographic (FECG) recordings of low-risk pregnancies and polysomnographic (PSG) study parameters in low-risk infants born at term as a measurement of perinatal sleep-development continuity.

We designed a short, prospective, observational follow-up of physiologic parameters between fetuses and newborns. We studied 10 fetuses from low-risk pregnant female out-patients and the same subjects as low-risk newborns delivered at term. Fetal state (FS) was defined in FECG recordings reassembling the following: fetal state I (quiet sleep or QS); fetal state II (active sleep or AS); fetal state III (quiet waking), and fetal state IV (active waking). Percentages of AS, QS, and wakefulness in PSG studies of newborns were also determined.

Comparisons of FS I with QS showed a significant reduction in QS, while comparison of FS II with AS showed significant reduction in AS. Negative correlations were found between FS I with QS, and FS II with AS. Number of cycles in FECG recordings and PSG sleep cycles also demonstrated significant correlation.

In conclusion our data showed partial but significant sleep function continuity from fetal to neonatal period.

]]> Adrián Poblano, Reyes Haro, Carmina Arteaga Ivyspring International Publisher 4 1 23 28 2007-12-13 Research Paper http://www.biolsci.org/v04p0015.htm Quantitative analysis on the characteristics of targets with FDA approved drugs http://www.biolsci.org/v04p0015.htm Accumulated knowledge of genomic information, systems biology, and disease mechanisms provide an unprecedented opportunity to elucidate the genetic basis of diseases, and to discover new and novel therapeutic targets from the wealth of genomic data. With hundreds to a few thousand potential targets available in the human genome alone, target selection and validation has become a critical component of drug discovery process. The explorations on quantitative characteristics of the currently explored targets (those without any marketed drug) and successful targets (targeted by at least one marketed drug) could help discern simple rules for selecting a putative successful target. Here we use integrative in silico (computational) approaches to quantitatively analyze the characteristics of 133 targets with FDA approved drugs and 3120 human disease genes (therapeutic targets) not targeted by FDA approved drugs. This is the first attempt to comparatively analyze targets with FDA approved drugs and targets with no FDA approved drug or no drugs available for them. Our results show that proteins with 5 or fewer number of homologs outside their own family, proteins with single-exon gene architecture and proteins interacting with more than 3 partners are more likely to be targetable. These quantitative characteristics could serve as criteria to search for promising targetable disease genes.

]]> Meena K. Sakharkar, Peng Li, Zhaowei Zhong, Kishore R. Sakharkar Ivyspring International Publisher 4 1 15 22 2007-12-10 Research Paper http://www.biolsci.org/v04p0008.htm Primary antioxidant free radical scavenging and redox signaling pathways in higher plant cells http://www.biolsci.org/v04p0008.htm Antioxidants in plant cells mainly include glutathione, ascorbate, tocopherol, proline, betaine and others, which are also information-rich redox buffers and important redox signaling components that interact with cellular compartments. As an unfortunate consequence of aerobic life for higher plants, reactive oxygen species (ROS) are formed by partial reduction of molecular oxygen. The above enzymatic and non-enzymatic antioxidants in higher plant cells can protect their cells from oxidative damage by scavenging ROS. In addition to crucial roles in defense system and as enzyme cofactors, antioxidants influence higher plant growth and development by modifying processes from miotosis and cell elongation to senescence and death. Most importantly, they provide essential information on cellular redox state, and regulate gene expression associated with biotic and abiotic stress responses to optimize defense and survival. An overview of the literature is presented in terms of primary antioxidant free radical scavenging and redox signaling in plant cells. Special attention is given to ROS and ROS-anioxidant interaction as a metabolic interface for different types of signals derived from metabolisms and from the changing environment. This interaction regulates the appropriate induction of acclimation processes or execution of cell death programs, which are the two essential directions for higher plant cells.

]]> Hong-Bo Shao, Li-Ye Chu, Zhao-Hua Lu, Cong-Min Kang Ivyspring International Publisher 4 1 8 14 2007-12-7 Review http://www.biolsci.org/v04p0001.htm Transplantation of adult neural progenitor cells transfected with Vascular Endothelial Growth Factor rescues grafted cells in the rat brain http://www.biolsci.org/v04p0001.htm Growth factors are currently evaluated as therapeutics in stroke and neurodegeneration. Besides direct neurotrophic effects, they promote proliferation, survival, and differentiation of both transplanted and endogenous neural precursor cells (NPCs). In the current study, we investigated whether NPCs expressing Vascular Endothelial Growth Factor VEGF-A165 are a useful vehicle for growth factor delivery after transplantation into the caudate putamen of the rat brain. We found an increased survival of adenovirally transfected NPCs after 11 days, but not after 24 hours or 4 days. Additional brain immunohistochemistry revealed increased expression of the endothelial cell marker PECAM-1 (CD31) after 24 hours, 4 day, and 11 days after transplantation. In conclusion, we show that the graft itself is a useful vehicle for growth factor delivery, promoting the survival of NPCs. Moreover, transplantation of VEGF-expressing NPCs supports angiogenesis in the brain, which may contribute to potential brain repair.

]]> Martin H. Maurer, Christine Thomas, Heinrich F. Bürgers, Wolfgang Kuschinsky Ivyspring International Publisher 4 1 1 7 2007-12-3 Short Research Communication