Selection pressure-driven evolution of the Epstein-Barr virus-encoded oncogene LMP1 in virus isolates from southeast Asia

The geographically constrained distribution of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in southeast Asian populations suggests that both viral and host genetics may influence disease risk. Although susceptibility loci have been mapped within the human genome, the role of viral genetics in the focal distribution of NPC remains an enigma. Here we report a molecular phylogenetic analysis of an NPC-associated viral oncogene, LMP1, in a large panel of EBV isolates from southeast Asia and from Papua New Guinea, Africa, and Australia, regions of the world where NPC is and is not endemic, respectively. This analysis revealed that LMP1 sequences show a distinct geographic structure, indicating that the southeast Asian isolates have evolved as a lineage distinct from those of Papua New Guinea, African, and Australian isolates. Furthermore, a likelihood ratio test revealed that the C termini of the LMP1 sequences of the southeast Asian lineage are under significant positive selection pressure, particularly at some sites within the C-terminal activator regions. We also present evidence that although the N terminus and transmembrane region of LMP1 have undergone recombination, the C-terminal region of the gene has evolved without any history of recombination. Based on these observations, we speculate that selection pressure may be driving the LMP1 sequences in virus isolates from southeast Asia towards a more malignant phenotype, thereby influencing the endemic distribution of NPC in this region.

HMG box transcription factor gene Hbp1 is expressed in germ cells of the developing mouse testis

HMG box containing protein 1 (HBP1) is a high mobility group domain transcriptional repressor that regulates proliferation in differentiated tissues. We have found mouse Hbp1 to be expressed strongly in the embryonic mouse testis from approximately 12.5 days post coitum, compared with low levels of expression in the embryonic ovary. Expression of Hbp1 is maintained in the developing testis beyond the onset of spermatogenesis after birth. Whole-mount in situ hybridisation analysis showed that expression of Hbp1 in the XY gonad is localized within the developing testis cords, the precursors of the seminiferous tubules. Expression of Hbp1 is not apparent in testis cords of gonads from homozygous We mutant embryos, which lack germ cells. In situ hybridisation analysis on cryosectioned embryonic testis indicated that Hbp1 expression resembles that of the germ cell marker Oct4. We conclude that Hbp1 is up-regulated specifically in germ cells of the developing XY gonad. The expression of Hbp1 in XY germ cells appears to correlate with the onset of mitotic arrest in these cells. (C) 2004 Wiley-Liss, Inc.

Specialised supported education for Australians with psychotic disorders

Australia has a network of Federally funded disability employment and vocational rehabilitation services, including a proportion of outlets that specialise in providing services for persons with psychiatric disabilities. However, neither Federal nor State Governments currently provide or fund disability-specific education assistance to persons with psychiatric disabilities. To begin considering whether Specialised Supported Education is indicated for persons with psychotic disorders, we examined data collected in a national 'Survey of Disability, Ageing and Carers Australia, 1998'. International studies of the effectiveness of overseas Supported Education programs were also examined to identify the forms of assistance most likely to warrant consideration in Australia. U.S.A. evidence indicates that Specialised Supported Education is emerging as an effective career development option for persons with psychotic disorders. An example of an innovative Specialised Supported Education program is provided to illustrate how this type of program can be implemented in Australia.

Reinforcement drives rapid allopatric speciation

Allopatric speciation results from geographic isolation between populations. In the absence of gene flow, reproductive isolation arises gradually and incidentally as a result of mutation, genetic drift and the indirect effects of natural selection driving local adaptation(1-3). In contrast, speciation by reinforcement is driven directly by natural selection against maladaptive hybridization(1,4). This gives individuals that choose the traits of their own lineage greater fitness, potentially leading to rapid speciation between the lineages(1,4). Reinforcing natural selection on a population of one of the lineages in a mosaic contact zone could also result in divergence of the population from the allopatric range of its own lineage outside the zone(4-6). Here we test this with molecular data, experimental crosses, field measurements and mate choice experiments in a mosaic contact zone between two lineages of a rainforest frog. We show that reinforcing natural selection has resulted in significant premating isolation of a population in the contact zone not only from the other lineage but also, incidentally, from the closely related main range of its own lineage. Thus we show the potential for reinforcement to drive rapid allopatric speciation.

Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis

Centrosomes in mammalian cells have recently been implicated in cytokinesis; however, their role in this process is poorly defined. Here, we describe a human coiled-coil protein, Cep55 (centrosome protein 55 kDa), that localizes to the mother centriole during interphase. Despite its association with gamma-TuRC anchoring proteins CG-NAP and Kendrin, Cep55 is not required for microtubule nucleation. Upon mitotic entry, centrosome dissociation of Cep55 is triggered by Erk2/Cdk1-dependent phosphorylation at S425 and S428. Furthermore, Cep55 locates to the midbody and plays a role in cytokinesis, as its depletion by siRNA results in failure of this process. S425/428 phosphorylation is required for interaction with Plk1, enabling phosphorylation of Cep55 at S436. Cells expressing phosphorylation-deficient mutant forms of Cep55 undergo cytokinesis failure. These results highlight the centrosome as a site to organize phosphorylation of Cep55, enabling it to relocate to the midbody to function in mitotic exit and cytokinesis.

Retinoid signaling determines germ cell fate in mice

Germ cells in the mouse embryo can develop as oocytes or spermatogonia, depending on molecular cues that have not been identified. We found that retinoic acid, produced by mesonephroi of both sexes, causes germ cells in the ovary to enter meiosis and inititate oogenesis. Meiosis is retarded in the fetal testis by the action of the retinoid-degrading enzyme CYP26B1, ultimately leading to spermatogenesis. In testes of Cyp26b1-knockout mouse embryos, germ cells enter meiosis precociously, as if in a normal ovary. Thus, precise regulation of retinoid levels during fetal gonad development provides the molecular control mechanism that specifies germ cell fate.

The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle

beta-Adrenergic receptor (beta-AR) agonists induce Nur77 mRNA expression in the C2C12 skeletal muscle cell culture model and elicit skeletal muscle hypertrophy. We previously demonstrated that Nur77 (NR4A1) is involved in lipolysis and gene expression associated with the regulation of lipid homeostasis. Subsequently it was demonstrated by another group that beta-AR agonists and cold exposure-induced Nur77 expression in brown adipocytes and brown adipose tissue, respectively. Moreover, NOR-1 (NR4A3) was hyperinduced by cold exposure in the nur77(-/-) animal model. These studies underscored the importance of understanding the role of NOR-1 in skeletal muscle. In this context we observed 30-480 min of beta-AR agonist treatment significantly and transiently increased expression of the orphan nuclear receptor NOR-1 in both mouse skeletal muscle tissue (plantaris) and C2C12 skeletal muscle cells. Specific beta(2)-and beta(3)-AR agonists had similar effects as the pan-agonist and were blocked by the beta-AR antagonist propranolol. Moreover, in agreement with these observations, isoprenaline also significantly increased the activity of the NOR-1 promoter. Stable exogenous expression of a NOR-1 small interfering RNA (but not the negative control small interfering RNA) in skeletal muscle cells significantly repressed endogenous NOR-1 mRNA expression and led to changes in the expression of genes involved in the control of lipid use and muscle mass underscored by a dramatic increase in myostatin mRNA expression. Concordantly the myostatin promoter was repressed by NOR-1 expression. In conclusion, NOR-1 is highly responsive to beta-adrenergic signaling and regulates the expression of genes controlling fatty acid use and muscle mass.

The use of electropalatography in the assessment and treatment of acquired motor speech disorders in adults: Current knowledge and future directions

Electropalatography (EPG) has been employed to measure speech articulation since the mid-1970s. This technique has predominately been used in experimental phonetic research and in the diagnosis and treatment of articulation disorders in children. However, there is a growing body of research employing EPG to diagnose and treat articulatory impairment associated with acquired motor speech disorder (MSD) in adults. The purpose of this paper was to (1) review the findings of studies pertaining to the assessment and treatment of MSDs in adults using EPG, (2) highlight current methodologies employed, and (3) discuss the potential limitations of EPG in the assessment and treatment of MSDs and examine directions for future applied research and treatment studies.

Using special events to motivate visitors to attend art galleries

The contemporary directions of art galleries worldwide are changing as social patterns and demands, as well as visitor expectations of their experiences at art galleries, change. New programs and strategies are being developed in galleries to make these institutions more appealing to people who would not normally visit them, and one such strategy is the staging of special events. However, because galleries are staging an increasing number of special events, the factors motivating visitors to attend these institutions are changing. Visitors hope to have different experiences and encounters in the gallery during special events. This paper presents the findings from a study in Australia about visitors’ motivations to attend special events in galleries. It highlights the different factors that motivate visitors to attend the gallery specifically for a special event in comparison to visiting the gallery's permanent collections.

Exploring Visitors' Perceptions of Art Gallery Festivals

The contemporary directions of art galleries worldwide are changing as social patterns and demands, and visitor expectations of their experiences at art galleries change. New programs and strategies are being developed in galleries to make these institutions more appealing to people who would not normally visit them. One such strategy is the staging of special events, which in galleries take a variety of forms. As special events are increasingly being employed by galleries to inspire new audiences, it is important that these institutions develop an awareness of how their visitors understand and respond to such events. Festivals are one type of special event that visitors identify as having a distinct role and nature. This paper explores visitors’ perceptions of festivals in art galleries and identifies several characteristics that distinguish festivals from other special events. These characteristics include the focus of the event, the audience attending, the degree of interactivity offered, the timing, and the place at which the event is staged. Understanding visitors’ perceptions and expectations of festivals will enable galleries to develop and further enhance their programs and special events to meet visitors’ needs.