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Biomedical subjects

G Shaw

Publications and source records attributed to G Shaw.

At least 37 records · Page 2Linked to original sources
PubMed2001

Investigation of Escherichia coli dimethyl sulfoxide reductase assembly and processing in strains defective for the sec-independent protein translocation system membrane targeting and translocation.

Dimethyl sulfoxide reductase is a heterotrimeric enzyme (DmsABC) localized to the cytoplasmic surface of the inner membrane. Targeting of the DmsA and DmsB catalytic subunits to the membrane requires the membrane targeting and translocation (Mtt) system. The DmsAB dimer is a member of a family of extrinsic, cytoplasmic facing membrane subunits that require Mtt in order to assemble on the membrane. We show that the MttA(2), MttB, and presumably MttA(1) but not the MttC proteins are required for targeting DmsAB to the membrane. Unlike other Mtt substrates such as trimethylamine N-oxide reductase, the soluble cytoplasmic DmsAB dimer that accumulates in the mtt deletions is very labile. Deletion of the mttA(2) or mttB genes also prevents anaerobic growth on fumarate even though fumarate reductase does not require Mtt for assembly. This was due to the lethality of membrane insertion of DmsC in the absence of the DmsAB subunits. In the absence of DmsC, DmsAB accumulates in the cytoplasm. A 45-amino acid leader on DmsA is removed during assembly. Processing does not require DmsC but does require Mtt. Translocation of DmsAB to the periplasm is not required for processing. The leader may be cleaved by a novel leader peptidase, or the long DmsA leader may traverse the membrane through the Mtt system resulting in cleavage by the periplasmic leader peptidase I followed by release of DmsA into the cytoplasm.

Arginine↗
PubMed2001

Photocatalytic degradation of the cyanotoxin cylindrospermopsin, using titanium dioxide and UV irradiation.

Cylindrospermopsis raciborskii produces the cyanotoxin cylindrospermopsin, which is commonly found in SouthEast Queensland water reservoirs, and has been responsible for the closure of these reservoirs as a source of drinking water in recent times. Thus, alternative more effective treatment methods need to be investigated for the removal of toxins such as cylindrospermopsin. This study examined the effectiveness of two brands of titanium dioxide under UV photolysis for the degradation of cylindrospermopsin. Results indicate that titanium dioxide is an efficient photocatalyst for cylindrospermopsin degradation. The titanium dioxide (TiO2), brand Degussa P-25 was found to be more efficient than the alternate brand Hombikat UV-100. There was an influence from solution pH (4, 7, and 9) with both brands of titanium dioxide, with high pH resulting in the best degradation rate. Importantly, there was no adsorption of cylindrospermopsin to titanium dioxide particles as seen with other cyanotoxins, which would adversely influence the degradation rate. Degradation rates were not influenced by temperature (19-34 degrees C) when P-25 was the source of TiO2, some temperature influence was observed with UV-100. Dissolved organic carbon concentration will reduce the efficiency of titanium dioxide for cylindrospermopsin degradation, however the presence of other inorganic matter in natural waters greatly assists the photocatalytic process. With minimal potentially toxic by-product formation expected with this treatment, and the effective degradation of cylindrospermopsin, titanium dioxide UV photolysis is a promising speculative alternative water treatment method.

Alkaloids↗
PubMed2001

Specific association of 36Cl with low molecular weight humic substances in soils.

Soils initially contaminated with 36Cl in the chloride form were subjected to solid-liquid extractions using a variety of reagents including deionised water and 1 M sodium hydroxide (NaOH). 1 M NaOH was found to result in the greatest recovery of 36Cl from the soils, a result which provided initial evidence that radioactive chlorine became attached to humic substances present naturally within the soils. Deionised water and 1 M NaOH extracts were subjected to analysis involving separation by gel filtration chromatography (GFC). It was found that 36Cl in 1 M NaOH extracts associated preferentially with low molecular weight (LMW) fractions of humic substances whereas, in deionised water extracts, 36Cl appeared to be present exclusively in the chloride form. Previous literature evidence, mainly from highly organic forest soils, suggests that conversion of stable chlorine from chloride to organic forms can occur as a result of biological action. The present paper also presents good evidence for the specific attachment of stable chlorine (37Cl) to a LMW humic fraction, again demonstrated using GFC separation. Current risk assessments of the deep geological disposal of solid radioactive wastes containing 36Cl typically assume a very low degree of sorption based on the notion that the predominant environmental species of radiochlorine is chloride. This paper concludes with a brief discussion on the implications of organochlorine formation in the biosphere for assessment of the radiological impact of deep geological disposal of solid radioactive wastes.

Adsorption↗
PubMed2001

Pectenotoxins--an issue for public health: a review of their comparative toxicology and metabolism.

Pectenotoxins (PTXs) are a group of toxins associated with diarrhetic shellfish poisoning (DSP) and isolated from DSP toxin-producing dinoflagellate algae. Consumption of shellfish contaminated with PTXs has been associated with incidences of severe diarrhetic illness resulting in hospitalisation. Concern has been raised for public health following the discovery that these toxins are not only hepatotoxic and can cause diarrhetic effects in mammals, but that they are potently cytotoxic to human cancer cell lines and have been found to be tumour promoters in animals. With advances in knowledge and technology, more PTXs are being identified, but little is known of their toxicology and the potential impact these toxins may have on public health in the long term. Without such information, adequate health-risk assessments for the consumption of shellfish contaminated with PTXs cannot be performed. This review gives a brief introduction to diarrhetic shellfish toxins, details the known toxicology and metabolism of PTXs in animals, and discusses known incidences of PTX poisoning in humans.

Animals↗
PubMed2001

A cost-benefit analysis of long-term management options for forests following contamination with 137Cs.

This paper provides a description of a cost-benefit analysis applied to determine the cost effectiveness, or otherwise, of nine management strategies potentially applicable to forests contaminated with 137Cs. The management strategies were considered singly and in a number of likely combinations. A management strategy was considered to be cost-effective if it resulted in a lower overall monetary detriment than was incurred if use of the contaminated forest was continued on a 'business as usual' basis. Only the banning of mushroom collection and restriction of public access proved to be cost-effective management strategies on the basis of this definition. However, even these strategies only proved cost-effective at high levels of 137Cs contamination, at which net savings in detriment in the form of public dose were achieved. Cost-effective savings of doses to forest workers were never achieved at any of the contamination levels considered in this study. It is suggested that novel alternative uses of contaminated forests are required which could provide added value to the standing crop in return for small increases in public and worker doses. One such use might be biofuel production.

Cesium Radioisotopes↗
PubMed2001

The influence of estrogen on the developing male marsupial.

The genes and hormones involved in gonadal differentiation are highly conserved between eutherians and marsupials, although the timing of the developmental events differs. In marsupials, the testis develops seminiferous cords two days after birth, and the ovaries are not distinguishable until around eight days after birth. Differentiation of the internal genitalia is controlled in marsupials, as in eutherians, by testicular testosterone and Müllerian inhibiting substance, but differentiation of the scrotum in males and mammary primordia in females is hormone-independent. Since the young are easily accessible in the pouch, it is possible to administer gonadal hormones during the period of sexual differentiation. In both Australian and South American marsupials, estradiol treatment of neonatal males can induce male-to-female gonadal sex reversal. The testicular transformations range from partial suppression of seminiferous tubule development to the development of a morphologically normal ovary depending on the stage that treatment starts. The sex-reversed testes have a clearly defined cortex and medulla, and there are significantly fewer germ cells. The germ cells are surrounded by follicle-like cells and are in the early stages of meiosis, as is normal for XX germ cells in ovaries. In normal males, germ cells only enter meiosis at the onset of puberty. As in eutherians, estrogen treatment of neonatal male marsupials prevents regression of the Müllerian ducts, which are hypertrophic. Neonatal estradiol exposure also causes hypertrophy of the prostate and urogenital sinus. Estradiol treatment also inhibits transabdominal testicular descent and many animals develop inguinal hernias. The ability of estradiol to cause testis-to-ovary sex reversal in marsupials provides a new way of studying the interactions between genes and hormones in testicular differentiation.

Animals↗
PubMed2001

Fetal control of parturition in marsupials.

Among marsupials, the control of birth is best understood in the tammar wallaby. The young is tiny relative to the mother and is highly altricial. Adult female tammar wallabies weigh 5 kg, whereas the neonate weighs about 400 mg. However, despite this small size, there is clear evidence that the fetus provides the signal that sets the timing of birth through several mechanisms. A fetal signal activates a nitric oxide-guanylate cyclase system in the myometrium that may maintain myometrial inactivity, and this is down-regulated at term. There is also up-regulation of prostaglandin (PG) production in the gravid endometrium during the last two days of gestation that parallels increased placental PG synthesis, and a pregnancy-specific up-regulation of oxytocin receptors in the gravid myometrium that increases the responsiveness of the gravid uterus to mesotocin. These changes facilitate parturition, but an acute fetus-derived signal appears to trigger parturition. The fetal signal is probably related to glucocorticoid production. The fetal adrenal matures and is able to synthesize cortisol by Day 22 of the 26-day gestation. The fetal adrenals double in size between Day 24 and term, and their cortisol content increases over 10-fold. The pituitary of the neonate contains presumptive corticotrophs, and the adrenals increase cortisol production in response to adrenocorticotrophin. Prostaglandin E2, which is produced by the placenta, is also a potent stimulant of fetal adrenal cortisol synthesis. Treatment of tammars in late gestation with the cortisol agonist, dexamethasone, triggers birth around 23 h later. There is thus a strong case that fetal adrenal cortisol plays a key role in the preparation for birth and the timing of it. Further studies are in progress to more clearly define the mechanisms behind these actions of cortisol.

Adrenal Glands↗
PubMed2001

Sex down under: the differentiation of sexual dimorphisms during marsupial development.

Marsupials have many characteristic features that make them ideal models to study the control of sexual differentiation and development. They are distinguished from eutherian mammals in their mode of reproduction and their greater dependence on the teat and mammary gland than on the placenta for development. They give birth to a highly altricial young which completes its development while firmly attached to a teat, usually within the confines of a pouch. At birth, the marsupial neonate has a well-developed digestive, respiratory and circulatory system, but retains its fetal excretory system with a fully functional mesonephric kidney and undifferentiated gonads and genitalia.

Androgens↗
PubMed2001

Estrogen-induced gonadal sex reversal in the tammar wallaby.

Estrogens have a feminizing effect on gonadal differentiation in fish, amphibians, reptiles, and birds. However, the role of estrogen during gonadal differentiation in mammals is less clear. We investigated the effect of estrogen on gonadal differentiation of male tammar wallabies. Male pouch young were treated orally with estradiol benzoate or oil from the day of birth, before seminiferous cords develop, to Day 25 postpartum and were killed at Day 50 postpartum. In all estrogen-treated neonates, a decrease in gonadal volume, volume of the seminiferous cords, thickness of the tunica albuginea, and number of germ cells was found. The stage of treatment affected the magnitude of the response. Two of three male young born prematurely after 25 days of gestation and treated subsequently with estradiol had ovary-like gonads, with well-developed cortical and medullary regions and primordial follicle formation. Furthermore, at Day 50 postpartum, many (21%) of the germ cells in these sex-reversed ovaries were in the leptotene and zygotene stages of meiosis, similar to female germ cells at the same stage of development. In the other males born on Day 26 of gestation or later, estradiol treatment from the day of birth caused development of dysgenetic testes, with abnormal Sertoli cells, atrophy of the seminiferous tubules and tunica albuginea, and absence of meiotic germ cells. In this marsupial, therefore, estradiol can induce either partial or complete transformation of the male gonads into an ovary with meiotic germ cells. These results confirm that estrogen can inhibit early testicular development, and that testis determination occurs during a narrow window of time.

Animals↗
PubMed2001

Differential regulation of contractility and nitric oxide sensitivity in gravid and nongravid myometrium during late pregnancy in a marsupial.

Marsupials have two anatomically separate uteri; and in macropodids (kangaroos and wallabies), there is a single ovulation from alternate ovaries in each cycle. During late pregnancy, the two uteri are differentially regulated by local hormonal influences from the corpus luteum, the fetus, and placenta on one side and by the developing Graafian follicle on the other. In this study, we report striking differences in contractile behavior of nongravid and gravid myometrium from the tammar wallaby (Macropus eugenii) in late pregnancy and immediately post partum. Nongravid myometrium, from the uterus ipsilateral to a Graafian follicle, was spontaneously active but unresponsive to the oxytocic peptide mesotocin and the smooth muscle relaxant nitric oxide. Myometrium from the contralateral, gravid uterus, which contained a conceptus and was associated with an active corpus luteum, was not spontaneously active. Gravid myometrium became increasingly sensitive to mesotocin stimulation as pregnancy progressed, and nitric oxide induced marked relaxation at all stages examined, by a guanylyl-cyclase mediated pathway. These results provide further evidence that the two uteri of marsupials are under differential control, suggesting that local endocrine and paracrine influences, derived from the ovaries, the fetus, and placenta, can regulate concurrent but distinct physiological responses in the reproductive tracts of these mammals.

Animals↗
PubMed2001

Germ cells, gonads and sex reversal in marsupials.

The formation of the testis or ovary is a critical step in development. Alterations in gonadal development during fetal or postnatal life can lead to intersexuality or infertility. Several model systems have been particularly useful in studying gonadal differentiation, the eutherian mammal and amphibia, fish, and birds. However, marsupials provide a unique opportunity to investigate gonadal development and the interactions of genes and hormones in gonadal differentiation and germ cell development in all mammals. On the one hand the genetic mechanisms appear to be identical to those in eutherian mammals, including the testis-determining SRY gene. On the other hand, marsupials retain in part the plasticity of the amphibian gonad to hormonal manipulation. It is possible to induce female to male and also male to female gonadal sex reversal in marsupials by hormonal manipulation, and oestradiol can induce male germ cells to enter meiosis at the time the oogonia do. In addition, in marsupials the development of the scrotum and mammary glands are independent of testicular androgens and instead are controlled by a gene or genes on the X-chromosome. Thus marsupials provide a number of opportunities for manipulating the sexual differentiation of the gonads that are not possible in eutherian mammals and so provide a unique perspective for understanding the common mechanisms controlling sexual development.

Animals↗
PubMed2000

Prostate formation in a marsupial is mediated by the testicular androgen 5 alpha-androstane-3 alpha,17 beta-diol.

Development of the male urogenital tract in mammals is mediated by testicular androgens. It has been tacitly assumed that testosterone acts through its intracellular metabolite dihydrotestosterone (DHT) to mediate this process, but levels of these androgens are not sexually dimorphic in plasma at the time of prostate development. Here we show that the 3 alpha-reduced derivative of DHT, 5 alpha-androstane-3 alpha,17 beta-diol (5 alpha-adiol), is formed in testes of tammar wallaby pouch young and is higher in male than in female plasma in this species during early sexual differentiation. Administration of 5 alpha-adiol caused formation of prostatic buds in female wallaby pouch young, and in tissue minces of urogenital sinus and urogenital tubercle radioactive 5 alpha-adiol was converted to DHT, suggesting that circulating 5 alpha-adiol acts through DHT in target tissues. We conclude that circulating 5 alpha-adiol is a key hormone in male development.

Androstane-3,17-diol↗
PubMed2000

Multiple roles for the twin arginine leader sequence of dimethyl sulfoxide reductase of Escherichia coli.

Dimethyl sulfoxide (Me(2)SO) reductase of Escherichia coli is a terminal electron transport chain enzyme that is expressed under anaerobic growth conditions and is required for anaerobic growth with Me(2)SO as the terminal electron acceptor. The trimeric enzyme is composed of a membrane extrinsic catalytic dimer (DmsAB) and a membrane intrinsic anchor (DmsC). The amino terminus of DmsA has a leader sequence with a twin arginine motif that targets DmsAB to the membrane via a novel Sec-independent mechanism termed MTT for membrane targeting and translocation. We demonstrate that the Met-1 present upstream of the twin arginine motif serves as the correct translational start site. The leader is essential for the expression of DmsA, stability of the DmsAB dimer, and membrane targeting of the reductase holoenzyme. Mutation of arginine 17 to aspartate abolished membrane targeting. The reductase was labile in the leader sequence mutants. These mutants failed to support growth on glycerol-Me(2)SO minimal medium. Replacing the DmsA leader with the TorA leader of trimethylamine N-oxide reductase produced a membrane-bound DmsABC with greatly reduced enzyme activity and inefficient anaerobic respiration indicating that the twin arginine leaders may play specific roles in the assembly of redox enzymes.

Amino Acid Sequence↗
PubMed2000

The Balanced Budget Act of 1997: its impact on U.S. teaching hospitals.

The Balanced Budget Act of 1997 had a profound impact on the financing and organization of many health care services. The Act disproportionately affected U.S. teaching hospitals, leading to substantial budget reductions in many institutions and the threat of cuts in major programs and services that teaching hospitals provide to communities. This paper examines the overall financial and organizational impact of the Balanced Budget Act on teaching hospitals and considers its effect on residency education. It also discusses to what degree the Balanced Budget Refinement Act of 1999 will mitigate these effects and posits other solutions to the serious financial issues facing teaching hospitals in the United States.

Budgets↗
PubMed2000

Effect of potassium (K) supply on the uptake of 137Cs by spring wheat (Triticum aestivum cv. Tonic): a lysimeter study.

A lysimeter experiment was carried out on a relatively infertile soil to examine the effect of potassium fertiliser application on the uptake of radiocaesium by spring wheat. Porous ceramic cups were used to obtain samples of soil solution. Results showed that the uptake of radiocaesium by spring wheat was reduced by the addition of potassium. However this inhibitory effect was less marked at later stages of plant growth due to factors such as the spatial variability of potassium within the soil, differences in root distribution down the soil profile and age-related demand for potassium by the plant. There was some evidence that a negative power function could be used to describe the relationship between the concentration of 137Cs in the plant and concentrations of potassium or 137Cs:K quotients in soil solution over the whole experimental period. Practical implications of potassium fertilisation in terms of reducing uptake of radiocaesium by crops are discussed.

Cesium Radioisotopes↗