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[Technical limitations of the positron emission tomography (PET) for small laboratory animals].

Visualization and quantification of organ function by PET in small laboratory animals is becoming an outstanding tool for characterization of phenotype of transgenic and knock-out animals, for the study of animal models of human diseases, and for the development of new therapeutic drugs and diagnostic biochemical probes. To be able to make use of the PET with small laboratory animals in the same way as it is operated with humans it is necessary to account for the volumetric scale factor as well as for the requirement of maintaining the counting statistics. This work sketches the problems that these requirements represent for the technical design of the scanners and for the execution of the experiments. Finally, some characteristics of commercially available scanners (microPET/ FOCUS, HiDAC, eXplore VISTA, MOSAIC, YAP-(S)PET and rPET) are briefly discussed.

Animals↗

Y-chromosomal diversity suggests that Baltic males share common Finno-Ugric-speaking forefathers.

OBJECTIVE: To elucidate the genetic relationships between Estonian, Latvian and Lithuanian men by studying Y-chromosomal variation in these people. METHODS: The allelic status of five deep-rooted marker loci (YAP, Tat, M9, 92R7 and SRY-1532) was determined for 346 Baltic males. On the basis of single nucleotide polymorphism (SNP) haplotypes, Y chromosomes were divided into six haplogroups, and the Baltic haplogroup distribution compared with that in 7 European reference populations. Haplogroup frequencies, diversities and genetic distances (F(ST) values) were calculated. The relationships between populations were further illustrated using Mantel test, neighbor-joining tree and principal-component map. RESULTS: We found the Indo-European-speaking Latvians and Lithuanians to be genetically very similar to the Finno-Ugric-speaking Estonians. When compared to the reference populations, Baltic males were most closely related to the Finno-Ugric-speaking Mari, followed by their Finnish and Slavonic neighbors. CONCLUSIONS: The genetic similarity existing between Estonian, Latvian and Lithuanian men suggests that they originate from the same male founder population. Since the Baltic Y-chromosomal haplogroup distribution more closely resembles that of Finno-Ugric than Indo-European-speaking populations, we propose a hypothesis that Baltic males share a common Finno-Ugric ancestry.

Alleles↗

Further studies on the genetics of the Chamorros of Guam: dermatoglyphics.

The present study represents a continuation of our efforts to further define the genetic structure of the Chamorro population of Guam. The dermatoglyphic features of Guamanian Chamorros differ significantly from those of Western Carolinians from the Outer Islands of Yap in fingerprint patterns, model types of C line, frequency of patterns in the thenar/I area and in the presence of Sydney creases. The results of this analysis confirm earlier data from serological and other genetic markers that Guamanian Chamorros are genetically more closely related to the people of southeastern Asia than to their Micronesian neighbors to the south.

Adult↗

Heterogeneity of the Y chromosome in Afro-Brazilian populations.

Sixteen biallelic markers (SRY10831a, SRY10831b, SRY4064, SRY2627, 92R7, P2, P3, M34, M9, M3, M2, YAP, M60, M89, M213, M216) located in the nonrecombinant region of the Y chromosome were analyzed in 209 individuals belonging to six Brazilian populations: four Afro-Brazilian populations, one population of white European descendants, and one population of Japanese descendants. The results showed that most of the Y chromosomes of the Afro-Brazilians were from sub-Saharan Africa and that the proportion of Y chromosomes of European origin was greater than that of Y chromosomes of Amerindian origin. No typical African or Amerindian haplogroup was detected among Japanese individuals, and only one white individual showed a typical African haplogroup. Haplogroup P-92R7, which is highly frequent in the Portuguese and Italian populations, was the most frequent among whites (54%), and haplogroup K-M9, which shows wide geographic distribution and is absent in Africa, was the most frequent among Japanese individuals (65.6%). The two semi-isolated Afro-Brazilian populations showed the highest and the lowest genetic diversity, respectively. These differences probably reflect the effect of greater or smaller gene flow between a small isolated group and other populations. These findings show that the process of admixture does not occur homogeneously, with a tendency toward preferential marriages within the ethnic group and a clear direction in unions between European men and Amerindian or African women in the past. The results agree with historical and social data about the formation of the Brazilian population and reveal some of the factors that contribute to its heterogeneity.

Africa South of the Sahara↗

Origin of pitcher plant mosquitoes in Aedes (Stegomyia): a molecular phylogenetic analysis using mitochondrial and nuclear gene sequences.

Two mosquito species of the subgenus Stegomyia (genus Aedes) (Diptera: Culicidae) on the islands of Palau and Yap (Aedes dybasi Bohart and Aedes maehleri Bohart) are adapted to aquatic habitats occupied by Nepenthes pitcher plants. To reveal the origin of these pitcher plant mosquitoes, we attempted a molecular phylogenetic analysis with 11 Stegomyia species by using sequence data from mitochondrial cytochrome oxidase subunit I and 16SrRNA genes as well as the nuclear 28SrRNA gene. Ae. dybasi, a pitcher plant specialist, was sister to Aedes palauensis Bohart within the scutellaris group from the same islands. Ae. maehleri, an opportunistic pitcher plant mosquito, was in a distinct lineage related to the scutellaris group. The adaptation to pitcher plants could have occurred independently in these two species, and recent differentiation of the pitcher plant mosquito Ae. dybasi from the nonpitcher plant mosquito Ae. palauensis was suggested by a relatively small sequence divergence between these species. We also discuss the implications of this analysis for the phylogeny of some other Stegomyia species.

Aedes↗

Cellular physiological effects of the MV Kyowa violet fuel-oil spill on the hard coral, Porites lobata.

The grounding of the Merchant Vessel (MV) Kyowa Violet on a coral reef near Yap, Federated States of Micronesia, in December 2002 resulted in the release of an estimated 55,000 to 80,000 gallons of intermediate fuel oil grade 180. The immediate impact was the widespread coating of mangroves and the intertidal zone along more than 8 km of coastline. Of greater concern, however, was the partitioning of the fuel oil in the water column, leading to chronic exposure of organisms in the ecosystem for a considerable period after the initial event. Herein, we report on our examination of one coral species, Porites lobata, nearly three months after the initial exposure. We investigated whether changes in cellular physiology were consistent with the pathological profile that results from the interaction of corals with polycyclic aromatic hydrocarbons, the principal constituent of fuel oil. Specifically, we document, to our knowledge for the first time, changes in the cellular physiological condition of an exposed coral population affected by a fuel-oil spill. We also provide evidence that the observed changes are consistent with a recent exposure to fuel oil, as evidenced by the presence of characteristic cellular lesions attributed to polycyclic aromatic hydrocarbons. Finally, our data support a model for a mechanistic relationship between the cellular pathological profile of the coral and a recent petroleum exposure, such as the MV Kyowa Violet fuel oil spill.

Animals↗

TAZ: a beta-catenin-like molecule that regulates mesenchymal stem cell differentiation.

Regulating the switch between proliferation and differentiation of mesenchymal stem cells is critical for the development of normal tissues, and the prevention of tumors. How mesenchymal stem cells exit from the cell cycle and differentiate into alternative cell fates such as bone, fat, and muscle, is incompletely understood. We recently discovered that a WW domain-containing molecule, TAZ, functions as a transcriptional modulator to stimulate bone development while simultaneous blocking the differentiation of mesenchymal stem cells into fat. These developmental effects occur through direct interaction between TAZ and the transcription factors Runx2 and PPARgamma, resulting in transcriptional enhancement and repression, respectively of selective programs of gene expression. We propose that TAZ, as well as a highly related molecule YAP, are functionally, though not structurally, similar to beta-catenin and integrate extracellular, membrane, and cytoskeletal-derived signals to influence mesenchymal stem cell fate.

Acyltransferases↗

A screening method for antimitotic and antifungal substances using conidia of Pyricularia oryzae, modification and application to tropical marine fungi.

A bioassay method detecting deformations of mycelia germinated from conidia of Pyricularia oryzae P-2b, has been modified to give quantitative estimations. The method was first developed using antimitotic agents which showed characteristic curling effect. Morphological deformations include curling, swelling, hyper-divergency, beads shape and so on, and inhibition of the germination was also observed. For quantitative estimations, indices were introduced for the hyphal growth inhibition and a quantity of conidia in each assay cell and concentration of test solutions were adjusted. Details of the modified method and the application to screening assay of marine fungi isolated in Yap Islands are described. Eight strains of 109 tested showed morphological deformations, and chaetoglobosin A was isolated from the broth filtrate of a strain assigned to Chaetomium sp. This bioassay is a cheap, quick and easy method to be applied to the primary screening for antimitotic and antifungal substances from natural sources.

Antifungal Agents↗

Negligible male gene flow across ethnic boundaries in India, revealed by analysis of Y-chromosomal DNA polymorphisms.

From the historically prevalent social structure of Indian populations it may be predicted that there has been very little male gene flow across ethnic boundaries. To test this finding, we have analyzed DNA samples of individuals belonging to 10 ethnic groups, speaking Indo-European or Austroasiatic languages and inhabiting the eastern and northern regions of India. Eight Y-chromosomal markers, two biallelic and six microsatellite, were studied. All populations were monomorphic for the deletion allele at the YAP (DYS287) locus and for the 119-bp allele at the DYS288 locus. Y-chromosomal haplotypes were constructed on the basis of one RFLP locus and five microsatellite loci. The haplotype distribution among the groups showed that different ethnic groups harbor nearly disjoint sets of haplotypes. This indicates that there has been virtually no male gene flow among ethnic groups. Analysis of molecular variance revealed that there was significant haplotypic variation between castes and tribes, but nonsignificant variation among ranked caste clusters. Haplotypic variation attributable to differences in geographical regions of habitat was also nonsignificant.

DNA↗

Ca2+-bound calmodulin forms a compact globular structure on binding four trifluoperazine molecules in solution.

Small-angle X-ray scattering (SAXS), which determines the radius of gyration, R(g), and the pair distance distribution function, was used to investigate the conformational changes of calmodulin (CaM) on binding to an antagonist, trifluoperazine (TFP), with or without Ca(2+) in solution. We previously applied this SAXS method to CaM complexed with N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7) [Osawa, Kuwamoto, Izumi, Yap, Ikura, Shibanuma, Yokokura, Hidaka and Matsushima (1999) FEBS Lett. 442, 173-177] and found that the binding of two W-7 TFP molecules to one Ca(2+)-saturated CaM molecule induces structural changes from a 'dumb-bell' shape to a compact globular shape. We report here that the most compact globular shape whose size is consistent with that of the 1:2 Ca(2+)-saturated CaM-W-7 complex is formed by the binding of four TFP molecules to one Ca(2+)-saturated CaM molecule. Even in the absence of Ca(2+), the conformational changes of CaM occur on TFP binding, giving a slightly smaller R(g) than Ca(2+)-free CaM alone.

Animals↗

[Analysis of Y-chromosomal diallelic loci polymorphism in populations of the Volga-Ural region].

Three diallelic polymorphisms of human Y chromosome, DYS287 (Y Alu polymorphism, YAP), T/C transition at the RBF5 locus (Tat), and G/A transition at the LLY22 locus, were studied in eight ethnic populations of the Volga-Ural region, representing Turkic (Bashkirs, Tatars, and Chuvashes) and Finno-Ugric (Maris, Mordovians, Udmurts, Komi-Zyryans, and Komi-Permyaks) branches of the Uralic linguistic family, and in the group of Slavic migrants, belonging to the Indo-European linguistic family (Russians). Ethnic populations of the Volga-Ural region were characterized by a low frequency of the Y chromosome Alu insertion. Examination of an association between the Alu polymorphism and Tat mutation revealed absolute C/YAP linkage. Analysis of the haplotype frequency distribution patterns constructed from the data on the DYS287 and RBF5 polymorphisms revealed substantial differences between Udmurts and the other ethnic populations. The differences were also observed between Komi-Zyryans and the populations of Bashkirs, Mordovians, Komi-Permyaks, and Russians. Analysis of the degree of genetic differentiation pointed to high level of genetic differentiation of the male lineages of the Finno-Ugric ethnic groups. The data on the linkage between mutations of the RBF5 and the LLY22 loci indicated the common origin of the Tat mutation in Bashkirs, Mordovians, Udmurts, and Komi-Zyryans, and of a number of ancestral C allele-bearing chromosomes in Tatars, Maris, and Chuvashes.

Alleles↗

Distance nursing education in Micronesia.

Distance education courses have been offered by the University of Guam for the past ten years, however there were no programs developed for the students of the region. In 1994, the College of Nursing and Health Sciences began teaching courses over PEACESAT (Pan Pacific Education and Communications Experiment by Satellite) every semester. The first course was written to serve Palau, the Commonwealth of the Marianas, Pohnpei, and the Marshall Islands. These jurisdictions have large community colleges. An overview of this program is given. In 1997 the courses were extended to include Palau, Yap, Chuuk, Pohnpei, Kosrae, and the Marshall islands. The organisational structure and training of the site operators and training coordinators is described. Two courses were taught in the first year. The first was 'Nutrition for Health Professionals and the second Leadership/Management for nurses. These are described, evaluated and discussed.

Education, Distance↗

[Y chromosome variations and hyplogroups from 15 biallelic markers in six Chinese populations].

By using 15 biallelic markers, 342 male individuals from six populations in China were genotyped with ASPCR (allele specific PCR). The 15 biallelic markers included M1 (YAP), M15 (9 bp insertion), M89 (C-->T), M9 (C-->G), M119 (A-->C), M50 (T-->C), M110 (T-->C), M103 (C-->T), M95 (C-->T), M88 (A-->G), M111 (2-bp deletion), M45 (G-->A), M122 (T-->C), M7 (C-->G) and M134 (1 bp deletion). The distribution of variation frequencies of 15 biallelic markers in six populations showed that with the extremely high frequencies of M9G (96.20% & 96.43%) and Han nationality displayed higher diversity than the four minority populations. It's noteworthy that M95T (82.14%) in Sichuan Han and M45A (18.57%) in Hui gave prominace to the two populations. The six populations displayed 34 (Fujian Han), 21 (Sichuan Han), 14 (Mongol), 26 (Hui), 10 (Xibo) and 8 (Hezhe) haplogroups respectively with 2, 1, 2, 1, 2 and 2 prominent haplogroups among them. Furthermore, the haplogroup analysis revealed that one predominant haplogroup was shared in the four minority populations and even two predominant haplogroups were shared in Mongol, Hezhe and Xibo. Unlike Han populations, the minority populations showed strikingly different haplogroups which were close to the ancestral pattern. However, the two Han populations exhibited divergence between them with the distinct frequencies of M89T and M95T. With the comparison of the number of people sharing the common haplogroups between any two of the four minority populations, relative genetic distance among them was deduced.

Alleles↗

Advances in animal PET scanners.

Nowadays, a growing number of research groups shows a great interest for the application of PET and SPECT techniques to the development of new drugs. Preliminary studies on small animals require high performance dedicated scanners with a higher spatial resolution and sensitivity than those of clinical systems. In this paper the potential applications of such innovative instruments are shown together with a brief review of the dedicated PET and SPECT tomographs developed worldwide. Most of the scanners have been built as research prototypes. Only two are commercially available: micro-PET(R), designed and developed at UCLA, Los Angeles as a research prototype, and now produced and distributed by Concorde Microsystems Inc. (USA) and HIDAC PET produced by Oxford Positron Systems Ltd. (UK). Also in Italy, a high performance tomograph, YAP-(S) PET able to perform both PET and SPECT studies, has been developed at the University of Ferrara. The technical characteristics and performance of this scanner are described. Tomographs with combined imaging techniques, such as PET/CT or SPECT/CT, are now under study in various international research centers. The advantages of this new generation of animal scanners will be briefly outlined.

Animals↗

Runx2/Cbfa1 functions: diverse regulation of gene transcription by chromatin remodeling and co-regulatory protein interactions.

Development of the osteoblast phenotype requires transcriptional mechanisms that regulate induction of a program of temporally expressed genes. Key components of gene activation, repression, and responsiveness to physiologic mediators require remodeling of the chromatin structure of a gene that renders promoter elements competent for the assembly of macromolecular transcriptional complexes. Here we review evidence that the Runx transcription factors support tissue-specific gene expression and bone formation by contributing to promoter structure, chromatin remodeling, and the integration of independent signaling pathways. In addition, we discuss the role of Runx2 in both activation and negative regulation of gene promoters (osteocalcin, bone sialoprotein, and Runx2/Cbfa1) in relation to the interaction of Runx with co-regulatory proteins in distinct subnuclear foci. The modifications in chromatin organization and transcription of the osteocalcin gene that are influenced by the activities of Runx2/Cbfa1 mediated by interacting proteins (YAP, TLE, SMAD, C/EBP) are emphasized. These functional properties of Runx2 provide novel insights into the requirements for multiple levels of transcriptional control within the context of nuclear architecture to support the convergence of regulatory signals that control tissue-specific gene expression.

Animals↗

Temporal and spatial parameters of skeletal gene expression: targeting RUNX factors and their coregulatory proteins to subnuclear domains.

Key components of the basal transcription machinery and several tissue-specific transcription factor complexes are functionally compartmentalized as specialized subnuclear domains. We have identified a unique 31-38 amino acid targeting signal (NMTS) that directs the Runx (Cbfa/AML) transcription factors to distinct nuclear matrix-(NM) associated sites within the nucleus that support gene expression. Our determination of the NMTS crystal structure, yeast 2 hybrid screens to identify NM interacting proteins, and in situ colocalization studies with Runx interacting factors (YAP, Smad, TLE) suggest that localization of Runx transcription factors at intranuclear sites facilitates the assembly and activity of regulatory complexes that mediate activation and suppression of target genes. Mice homozygous for the deletion of the intranuclear Runx2 targeting signal in a homologous recombination (Runx2 deltaC) do not form bone due to maturational arrest of osteoblasts, demonstrating the importance of fidelity of subnuclear localization for tissue-differentiating activity. These results provide evidence that Runx2 subnuclear targeting and the associated regulatory functions are essential for a spatiotemporal placement that facilitates activation of Runx-dependent genes involved in tissue differentiation during embryonic development.

Animals↗

Clinical manifestations of ocular toxoplasmosis in Yogyakarta, Indonesia: a clinical review of 173 cases.

Toxoplasmosis was the most common cause of primary retinochoroiditis. The majority of cases of ocular toxoplasmosis were congenital. However, cases of acquired ocular toxoplasmosis have been reported. The clinical manifestations of congenital ocular toxoplasmosis were choroidal coloboma, strabismus, nystagmus, ptosis, microphthalmia, cataract and enophthalmia. The purpose of this study was to determine the clinical presentation and visual outcome of 173 patients with ocular toxoplasmosis at Dr Sardjito Hospital, Dr Yap Eye Hospital, and private practice during the last six years. A total of 173 subjects were studied--98 males and 75 females. The ages at which first diagnosis was established ranged from 3 months to 68 years, frequently in young adults and occurring mostly in students. The most-reported chief complaint was blurred vision in 70.5% and floaters in 6.1% of cases. The most frequent clinical manifestations were chorioretinitis (71.2%), macular scars (22.4%), squint (6.4%), congenital cataract (2.8%), nystagmus (6.4%) and atrophic optic papilla (2.8%). Bilateral involvement was found in 32.4% of all patients. The therapeutic outcome showed improvement, especially visual acuity in acute cases (25.6%). However, visual acuity categorized as blindness was 13.9%. The results of the study imply that suddenly blurred vision in the quiet eye in the young adult, squint, and nystagmus in children could be chorioretinal inflammation and scar caused by Toxoplasma gondii.

Adolescent↗

The hepatitis B immunization campaign for children in the Federated States of Micronesia.

Hepatitis B has long been recognized as hyperendemic among persons residing in the western Pacific. Effective control strategies have not been described. From December 1988 through October 1989, the Federated States of Micronesia (FSM) conducted a campaign to immunize children through age 6 years with three doses of hepatitis B (HB) vaccine. In addition, HB vaccination was incorporated into the routine immunization schedule for all children born in FSM, with the first dose given to newborns. Between December 1988 and October 1989, a total of 64,085 doses of HB vaccine were administered to the children. After the start of the campaign, the subject group was enlarged to include children through 15 years of age in the States of Yap and Kosrae. Fifty-nine percent of the enlarged group in all States received a complete series of HB vaccinations. During each client encounter, individual immunization records were examined and diphtheria-pertussis-tetanus, oral polio vaccine, and measles-mumps-rubella antigens were administered to children who were not adequately immunized. The annual immunization assessment for 1990 showed coverage improved significantly from previous years in every FSM State.

Child, Preschool↗