Evidence for a common role for the serine-type Plasmodium falciparum serine repeat antigen proteases : implications for vaccine and drug design

Serine repeat antigens (SERAs) are a family of secreted “cysteine-like” proteases of Plasmodium parasites. Several SERAs possess an atypical active-site serine residue in place of the canonical cysteine. The human malaria parasite Plasmodium falciparum possesses six “serine-type” (SERA1 to SERA5 and SERA9) and three “cysteine-type” (SERA6 to SERA8) SERAs. Here, we investigate the importance of the serine-type SERAs to blood-stage parasite development and examine the extent of functional redundancy among this group. We attempted to knock out the four P. falciparum serine-type SERA genes that have not been disrupted previously. SERA1, SERA4, and SERA9 knockout lines were generated, while only SERA5, the most strongly expressed member of the SERA family, remained refractory to genetic deletion. Interestingly, we discovered that while SERA4-null parasites completed the blood-stage cycle normally, they exhibited a twofold increase in the level of SERA5 mRNA. The inability to disrupt SERA5 and the apparent compensatory increase in SERA5 expression in response to the deletion of SERA4 provides evidence for an important blood-stage function for the serine-type SERAs and supports the notion of functional redundancy among this group. Such redundancy is consistent with our phylogenetic analysis, which reveals a monophyletic grouping of the serine-type SERAs across the genus Plasmodium and a predominance of postspeciation expansion. While SERA5 is to some extent further validated as a target for vaccine and drug development, our data suggest that the expression level of other serine-type SERAs is the only barrier to escape from anti-SERA5-specific interventions.

Bad habits and prosthetic performances : negotiation of individuality and embodiment of social status in Australian shark fishing

Anthropological discussion of individuality, as a component of masculinity, has tended to focus on either the performance and championing of autonomy in the West (e.g., Kapferer) or the manner in which people in non-Western contexts become explicitly manifest through relationships with others (e.g., Strathern). In this paper, I consider an atypical example of masculine identity by describing intimate interpersonal relationships between Australian commercial shark boat skippers and their young deckhands. As in other Western fisheries (e.g., Icelandic), economic success and physical safety are promoted through synergism among fishers. In the Australian case, however, the degree of corporeal cooperation is so extreme that deckhands resemble living prostheses of their skipper, embodying their peripheral socio-productive status. I consider this bond in the context of the Australian ethos of masculinity, in which displays of "individuality" are key. However, for young deckhands, their prosthetic role can compromise their passage into manhood.

The lactation cycle of the fur seal

The fur seal is a mammal with an unusual ability to turn its milk production on and off without significantly altering the gross morphology of the mammary gland. This atypical lactation cycle is due to the fact that maternal foraging and infant nursing are spatially and temporally separate (Bonner, 1984). Maternal care involves the suckling of offspring over a period of at least 4 months, but lactation can extend to more than 12 months. Following a perinatal fast of approximately 1 week, females depart the breeding colony to forage at sea and, for the remainder of lactation, alternate between short periods ashore suckling their young with longer periods of up to 4 weeks foraging at sea. Whilst foraging at sea, milk production in the fur seal mammary gland either ceases or is reduced (Arnould & Boyd, 1995b).

David v. Goliath: the gay games, the Olympics, and the ownership of language

The Gay Games is firmly established on the contemporary global sports calendar, but is seldom canvassed in mainstream sports media, or considered a model for sports administrators. This is regrettable, as the Games’ ethos offers many clues into the relationships between individual and communal empowerment for homosexual and heterosexual participants alike, while providing a site of resistance against entrenched norms of elitism, nationalism, victory and record-breaking indicative of the modern Olympic movement. Credit for this inclusive ethos rests with the vision of inaugural Gay Games organiser Dr. Tom Waddell. Drawing on Games archives, this paper outlines Waddell’s vision, then discusses the impact of a protracted legal dispute instigated by the United States Olympic Committee in 1982 over the use of the term ‘Olympics’ in association with Gay Games I and II. Four United States Federal court rulings are examined, with particular reference to the contrasting hierarchy of private intellectual property and public civil rights considered under United States law of the time. Domestic and international legacies of the dispute are also briefly examined, focusing on the inherent tensions between the state-sanctioned protection of Olympic terminology, the ideals of free speech, the ownership of common sporting terms, and the potential discriminatory effects of selective trademark enforcement. The paper concludes with a brief discussion of how Waddell’s vision superseded each of these legal technicalities to ensure the Games continues to provide a viable model for inclusive and engaged participation for all people.

Fur seal adaptations to lactation: insights into mammary gland function

The fur seal (Arctocephalus spp. and Callorhinus spp., members of the pinniped family) is a mammal with the unusual capability to modulate its lactation cycle by turning milk production on and off without the typical mammalian regression and involution of the mammary gland. Lactation has evolved from constraints arising from the spatial and temporal separation of infant nursing and maternal foraging as the mother gives birth and feeds the pup on land while acquisition of nutrients for milk production occurs at sea. The lactation cycle begins with the female fur seal undergoing a perinatal fast of approximately 1 wk, after which time she departs the breeding colony to forage at sea. For the remainder of the long lactation period (116–540 days), the mother alternates between short periods ashore suckling the young with longer periods of up to 4 wk of foraging at sea. Milk production continues while foraging at sea, but at less than 20% the rate of production on land. Fur seals produce one of the richest milk reported, with a very high lipid content contributing up to 85% of total energy. This feature serves as an adaptation to the young's need to produce an insulating blubber layer against heat loss and to serve as an energy store when the mother is away foraging at sea. This atypical pattern of lactation means mothers have long periods with no suckling stimulus and can transfer high-energy milk rapidly while on land to minimize time away from foraging grounds. The absence of suckling stimulus and milk removal during foraging does not result in the onset of involution with associated apoptosis of mammary secretory cells and a subsequent progressive breakdown of the cellular structure of the mammary gland. The mechanisms controlling lactation in the fur seal mammary gland have been investigated using molecular and cellular techniques. These findings have shed light on the processes by which the unique features of lactation in the fur seal are regulated.

Intent and Method: A Study of Female Characters in Aeschylean and Euripidean Drama

Aeschylus and Euripides used tragic female characters to help fulfill the purpose of religious celebration and to achieve the motivation of public reaction. The playwrights, revising myths about tragic woman and redefining the Greek definition of appropriate femininity, supported or questioned the very customs which they changed. Originally composed as part of a religious festival for Dionysus, the god of wine, revelry and fertility, the tragedies of Aeschylus and Euripides were evaluated by Aristotle. He favored Aeschylus over Euripides, but it appears as if his stipulations for tragic characterization do not apply to Aeschylean and Euripidean women. Modem critics question both Aristotle's analysis in the Poetics as well as the tragedies which he evaluated. As part of the assessment of Aeschylus, the character of the Persian Queen, Atossa, appears as a conradiction the images that Greeks maintain of non-Greeks. The Persians is discussed in relation to modem criticisms and as on its function as a warning against radical changes in Athenian domestic life. The Oresteia, a trilogy, also charts the importance of an atypical woman in Aeschylean tragedy, and how this role, Clytaemnestra, represents an extreme example of the natural and necessary evolution of families, households and kingdoms. In contrast to Aeschylus' plea to retain nomoi (traditional custom and law), EUripides' tragedy, the Medea, demonstrates the importance of a family and a country to provide security, especially for women. Medea's abandonment by Jason and subsequent desperation drives her to commit murder in the hope of revenge. Ultimately, Euripides advocates changes in social convention away from the alienation of non-Greek, non-citizens, and females. Euripides is, unfortunately, tagged a misogynist by some in this tragedy and another example-the Hippolytus. Euripides' Phaedra becomes entangled in a scheme of divine vengeance and ultimately commits suicide in an attempt to avoid societal shame. Far from treatises of hate, Euripidean women take advantage of the little power they possess within a constrictive social system. While both Aeschylus and Euripides revise customary images and expectations of women in the context of religiously-motivated drama, one playwright intends to maintain civic order and the other intends to challenge the secular norm.

Antinomies of Slavoj Zizek

For the last decade, Slavoj Zizek's provocative and insightful interventions have contested the contemporary abandonment of radical politics and the postmodern retreat from the Enlightenment. Rejecting talk of the "victory of liberalism," Zizek calls for a revolutionary analysis of the connection between multinational capitalism and political subjectivity capable of reconstructing the project of global emancipation. In opposition to postmodern relativism, Zizek positions Lacan not as a postmodern theorist but as an Enlightenment thinker. His Lacanian interpretation of ideology proposes that the missing link in post-Althusserian theories is the unconscious subject, as the unruly by-product of ideological interpellation. Zizek combines this...

How do parents and teenagers get along together?

The article focuses on the relationship between parents and teenagers. It presents a study on developing children based on the Australian Temperament Project (ATP), which examines the contribution of personal, family, and broader environmental factors to adjustment and well-being. It explores how Australian teenagers and parents view their relationship, to what extent they do agree, and the differences among adolescents with good, poor or discrepant perceptions of their relationships on personal characteristics, family, and school functioning. It is found out that difficult parent-adolescent relationships are atypical and that community perceptions of the relationship are out of order.

Estimating the demand for money in an unstable open economy : the case of the Fiji Islands

In this paper, we estimate Fiji's money demand function for the period 1971-2002 based on the bounds testing approach to cointegration, which is applicable irrespective of whether or not the underlying variables are non-stationary. We estimate models with and without a time trend and for lag lengths ranging from 1-3, but fail to find any evidence for a long-run relationship. Moreover, our structural break analysis suggests that the unstable nature of Fiji's money demand may be due to atypical events, such as coups; the implementation of policies, such as devaluations and value added tax; and the onset of trade liberalisation policies over the last two decades.

Preliminary evaluation of monolithic column high-performance liquid chromatography with tris(2,2’-bipyridyl)ruthenium(II) chemiluminescence detection for the determination of quetiapine in human body fluids

High-performance liquid chromatography (HPLC) with tris(2,2-bipyridyl)ruthenium(II) chemiluminescence detection methodology is reported for the determination of the atypical antipsychotic drug quetiapine and the observation of its major active and inactive metabolites in human urine and serum. The method uses a monolithic chromatographic column allowing high flow rates of 3mL min−1 enabling rapid quantification. Flow injection analysis (FIA) with tris(2,2-bipyridyl)ruthenium(II) chemiluminescence detection and HPLC time of flight mass spectrometry (TOF-MS) were used for the determination of quetiapine in a pharmaceutical preparation to establish its suitability as a calibration standard. The limit of detection achieved with FIA was 2×10−11 mol L−1 in simple aqueous solution. The limits of detection achieved with HPLC were 7×10−8 and 2×10−10 mol L−1 in urine and serum, respectively. The calibration range for FIA was between 5×10−9 and 1×10−6 mol L−1. The calibration ranges for HPLC were between 1×10−7–1×10−4 and 1×10−8–1×10−4 mol L−1 in urine and serum, respectively. The quetiapine concentrations in patient samples were found to be 3×10−6 mol L−1 in urine and 7×10−7 mol L−1 in serum. Without the need for preconcentration, the HPLC detection limits compared favourably with those in previously published methodologies. The metabolites were identified using HPLC-TOF-MS.

A high altitude observation of the beautiful firetail Stagonopleura bella from East Gippsland, Victoria

There has been little research on the ecological requirements of the Beautiful Firetail Stagonopleura bella, and its habitat preferences are poorly understood. On mainland Australia, the Beautiful Firetail is generally considered to be a bird of coastal regions and the lowlands. This note reports an observation of Beautiful Firetails on the Great Dividing Range at a height of more than 1100 metres above sea level from an atypical habitat for mainland Australia. It appears that the observation may be the highest altitude at which this species has been recorded on the mainland.

A typical meteorological year for energy simulations in Hamilton, New Zealand

Typical Meteorological Year (TMY) data is used extensively in building energy simulations and solar energy analysis. TMY data for New Zealand, however, is relatively limited and no such data existed for Hamilton. Ten years of hourly meteorological data was analysed, and a TMY was developed. Simulations using the TMY data were conducted to determine the performance of a solar pool-heating system. It was found that the TMY was able to predict the annual performance of this system to within 2% of the long-term mean. It is intended that this TMY could be used to perform simulations on building energy use and solar heating systems in Hamilton.

Population dynamics of the infaunal bivalve, Soletellina alba

The population dynamics of the infaunal bivalve Soletellina alba was investigated at three sites situated within close proximity to the mouth of the Hopkins River estuary. The initial study design was planned to examine the importance of winter flooding to the persistence of this bivalve mollusc within the Hopkins estuary, since mass mortalities have been observed during previous years coincident with periods of winter flooding. Unfortunately, the climatic conditions experienced during this study were atypical compared to the long-term average, so detailed sampling was limited to two, unanticipated, non-flood years rather than two, highly anticipated, flood years. This hampered my ability to conduct complete tests of the importance of winter flooding. Patterns of river discharge and the frequency and duration of mouth opening and closing differed greatly from that expected. Unexpectedly, periods of mouth closure were not always associated with periods of minimal river discharge; low salinities were another unexpected result during an extended period of mouth closure during 1998. As expected, salinities varied considerably with increasing water depth when the estuary mouth was open. Mouth closure lead to salinities becoming more uniform between water depths but hypoxic and anoxic conditions became evident via stratification in the water column at 1 m below the Australian Height Datum (AHD). Other than trends associated with increased water depth, significant variation was not evident between measurements of salinity taken from three sites within close proximity of the estuary mouth (approximately 500 m), or during changes in tide. The most pertinent anomaly was the absence of winter flooding. The distribution and abundance of juvenile and adult S. alba was variable across all Dates, Sites and Channel elevations (i.e. water depths) sampled during this study. An experimental test comparing the recruitment of juveniles at different channel elevations and in sediments of varying particle size was conducted during an exceptionally successful period of recruitment during 1999. The results of these tests showed that recruitment was greatest at the shallowest channel elevation used, and there was little evidence that sediment particle size influenced recruitment. In contrast to 1999, recruitment during 1997 or 1998 was extremely poor. Growth rates were monitored using tagged individuals held in caged and uncaged plots, which revealed that growth was highly variable among individuals, but not between Sites. These tests also revealed that growth was negligible during the colder, winter months, and that the fastest growing individuals were capable of growing 0.2 mm/day. Mixed results were obtained for tests of potential cage artifacts and the influence of handling. Caging and differing amounts of handling did not appear to influence growth, but there was evidence that cages and handling influenced bivalve condition and number of mortalities. These direct tests appeared to be the most appropriate method for determining growth rates of this species, since attempts to analyse length-frequency data were made difficult by the apparent convergence of cohorts, and shell aging is difficult due to the thin, fragile nature of the shell. As expected, mass mortalities were observed during the flood of 1996, but not during the two non-flood years of 1997 and 1998. There were, however, some considerable declines in abundances at some channel elevations during the two non-flood years. However, these declines were attributable to the complete disappearance of individuals, rather than the sudden presence of numerous, recently dead individuals that typify observed declines during winter flooding. The complete disappearance of individuals suggest that S. alba may be capable of post-settlement emigration, or that they were consumed by an unknown predator. Salinity tolerance tests showed that bivalves exposed to low salinities (≤6 ppt), exhibited poorer condition and took longer to re-burrow into sediments than those exposed to greater salinities (≥14 ppt), while death of bivalves exposed to salinities ≤1 ppt occurred after 8 days of exposure. These tests provide evidence that low salinities are probably the principal cause of mass mortalities during winter flooding, although the interaction between salinity, temperature and turbidity also deserve consideration. The results of this study indicate that certain aspects of winter flooding, especially salinity, are responsible for the mass mortalities of S. alba rather than the result of a short-lived life history. I hypothesise that the survival of very young juveniles (between 0.5 and 1 mm shell length) and rapid growth rates are important features of the life history of S. alba that explain its successful persistence within the Hopkins River estuary. The rapid rates of growth suggest that it may be possible for juveniles that survive winter flooding to grow, reach sexual maturity, and reproduce before the onset of the next flood event. Unfortunately, the increased survivorship of juveniles during periods of winter flooding was not demonstrated by this study because of the absence of winter flooding and also relatively poor recruitment. It is highly likely that this species is capable of completing it entire life cycle within the estuary since the absence of other nearby populations, together with periods of mouth closure, are likely to greatly limit the potential contribution made by larvae entering from the surrounding marine environment. This study has added considerably to our knowledge of how infauna cope with life in the intermittently closing estuaries that typify semi-arid coastlines in the Southern Hemisphere.

The Ikaros gene family

Ikaros-related transcription factors are essential for adaptive immunity. Evolutionary analysis suggested derivation from a precursor similar to the 'atypical' Pegasus protein, and possibly related to invertebrate Hunchback. Pegasus was shown to regulate neural, gut and blood cell development in zebrafish, with Ikaros identified as one of several potential gene targets.

Restless leg syndrome caused by olanzapine: a case series

Restless leg syndrome (RLS) is a common disorder associated with significant distress. We report three cases of drug induced RLS caused by olanzapine. In each case, RLS commenced after initiation of treatment with olanzapine and resolved after ceasing olanzapine. All three patients were subsequently treated with other atypical antipsychotics, risperidone, quetiapine or aripiprazole, without re-emergence of RLS. RLS is associated with central dopaminergic dysfunction. Dopamine agonists and l-dopa reduce the symptoms of RLS, and some agents that block the dopaminergic system aggravate RLS. Greater awareness of potential causes of RLS, and its differentiation from akathisia and illness related agitation might help in reducing the distress associated with it and improving patient compliance.