Contrasting population structure from nuclear intron sequences and mtDNA of humpback whales

Powerful analyses of population structure require information from multiple genetic loci. To help develop a molecular toolbox for obtaining this information, we have designed universal oligonucleotide primers that span conserved intron-exon junctions in a wide variety of animal phyla. We test the utility of exon-primed, intron-crossing amplifications by analyzing the variability of actin intron sequences from humpback, blue, and bowhead whales and comparing the results with mitochondrial DNA (mtDNA) haplotype data. Humpback actin introns fall into two major clades that exist in different frequencies in different oceanic populations. It is surprising that Hawaii and California populations, which are very distinct in mtDNAs, are similar in actin intron alleles. This discrepancy between mtDNA and nuclear DNA results may be due either to differences in genetic drift in mitochondrial and nuclear genes or to preferential movement of males, which do not transmit mtDNA to offspring, between separate breeding grounds. Opposing mtDNA and nuclear DNA results can help clarify otherwise hidden patterns of structure in natural populations.     

The thyroid gland of humpback salmon (Oncorhynchus gorbuscha) fry and of humpback and cherry salmon (Oncorhynchus masu) hybrids during smoltification

Skin cover for losses of substance on the dorsum of the thumb is often difficult. The "kite flap", introduced by Foucher, is ideal for this purpose. In the period between 1988 and 1993, this flap was used in five patients presenting with skin defects on the dorsum of the thumb. The results obtained have convinced us to consider this technique as the first method of choice in this area of reconstructive surgery.     

Complementation tagging of cooperating oncogenes in knockout mice

In the testis, 'hyalinization' of the lamina propria of seminiferous tubules is often accompanied by similar changes within the walls of testicular blood vessels. The aim of our study was to investigate the structure of small blood vessels in hyalinized human testes by means of immunohistochemistry, electron microscopy and image analysis methods. Results of immunohistochemical analysis indicated that, despite hyalinization, testicular small blood vessels retained positive immunostaining for desmin and actin. Their basement membranes remained immunopositive for collagen IV and laminin. No proliferative (Ki-67) activity was observed in the blood vessel walls in testes from both control and infertile men. P-170 glycoprotein was found to be expressed only in primary spermatocytes. No difference in expression and localization of this antigen was observed between control and affected testes. Electron microscopy revealed a number of testicular arterioles with a notably narrow lumen due to enlarged endothelial cells in infertile men. Such arterioles also had a thickened subendothelial layer and an abundant tunica adventitia rich in connective tissue fibres and ground substance. Some venules in hyalinized testes displayed increased connective fibres and ground substance in the subendothelial layer, between the smooth muscle cells of the tunica media and the tunica adventitia. However, no changes were found in the capillary network, when compared to controls. Image analysis data showed a statistically significant increase in the surface of tunica intima and adventitia of arterioles and tunica media of venules. It is concluded that hyalinization mostly affects testicular arterioles and venules, but not capillaries. Our immunohistochemical data indicate that the 'nature' and/or extent of hyalinization in testicular small blood vessels differs from that described previously for the lamina propria of seminiferous tubules.     

Cultural selection and genetic diversity in matrilineal whales

Low diversities of mitochondrial DNA (mtDNA) have recently been found in four species of matrilineal whale. No satisfactory explanation for this apparent anomaly has been previously suggested. Culture seems to be an important part of the lives of matrilineal whales. The selection of matrilineally transmitted cultural traits, upon which neutral mtDNA alleles "hitchhike," has the potential to strongly reduce genetic variation. Thus, in contrast to other nonhuman mammals, culture may be an important evolutionary force for the matrilineal whales.     

Adrenal hyperplastic and degenerative changes in beluga whales

Thirty stranded beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary (Quebec, Canada) population and five animals from the Hudson Bay aboriginal hunt (North-west Territories, Canada) were examined. Twenty one animals from the St. Lawrence Estuary had mild to severe adrenal lesions and four whales from the Hudson Bay population were affected by minimal adrenal changes. Cortical hyperplasia was observed in 24 adult beluga whales all from the St. Lawrence Estuary. Bilateral cortical cysts and cellular vacuolar degeneration were observed in the adrenal glands of 19 beluga whales from both populations. The cysts, filled with a cortisol-rich liquid, were present in both sexes. Beluga whales with adrenal cysts were significantly older than animals without cysts, and the severity of the lesions increased with age. Nodular hyperplasia of the medulla was observed in seven of the beluga whales, all from the St. Lawrence Estuary population. All lesions could be part of a normal aging process. The adrenocortical lesions might be due to stress or adrenocorticolytic xenobiotics, while the medullary hyperplasia might be caused by hypoxia or exposure to estrogenic xenobiotics.     

Improved sampling of myocardial motion with variable separation tagging

We conducted a study to quantify and characterize household transmission of Shiga toxin (Vero cytotoxin)-producing Escherichia coli O157 (STEC O157) following sporadic infection in Wales. Through total population surveillance, we identified 83 index case-patients and their household contacts. We screened fecal samples submitted from household contacts for STEC O157 and calculated the household transmission rate for sporadic STEC O157 infection to be 4% to 15%. Household contacts in groups at high risk (particularly children under 5 years of age) present a risk of spreading the infection in the wider community.     

Molecular mapping and tagging of genes in crop plants

In India, molecular mapping and tagging of agronomically important genes using RFLP and RAPD markers have been carried out in three different crops: rice, mustard and chickpea. In rice, tagging of genes for resistance to gall midge and blast has been accomplished. Molecular mapping of cooking quality traits in rice is in progress. For fingerprinting rice cultivars, suitable probe enzyme combinations have been identified. In mustard, a partial RFLP linkage map has been constructed and one of the yellow seed-coat colour loci has been mapped. Significant associations of RFLP markers with quantitative traits have also been established. Potential use of RAPD markers to identify heterotic groups among mustard accessions has been demonstrated. In chickpea, the occurrence of considerable interspecific DNA polymorphism as revealed by RAPD analysis has facilitated construction of a partial linkage map.     

From syntactic-semantic tagging to knowledge discovery in medical texts

In the GALEN project, the syntactic-semantic tagger MultiTALE is upgraded to extract knowledge from natural language surgical procedure expressions. In this paper, we describe the methodology applied and show that out of a randomly selected sample of such expressions coming from the procedure axis of Snomed International, 81% could be analysed correctly. The problems encountered fall in three different categories: unusual grammatical configurations within the Snomed terms, insufficient domain knowledge and different categorisation of concepts and semantic links in the domain and linguistic models used. It is concluded that the Multi-TALE system can be used to attach meaning to words that not have been encountered previously, but that an interface ontology mediating between domain models and linguistic models is needed to arrive at a higher level of independence from both particular languages and from particular domains.     

Transposon tagging of the Defective embryo and meristems gene of tomato

The shoot and root apical meristems (SAMs and RAMs, respectively) of higher plants are mechanistically and structurally similar. This has led previously to the suggestion that the SAM and RAM represent modifications of a fundamentally homologous plan of organization. Despite recent interest in plant development, especially in the areas of meristem regulation, genes specifically required for the function of both the SAM and RAM have not yet been identified. Here, we report on a novel gene, Defective embryo and meristems (Dem), of tomato. This gene is required for the correct organization of shoot apical tissues of developing embryos, SAM development, and correct cell division patterns and meristem maintenance in roots. Dem was cloned using transposon tagging and shown to encode a novel protein of 72 kD with significant homology to YNV2, a protein of unknown function of Saccharomyces cerevisiae. Dem is expressed in root and shoot meristems and organ primordia but not in callus. The expression pattern of Dem mRNA in combination with the dem mutant phenotype suggests that Dem plays an important role within apical meristems.     

Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation

A novel property of hippocampal LTP, 'variable persistence', has recently been described that is, we argue, relevant to the role of LTP in information storage. Specifically, new results indicate that a particular pattern of synaptic activation can give rise, either to a relatively short-lasting LTP, or to a longer-lasting LTP as a function of the history of activation of the neuron. This has led to the idea that the induction of LTP is associated with the setting of a'synaptic tag' at activated synapses, whose role is to sequester plasticity-related proteins that then serve to stabilize temporary synaptic changes and so extend their persistence. In this article, we outline the synaptic tag hypothesis, compare predictions it makes with those of other theories about the persistence of LTP, and speculate about the cellular identity of the tag. In addition, we outline the requirement for aminergic activation to induce late LTP and consider the functional implications of the synaptic tag hypothesis with respect to long-term memory.     

Solid-phase combinatorial chemistry and novel tagging methods for identifying leads

Encoded combinatorial chemical synthesis on solid phase is a new paradigm in organic chemistry that provides chemists with powers similar to those enjoyed by molecular biologists. Encoded chemical libraries will have a profound impact on all endeavors that seek to identify molecules with optimized properties and to understand the factors governing molecular interactions. In particular, the discovery and optimization of new therapeutic and diagnostic drug molecules, traditionally a slow manual process, will be greatly accelerated by this technology.     

Breath-hold dobutamine magnetic resonance myocardial tagging: normal left ventricular response

Analysis of the changes in myocardial deformation produced by adrenergic stress has been limited by the imaging techniques used. We used rapid magnetic resonance imaging (MRI) myocardial tagging to map the dose-dependent response to incremental dobutamine in the normal human left ventricle. Thirteen volunteers underwent breath-hold tagged cine MRI during dobutamine infusion. Images were acquired throughout systole to a peak dose of 20 microg/kg/min. End-systolic percent circumferential shortening (%S) was measured at 3 transmural locations and 4 circumferential locations at 3 long-axis positions. Mean circumferential shortening velocity (CSV) was also calculated at each location and dose. Mean %S reached a maximum of 26 +/- 3% at 10 microg/kg/min compared with 21 +/- 4% at baseline (p <0.003). Peak %S was reached by 10 microg/kg/min before a significant increase in heart rate or blood pressure and was unchanged at higher doses. In contrast, CSV increased linearly with dobutamine dose from 4.4 +/- 0.9 mm/s at baseline to 9.8 +/- 1.4 mm/s at 20 microg/kg/min (p <0.0001). Breath-hold tagged dobutamine MRI is safe and effective in detecting regional and transmural changes in function during incremental dobutamine. CSV increased continuously across the dobutamine dose range. At low dose (< or =10 microg/kg/min) %S increased without any change in blood pressure or heart rate. Maintenance of peak %S beyond 10 microg/kg/min in the presence of decreasing systolic intervals resulted from a continued increase in CSV. Thus, CSV may be the preferred measure of contractile function during dobutamine stimulation in human myocardium.     

Molecular evidence from retroposons that whales form a clade within even-toed ungulates

The origin of whales and their transition from terrestrial life to a fully aquatic existence has been studied in depth. Palaeontological, morphological and molecular studies suggest that the order Cetacea (whales, dolphins and porpoises) is more closely related to the order Artiodactyla (even-toed ungulates, including cows, camels and pigs) than to other ungulate orders. The traditional view that the order Artiodactyla is monophyletic has been challenged by molecular analyses of variations in mitochondrial and nuclear DNA. We have characterized two families of short interspersed elements (SINEs) that were present exclusively in the genomes of whales, ruminants and hippopotamuses, but not in those of camels and pigs. We made an extensive survey of retropositional events that might have occurred during the divergence of whales and even-toed ungulates. We have characterized nine retropositional events of a SINE unit, each of which provides phylogenetic resolution of the relationships among whales, ruminants, hippopotamuses and pigs. Our data provide evidence that whales, ruminants and hippopotamuses form a monophyletic group.     

Morphofunctional characteristics of the Leydig cells in the testes of the humpback salmon Oncorhynchus gorbuscha during spawning migration

By means of electron microscopic study of ultrastructure of Leydig cells of male adult humpback salmons in the period of spawning migration (stages III-IV of gonad maturity) they were found to be most active before the spawning. Maximum number of mitochondria with tubulovesicular crysts and normal development of Golgi apparatus and smooth endoplasmic reticulum were marked in this period. Decrease of mitochondria number and Golgi apparatus dictyosomes so as liposome-like bodies appearance in the cytoplasm indicated reduction of Leydig cells activity in the period of spawning. After this period fatty drops were presented in the Leydig cells cytoplasm, mitochondrial matrix acquired greater electron density and dark granules appeared in it. Signs of physiological regeneration outset were seen in dying male salmons. This is regarded as an evidence of secondary monocyclicity of the Pacific Ocean salmons.     

Global matrilineal population structure in sperm whales as indicated by mitochondrial DNA sequences

The genetic variability and population structure of worldwide populations of the sperm whale was investigated by sequence analysis of the first 5'L 330 base pairs in the mitochondrial DNA (mtDNA) control region. The study included a total of 231 individuals from three major oceanic regions, the North Atlantic, the North Pacific and the Southern Hemisphere. Fifteen segregating nucleotide sites defined 16 mtDNA haplotypes (lineages). The most common mtDNA types were present in more than one oceanic region, whereas ocean-specific types were rare. Analyses of heterogeneity of mtDNA type frequencies between oceans indicated moderate (GST = 0.03) but statistically significant (p = 0.0007) genetic differentiation on a global scale. In addition, strong genetic differentiation was found between potential social groups (GST = 0.03-0.6), indicating matrilineal relatedness within groups. The global nucleotide diversity was quite low (pi = 0.004) implying a recent common mtDNA ancestry (< 100,000) years ago) and a young global population structure. However, within this time period, female dispersal has apparently been limited enough to allow the development of global mtDNA differentiation. The results are consistent with those from observational studies and whaling data indicating stable social affiliations, some degree of area fidelity and latitudinal range limitations in groups of females and juveniles.     

MRI-radiofrequency tissue tagging in patients with aortic insufficiency before and after operation

We examined the relation between language dominance and regional cerebral blood flow (rCBF) during the intracarotid amobarbital procedure (IAP). A previous report limited to three patients suggested that dominant rather than nondominant hemisphere IAP may have a differential effect on rCBF. Behavioral assessment during the IAP also suggests that dominant hemisphere injection results in a differential effect on memory and affective symptoms rather than nondominant injection. Thirteen patients were assessed using single-photon emission CT (SPECT) brain imaging during both left and right IAP. The SPECTs were coregistered with the individual's MRI. Changes in rCBF during each IAP were compared with the patient's baseline SPECT. Nine patients had left hemisphere dominance, two were right dominant, and two had bilateral speech representation. In the left dominant subjects, left-hemisphere injection had a consistently greater effect on rCBF than right-hemisphere injection in the anterior (p < 0.005) and posterior (p < 0.01) temporal neocortex. There was also a trend for greater hypoperfusion in the frontal lobe of the left hemisphere. rCBF in the ipsilateral hippocampus was not significantly different after each injection (p > 0.05). In the two patients with right hemisphere speech, the reverse pattern was seen, with greater hypoperfusion after right (dominant) hemisphere injection. There was no consistent asymmetry in the two patients with bilateral speech. Dominant hemisphere IAP results in significantly greater hypoperfusion than does nondominant injection. These data provide a physiologic basis for behavioral differences noted after dominant versus nondominant IAP.