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The venous drainage of nerves; anatomical study and clinical implications.

The venous drainage of the peripheral nerves was studied in the upper and lower limbs of two human fresh cadaver subjects after total body perfusion with a radio-opaque lead oxide mixture. Four patterns of extraneural drainage were identified in which the venae nervosa drained: directly to the venae comitantes of the neurovascular bundle; indirectly via nearby veins, derived usually from muscles; to the periarterial venous plexus; or, in the case of the cutaneous nerves, to the perivenous plexus. The various patterns of the drainage along the length of the radial, median, ulnar, sciatic, anterior and posterior tibial nerves were identified. A rich longitudinal plexus of veins exists on and within the nerve which appears to be mainly free of valves. The large venae nervosa usually contained valves, whereas the tiny veins draining the nerves were valveless or exhibited a sentinel valve at their entry point into a larger venous channel. The clinical implications of these results are discussed in relation to the mobilisation of nerves, the use of island nerve flaps, possible donor sites for free arteriolised neurovenous flaps and the compressive nerve syndromes.

Brachial Plexus↗

Metadata-based generation and management of knowledgebases from molecular biological databases.

Present-day knowledge-based systems (or expert systems) and databases constitute 'islands of computing' with little or no connection to each other. The use of software to provide a communication channel between the two, and to integrate their separate functions, is particularly attractive in certain data-rich domains where there are already pre-existing database systems containing the data required by the relevant knowledge-based system. Our evolving program, GENPRO, provides such a communication channel. The original methodology has been extended to provide interactive Prolog clause input with syntactic and semantic verification. This enables automatic generation of clauses from the source database, together with complete management of subsequent interfacing to the specified knowledge-based system. The particular data-rich domain used in this paper is protein structure, where processes which require reasoning (modelled by knowledge-based systems), such as the inference of protein topology, protein model-building and protein structure prediction, often require large amounts of raw data (i.e., facts about particular proteins) in the form of logic programming ground clauses. These are generated in the proper format by use of the concept of metadata.

Artificial Intelligence↗

Interstitial trophoblast invasion in the decidua and mesometrial triangle during the last third of pregnancy in the rat.

Like other species with haemochorial placentation, pregnant rats show marked invasion of the uterine wall by trophoblast. While an endovascular pathway of invasion has been recognized for a long time, only recently, by application of cytokeratin immunostaining, the existence of an interstitial pathway of invasion has been established. Interstitial invasion is mainly effected by glycogen cell-like trophoblast arising from glycogen cell islands of the trophospongium opening up into the decidua, and from glycogen cell sheaths surrounding the intraplacental maternal arterial channels which are connected with the spiral arteries in decidua and mesometrial triangle. Quantitative evaluation of interstitial invasion in both maternal compartments was carried out on days 15-21, using PAS staining and cytokeratin and alpha-actin immunostaining for detecting trophoblast and defining maternal tissue compartments. Measurements of compartment size, cytokeratin-positive areas and invasion extent were performed using the KS400 image analysis system. A distinct pattern of interstitial trophoblast invasion emerged, starting from central decidual areas around the maternal arterial channels, and mushrooming into the mesometrial triangle reaching a peak at day 18, followed by gradual regression of the invaded areas. These measurements may serve as a basis for further experiments to evaluate factors which may influence the depth of trophoblast invasion.

Animals↗

Public health: tobacco taxes and Internet sales--2005. End of Year Issue Brief.

Raising tobacco taxes is an action that resonates with lawmakers, public health and anti-tobacco advocates, and the majority of the electorate. The relatively broad base of support for increasing excise taxes and the potential for increased tax revenue mitigate the concerns over targeting tobacco-users--23 percent of the population--to pay for state programs and the unreliability of the tobacco tax as a permanent source of revenue. Tobacco excise taxes generated $10.2 billion, or about 1.5 percent of all states' revenue. Characterized as sin taxes or user fees and viewed as an effective method to deter price-sensitive adolescents from using tobacco, excise taxes on tobacco have increased in an unprecedented number of states since November 2001. Previously, no more than three states, on average, had increased cigarette taxes in a year. The legislative action is viewed as a politically safe and relatively easy way to raise taxes and increase revenue without incurring the wrath of anti-tax voters. During this period the increases in tobacco taxes ranged from a $0.12 per pack increase in Louisiana to a $0.75 increase in Massachusetts and Michigan. Nationwide the state tax rate per pack of cigarettes ranges from a low in South Carolina of $0.07 to $2.46 in Rhode Island. The mean tobacco excise tax for the nation is approximately $0.92. With an excise tax increase, states can channel needed funds to programs favored by voters in economically strapped times. Indeed, many of the 44 states that increased their tobacco tax announced that the revenue would permit the state to restore or at least reduce proposed cuts to Medicaid and other health programs. Excise taxes also place little administrative burden on states, since the wholesaler pays the tax directly to the state and the additional cost then is passed on to the consumer.

Adolescent↗

Does the wood-borer Sphaeroma terebrans (Crustacea) shape the distribution of the mangrove Rhizophora mucronata?

Field surveys were conducted to evaluate the occurrence of the isopod borer Sphaeroma terebrans (Crustacea) in aerial roots (prop roots) of the red mangrove Rhizophora mucronata on several different spatial scales (m to 100 km) in East Africa. In 6 out of 17 sites studied in Kenya and on Zanzibar Island, Tanzania, no signs of the isopods were found. When the isopods were present the frequency of infestation was high. Trees in muddy substrates in the lower intertidal, in particular at fringing channels or the open sea, showed high prevalence and intensity of infestation, with large part of their roots damaged or dead. Trees at the upper range of Rhizophora, in sandy and muddy areas, showed no signs of isopod infestation. This pattern recurred in mangrove forests on large spatial scales and there was no indication that island forests differed from the mainland forests. This indicates that sediment characteristics, vertical height in the tidal zone, and direct exposure to incoming water are the major factors controlling the abundance of S. terebrans. The isopod may play an important role in determining the lower intertidal limits of R. mucronata. Trees with numerous dead or nongrowing roots, as result of Sphaeroma attack, are likely to tumble due to a lack of root support and this is most likely to occur along channels at the lower, muddy intertidal. Tumbled trees were frequently observed along channels in the lower, muddy intertidal, but rarely in the mid or high intertidal. Implications for management of mangrove forests are discussed.

Animals↗

Detailed analysis of the methylation patterns of the KvDMR1 imprinting control region of human chromosome 11.

The paternal repression of several genes in human chromosome 11p15.5 (mouse chromosome 7) is associated with paternal expression of a transcript called KCNQ1OT1 (also known as LIT1). This long transcript originates from a promoter that resides in a CpG island in intron 10 of the KCNQ1 gene and runs in an antisense orientation to the direction of the coding KCNQ1 transcript. The CpG island is maternally methylated but paternally nonmethylated. The CpG island loses its maternal methylation in over 50% of cases of Beckwith-Wiedemann syndrome who lack uniparental disomy. This loss is usually accompanied by biallelic expression of the KCNQ1OT1 transcript. We have examined the methylation status of this CpG island in somatic cell hybrids and diploid lymphoblasts using Southern hybridization and bisulfite sequencing techniques. We find that the maternal copy of the CpG island is methylated at all CpGs examined within the CpG island and uniformly paternally unmethylated. In addition, in BWS patients who have lost methylation of the CpG island, this loss occurs throughout the CpG island. Finally, we find that there is a switch in methylation patterns outside the CpG island from maternal methylation within the island to predominantly paternal methylation at sites flanking the CpG island.

Animals↗

Recombination between the postulated CCD/MHE/MHS locus and RYR1 gene markers.

Malignant hyperthermia (MH) susceptibility is considered a subclinical myopathy or a pharmacogenetic trait, and is believed to be closely associated with central core disease (CCD). Data support the notion that MH susceptibility is heterogeneous, with the ryanodine receptor I (RYR1) locus on chromosome 19 being one locus harboring a gene that can cause MH susceptibility. The gene for CCD is believed to reside in the locus on chromosome 19. In the family presented here, a girl has CCD, and several close relatives are MH susceptible (MHS). DNA studies conducted on available family members uncovered recombination between the MH susceptibility locus and RYR1 markers. Consequently, if one postulates that the CCD gene in this family resides in the same locus as the MH susceptibility gene, an additional CCD locus different from the RYR1 locus must also be postulated.

Alleles↗

Pituitary intracisternal granule formation during the estrus cycle of the rat.

An ultrastructural study of the anterior pituitaries of cycling rats reveals changes in the ultrastructure of the gonadotrophs during the afternoon of proestrus when the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) is high. The rough endoplasmic reticulum cisternae become greatly dilated, forming extensive channels which are continuous with the perivascular space and provide an increased surface for the release of hormones. Granules and cytoplasmic islands of granules are seen in these spaces. Such changes are not observed during diestrus and early proestrus when the release of FSH/LH is low. The data indicate that intracisternal granule formation is an important mechanism by which anterior pituitary cells respond to increased hormonal requirements.

Animals↗

The Wilhelmine E. Key 1996 Invitational Lecture. Sexual selection: a driver of genetic change in Hawaiian Drosophila.

Within the last five million years, the Hawaiian archipelago has successively added 14, spaced, subaerial volcanoes at its southeast end. Each has received endemic terrestrial colonists; established populations appear to stem mainly from the immediately adjacent older island. Chromosome markers were used to trace the evolution of a phylad of 106 unique and closely related Drosophila species. With one exception, each species is restricted to one of the four groups of islands; 57 species appear to be restricted to single volcanoes. Founding of new populations across each of the three major oceanic channels appears to be infrequent. Genetic and morphological analysis suggests that each founding event has resulted in a newly organized, highly specific gene pool, not simply a transplanted colony of the source species. Progressive volcanic forces have thus provided an instructive spatiotemporal environment for the formation of new species. In Drosophila genetic change involves primarily spectacular premating sexual behavior, marked by novel male characters that appear to have evolved under the driving force of sexual selection. Permanent genetic changes in reproductive biology are thus elicited by selection for intrademe Darwinian fitness of individuals and are not the result of ad hoc selection for interpopulation reproductive isolation. The facts reinforce the view that reproductive isolation from other species is largely an incidental by-product of selection imposed by both the ambient and sexual environments in local populations.

Animals↗

Phospholipid scramblase 1 binds to the promoter region of the inositol 1,4,5-triphosphate receptor type 1 gene to enhance its expression.

Phospholipid scramblase 1 (PLSCR1) is a multiply palmitoylated, endofacial membrane protein originally identified based on its capacity to promote accelerated transbilayer phospholipid movement in response to Ca(2+). Recent evidence suggests that this protein also participates in cell response to various growth factors and cytokines, influencing myeloid differentiation, tumor growth, and the antiviral activity of interferon. Whereas plasma membrane PLSCR1 was shown to be required for normal recruitment and activation of Src kinase by stimulated cell surface growth factor receptors, PLSCR1 was also found to traffic into the nucleus and to tightly bind to genomic DNA, suggesting a possible additional nuclear function. We now report evidence that PLSCR1 directly binds to the 5'-promoter region of the inositol 1,4,5-triphosphate receptor type 1 gene (IP3R1) to enhance expression of the receptor. Probing a CpG island genomic library with PLSCR1 as bait identified four clones with avidity for PLSCR1, including a 191-bp fragment of the IP3R1 promoter. Using electrophoretic mobility shift and transcription reporter assays, the PLSCR1-binding site in IP3R1 was mapped to residues (-101)GTAACCATGTGGA(-89), and the segment spanning Met(86)-Glu(118) in PLSCR1 was identified to mediate its transcriptional activity. The significance of this interaction between PLSCR1 and IP3R1 in situ was confirmed by comparing levels of IP3R1 mRNA and protein in matched cells that either expressed or were deficient in PLSCR1. These data suggest that in addition to its role at the plasma membrane, effects of PLSCR1 on cell proliferative and maturational responses may also relate to alterations in expression of cellular IP3 receptors.

Animals↗

Tissue specificity of methylation of cytosines in regulatory regions of four genes located in the locus FXYD5-COX7A1 of human chromosome 19: correlation with their expression level.

In this study, we compared degree of methylation of selected CpG sites in CCGG sequences located in promoter regions of four human genes with expression level of these genes in several human cell lines and tissues. These genes were subdivided into two groups according to the dependence of their expression on CpG methylation in the 5 -regions. The first group, characterized by clear correlation of methylation with the transcription level, includes housekeeping gene COX6B (the absence of methylation unambiguously correlates with expression) and urothelium-specific uroplakin gene (the methylation coincides with absence of expression). The second group includes genes that are expressed in many, but not all tissues and cells. For these genes (LEAP-1 and ATP4A), there was no correlation between methylation and expression. It is possible that methylation provides some basal level of gene repression, which is overcome by binding of tissue-specific transcription factors, whereas lack of methylation gives the opportunity for gene expression in various cells and tissues.

Adenosine Triphosphatases↗

Genetic recombination between malignant hyperthermia and calcium release channel in skeletal muscle.

Absolute linkage between the gene, on chromosome 19, for the calcium release channel (CRC) of the sarcoplasmic reticulum in skeletal muscle and malignant hyperthermia (MH) has been reported by other workers. In the present study of three Swedish Families informative with respect to this linkage relationship, definite recombinants were found in two families. We conclude that mutations in other genes than the CRC gene can cause the clinical picture of MH. Accordingly, MH appears to be genetically heterogeneous.

Alleles↗

The relationship between the density of Aedes vigilax (Diptera: Culicidae) eggshells and environmental factors on Kooragang Island, New South Wales, Australia.

Knowledge of oviposition sites selected by wetland mosquitoes could improve mosquito control and guide wetland rehabilitation practices to avoid creating or exacerbating a mosquito problem. Two studies that enumerated Aedes vigilax eggshells found in salt marsh soil on the western portion of Kooragang Island in New South Wales, Australia, allowed an evaluation of oviposition sites. In one study, the density of eggshells found in samples collected from a large area was related to environmental factors, including distance from nearby drainage channels, vegetation cover, elevation, and terrain characteristics. Multiple-regression analysis suggested eggshell densities were positively correlated with the presence of depressions and ponds, vegetation cover, and distance from culverts, but negatively related to elevation. In another study, eggshell density was related to relative elevation and vegetation species within each of two 400-m2 plots on Kooragang Island. In all but one instance, samples from bare soil contained fewer eggshells than samples with vegetation cover at both plots. Eggshell density did not differ between the two dominant vegetation species, Sarcocornia quinqueflora and Sporobolus virginicus, although bare soil of one plot had a mean eggshell density similar to that of soil with S. quinqueflora cover. Eggshells were at highest density at intermediate elevations at one plot but at low elevations at the other.

Aedes↗

Organochlorine and metal contaminant exposure and effects in hatching black-crowned night herons (Nycticorax nycticorax) in Delaware Bay.

Pea Patch Island in Delaware Bay is the site of the largest heronry north of Florida. From 1989-93, the population of nine species of wading birds numbered approximately 12,000 pairs, but has recently declined to about 7,000 pairs. Because Delaware Bay is a major shipping channel and receives anthropogenic releases of toxic substances from agricultural, industrial, and municipal point and nonpoint sources, contaminant exposure and effects to the heronry have been an ongoing concern. In 1997, pipping (early hatching stage) black-crowned night herons (Nycticorax nycticorax) were collected from separate nests at Pea Patch Island and from a coastal reference site, Middle Island in Rehoboth Bay, Delaware. There was no evidence of malformations or hepatic histopathological lesions in embryos, and their body and liver weights did not differ between sites. Biomarkers of petroleum hydrocarbons, polyhalogenated contaminant, and metal exposure (cytochrome P450 induction and oxidative stress responses) did not differ (p > 0.05) between sites, although activities of benzyloxy-O-dealkylase and ethoxyresorufin-O-dealkylase were somewhat elevated in 3 of the 15 embryos collected from Pea Patch Island. Concentrations of 21 organochlorine pesticides and metabolites were relatively low at both sites, with p,p'-DDE values well below the threshold associated with eggshell thinning. Although total PCB concentration was modestly elevated (p < 0.05) in Pea Patch Island heron embryos, levels of arylhydrocarbon receptor-active PCB congeners, polychlorinated dibenzodioxins and dibenzofurans, and toxic equivalents were low and did not differ between sites. Concentrations of Cd and Mn in pipping embryos from Pea Patch Island were slightly greater (p < 0.05) than values observed in Middle Island embryos, but levels of these and the other metals and metalloids (e.g., Hg and Se) were below values associated with toxicity. In conclusion, it seems unlikely that chlorinated hydrocarbon and metal contaminant exposure constitutes a direct threat to the reproductive success of black-crowned night herons at Pea Patch Island. However, low-level exposure to these contaminants may constitute one of many stressors that in combination could adversely affect the stability of the wading bird population at this large heronry.

Animals↗

Several interacting genes influence the malignant hyperthermia phenotype.

Malignant hyperthermia (MH), a potentially lethal disorder of skeletal muscle calcium homeostasis, manifests only on exposure to certain anaesthetic drugs. The mode of inheritance appears to be autosomal dominant with both locus and allelic heterogeneity having been reported. Association analysis of eight MH candidate loci in UK families has indicated that several genes influence susceptibility in individual families, rather than MH simply being a major gene defect. In support of this hypothesis, we present data on a replica analysis of an independent sample of European MH families.

Calcium Channels, L-Type↗

LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids.

Mammalian imprinted genes are frequently arranged in clusters on particular chromosomes. The imprinting cluster on human chromosome 11p15 is associated with Beckwith-Wiedemann syndrome (BWS) and a variety of human cancers. To clarify the genomic organization of the imprinted cluster, an extensive screen for differentially expressed transcripts in the 11p15 region was performed using monochromosomal hybrids with a paternal or maternal human chromosome 11. Here we describe an imprinted antisense transcript identified within the KvLQT1 locus, which is associated with multiple balanced chromosomal rearrangements in BWS and an additional breakpoint in embryonal rhabdoid tumors. The transcript, called LIT1 (long QT intronic transcript 1), was expressed preferentially from the paternal allele and produced in most human tissues. Methylation analysis revealed that an intronic CpG island was specifically methylated on the silent maternal allele and that four of 13 BWS patients showed complete loss of maternal methylation at the CpG island, suggesting that antisense regulation is involved in the development of human disease. In addition, we found that eight of eight Wilms' tumors exhibited normal imprinting of LIT1 and five of five tumors displayed normal differential methylation at the intronic CpG island. This contrasts with five of six tumors showing loss of imprinting of IGF2. We conclude that the imprinted gene domain at the KvLQT1 locus is discordantly regulated in cancer from the imprinted domain at the IGF2 locus. Thus, this positional approach using human monochromosomal hybrids could contribute to the efficient identification of imprinted loci in humans.

Animals↗

Fast formation of magnetic islands in a plasma in the presence of counterstreaming electrons.

With the help of 2D-3V (two dimensional in space and three dimensional in velocity) Vlasov simulations we show that the magnetic field generated by the electromagnetic current filamentation instability develops magnetic islands due to the onset of a fast reconnection process that occurs on the electron dynamical time scale. This process is relevant to magnetic channel coalescence in relativistic laser plasma interactions.

Journal Article↗

The epigenetic imprinting defect of patients with Beckwith-Wiedemann syndrome born after assisted reproductive technology is not restricted to the 11p15 region.

BACKGROUND: Genomic imprinting refers to an epigenetic marking resulting in monoallelic gene expression and has a critical role in fetal development. Various imprinting diseases have recently been reported in humans and animals born after the use of assisted reproductive technology (ART). All the epimutations implicated involve a loss of methylation of the maternal allele (demethylation of KvDMR1/KCNQ1OT1 in Beckwith-Wiedemann syndrome (BWS), demethylation of SNRPN in Angelman syndrome and demethylation of DMR2/IGF2R in large offspring syndrome), suggesting that ART impairs the acquisition or maintenance of methylation marks on maternal imprinted genes. However, it is unknown whether this epigenetic imprinting error is random or restricted to a specific imprinted domain. AIM: To analyse the methylation status of various imprinted genes (IGF2R gene at 6q26, PEG1/MEST at 7q32, KCNQ1OT1 and H19 at 11p15.5, and SNRPN at 15q11-13) in 40 patients with BWS showing a loss of methylation at KCNQ1OT1 (11 patients with BWS born after the use of ART and 29 patients with BWS conceived naturally). RESULTS: 3 of the 11 (27%) patients conceived using ART and 7 of the 29 (24%) patients conceived normally displayed an abnormal methylation at a locus other than KCNQ1OT1. CONCLUSIONS: Some patients with BWS show abnormal methylation at loci other than the 11p15 region, and the involvement of other loci is not restricted to patients with BWS born after ART was used. Moreover, the mosaic distribution of epimutations suggests that imprinting is lost after fertilisation owing to a failure to maintain methylation marks during pre-implantation development.

Autoantigens↗