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Human Adults (human + adult)
Selected AbstractsPAR-1 activation has different effects on the angiogenic activity of endothelial progenitor cells derived from human adult and cord bloodJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2006D. M. SMADJA [source] Growth factors improve gene expression after lentiviral transduction in human adult and fetal hepatocytesTHE JOURNAL OF GENE MEDICINE, Issue 2 2007Clare Selden Abstract Background Lentiviral vectors may be vectors of choice for transducing liver cells; they mediate integration in quiescent cells and offer potential for long-term expression. In adult liver, hepatocytes are generally mitotically quiescent. There has been controversy as to the necessity for lentiviral vector target cells to be in the cell cycle; currently, there is consensus that effective transduction can be achieved in quiescent hepatocytes, by using virus at high titre. However, transduction approaches which reduce the multiplicities of infection (MOIs) required provide potential benefit of cost and safety for therapeutic use. Methods We used two late-generation HIV-based lentiviral vector systems (pHR-SIN-cppT SGW and pRRLSIN.cPPT.PGK.WPRE) encoding LacZ/GFP reporter genes to transduce adult and fetal human hepatocytes in vitro + /, growth factors, hepatocyte growth factor (HGF) and epidermal growth factor (EGF). Green fluorescent protein (GFP) expression was observed microscopically, and quantified by fluorescence spectrometry for protein expression, fluorescence-activated cell sorting (FACS) analysis to identify the proportion of cells expressing GFP, and real-time quantitative polymerase chain reaction (PCR) for number of integrations. Results Gene expression following lentiviral transduction of human liver cells in vitro was markedly enhanced by the growth factors HGF and EGF. In adult cells growth factors led to a greater proportion of cells expressing more GFP per cell, from more integration events. In human fetal cells, the proportion of transduced hepatocytes remained identical, but cells expressed more GFP protein. Conclusions This has implications for the design of regimes for liver cell gene therapy, allowing marked reduction of MOIs, and reducing both cost and risk of viral-mediated toxicity. Copyright © 2007 John Wiley & Sons, Ltd. [source] Extent of cell differentiation and capacity for cartilage synthesis in human adult adipose-derived stem cells: Comparison with fetal chondrocytesBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2010Nastaran Mahmoudifar Abstract This study evaluated the extent of differentiation and cartilage biosynthetic capacity of human adult adipose-derived stem cells relative to human fetal chondrocytes. Both types of cell were seeded into nonwoven-mesh polyglycolic acid (PGA) scaffolds and cultured under dynamic conditions with and without addition of TGF-,1 and insulin. Gene expression for aggrecan and collagen type II was upregulated in the stem cells in the presence of growth factors, and key components of articular cartilage such as glycosaminoglycan (GAG) and collagen type II were synthesized in cultured tissue constructs. However, on a per cell basis and in the presence of growth factors, accumulation of GAG and collagen type II were, respectively, 3.4- and 6.1-fold lower in the stem cell cultures than in the chondrocyte cultures. Although the stem cells synthesized significantly higher levels of total collagen than the chondrocytes, only about 2.4% of this collagen was collagen type II. Relative to cultures without added growth factors, treatment of the stem cells with TGF-,1 and insulin resulted in a 59% increase in GAG synthesis, but there was no significant change in collagen production even though collagen type II gene expression was upregulated 530-fold. In contrast, in the chondrocyte cultures, synthesis of collagen type II and levels of collagen type II as a percentage of total collagen more than doubled after growth factors were applied. Although considerable progress has been achieved to develop differentiation strategies and scaffold-based culture techniques for adult mesenchymal stem cells, the extent of differentiation of human adipose-derived stem cells in this study and their capacity for cartilage synthesis fell considerably short of those of fetal chondrocytes. Biotechnol. Bioeng. 2010;107: 393,401. © 2010 Wiley Periodicals, Inc. [source] Single genetic mutations can account for melanocytic naeviBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2005R.W. Blewitt Summary Background, The nature of melanocytic naevi is unknown notwithstanding their considerable significance for clinician and pathologist and despite the wealth of existing knowledge about melanocyte biology. Objectives, To investigate how far a simple mutational model can explain the clinical and pathological features of melanocytic naevi, in particular their pattern of onset and frequency. Methods, I have constructed a model of the development of the adult melanocyte population from a single stem cell. The total cutaneous melanocyte population in a human adult is already known, as well as the range of spontaneous mutation rates at a given gene site. For each cycle of mitosis during the post stem-cell expansion of the melanocyte population, I calculate the accumulated number of cells likely to be mutated at a particular (although unknown) gene site. The results are interpreted in the light of a hypothesis that each of these mutant melanocytes will go on to form a melanocytic naevus. Comparisons are made with neurofibromas, occurring in type 1 neurofibromatosis and as sporadic lesions. Results, A single genetic mutation in melanocyte precursors is found to be sufficient to explain the clinical and pathological features of melanocytic naevi. Conclusions, I propose that melanocytic naevi are a consequence of single spontaneous genetic mutations which inevitably occur during the development of the adult population of cutaneous melanocytes. [source] Six-month-old infants use analog magnitudes to represent durationDEVELOPMENTAL SCIENCE, Issue 5 2006Kristy VanMarle While many studies have investigated duration discrimination in human adults and in nonhuman animals, few have investigated this ability in infants. Here, we report findings that 6-month-old infants are able to discriminate brief durations, and, as with other animal species, their discrimination function is characterized by Weber's Law: proportionate difference rather than absolute difference between stimuli determined successful discrimination. Importantly, paralleling results found with nonhuman animals, the Weber function that we found for infants' discrimination of time is the same as that found for their discrimination of number. Infants discriminated durations of an audiovisual event differing by a 1:2 ratio, but not those differing by a 2:3 ratio, over a range of durations. This suggests that (a) in human as in nonhuman animals, the same mental mechanism may underlie the ability to measure duration as to represent number, and (b) we may share this mental mechanism with other animal species. [source] Number sense in human infantsDEVELOPMENTAL SCIENCE, Issue 1 2005Fei Xu Four experiments used a preferential looking method to investigate 6-month-old infants' capacity to represent numerosity in visual-spatial displays. Building on previous findings that such infants discriminate between arrays of eight versus 16 discs, but not eight versus 12 discs (Xu & Spelke, 2000), Experiments 1 and 2 investigated whether infants' numerosity discrimination depends on the ratio of the two set sizes with even larger numerosities. Infants successfully discriminated between arrays of 16 versus 32 discs, but not 16 versus 24 discs, providing evidence that their discrimination shows the set-size ratio signature of numerosity discrimination in human adults, children and many non-human animals. Experiments 3 and 4 addressed a controversy concerning infants' ability to discriminate large numerosities (observed under conditions that control for total filled area, array size and density, item size and correlated properties such as brightness: Brannon, 2002; Xu, 2003b; Xu & Spelke, 2000) versus small numerosities (not observed under conditions that control for total contour length: Clearfield & Mix, 1999). To investigate the sources of these differing findings, Experiment 3 tested infants' large-number discrimination with controls for contour length, and Experiment 4 tested small-number discrimination with controls for total filled area. Infants successfully discriminated the large-number displays but showed no evidence of discriminating the small-number displays. These findings provide evidence that infants have robust abilities to represent large numerosities. In contrast, infants may fail to represent small numerosities in visual-spatial arrays with continuous quantity controls, consistent with the thesis that separate systems serve to represent large versus small numerosities. [source] Assessment of bronchial wall thickness and lumen diameter in human adults using multi-detector computed tomography: comparison with theoretical modelsJOURNAL OF ANATOMY, Issue 5 2007M. Montaudon Abstract A thickened bronchial wall is the morphological substratum of most diseases of the airway. Theoretical and clinical models of bronchial morphometry have so far focused on bronchial lumen diameter, and bronchial length and angles, mainly assessed from bronchial casts. However, these models do not provide information on bronchial wall thickness. This paper reports in vivo values of cross-sectional wall area, lumen area, wall thickness and lumen diameter in ten healthy subjects as assessed by multi-detector computed tomography. A validated dedicated software package was used to measure these morphometric parameters up to the 14th bronchial generation, with respect to Weibel's model of bronchial morphometry, and up to the 12th according to Boyden's classification. Measured lumen diameters and homothety ratios were compared with theoretical values obtained from previously published studies, and no difference was found when considering dichotomic division of the bronchial tree. Mean wall area, lumen area, wall thickness and lumen diameter were then provided according to bronchial generation order, and mean homothety ratios were computed for wall area, lumen area and wall thickness as well as equations giving the mean value of each parameter for a given bronchial generation with respect to its value in generation 0 (trachea). Multi-detector computed tomography measurements of bronchial morphometric parameters may help to improve our knowledge of bronchial anatomy in vivo, our understanding of the pathophysiology of bronchial diseases and the evaluation of pharmacological effects on the bronchial wall. [source] A meta-analysis of serotonin metabolite 5-HIAA and antisocial behaviorAGGRESSIVE BEHAVIOR, Issue 4 2002Todd M. Moore Abstract During the past 25 years, researchers have examined the relationship between neurochemical variables and antisocial behavior in human adults, but none has been studied more intensely than the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA). The goal of the current study was to employ meta-analytic procedures to quantitatively evaluate selected evidence on the relationship between 5-HIAA and antisocial behavior. It was expected that antisocial groups would show reduced cerebrospinal fluid 5-HIAA compared with non,antisocial groups. This study also aimed to assess moderators that could influence the relationship between 5-HIAA and antisociality. An electronic search and strict inclusion criteria identified 20 reports used in this meta-analysis. Results showed a significant overall mean effect size (ES = ,.45, P < .05) in the direction of lowered 5-HIAA in antisocial vs. non,antisocial groups. A significant moderating effect for age indicated that groups comprised of antisocial individuals younger than 30 years exhibited larger negative effect sizes (ES = ,1.37, P < .05) than groups with older subjects (ES = ,.31, P < .05). There were no moderating effects for gender, target of violence, history of suicide, and alcoholism. Age effects may help explain age-related declines in crime. The fact that effects did not differ based on other moderating variables supports models of reduced serotonin in antisocial individuals, regardless of type of crime or psychiatric problems. Aggr. Behav. 28:299,316, 2002. © 2002 Wiley-Liss, Inc. [source] Radiation sensitivity increases with proliferation-associated telomere dysfunction in nontransformed human epithelial cellsAGING CELL, Issue 4 2009David Soler Summary Epidemiological studies have demonstrated age differences among human adults in susceptibility to radiation, with cancer cases attributable to radiation being more frequent for older individuals at time of exposure. In addition to the notion that susceptibility increases because of progressive decline in DNA monitoring and immunosurveillance, telomere function is now emerging as a new and important factor in modulating cellular and organism sensitivity to ionizing radiation. The link between telomeres and radiosensitivity is well-documented in humans, but the causal events remain elusive. In this paper, it is shown that irradiated human epithelial cells with short dysfunctional telomeres derived from normal mammary gland display elevated DNA damage. An approach identifying the specific chromosomes with critically shortened telomeres in each donor has allowed us to conclude that short dysfunctional telomeres in human epithelial cells join radiation-induced DNA broken ends, thus interfering with their efficient repair. These findings argue against telomeres participating as sensors or transducers of DNA damage, as previously suggested. Rather, our current findings give support to the idea that dysfunctional telomeres, by acting as an additional joining option, reduce the repair fidelity of DNA broken-ends induced by radiation throughout the genome. In the mammary gland, age-dependent telomere attrition due to epithelial turnover, together with the accretion of checkpoint deficiencies, might render the accumulation of short dysfunctional telomeres. This implies that the risks associated with mammography screening could be higher than previously assumed. Our results have the possibility of imprinting a temporal dimension onto radiation sensitivity, namely, that shortened telomeres in aged cells may more easily compromise normal tissue function in the elderly. [source] Lumbar ontogenetic growth and sexual dimorphism in modern humansAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2010Elías Valverde To detect and differentiate between possible heterochronic processes in the ontogenetic growth pattern of the human lumbar region, in relationship with sexual dimorphism. We measured the growth trajectories of average length and width, length/width ratio, posterior projected surface area, and bone mineral density using dual energy X-ray absorptiometry, in a sample group of 1718 modern humans. These growth patterns were analyzed using the Gompertz model. In adult lumbar region, only surface area and width were significantly higher in men. Regarding the ontogenetic growth pattern leading to the dimorphic states, all values obtained for women were significantly higher than those obtained for men. Maximum initial growth rates occurred for surface area and density in women. Width scaled faster than length in both sexes. The lumbar region followed patterns similar to those of other skeletal elements when compared with a previous classification of growth patterns in the human skeleton; however, in this study, the growth rate was slower. With regard to the effect of dimorphism, sexual differences in growth rate accounted for only a small proportion of the variation in lumbar length, mineral density, and surface area. Nevertheless, these sexual differences played an important role in the increase of the length/width ratio, which was reflected in the ages at which sexual dimorphism developed. The sexual dimorphism found in the lumbar region of human adults is not caused by any heterochronic process. The lower values of bone mineral density in adult women could explain the origin of some pathologies related. Am. J. Hum. Biol. 22:596,603, 2010. © 2010 Wiley-Liss, Inc. [source] Gender differences in behavioral inhibitory control: ERP evidence from a two-choice oddball taskPSYCHOPHYSIOLOGY, Issue 6 2008Jiajin Yuan Abstract The inhibition of inappropriate behaviors is important for adaptive living in changing environments. The present study investigated gender-related behavioral inhibitory control by recording event-related potentials for standard and deviant stimuli while subjects performed a standard/deviant distinction task by accurately pressing different keys within 1000 ms. The results showed faster reaction times (RTs) for deviant stimuli in women than in men, although RTs for standard stimuli were similar across genders. There were significant gender and stimulus interaction effects on mean amplitudes during each of the 170,230-ms, 250,330-ms, and 350,600-ms intervals, and women exhibited shorter latencies and larger amplitudes than men at deviant-related P2, N2, and P3 components. As an accurate, fast response to the rare deviant stimuli involves behavioral inhibitory control on the prepotent response whereas the response to the standard stimuli does not, it is clear that there is a general gender difference in behavioral control for human adults. This may relate to differential inhibitory demands by each gender during evolution. [source] | ||||||||||||||||