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Human Counterpart (human + counterpart)
Selected AbstractsUnderstanding the recent evolution of the human genome: insights from human,chimpanzee genome comparisons,HUMAN MUTATION, Issue 2 2007Hildegard Kehrer-Sawatzki Abstract The sequencing of the chimpanzee genome and the comparison with its human counterpart have begun to reveal the spectrum of genetic changes that has accompanied human evolution. In addition to gross karyotypic rearrangements such as the fusion that formed human chromosome 2 and the human-specific pericentric inversions of chromosomes 1 and 18, there is considerable submicroscopic structural variation involving deletions, duplications, and inversions. Lineage-specific segmental duplications, detected by array comparative genomic hybridization and direct sequence comparison, have made a very significant contribution to this structural divergence, which is at least three-fold greater than that due to nucleotide substitutions. Since structural genomic changes may have given rise to irreversible functional differences between the diverging species, their detailed analysis could help to identify the biological processes that have accompanied speciation. To this end, interspecies comparisons have revealed numerous human-specific gains and losses of genes as well as changes in gene expression. The very considerable structural diversity (polymorphism) evident within both lineages has, however, hampered the analysis of the structural divergence between the human and chimpanzee genomes. The concomitant evaluation of genetic divergence and diversity at the nucleotide level has nevertheless served to identify many genes that have evolved under positive selection and may thus have been involved in the development of human lineage-specific traits. Genes that display signs of weak negative selection have also been identified and could represent candidate loci for complex genomic disorders. Here, we review recent progress in comparing the human and chimpanzee genomes and discuss how the differences detected have improved our understanding of the evolution of the human genome. Hum Mutat 28(2), 99,130, 2007. © 2006 Wiley-Liss, Inc. [source] Meningioangiomatosis in Young Dogs: A Case Series and Literature ReviewJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2004Todd M. Bishop Meningioangiomatosis (MA) is a proliferative disorder of the central nervous system (CNS) that has been reported rarely in humans and sporadically in dogs. Meningioangiomatosis may occur in the brainstem or cervical spinal cord of young dogs and can be identified tentatively by magnetic resonance imaging. The histopathologic hallmark of MA is a leptomeningeal plaque that extends along the CNS microvasculature and invades the adjacent neural parenchyma. This case series describes the neurologic signs, clinical progression, diagnostic imaging, and neuropathology of 4 dogs with MA. The 4 dogs with MA are compared and contrasted with 4 previously reported cases in dogs as well as with their human counterpart. [source] Intratesticular localization of the organic solute carrier protein, OSCP1, in spermatogenic cells in miceMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 10 2008Kazuyuki Hiratsuka Abstract Organic solute carrier protein 1 (OSCP1) is a recently described human gene that facilitates the transport of various organic solutes into the cell, when expressed in frog eggs. In this study, we cloned a mouse ortholog of OSCP1 encoding 379 amino acid protein, with 94% homology to the human counterpart. The mouse OSCP1 mRNA was predominantly expressed in the testis, in which it was attributed to the spermatogenic cells, except the spermatogonia. Immunohistochemistry confirmed that OSCP1 protein is continuously expressed during spermatogenesis in a stage- and cell type-specific manner, in the leptotene spermatocytes at stage IX through step 15 spermatids. Subcellular fractionation of mouse testis homogenates indicated that OSCP1 is a 45-kDa cytosolic protein. Moreover, when green fluorescent protein-OSCP1 fusion constructs were transfected into cultured cells, the fluorescence localized evenly in the cytoplasm. These results suggest that mouse testis OSCP1 may indirectly mediate substrate uptake into meiotic and spermiogenic germ cells, within the cytosol. Mol. Reprod. Dev. 75: 1495,1504 © 2008 Wiley-Liss, Inc. [source] Distal enhancer of the mouse FGF-4 gene and its human counterpart exhibit differential activity: Critical role of a GT boxMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2005Brian Boer Abstract Previous studies have shown that there is a strict requirement for fibroblast growth factor-4 (FGF-4) during mammalian embryogenesis, and that FGF-4 expression in embryonic stem (ES) cells and embryonal carcinoma (EC) cells are controlled by a powerful downstream distal enhancer. More recently, mouse ES cells were shown to express significantly more FGF-4 mRNA than human ES cells. In the work reported here, we demonstrate that mouse EC cells also express far more FGF-4 mRNA than human EC cells. Using a panel of FGF-4 promoter/reporter gene constructs, we demonstrate that the enhancer of the mouse FGF-4 gene is approximately tenfold more active than its human counterpart. Moreover, we demonstrate that the critical difference between the mouse and the human FGF-4 enhancer is a 4 bp difference in the sequence of an essential GT box. Importantly, we demonstrate that changing 4 bp in the human enhancer to match the sequence of the mouse GT box elevates the activity of the human FGF-4 enhancer to the same level as that of the mouse enhancer. We extended these studies by examining the roles of Sp1 and Sp3 in FGF-4 expression. Although we demonstrate that Sp3, but not Sp1, can activate the FGF-4 promoter when artificially tethered to the FGF-4 enhancer, we show that Sp3 is not essential for expression of FGF-4 mRNA in mouse ES cells. Finally, our studies with human EC cells suggest that the factor responsible for mediating the effect of the mouse GT box is unlikely to be Sp1 or Sp3, and this factor is either not expressed in human EC cells or it is not sufficiently active in these cells. Mol. Reprod. Dev. © 2005 Wiley-Liss, Inc. [source] Expression of Genes in the Canine Pre-implantation Uterus and Embryo: Implications for an Active Role of the Embryo Before and During InvasionREPRODUCTION IN DOMESTIC ANIMALS, Issue 6 2008S Schäfer-Somi Contents The aim of the present study was to assess genes expressed in maternal uterine tissue and pre-implantation embryos which are presumably involved in maternal recognition and establishment of canine pregnancy. For this purpose, 10 pregnant bitches were ovariohysterectomized between days 10 and 12 after mating. Four non-pregnant bitches served as controls. Early pregnancy was verified by flushing the uterine horns with PBS solution. The collected embryos (n = 60) were stored deep-frozen (,80°C). Uterine tissue was excised, snaps frozen in liquid nitrogen and homogenized using TRI Reagent. All embryos from one litter were thawed together and also homogenized in TRI Reagent. RT-PCR was performed to prove mRNA expression of progesterone receptor, key enzymes of the prostaglandin synthesis pathway, selected growth factors, cytokines, immune cell receptors, major histocompatibility complex (MHC) and matrix-metalloproteinases (MMP). Only pregnant uteri revealed the presence of mRNA for interferon (IFN)-,, IL-4 and CD-8, which resembles the milieu in humans and other mammalians. Similarly, in day 10 embryos, mRNA for transforming growth factor-,, insulin-like growth factor-1,-2, hepatocyte growth factor, leukaemia inhibitor factor, tumour necrosis factor-,, interleukin-1,,-6,-8, cyclooxygenase-2, CD4+ cells, and MMP-2 and -9 were detected, but not MHC-I or -II. We therefore suppose that the canine embryo, like its human counterpart, actively initiates measures to prevent attacks from the maternal immune system to prepare its own adhesion, nidation, growth and further development. [source] Update on Semen Technologies for Animal Breeding,REPRODUCTION IN DOMESTIC ANIMALS, Issue 1 2006JM Morrell Contents Despite the scale of the livestock breeding industry, where many millions of insemination doses are prepared each year, sperm preparation techniques are used infrequently in animal assisted reproduction compared with its human counterpart. However, some of the techniques used for human sperm preparation, for example, density gradient centrifugation, improve the quality of sperm preparations which is, in turn, reflected by an increased conception rate. The preparation technique separates motile spermatozoa with normal morphology and intact DNA from the total sperm population, leaving behind immature or senescent spermatozoa, morphologically abnormal ones and those with damaged DNA. Furthermore, the motile spermatozoa are removed from the seminal plasma which carries cells, cellular debris and reactive oxygen species, as well as pathogens. Gradient-prepared spermatozoa survive longer, either in liquid storage or when cryopreserved, and are free of bacteria and viral infectivity if prepared carefully. Preparation techniques such as density gradient centrifugation, or the simplified single layer centrifugation technique, have considerable potential for aiding sperm preparation from poor quality semen samples, such as may be obtained from unselected semen donors in captive breeding programmes, or from performance horses. Moreover, the removal of pathogens has important implications, both for disease control and for avoiding the use of antibiotics in semen extenders, which can be detrimental to sperm survival. [source] Structures of dihydrofolate reductase-thymidylate synthase of Trypanosoma cruzi in the folate-free state and in complex with two antifolate drugs, trimetrexate and methotrexateACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2009Olga Senkovich The flagellate protozoan parasite Trypanosoma cruzi is the pathogenic agent of Chagas disease (also called American trypanosomiasis), which causes approximately 50,000 deaths annually. The disease is endemic in South and Central America. The parasite is usually transmitted by a blood-feeding insect vector, but can also be transmitted via blood transfusion. In the chronic form, Chagas disease causes severe damage to the heart and other organs. There is no satisfactory treatment for chronic Chagas disease and no vaccine is available. There is an urgent need for the development of chemotherapeutic agents for the treatment of T. cruzi infection and therefore for the identification of potential drug targets. The dihydrofolate reductase activity of T. cruzi, which is expressed as part of a bifunctional enzyme, dihydrofolate reductase,thymidylate synthase (DHFR-TS), is a potential target for drug development. In order to gain a detailed understanding of the structure,function relationship of T. cruzi DHFR, the three-dimensional structure of this protein in complex with various ligands is being studied. Here, the crystal structures of T. cruzi DHFR-TS with three different compositions of the DHFR domain are reported: the folate-free state, the complex with the lipophilic antifolate trimetrexate (TMQ) and the complex with the classical antifolate methotrexate (MTX). These structures reveal that the enzyme is a homodimer with substantial interactions between the two TS domains of neighboring subunits. In contrast to the enzymes from Cryptosporidium hominis and Plasmodium falciparum, the DHFR and TS active sites of T. cruzi lie on the same side of the monomer. As in other parasitic DHFR-TS proteins, the N-terminal extension of the T. cruzi enzyme is involved in extensive interactions between the two domains. The DHFR active site of the T. cruzi enzyme shows subtle differences compared with its human counterpart. These differences may be exploited for the development of antifolate-based therapeutic agents for the treatment of T. cruzi infection. [source] Differential expression of CaMK-II genes during early zebrafish embryogenesisDEVELOPMENTAL DYNAMICS, Issue 1 2007Sarah C. Rothschild Abstract CaMK-II is a highly conserved Ca2+/calmodulin-dependent protein kinase expressed throughout the lifespan of all vertebrates. During early development, CaMK-II regulates cell cycle progression and "non-canonical" Wnt-dependent convergent extension. In the zebrafish, Danio rerio, CaMK-II activity rises within 2 hr after fertilization. At the time of somite formation, zygotic expression from six genes (camk2a1, camk2b1, camk2g1, camk2g2, camk2d1, camk2d2) results in a second phase of increased activity. Zebrafish CaMK-II genes are 92,95% identical to their human counterparts in the non-variable regions. During the first three days of development, alternative splicing yields at least 20 splice variants, many of which are unique. Whole-mount in situ hybridization reveals that camk2g1 comprises the majority of maternal expression. All six genes are expressed strongly in ventral regions at the 18-somite stage. Later, camk2a1 is expressed in anterior somites, heart, and then forebrain. Camk2b1 is expressed in somites, mid- and forebrain, gut, retina, and pectoral fins. Camk2g1 appears strongly along the midline and then in brain, gut, and pectoral fins. Camk2g2 is expressed early in the midbrain and trunk and exhibits the earliest retinal expression. Camk2d1 is elevated early at somite boundaries, then epidermal tissue, while camk2d2 is expressed in discrete anterior locations, steadily increasing along either side of the dorsal midline and then throughout the brain, including the retina. These findings reveal a complex pattern of CaMK-II gene expression consistent with pleiotropic roles during development. Developmental Dynamics 236:295,305, 2007. © 2006 Wiley-Liss, Inc. [source] Classical sheep transmissible spongiform encephalopathies: pathogenesis, pathological phenotypes and clinical diseaseNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2007M. Jeffrey Scrapie is a prion disease or transmissible spongiform encephalopathy (TSE) of sheep, goats and moufflon. As with its human counterparts, pathology consists of vacuolation, gliosis and accumulations of abnormal forms of a host prion protein (PrPd) in the brain of affected individuals. Immunohistochemical methods can be used to identify both the intracellular truncation sites of PrPd in different cell types (PrPd epitope mapping) and the different morphological patterns of accumulation (PrPd profiling). Differences in the inferred truncation sites of PrPd are found for different strains of sheep TSEs and for different infected cell types within individual strains. Immunochemical methods of characterizing strains broadly correspond to PrPd mapping discriminatory results, but distinct PrPd profiles, which provide strain- and source-specific information on both the cell types which sustain infection (cellular tropisms) and the cellular processing of PrPd, have no immunoblotting counterparts. The cause of neurological dysfunction in human is commonly considered to be neuronal loss secondary to a direct or indirect effect of the accumulation of PrPd. However, in sheep scrapie there is no significant neuronal loss, and relationships between different magnitudes, topographical and cytological forms of PrPd accumulation and clinical signs are not evident. PrPd accumulation also occurs in lymphoid tissues, for which there is indirect evidence of a pathological effect, in the peripheral nervous system and in other tissues. It is generally assumed that neuroinvasion results from infection of the enteric nervous system neurones subsequent to amplification of infectivity in lymphoid tissues and later spread via sympathetic and parasympathetic pathways. The evidence for this is, however, circumstantial. Accumulation of PrPd and presence of infectivity in tissues other than the nervous and lymphoreticular systems gives insights on the ways of transmission of infection and on food safety. [source] Co-Culture of Mouse Epidermal Cells for Studies of PigmentationPIGMENT CELL & MELANOMA RESEARCH, Issue 2 2003Tae-Jin Yoon Interactions between melanocytes and keratinocytes in the skin suggest bi-directional interchanges between these two cell types. Thus, melanocytes cultured alone may not accurately reflect the physiology of the skin and the effects of physiological regulators in vivo, because they do not consider possible interactions with keratinocytes. As more and more pigment genes are identified and cloned, the characterization of their functions becomes more of a challenge, particularly with respect to their roles in the processing and transport of melanosomes and their transfer to keratinocytes. Immortalized melanocytes mutant at these loci are now being routinely generated from mice, but interestingly, successful co-culture of murine melanocytes and keratinocytes is very difficult compared with their human counterparts. Thus, we have now optimized co-culture conditions for murine melanocytes and keratinocytes so that pigmentation and the effects of specific mutations can be studied in a more physiologically relevant context. [source] The preterm piglet , a model in the study of oesophageal development in preterm neonatesACTA PAEDIATRICA, Issue 2 2010S Rasch Abstract Aim:, Preterm infants have difficulty in attaining independent oral feeding. This can ensue from inadequate sucking, swallowing and/or respiration. In impeding bolus transport, immature oesophageal motility may also be a cause. As studies on the development of oesophageal motility are invasive in preterm infants, the preterm piglet was investigated as a potential research model. Methods:, Oesophageal motility (EM) of term (n = 6) and preterm (n = 15) piglets were monitored by manometry for 10 min immediately following bottle feeding on days 1,2 and 3,4 of life. Results:, Piglets' oral feeding performance and EM were similar to those of their human counterparts. Term piglets readily completed their feeding, whereas their preterm counterparts did not. They also presented with greater peristaltic activity and propagating velocity. Peristaltic activity remained unchanged over time in preterm piglets, but an increase in synchronous and decrease in incomplete motor activity were noted. Preterm piglets that developed symptoms analogous to necrotizing enterocolitis (NEC) demonstrated uncharacteristic oesophageal activity. Conclusion:, Immature EM may cause oral feeding difficulties. NEC-like symptoms may adversely affect EM. The piglet is a valid research model for studying human infant oral feeding and oesophageal development. [source] | |||||||||||||