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Biomedical subjects

A G Jones

Publications and source records attributed to A G Jones.

At least 19 recordsLinked to original sources
PubMed2001

Genetic evidence for extreme polyandry and extraordinary sex-role reversal in a pipefish.

Due to the phenomenon of male pregnancy, the fish family Syngnathidae (seahorses and pipefishes) has historically been considered an archetypal example of a group in which sexual selection should act more strongly on females than on males. However, more recent work has called into question the idea that all species with male pregnancy are sex-role reversed with respect to the intensity of sexual selection. Furthermore, no studies have formally quantified the opportunity for sexual selection in any natural breeding assemblage of pipefishes or seahorses in order to demonstrate conclusively that sexual selection acts most strongly on females. Here, we use a DNA-based study of parentage in the Gulf pipefish Syngnathus scovelli in order to show that sexual selection indeed acts more strongly on females than on males in this species. Moreover, the Gulf pipefish exhibits classical polyandry with the greatest asymmetry in reproductive roles (as quantified by variances in mating success) between males and females yet documented in any system. Thus, the intensity of sexual selection on females in pipefish rivals that of any other taxon yet studied.

Animals↗
PubMed2001

[99mTc]oxotechnetium(V) complexes amine-amide-dithiol chelates with dialkylaminoalkyl substituents as potential diagnostic probes for malignant melanoma.

[99mTc]oxotechnetium(V) complexes of amine-amide-dithiol (AADT) chelates containing tertiary amine substituents were synthesized and shown to have affinity for melanoma. For complexation the AADT-CH2[CH2]nNR2 (n = 1, 2; R = Et, n-Bu) ligand was mixed with a [99mTc]oxotechnetium(V)-glucoheptonate precursor to make the AADT-[99mTc]oxotechnetium(V) complexes in nearly quantitative yield. Structurally analogous nonradioactive oxorhenium(V) complexes were also synthesized and characterized. In vitro sigma-receptor affinity measurements indicate these complexes to possess sigma-affinity in the low micromolar range with K(i) values in the 7.8-26.1 and 0.18-2.3 microM range for the sigma1- and sigma2-receptors, respectively. In vitro cell uptake of the 99mTc complexes in intact B16 murine melanoma cells at 37 degrees C after a 60-min incubation ranged from 12% for complex 2 (n = 1, R = n-Bu) to 68% for complex 4 (n = 2, R = n-Bu). In vivo evaluation of complexes 1-Tc-4-Tc in the C57Bl/B16 mouse melanoma model demonstrated significant tumor localization. Complex 1-Tc (n = 1, R = Et) displayed an in vivo tumor uptake of 7.6% ID/g at 1 h after administration with initial melanoma/blood (M/B), melanoma/spleen (M/S), and melanoma/lung (M/L) ratios >4; these ratios increased to 10.8, 10.1, and 7.3, respectively, at 6 h. While complex 3-Tc (n = 3, R = Et) had an initial tumor uptake of 3.7% ID/g 1 h after administration with M/B, M/S, and M/L ratios >2, a greater tumor retention and slightly faster clearance from nontumor-containing organs resulted in M/B, M/S, and M/L ratios of 19.1, 19.1, and 12.7, respectively, at 6 h. The high tumor uptake and significant tumor/nontumor ratios indicate that such small technetium-99m-based molecular probes can be developed as in vivo diagnostic agents for melanoma and its metastases.

Animals↗
PubMed2001

How cuckoldry can decrease the opportunity for sexual selection: data and theory from a genetic parentage analysis of the sand goby, Pomatoschistus minutus.

Alternative mating strategies are common in nature and are generally thought to increase the intensity of sexual selection. However, cuckoldry can theoretically decrease the opportunity for sexual selection, particularly in highly polygamous species. We address here the influence of sneaking (fertilization thievery) on the opportunity for sexual selection in the sand goby Pomatoschistus minutus, a marine fish species in which males build and defend nests. Our microsatellite-based analysis of the mating system in a natural sand goby population shows high rates of sneaking and multiple mating by males. Sneaker males had fertilized eggs in approximately 50% of the assayed nests, and multiple sneakers sometimes fertilized eggs from a single female. Successful males had received eggs from 2 to 6 females per nest (mean = 3.4). We developed a simple mathematical model showing that sneaking in this polygynous sand goby population almost certainly decreases the opportunity for sexual selection, an outcome that contrasts with the usual effects of cuckoldry in socially monogamous animals. These results highlight a more complex and interesting relationship between cuckoldry rates and the intensity of sexual selection than previously assumed in much of the literature on animal mating systems.

Animals↗
PubMed2001

The electric Moho.

Since Mohorovicić discovered a dramatic increase in compressional seismic velocity at a depth of 54 km beneath the Kulpa Valley in Croatia, the 'Moho' has become arguably the most important seismological horizon in Earth owing to its role in defining the crust-mantle boundary. It is now known to be a ubiquitous feature of the Earth, being found beneath both the continents and the oceans, and is commonly assumed to separate lower-crustal mafic rocks from upper-mantle ultramafic rocks. Electromagnetic experiments conducted to date, however, have failed to detect a corresponding change in electrical conductivity at the base of the crust, although one might be expected on the basis of laboratory measurements. Here we report electromagnetic data from the Slave craton, northern Canada, which show a step-change in conductivity at Moho depths. Such resolution is possible because the Slave craton is highly anomalous, exhibiting a total crustal conductance of less than 1 Siemens--more than an order of magnitude smaller than other Archaean cratons. We also found that the conductivity of the uppermost continental mantle directly beneath the Moho is two orders of magnitude more conducting than laboratory studies on olivine would suggest, inferring that there must be a connected conducting phase.

Journal Article↗
PubMed2001

In vivo near-infrared fluorescence imaging of osteoblastic activity.

In vertebrates, the development and integrity of the skeleton requires hydroxyapatite (HA) deposition by osteoblasts. HA deposition is also a marker of, or a participant in, processes as diverse as cancer and atherosclerosis. At present, sites of osteoblastic activity can only be imaged in vivo using gamma-emitting radioisotopes. The scan times required are long, and the resultant radioscintigraphic images suffer from relatively low resolution. We have synthesized a near-infrared (NIR) fluorescent bisphosphonate derivative that exhibits rapid and specific binding to HA in vitro and in vivo. We demonstrate NIR light-based detection of osteoblastic activity in the living animal, and discuss how this technology can be used to study skeletal development, osteoblastic metastasis, coronary atherosclerosis, and other human diseases.

Animals↗
PubMed2001

The genetic mating system and tests for cuckoldry in a pipefish species in which males fertilize eggs and brood offspring externally.

Highly variable microsatellite loci were used to study the mating system of Nerophis ophidion, a species of pipefish in which pregnant males carry embryos on the outside of their body rather than in an enclosed brood pouch. Despite this mode of external fertilization and brooding, otherwise rare in the family Syngnathidae, the genotypes of all embryos proved to be consistent with paternity by the tending male, thus indicating that cuckoldry by sneaker males is rare or nonexistent in this species. N. ophidion is a phylogenetic outlier within the Syngnathidae and its reproductive morphology is thought to be close to the presumed ancestral condition for pipefishes and seahorses. Thus, our genetic results suggest that the evolutionary elaboration of the enclosed brood pouch elsewhere in the family was probably not in response to selection pressures on pregnant males to avoid fertilization thievery. With regard to maternity assignments, our genotypic data are consistent with behavioural observations indicating that females sometimes mate with more than one male during a breeding episode, and that each male carries eggs from a single female. Thus, the polyandrous genetic mating system in this species parallels the social mating system, and both are consistent with a more intense sexual selection operating on females, and the elaboration of secondary sexual characters in that gender.

Animals↗
PubMed2001

Surprising similarity of sneaking rates and genetic mating patterns in two populations of sand goby experiencing disparate sexual selection regimes.

Molecular markers have proved extremely useful in resolving mating patterns within individual populations of a number of species, but little is known about how genetic mating systems might vary geographically within a species. Here we use microsatellite markers to compare patterns of sneaked fertilization and mating success in two populations of sand goby (Pomatoschistus minutus) that differ dramatically with respect to nest-site density and the documented nature and intensity of sexual selection. At the Tvärminne site in the Baltic Sea, the microsatellite genotypes of 17 nest-tending males and mean samples of more than 50 progeny per nest indicated that approximately 35% of the nests contained eggs that had been fertilized by sneaker males. Successful nest holders mated with an average of 3.0 females, and the distribution of mate numbers for these males did not differ significantly from the Poisson expectation. These genetically deduced mating-system parameters in the Tvärminne population are remarkably similar to those in sand gobies at a distant site adjoining the North Sea. Thus, pronounced differences in the ecological setting and sexual selection regimes in these two populations have not translated into evident differences in cuckoldry rates or other monitored patterns of male mating success. In this case, the ecological setting appears not to be predictive of alternative male mating strategies, a finding of relevance to sexual selection theory.

Animals↗
PubMed2000

'3+1' mixed-ligand oxotechnetium(V) complexes with affinity for melanoma: synthesis and evaluation in vitro and in vivo.

'3+1' Mixed-ligand [(99m)Tc]oxotechnetium complexes with affinity for melanoma were synthesized in a one-pot reaction. Complexation of technetium-99m with a mixture of N-R(3-azapentane-1,5-dithiol) [R = Me, Pr, Bn, Et(2)N(CH(2))(2)] and N-(2-dialkylamino)ethanethiol [alkyl = X = Et, Bu, morpholinyl] using Sn(2+) as the reducing agent resulted in the formation of '3+1' mixed-ligand technetium-99m complexes [TcO(SN(R)S)(SNX(2))] in high radiochemical yield (60-98%). In vitro uptake studies in B16 murine melanoma cells indicated a moderate tumor-cell accumulation (40%) of compound 1 [R = Me, X = Et] and a higher accumulation (69%) of compound 2 [R = Me, X = Bu] after a 60-min incubation. In vivo evaluation of compounds 1-6 in the C57Bl6/B16 mouse melanoma model demonstrated tumor localization. Compound 2 displayed the highest accumulation with up to 5% ID/g at 60 min after injection. In vivo, 2 also showed a low blood-pool activity and high melanoma/spleen (4.3) and melanoma/lung (1.9) ratios at 1 h. These results suggest that small technetium-99m complexes could be useful as potential melanoma-imaging agents.

Animals↗
PubMed2000

The Bateman gradient and the cause of sexual selection in a sex-role-reversed pipefish.

As a conspicuous evolutionary mechanism, sexual selection has received much attention from theorists and empiricists. Although the importance of the mating system to sexual selection has long been appreciated, the precise relationship remains obscure. In a classic experimental study based on parentage assessment using visible genetic markers, more than 50 years ago A. J. Bateman proposed that the cause of sexual selection in Drosophila is 'the stronger correlation, in males (relative to females), between number of mates and fertility (number of progeny)'. Half a century later, molecular genetic techniques for assigning parentage now permit mirror-image experimental tests of the 'Bateman gradient' using sex-role-reversed species. Here we show that, in the male-pregnant pipefish Syngnathus typhle, females exhibit a stronger positive association between number of mates and fertility than do males and that this relationship responds in the predicted fashion to changes in the adult sex ratio. These findings give empirical support to the idea that the relationship between mating success and number of progeny, as characterized by the Bateman gradient, is a central feature of the genetic mating system affecting the strength and direction of sexual selection.

Animals↗
PubMed1999

Clustered microsatellite mutations in the pipefish Syngnathus typhle.

Clustered mutations are copies of a mutant allele that enter a population's gene pool together due to replication from a premeiotic germline mutation and distribution to multiple successful gametes of an individual. Although the phenomenon has been studied in Drosophila and noted in a few other species, the topic has received scant attention despite claims of being of major importance to population genetics theory. Here we capitalize upon the reproductive biology of male-pregnant pipefishes to document the occurrence of clustered microsatellite mutations and to estimate their rates and patterns from family data. Among a total of 3195 embryos genetically screened from 110 families, 40% of the 35 detected de novo mutant alleles resided in documented mutational clusters. Most of the microsatellite mutations appeared to involve small-integer changes in repeat copy number, and they arose in approximately equal frequency in paternal and maternal germlines. These findings extend observations on clustered mutations to another organismal group and motivate a broader critique of the mutation cluster phenomenon. They also carry implications for the evolution of microsatellites with respect to mutational models and homoplasy among alleles.

Animals↗
PubMed1998

Characterization of P-glycoprotein transport and inhibition in vivo.

The P-glycoprotein is an energy-dependent efflux pump capable of decreasing the intracellular concentration of a broad range of chemotherapeutic agents. [99mTc]Sestamibi, a P-glycoprotein transport substrate, is a sensitive probe of P-glycoprotein function both in vitro and in vivo. A human tumor model in nude mice was evaluated to determine whether [99mTc]Sestamibi could detect in vivo differences in P-glycoprotein expression and P-glycoprotein modulation by the reversal agent SDZ PSC 833. Differential [99mTc]Sestamibi accumulation based upon P-glycoprotein expression was demonstrated in xenografts in vivo. Dose-dependent inhibition of P-glycoprotein function was achieved with SDZ PSC 833. Administration of the reversal agent increased [99mTc]Sestamibi accumulation in the xenografts expressing P-glycoprotein. These observations show that [99mTc]Sestamibi as capable of detecting the modulation of P-glycoprotein in a solid tumor model by the reversal agent SDZ PSC 833.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

The validity of two methods of mandibular superimposition: a comparison with tantalum implants.

The aim of this investigation was to examine and compare the validity of Björk's and Ricketts' methods for the superimposition of serial cephalometric radiographs of the mandible for the analysis of changes over the duration of routine orthodontic treatment in growing subjects (approximately 2 years). Pre- and posttreatment lateral cephalometric radiographs of 23 children, with tantalum markers implanted in the mandible, were studied. The differences in position of six dental and skeletal landmarks between superimposition on Björk's structures and on Ricketts' corpus axis were compared with those on the basis of the implants. A rotational effect was found for corpus axis resulting from differential movement of Xi point with growth, whereas Björk's method yielded results essentially similar to those of the implant-based superimposition. This resulted in statistically significant median differences between the two methods for all landmarks except pogonion and menton. The magnitude of the differences increased with distance from the central core of the mandible and were generally greater horizontally than vertically. Although most differences were less than 2 mm, approximately 10% of the subjects showed differences greater than 4 mm for molar and incisor landmarks. These findings suggest that, for growing subjects, Björk's method should be preferred Ricketts', which cannot be relied on to indicate the true (intramandibular) changes during orthodontic treatment in growing subjects.

Analysis of Variance↗
PubMed1998

Uptake of cationic technetium complexes in cultured human carcinoma cells and human xenografts.

We evaluated lipophilicity, in vitro cell accumulation, and biodistribution of a series of 99mTc-ether isonitrile complexes to determine whether increased lipophilicity promotes extraction by tumor or enhances imaging properties of the radiopharmaceutical. Nine 99mTc-sestamibi analogs were synthesized and their lipophilicity was determined. Net cellular accumulation and membrane-potential-independent uptake were quantitatively compared in cultured human colon, breast, and lung carcinoma cells. The biodistribution of [99mTc-(2-methoxy-2-ethyl-isocyanopropane)6]+ (99mTc-MMBI) and [99mTc-(2-ethoxy-2-methyl-1-isocyanopropane)6]+ (99mTc-EIBI) was studied in nude mice using subcutaneous, subrenal capsule, and hepatic tumor xenografts. Accumulation of these compounds in colon cells correlated with increasing lipophilicity. Compared with 99mTc-sestamibi, 99mTc-EIBI exhibited (i) in colon cells both higher net accumulation and a higher specific/nonspecific uptake ratio; (ii) in all three cell lines higher membrane-potential-dependent accumulation; and (iii) in all subcutaneous tumor xenografts and in colon subrenal capsule and hepatic tumor xenografts higher tumor/background ratios.

Animals↗
PubMed1998

Microsatellite evidence for monogamy and sex-biased recombination in the Western Australian seahorse Hippocampus angustus.

Four polymorphic microsatellite loci were used to assess biological parentage of 453 offspring from 15 pregnant males from a natural population of the Western Australian seahorse Hippocampus angustus. Microsatellite genotypes in the progeny arrays were consistent with a monogamous mating system in which both females and males had a single mate during a male brooding period. Multilocus genotypes implicated four females in the adult population sample as contributors of eggs to the broods of collected males, but there was no evidence for multiple mating by females. Based on genotypic data from the progeny arrays, two loci were linked tightly and the recombination rate appeared to be approximately 10-fold higher in females than in males. The utility of linked loci for parentage analyses is discussed.

Animals↗
PubMed1998

A case of rapid deterioration: acute multiple sclerosis of the Marburg type.

Multiple sclerosis (MS) is a chronic, progressive, degenerative, autoimmune disease that usually follows a relapsing-remitting course. In most cases of MS, the clinical course is variable with the vast majority of patients having mild to moderate disabilities that develop over the course of years. A subset of acute forms of MS exist and may be relatively unknown to neuroscience nurses. The acute forms follow a virulent course and are associated with high morbidity and mortality. A case presentation of a patient with the Marburg variant of MS raises the neuroscience nurse's understanding of the challenges associated with caring for patients with this unusual form of MS.

Acute Disease↗
PubMed1997

A technetium-99m SPECT imaging agent which targets the dopamine transporter in primate brain.

The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for certain neurological diseases. In particular, the DAT is depleted in Parkinson's disease, and the extent of depletion correlates with the loss of dopamine. Herein we describe the design, synthesis, and biological evaluation of technepine, the first 99mTc-labeled SPECT imaging agent which targets the dopamine transporter in striatum. We have demonstrated that the DAT can accommodate a chelating unit attached to the 8-amine function of a tropane skeleton. Further, we have demonstrated for the first time that a molecule can be designed to carry the radionuclide 99mTc across the blood-brain barrier in sufficient quantity to obtain in vivo images of the striatum in monkeys. This advance will undoubtedly lead to the design of new receptor and transporter-mediated 99mTc agents which can label specific transporter and receptor targets in the central nervous system.

Animals↗