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Primate-Specific Evolution of an LDLR Enhancer

Description: Sequence changes in regulatory regions have often beeninvoked to explain phenotypic divergence among species, but molecularexamples of this have been difficult to obtain. In this study, weidentified an anthropoid primate specific sequence element thatcontributed to the regulatory evolution of the LDL receptor. Using acombination of close and distant species genomic sequence comparisonscoupled with in vivo and in vitro studies, we show that a functionalcholesterol-sensing sequence motif arose and was fixed within apre-existing enhancer in the common ancestor of anthropoid primates. Ourstudy demonstrates one molecular mechanism by which ancestral mammalianregulatory elements can evolve to perform new functions in the primatelineage leading to human.
Date: June 28, 2006
Creator: Wang, Qian-fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles et al.
Partner: UNT Libraries Government Documents Department

Primate-specific evolution of an LDLR enhancer

Description: Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates. Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human.
Date: December 1, 2005
Creator: Wang, Qian-Fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles et al.
Partner: UNT Libraries Government Documents Department

The PanK2 Genes of Mouse and Human Specify Proteins with DistinctSubcellular Locations

Description: Coenzyme A (CoA) biosynthesis is initiated by pantothenatekinase (PanK) and CoA levels are controlled through differentialexpression and feedback regulation of PanK isoforms. PanK2 is amitochondrial protein in humans, but comparative genomics revealed thatacquisition of a mitochondrial targeting signal was limited to primates.Human and mouse PanK2 possessed similar biochemical properties, withinhibition by acetylCoA and activation by palmitoylcarnitine. Mouse PanK2localized in the cytosol, and the expression of PanK2 was higher in humanbrain compared to mouse brain. Differences in expression and subcellularlocalization should be considered in developing a mouse model for humanPanK2 deficiency. (c) 2007 Federation of European Biochemical Societies.Published by Elsevier B.V.
Date: May 1, 2007
Creator: Leonardi, Roberta; Zhang, Yong-Mei; Lydikis, Athanasios; Stevens,Robert D.; Ilkayeva, Olga R.; Wenner, Brett R. et al.
Partner: UNT Libraries Government Documents Department

Detection of Weakly Conserved Ancestral Mammalian RegulatorySequences by Primate Comparisons

Description: Genomic comparisons between human and distant, non-primatemammals are commonly used to identify cis-regulatory elements based onconstrained sequence evolution. However, these methods fail to detectcryptic functional elements, which are too weakly conserved among mammalsto distinguish from nonfunctional DNA. To address this problem, weexplored the potential of deep intra-primate sequence comparisons. Wesequenced the orthologs of 558 kb of human genomic sequence, coveringmultiple loci involved in cholesterol homeostasis, in 6 nonhumanprimates. Our analysis identified 6 noncoding DNA elements displayingsignificant conservation among primates, but undetectable in more distantcomparisons. In vitro and in vivo tests revealed that at least three ofthese 6 elements have regulatory function. Notably, the mouse orthologsof these three functional human sequences had regulatory activity despitetheir lack of significant sequence conservation, indicating that they arecryptic ancestral cis-regulatory elements. These regulatory elementscould still be detected in a smaller set of three primate speciesincluding human, rhesus and marmoset. Since the human and rhesus genomesequences are already available, and the marmoset genome is activelybeing sequenced, the primate-specific conservation analysis describedhere can be applied in the near future on a whole-genome scale, tocomplement the annotation provided by more distant speciescomparisons.
Date: June 1, 2006
Creator: Wang, Qian-fei; Prabhakar, Shyam; Chanan, Sumita; Cheng,Jan-Fang; Rubin, Edward M. & Boffelli, Dario
Partner: UNT Libraries Government Documents Department

Convergent evolution in primates and an insectivore

Description: The cardiovascular risk factor apolipoprotein(a) (apo(a)) has a puzzling distribution among mammals, its presence being limited to a subset of primates and a member of the insectivore lineage, the hedgehog. To explore the evolutionary history of apo(a), we performed extensive genomic sequence comparisons of multiple species with and without an apo(a) gene product, such as human, baboon, hedgehog, lemurand mouse. This analysis indicated that apo(a) arose independently in a subset of primates, including baboon and human, and an insectivore, the hedgehog, and was not simply lost by species lacking it. The similar structural domains shared by the hedgehog and primate apo(a) indicate that they were formed by a unique molecular mechanism involving the convergent evolution of paralogous genes in these distantspecies.
Date: April 16, 2003
Creator: Boffelli, Dario; Cheng, Jan-Fang & Rubin, Edward M.
Partner: UNT Libraries Government Documents Department

Accelerated Evolution of Conserved Noncoding Sequences in theHuman Genome

Description: Genomic comparisons between human and distant, non-primatemammals are commonly used to identify cis-regulatory elements based onconstrained sequence evolution. However, these methods fail to detect"cryptic" functional elements, which are too weakly conserved amongmammals to distinguish from nonfunctional DNA. To address this problem,we explored the potential of deep intra-primate sequence comparisons. Wesequenced the orthologs of 558 kb of human genomic sequence, coveringmultiple loci involved in cholesterol homeostasis, in 6 nonhumanprimates. Our analysis identified 6 noncoding DNA elements displayingsignificant conservation among primates, but undetectable in more distantcomparisons. In vitro and in vivo tests revealed that at least three ofthese 6 elements have regulatory function. Notably, the mouse orthologsof these three functional human sequences had regulatory activity despitetheir lack of significant sequence conservation, indicating that they arecryptic ancestral cis-regulatory elements. These regulatory elementscould still be detected in a smaller set of three primate speciesincluding human, rhesus and marmoset. Since the human and rhesus genomesequences are already available, and the marmoset genome is activelybeing sequenced, the primate-specific conservation analysis describedhere can be applied in the near future on a whole-genome scale, tocomplement the annotation provided by more distant speciescomparisons.
Date: July 6, 2006
Creator: Prambhakar, Shyam; Noonan, James P.; Paabo, Svante & Rubin, EdwardM.
Partner: UNT Libraries Government Documents Department

The sequence and analysis of duplication rich human chromosome 16

Description: Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes, and 3 RNA pseudogenes. These genes include metallothionein, cadherin, and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. While the segmental duplications of chromosome 16 are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events likely to have had an impact on the evolution of primates and human disease susceptibility.
Date: April 6, 2005
Creator: Martin, J; Han, C; Gordon, L A; Terry, A; Prabhakar, S; She, X et al.
Partner: UNT Libraries Government Documents Department

Functional analysis and elimination of SIB in an olive baboon (Papio hamadryas anubis).

Description: Self injurious behavior (SIB), such as self-biting and head-banging, has been reported to occur in approximately 10% of captive, individually housed primates (Novak, Kinsely, Jorgensen, and Hazen, 1998). Accounts of the causes of SIB range from environmental to physiological. However, to date, no researchers have investigated the possible influence of social consequences, delivered by handlers and keepers, in the maintenance of SIB. There is only one research report showing that self-injury can be shaped in primates by the manipulation of food as a reinforcing consequence for the animal's behavior. The current study investigated the effects of social contact as potentially reinforcing consequences for the SIB displayed by an olive baboon (Papio hamadryas anubis). Results indicated that the behavior was maintained by attention from humans. As treatment, reinforcement was arranged for an appropriate alternative attention-getting behavior, resulting in increases in the appropriate alternative behavior and decreases in SIB.
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Date: August 2004
Creator: Dorey, Nicole R.
Partner: UNT Libraries

eShadow: A tool for comparing closely related sequences

Description: Primate sequence comparisons are difficult to interpret due to the high degree of sequence similarity shared between such closely related species. Recently, a novel method, phylogenetic shadowing, has been pioneered for predicting functional elements in the human genome through the analysis of multiple primate sequence alignments. We have expanded this theoretical approach to create a computational tool, eShadow, for the identification of elements under selective pressure in multiple sequence alignments of closely related genomes, such as in comparisons of human to primate or mouse to rat DNA. This tool integrates two different statistical methods and allows for the dynamic visualization of the resulting conservation profile. eShadow also includes a versatile optimization module capable of training the underlying Hidden Markov Model to differentially predict functional sequences. This module grants the tool high flexibility in the analysis of multiple sequence alignments and in comparing sequences with different divergence rates. Here, we describe the eShadow comparative tool and its potential uses for analyzing both multiple nucleotide and protein alignments to predict putative functional elements. The eShadow tool is publicly available at http://eshadow.dcode.org/
Date: January 15, 2004
Creator: Ovcharenko, Ivan; Boffelli, Dario & Loots, Gabriela G.
Partner: UNT Libraries Government Documents Department

Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons

Description: Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent with haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human QTL genes in a highly controlled non-human primate model.
Date: September 15, 2003
Creator: Wang, Qian-fei; Liu, Xin; O'Connell, Jeff; Peng, Ze; Krauss, Ronald M.; Rainwater, David L. et al.
Partner: UNT Libraries Government Documents Department

Aging and Gene Expression in the Primate Brain

Description: It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.
Date: February 18, 2005
Creator: Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante & Eisen, Michael B.
Partner: UNT Libraries Government Documents Department

Value engineering: A new focus for women in engineering

Description: Value Engineering is an organized problem solving technique that utilizes communication and teamwork skills -- skills heralded as strengths for women. Value Engineering offers an excellent career opportunity for women in the engineering profession. It is an expanded career path that is currently being overlooked by women. Value Engineering is supported by SAVE (Society of American Value Engineers) and certification in the process can be achieved in two years. For women in the engineering profession, VE is an ideal place to redirect their existing skills and training. The number of certified women is a minority, creating a wide-open field of opportunity in federal and state agencies as well as private industry. Value Engineering can provide that new avenue for engineering careers -- a new direction where current skills can be applied to a diverse and exciting profession. 1 fig.
Date: April 20, 1990
Creator: Anderson, L.C.
Partner: UNT Libraries Government Documents Department

From Africa to the stars

Description: The thesis is developed that our evolutionary future, like our past, is tied to our penchant for exploration and migration. The main stages of human exploration and migration are examined, with the evolutionary implications of each, starting from the time our distant ancestors first stood upright and continuing into the coming era of space expansion. (ACR)
Date: January 1, 1983
Creator: Finney, B.R. & Jones, E.M.
Partner: UNT Libraries Government Documents Department

Evolutionary expansion and divergence in a large family of primate-specific zinc finger transcription factor genes

Description: Although most genes are conserved as one-to-one orthologs in different mammalian orders, certain gene families have evolved to comprise different numbers and types of protein-coding genes through independent series of gene duplications, divergence and gene loss in each evolutionary lineage. One such family encodes KRAB-zinc finger (KRAB-ZNF) genes, which are likely to function as transcriptional repressors. One KRAB-ZNF subfamily, the ZNF91 clade, has expanded specifically in primates to comprise more than 110 loci in the human genome, yielding large gene clusters in human chromosomes 19 and 7 and smaller clusters or isolated copies at other chromosomal locations. Although phylogenetic analysis indicates that many of these genes arose before the split between old world monkeys and new world monkeys, the ZNF91 subfamily has continued to expand and diversify throughout the evolution of apes and humans. The paralogous loci are distinguished by sequence divergence within their zinc finger arrays indicating a selection for proteins with different DNA binding specificities. RT-PCR and in situ hybridization data show that some of these ZNF genes can have tissue-specific expression patterns, however many KRAB-ZNFs that are near-ubiquitous could also be playing very specific roles in halting target pathways in all tissues except for a few, where the target is released by the absence of its repressor. The number of variant KRAB-ZNF proteins is increased not only because of the large number of loci, but also because many loci can produce multiple splice variants, which because of the modular structure of these genes may have separate and perhaps even conflicting regulatory roles. The lineage-specific duplication and rapid divergence of this family of transcription factor genes suggests a role in determining species-specific biological differences and the evolution of novel primate traits.
Date: September 28, 2005
Creator: Hamilton, A T; Huntley, S; Tran-Gyamfi, M; Baggott, D; Gordon, L & Stubbs, L
Partner: UNT Libraries Government Documents Department

Fabrication of a set of realistic torso phantoms for calibration of transuranic nuclide lung counting facilities

Description: A set of 16 tissue equivalent torso phantoms has been fabricated for use by major laboratories involved in counting transuranic nuclides in the lung. These phantoms, which have bone equivalent plastic rib cages, duplicate the performance of the DOE Realistic Phantom set. The new phantoms (and their successors) provide the user laboratories with a highly realistic calibration tool. Moreover, use of these phantoms will allow participating laboratories to intercompare calibration information, both on formal and informal bases. 3 refs., 2 figs.
Date: October 26, 1983
Creator: Griffith, R.V.; Anderson, A.L.; Sundbeck, C.W. & Alderson, S.W.
Partner: UNT Libraries Government Documents Department

Chimpanzee chromosome 12 is homologous to human chromosome 2q

Description: Most of the 46 human chromosomes find their counterparts in the 48 chimpanzee chromosomes except for chromosome 2 which has been hypothesized to have been derived from a centric fusion of two chimpanzee acrocentric chromosomes. These two chromosomes correspond to the human chromosomes 2p and 2g. This conclusion is based primarily on chromosome banding techniques, and the somatic cell hybridization technique has also been used. (HLW)
Date: January 1, 1977
Creator: Sun, N. C.; Sun, C. R.Y. & Ho, T.
Partner: UNT Libraries Government Documents Department

Chimpanzee chromosome 13 is homologous to human chromosome 2p

Description: Similarities between human and chimpanzee chromosomes are shown by chromosome banding techniques and somatic cell hybridization techniques. Cell hybrids were obtained from the chimpanzee lymphocyte LE-7, and the Chinese hamster mutant cell, Gal-2. Experiments showed that the ACPL, MDHs, and Gal-Act genes could be assigned to chimpanzee chromosome 13, and since these genes have been assigned to human chromosme 2p, it is suggested that chimpanzee chromosome 13 is homologous to human chromosome 2p. (HLW)
Date: January 1, 1977
Creator: Sun, N. C.; Sun, C. R.Y. & Ho, T.
Partner: UNT Libraries Government Documents Department

Progress in Understanding the Toxicity of Gasoline and Diesel Engine Exhaust Emissions

Description: To help guide heavy vehicle engine, fuel, and exhaust after-treatment technology development, the U.S. Department of Energy and the Lovelace Respiratory Research Institute are conducting research not addressed elsewhere on aspects of the toxicity of particulate engine emissions. Advances in these technologies that reduce diesel particulate mass emissions may result in changes in particle composition, and there is concern that the number of ultrafine (<0.1 micron) particles may increase. All present epidemiological and laboratory data on the toxicity of diesel emissions were derived from emissions of older-technology engines. New, short-term toxicity data are needed to make health-based choices among diesel technologies and to compare the toxicity of diesel emissions to those of other engine technologies. This research program has two facets: (1) development and use of short-term in vitro and in vivo toxicity assays for comparing the toxicities of gasoline and diesel exhaust emissions; and (2) determination of the disposition of inhaled ultrafine particles deposited in the lung. Responses of cultured cells, cultured lung slices, and rodent lungs to various types of particles were compared to develop an improved short-term toxicity screening capability. To date, chemical toxicity indicators of cultured human A549 cells and early inflammatory and cytotoxic indicators of rat lungs have given the best distinguishing capability. A study is now underway to determine the relative toxicities of exhaust samples from in-use diesel and gasoline engines. The samples are being collected under the direction of the National Renewable Energy Laboratory with support from DOE's Office of Heavy Vehicle Technologies. The ability to generate solid ultrafine particles and to trace their movement in the body as particles and soluble material was developed. Data from rodents suggest that ultrafine particles can move from the lung to the liver in particulate form. The quantitative disposition of inhaled ultrafine particles will be determined ...
Date: April 26, 1999
Creator: Nikula, Kristen J.; Finch, Gregory L.; Westhouse, Richard A.; Seagrave, JeanClare; Mauderly, Joe L.; Lawson, Doughlas R. et al.
Partner: UNT Libraries Government Documents Department

Final Report of LDRD Project Number 34693: Building Conscious Machines Based Upon the Architecture of Visual Cortex in the Primate Brain

Description: Our research plan is two-fold: first, we have extended our biological model of bottom-up visual attention with several recently characterized cortical interactions that are known to be responsible for human performance in certain visual tasks, and second, we have used an eyetracking system for collecting human eye movement data, from which we can calibrate the new additions to the model. We acquired an infrared video eyetracking system, which we are using to record observers' eye position with high temporal (120Hz) and spatial ({+-} 0.25 deg visual angle) accuracy. We collected eye movement scan paths from observers as they view computer-generated fractals, rural and urban outdoor scenes, and overhead satellite imagery. We found that, with very high statistical significance (10 to 12 z-scores), the saliency model accurately predicts locations that human observers will find interesting. We adopted our model of short-range interactions among overlapping spatial orientation channels to better predict bottom-up stimulus-driven attention in humans. This enhanced model is even more accurate in its predictions of human observers' eye movements. We are currently incorporating biologically plausible long-range interactions among orientation channels, which will aid in the detection of elongated contours such as rivers, roads, airstrips, and other man-made structures.
Date: January 1, 2003
Creator: KOCH, CHRISTOF
Partner: UNT Libraries Government Documents Department

Emeritus Scientists, Mathematicians and Engineers (ESME) program

Description: The Emeritus Scientists, Mathematicians and Engineers (ESME) program matches retired scientists and engineers with wide experience with elementary school children in order to fuel the children's natural curiosity about the world in which they live. The long-range goal is to encourage students to maintain the high level of mathematical and science capability that they exhibit at an early age by introducing them to the fun and excitement of the world of scientific investigation and engineering problem solving. Components of the ESME program are the emeriti, established teacher-emeriti teams that work to produce a unit of 6 class hours of demonstration or hands-on experiments, and the encounter by students with the world of science/engineering through the classroom sessions and a field trip to a nearby plant or laboratory.
Date: September 1, 1992
Creator: Sharlin, H.I.
Partner: UNT Libraries Government Documents Department

The Human Genome Program

Description: Early in 1986, Charles DeLisi, then head of the Office of Health and Environmental Research at the Department of Energy (DOE) requested the Los Alamos National Laboratory (LANL) to organize a workshop charged with inquiring whether the state of technology and potential payoffs in biological knowledge and medical practice were such as to justify an organized program to map and sequence the human genome. The DOE's interest arose from its mission to assess the effects of radiation and other products of energy generation on human health in general and genetic material in particular. The workshop concluded that the technology was ripe, the benefits would be great, and a national program should be promptly initiated. Later committees, reporting to DOE, to the NIH, to the Office of Technology Assessment of the US Congress, and to the National Academy of Science have reviewed these issues more deliberately and come to the same conclusion. As a consequence, there has been established in the United States, a Human Genome Program, with funding largely from the NIH and the DOE, as indicated in Table 1. Moreover, the Program has attracted international interest, and Great Britain, France, Italy, and the Soviet Union, among other countries, have been reported to be starting human genome initiatives. Coordination of these programs, clearly in the interests of each, remains to be worked out, although an international Human Genome Organization (HUGO) is considering such coordination. 5 refs., 1 fig., 2 tabs.
Date: January 1, 1989
Creator: Bell, G.I.
Partner: UNT Libraries Government Documents Department

[News Clip: Ape picnic]

Description: Video footage from the KXAS-TV/NBC station in Fort Worth, Texas, to accompany a news story. This story aired at 6:00 P.M.
Date: 1980
Creator: KXAS-TV (Television station : Fort Worth, Tex.)
Partner: UNT Libraries Special Collections