Emergence of the individual as an international juristic entity: enforcement of International Human Rights

In this article it is contended that state practice, as evidenced in the  declarations of the judiciary and the many treaties and conventions  guaranteeing human rights, reveals a consensus of opinion acknowledging the individual to be an international juristic entity. So extensive is this practice that it could be seen as marking the emergence of a new customary international norm; or at least a general principle of international law, yet to crystallise into a custom; acknowledging the individual as the beneficiary of international rights. This is important for individuals and minority groups because if they possess international rights independently of the State, enforcement of their rights will no longer depend on the interests of the State. Where the State is often the offender of human rights, international law will not effectively confer any real rights unless the individual is so recognised as an international juristic entity.

Expression, localisation and hormone regulation of the human copper transporter hCTR1 in placenta and choriocarcinoma Jeg-3 cells

Copper is an essential trace element necessary for normal growth and development. During pregnancy, copper is transported from the maternal circulation to the fetus by mechanisms which have not been clearly elucidated. The copper uptake protein, hCTR1 is predicted to play a role in copper transport in human placental cells. This study has examined the expression and localisation of hCTR1 in human placental tissue and Jeg-3 cells. In term placental tissue the hCTR1 protein was detected as a 105 kDa protein, consistent with the size of a trimer which may represent the functional protein. A 95 kDa band, possibly representing the glycosylated protein, was also detected. hCTR1 was localised within the syncytiotrophoblast layer and the fetal vascular endothelial cells in the placental villi and interestingly was found to be localised toward the basal plasma membrane. It did not co-localise with either the Menkes or the Wilson copper transporting ATPases. Using the placental cell line Jeg-3, it was shown that the 35 kDa monomer was absent in the extracts of cells exposed to insulin, estrogen or progesterone and in cells treated with estrogen an additional 65 kDa band was detected which may correspond to a dimeric form of the protein. The 95 kDa band was not detected in the cultured cells. These results provide novel insights indicating that hormones have a role in the formation of the active hCTR1 protein. Furthermore, insulin altered the intracellular localisation of hCTR1, suggesting a previously undescribed role of this hormone in regulating copper uptake through the endocytic pathway.

A review of international human resource management : integration, interrogation, imitation

International human resource management (IHRM) represents an important dimension of international management. Over the past three decades, there has been considerable growth in research and practice in IHRM. While there have been extensive developments in this field, numerous scholars have identified aspects requiring review and revision. Hence, this paper reviews and interrogates the progress in IHRM's theoretical development. The review leads to the conclusion that research in IHRM has tended to emphasize integration over other forms of progress. In response, and in provocation, imitation rather than integration is suggested as an approach for the development of future theoretical and conceptual directions in IHRM.

Environmental factors affecting transcription of the human L1 retrotransposon. I. Steroid hormone-like agents

The L1 retrotransposon has significantly shaped the structure of the human genome. At least 30% of human genome sequence can be attributed to L1 reverse transcriptase activity. There are 105 copies of the human L1 retrotransposon, L1Hs, most of which are defective, although ~8–9x103 are full length. L1Hs elements transpose through an RNA intermediate and transcription is thought to be the rate limiting step in retrotransposition. Because transcription of retrotransposons in a variety of organisms has been shown to respond to environmental stimuli, we investigated the influence of various agents on transcription from two different L1Hs promoters. The activity of the L1Hs promoters was analyzed by transfecting L1Hs-expressing cell lines with plasmids containing the L1Hs promoters fused to the LacZ reporter gene and monitoring expression with a ß-galactosidase assay. Small increases in ß-galactosidase activity were observed with both L1Hs promoters after treatment with serum, testosterone, dihydrotestosterone and organochloride pesticides, indicating that these agents can influence L1Hs transcription.

Environmental factors affecting transcription of the human L1 retrotransposon. II. Stressors

Retrotransposons have clearly molded the structure of the human genome. The reverse transcriptase coded for by long interspersed nuclear elements (LINEs) accounts for 35% of the human genome, with 8–9 x 105 copies of the most common human LINE element, L1Hs. Retrotransposons cycle through an RNA intermediate with transcription as the rate limiting step. Because various retrotransposons have been demonstrated to be induced by environmental stimuli, we investigated the response of the L1Hs promoter to various agents. L1Hs promoter activity was analyzed by transfecting an L1Hs-expressing cell line with plasmids containing one of two L1Hs promoters fused to the LacZ reporter gene. L1Hs promoter activity was then monitored with a ß-galactosidase assay. Treatment with UV light and heat shock resulted in a small increase in ß-galactosidase activity from one promoter, while treatment with tetradecanoylphorbol 13-acetate resulted in small increases in ß-galactosidase activity from both promoters. No increase in ß-galactosidase activity was observed after exposure to X-rays or hydrogen peroxide.

Prevalence of genital human papillomavirus DNA in a sample of senior school-aged women in the Australian Capital Territory

Background: A strong association between persistent infection with oncogenic types of human papillomavirus (HPV) and cervical cancer is well established. Small numbers of international studies examining adolescent HPV infection and the risk factors associated are published, but there is currently no evidence on the prevalence and risk factors for HPV in an Australian, sexually active female adolescent population. Methods: To provide prevalence and risk factors for HPV in a female sexually active, senior high school population in the Australian Capital Territory (ACT), a convenience sample of 161, 16–19-year-old females attending a senior high school was evaluated. The sample formed part of a larger sample recruited for a study of sexually transmitted infections and blood-borne viruses in senior high school students. A clinical record was used to collect information about sexual and other risk behaviours, while self-collected vaginal swabs were tested for HPV DNA detection and genotyping using polymerase chain reaction. Results: The prevalence of HPV DNA in this sample overall was 11.2%, with multiple genotypes in 38%. No statistically significant associations were found between HPV DNA and the number of male partners, age of coitarche, time since first sexually active, condom use, smoking or alcohol intake. Conclusions: This is the first Australian study that has examined the prevalence and risk factors for genital HPV in this demographic group. The prevalence of HPV infection is slightly lower than reported in similar age groups overseas and is lower than other Australian studies in older women and those attending sexual health centres. Of HPV-positive young women, high-risk genotypes were found in over half, with more than one-third of HPV existing as multiple genotypes. Large community-based prevalence studies are needed to guide the development of recommendations for the vaccination of young women against HPV and to support other health promotion initiatives.

Pharmacokinetics of recombinant human endostatin in rats

The pharmacokinetics of recombinant human endostatin (rh-Endo) has not been established in the rat, although this species of animal is commonly used in the pharmacological studies of rh-Endo. This study aimed to investigate the pharmacokinetics, tissue distribution, and excretion of rh-Endo in rats. 125I-radiolabeled rh-Endo was administered to healthy rats by intravenous (i.v) bolus injection at 1.5, 4.5 and 13.5 mg/kg. The maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) of rh-Endo increased proportionally with the increase of the dosage. There were no significant differences in total body clearance (CL) and elimination half-life (t1/2beta) of rh-Endo among the three dosages used. A 93.5% and 2.2% of the radioactivity was recovered in the urine and feces, respectively, in bile-duct intact rats; whereas only 0.1% of the total radioactivity was excreted into the bile in bile-duct cannulated rats. rh-Endo was rapidly and widely distributed in the liver, kidneys, spleen and lungs. Furthermore, a significant allometric relationship between CL, but not volume of distribution (Vd) and t1/2beta of rh-Endo, and the body weight was observed across mouse, rat and monkey, with the predicted values in humans significantly lower than those observed in cancer patients. rh-Endo exhibited a linear pharmacokinetics in rats and it is mainly excreted through the urine.

A model for the implementation of strategic human resource management

This paper has been developed out of an action research project involving the Australian Taxation Office (ATO). One of the outcomes of this project was the development of a model for the implementation of Strategic Human Resource Management (SHRM) for the purpose of cultural change and/or alignment to business strategy.

The paper brings together many of the theories that have arisen in SHRM in the last decade or so, including theories around human capital, the resource-based view, HR configuration, HR architecture, vertical and horizontal fit, HR systems and HR roles.

Studies of the human lymphocyte P2Z receptor and its activation of phospholipase D

Extracellular adenosine 5′-triphosphate (ATP) is an agonist for the P2Z receptor of human leukaemic lymphocytes and opens a Ca ²⁺-selective ion channel, which also conducts Ba²⁺, Sr²⁺ and the small fluorescent dye, ethidium⁺. A wide range of receptor agonists, many of which raise cytosolic [Ca²⁺] activate phospholipase D (PLD). In the present study, it was shown that both ATP and 3′-O-(4-benzoylbenzoyl)-ATP (BzATP) stimulated PLD activity in a concentration-dependent manner, and the inhibitory effects of suramin, oxidised ATP, extracellular Na⁺ and Mg²⁺ suggested that the effect of these agonists is mediated by P2Z receptors. The role of divalent cations in ATP-stimulated PLD activity was investigated. Several agonists (eg ATP, thapsigargin, ionomycin) stimulated a rise in cytosolic [Ca²⁺] in human lymphocytes, but only ATP and ionomycin stimulated PLD activity. When Ca²⁺ influx was prevented by EGTA, the majority of ATP-stimulated and all of ionomycin-stimulated PLD activity was inhibited. Preloading cells with the Ca²⁺ chelator, BAPTA, reduced cytosolic [Ca²⁺] and, paradoxically, ATP-stimulated PLD activity was potentiated. ATP-stimulated PLD activity was supported by both Ba²⁺ and Sr²⁺ when they were substituted for extracellular Ca²⁺. Furthermore, both ATP-stimulated PLD activity and ATP-stimulated ¹³³Ba²⁺ influx showed a linear dependence on extracellular [Ba²⁺]. Thus it was concluded that ATP stimulated PLD activity in direct proportion to the influx of divalent cations through the P2Z ion channel and this PLD activity was insensitive to changes in bulk cytosolic [Ca²⁺]. The calmodulin (Ca²⁺/CaM) inhibitor, trifluoperazine (TFP) inhibited ionomycin- and ATP-stimulated PLD activity and ATP-stimulated apoptosis, but had no effect on PLD activity already activated by ATP. However, TFP inhibited ATP-stimulated Ca²⁺, Ba²⁺ and ethidium⁺ fluxes, at concentrations below those which inhibit Ca²⁺/CaM, suggesting that TFP inhibits the P2Z receptor. Similarly, the isoquinolinesulphonamide, KN-62, a selective inhibitor of Ca²⁺/CaM-dependent protein kinase II (CaMKII), also prevented ATP-stimulated apoptosis, but had no effect on pre-activated PLD. In addition, KN-62, and an analogue, KN-04, which has no effect on CaMKII, potently inhibited ATP-stimulated Ba²⁺ influx (IC₅₀ 12.7 ± 1.5 and 17.3 ± 2.7 nM, respectively), ATP-stimulated ethidium⁺ uptake (IC₅₀ 13.1 ± 2.6 and 37.2 ± 8.9 nM, respectively), ATP-stimulated phospholipase D activity (50% inhibition 5.9 ± 1.2 and 9.7 ± 2.8 nM, respectively) and ATP-induced shedding of the surface adhesion molecule, L-selectin (IC₅₀ 31.5 ± 4.5 and 78.7 ± 10.8 nM, respectively). They did not inhibit phorbol ester- or ionomycin-stimulated PLD activity or phorbol ester-induced L-selectin shedding. Neither KN-62 nor KN-04 (both 500 nM) have any effect on UTP-stimulated Ca²⁺ transients in fura-2-loaded human neutrophils, a response which is mediated by the P2Y₂ receptor, neither did they inhibit ATP-stimulated contractile responses mediated by the P2X₁ receptor of guinea pig urinary bladder. Thus, KN-62 and KN-04 are almost equipotent as P2Z inhibitors with IC₅₀s in the nanomolar, indicating that their actions cannot be due to CaMKII inhibition, but rather that they are potent and direct inhibitors of the P2Z receptor. Extracellular ATP-induced shedding of L-selectin from lymphocytes into the medium is a Ca²⁺-independent response. L-selectin is either cleaved by a metalloproteinase or a PLD with specificity for glycosylphosphatidylinositol (GPI). The novel hydroxamic acid-based zinc chelator, Ro-31-9790 blocks ATP-induced L-selectin shedding, but was without effect on ATP-induced Ba²⁺ influx or ATP-stimulated PLD activity. Furthermore, another zinc chelator, 1,10-phenanthroline, an inhibitor of a GPI-PLD, potentiated rather than inhibited ATP-stimulated PLD activity, suggesting that ATP-induced L-selectin shedding and ATP-stimulated PLD activity are independent of each other. Although extracellular ATP is the natural ligand for the lymphocyte P2Z receptor, it is less potent than BzATP in stimulating Ba²⁺ influx. Concentration-response curves for BzATP- and ATP-stimulated ethidium⁺ influx gave EC₅₀s 15.4 ± 1.4 µM and 85.6 ± 8.8 µM, respectively. The maximal response to ATP was only 69.8 ± 1.9% of that for BzATP. Hill coefficients were 3.17 ± 0.24 and 2.09 ± 0.45 for BzATP and ATP respectively, suggesting greater positive cooperativity for BzATP than for ATP in opening the P2Z-operated ion channel. A rank order of agonist potency of BzATP > ATP = 2MeSATP > ATPγS was observed for agonist-stimulated ethidium⁺ influx, while maximal influxes followed a rank order of BzATP > ATP > 2MeSATP > ATPγS. When ATP (300 -1000 µM) was added simultaneously with 30 µM BzATP (EC₉₀), it reduced both ethidium⁺ and Ba²⁺ fluxes by 30 - 40% relative to values observed with BzATP alone. KN-62, previously shown to be a specific inhibitor of the lymphocyte P2Z receptor, was a less potent antagonist of BzATP-induced fluxes than ATP, when maximal concentrations of both agonists (50 and 500 µM respectively) were used. However, when BzATP (18 µM) was used at a concentration equiactive with a maximally effective ATP concentration, KN-62 showed the same inhibitory potency for both agonists. The ecto-ATPase antagonist, ARL-67156, inhibited both ATP- and BzATP-stimulated Ba²⁺ influx, suggesting that the lower efficacy of ATP compared with BzATP was not due to preferential hydrolysis of ATP. Thus, the natural ligand, ATP, is a partial agonist for the P2Z receptor while BzATP is a full agonist. Moreover the competitive studies show that only a single class of P2-receptor (P2Z class) is expressed on human leukaemic lymphocytes. Both ATP- and BzATP-stimulated PLD activity were significantly inhibited (P < 0.05) when cells were suspended in iso-osmotic choline Cl medium. Choline⁺ was found to be a permeant for the P2Z ion channel, since ATP induced a large uptake of [¹⁴C]choline⁺ (60 to 150 µmol/ml intracellular water) during a 5 min incubation, which remained in the cells for several hours, and ATP was used to load cells with these levels of choline⁺. Intracellular choline⁺ inhibited ATP-, BzATP-, PMA- and ionomycin-stimulated PLD activity. Brief exposure of lymphocytes to ATP increased the subsequent basal rate of ethidium⁺ uptake, and this was prevented by intracellular choline⁺. It is proposed that P2Z-mediated Ca²⁺ influx in lymphocytes activates PLD leading to significantly changes of the phospholipid composition of the plasma membrane, which subsequently produces a permeability lesion, which in turn contributes to cell death.

Temporal causality and the dynamics of exports, human capital and real income in China

This article employs cointegration and error-correction modelling to test the causal relationship between real income, exports and human capital stock using data for China over the period 1960 to 1999. We find that real exports, human capital and real income are cointegrated when real exports is the dependent variable, but are not cointegrated when human capital or real income are the dependent variable. In the short-run we find evidence of bi-directional Granger causality between human capital and real exports, unidirectional Granger causality running from real income to human capital and neutrality between real exports and real income.

Molecular analysis of the human copper uptake protein hCTR1

This study examined the role of the high-affinity copper uptake protein hCTR1 in cellular copper homeostasis and found hCTR1 was internalized in response to raised copper levels. The work from this thesis supports a model in which the regulation of hCTR1 is partially or wholly dependent upon internal copper levels.

The clp chaperones and proteases of the human malaria parasite Plasmodium falciparum

The Clp chaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clp chaperones and proteases in the human malaria parasite Plasmodium falciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Expression of all Clp chaperones and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.