Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

Frozen magma lenses below the oceanic crust

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 436 (2005): 1149-1152, doi:10.1038/nature03944.The Earth's oceanic crust crystallizes from magmatic systems generated at mid-ocean ridges. Whereas a single magma body residing within the mid-crust is thought to be responsible for the generation of the upper oceanic crust, it remains unclear if the lower crust is formed from the same magma body, or if it mainly crystallizes from magma lenses located at the base of the crust. Thermal modelling, tomography, compliance and wide-angle seismic studies, supported by geological evidence, suggest the presence of gabbroic-melt accumulations within the Moho transition zone in the vicinity of fast- to intermediate-spreading centres. Until now, however, no reflection images have been obtained of such a structure within the Moho transition zone. Here we show images of groups of Moho transition zone reflection events that resulted from the analysis of approximately 1,500 km of multichannel seismic data collected across the intermediate-spreading-rate Juan de Fuca ridge. From our observations we suggest that gabbro lenses and melt accumulations embedded within dunite or residual mantle peridotite are the most probable cause for the observed reflectivity, thus providing support for the hypothesis that the crust is generated from multiple magma bodies

The role of routine post-natal abdominal ultrasound for newborns in a resource-poor setting: a longitudinal study

<p>Abstract</p> <p>Background-</p> <p>Neonatal abdominal ultrasound is usually performed in Nigeria to investigate neonatal symptoms rather than as a follow up to evaluate fetal abnormalities which were detected on prenatal ultrasound. The role of routine obstetric ultrasonography in the monitoring of pregnancy and identification of fetal malformations has partly contributed to lowering of fetal mortality rates. In Nigeria which has a high maternal and fetal mortality rate, many pregnant women do not have ante-natal care and not infrequently, women also deliver their babies at home and only bring the newborns to the clinics for immunization. Even when performed, most routine obstetric scans are not targeted towards the detection of fetal abnormalities.</p> <p>The aim of the present study is to evaluate the benefit of routinely performing abdominal scans on newborns with a view to detecting possible abnormalities which may have been missed ante-natally.</p> <p>Methods-</p> <p>This was a longitudinal study of 202 consecutive, apparently normal newborns. Routine clinical examination and abdominal ultrasound scans were performed on the babies by their mother's bedside, before discharge. Neonates with abnormal initial scans had follow-up scans.</p> <p>Results-</p> <p>There were 108 males and 94 females. There were 12 (5.9%) abnormal scans seen in five male and seven female neonates. Eleven of the twelve abnormalities were in the kidneys, six on the left and five on the right. Three of the four major renal anomalies- absent kidney, ectopic/pelvic kidney and two cases of severe hydronephrosis were however on the left side. There was one suprarenal abnormality on the right suspected to be a possible infected adrenal haemorrage. Nine of the abnormal cases reported for follow- up and of these, two cases had persistent severe abnormalities.</p> <p>Conclusions-</p> <p>This study demonstrated a 5.9% incidence of genito urinary anomalies on routine neonatal abdominal ultrasound in this small population. Routine obstetric USS is very useful but inadequate availability of skilled personnel and cost implications create great challenges in poor resource settings like Nigeria. However, awareness should be created so that parents who can afford such investigations can make informed decisions.</p

Chimerism in Wild Adult Populations of the Broadcast Spawning Coral Acropora millepora on the Great Barrier Reef

Chimeras are organisms containing tissues or cells of two or more genetically distinct individuals, and are known to exist in at least nine phyla of protists, plants, and animals. Although widespread and common in marine invertebrates, the extent of chimerism in wild populations of reef corals is unknown.The extent of chimerism was explored within two populations of a common coral, Acropora millepora, on the Great Barrier Reef, Australia, by using up to 12 polymorphic DNA microsatellite loci. At least 2% and 5% of Magnetic Island and Pelorus Island populations of A. millepora, respectively, were found to be chimeras (3% overall), based on conservative estimates. A slightly less conservative estimate indicated that 5% of colonies in each population were chimeras. These values are likely to be vast underestimates of the true extent of chimerism, as our sampling protocol was restricted to a maximum of eight branches per colony, while most colonies consist of hundreds of branches. Genotypes within chimeric corals showed high relatedness, indicating that genetic similarity is a prerequisite for long-term acceptance of non-self genotypes within coral colonies.While some brooding corals have been shown to form genetic chimeras in their early life history stages under experimental conditions, this study provides the first genetic evidence of the occurrence of coral chimeras in the wild and of chimerism in a broadcast spawning species. We hypothesize that chimerism is more widespread in corals than previously thought, and suggest that this has important implications for their resilience, potentially enhancing their capacity to compete for space and respond to stressors such as pathogen infection

Recruitment Constraints in Singapore's Fluted Giant Clam (Tridacna squamosa) Populations - A Dispersal Model Approach

10.1371/journal.pone.0058819PLoS ONE83

Soluble CD4 and CD4-Mimetic Compounds Inhibit HIV-1 Infection by Induction of a Short-Lived Activated State

Binding to the CD4 receptor induces conformational changes in the human immunodeficiency virus (HIV-1) gp120 exterior envelope glycoprotein. These changes allow gp120 to bind the coreceptor, either CCR5 or CXCR4, and prime the gp41 transmembrane envelope glycoprotein to mediate virus–cell membrane fusion and virus entry. Soluble forms of CD4 (sCD4) and small-molecule CD4 mimics (here exemplified by JRC-II-191) also induce these conformational changes in the HIV-1 envelope glycoproteins, but typically inhibit HIV-1 entry into CD4-expressing cells. To investigate the mechanism of inhibition, we monitored at high temporal resolution inhibitor-induced changes in the conformation and functional competence of the HIV-1 envelope glycoproteins that immediately follow engagement of the soluble CD4 mimics. Both sCD4 and JRC-II-191 efficiently activated the envelope glycoproteins to mediate infection of cells lacking CD4, in a manner dependent on coreceptor affinity and density. This activated state, however, was transient and was followed by spontaneous and apparently irreversible changes of conformation and by loss of functional competence. The longevity of the activated intermediate depended on temperature and the particular HIV-1 strain, but was indistinguishable for sCD4 and JRC-II-191; by contrast, the activated intermediate induced by cell-surface CD4 was relatively long-lived. The inactivating effects of these activation-based inhibitors predominantly affected cell-free virus, whereas virus that was prebound to the target cell surface was mainly activated, infecting the cells even at high concentrations of the CD4 analogue. These results demonstrate the ability of soluble CD4 mimics to inactivate HIV-1 by prematurely triggering active but transient intermediate states of the envelope glycoproteins. This novel strategy for inhibition may be generally applicable to high–potential-energy viral entry machines that are normally activated by receptor binding

The Effect of Service on Research Performance: A Study on Italian Academics in Management

Academics all over the world are feeling the increasing pressure to attain satisfactory research performance. Since research is not the only activity required of academics, though, the debate on how it may be coupled with other knowledge transfer activities like teaching, patenting, and dissemination has been captivating scholars interested in higher education. Literature is surprisingly silent about the interplay between research performance and other roles and tasks that faculty are expected to carry out, namely academic citizenship, intended as the service that they provide to their institution, to the scientific community, and to the larger society. Through a negative binomial regression conducted on 692 Italian academics in management, this paper investigates both the direct and moderating effect exerted by academic citizenship on the relationship between research performance in two subsequent evaluation exercises, thus advancing our knowledge of the relationship between research and service. Findings show that institutional service acts as a pure moderator, discipline-based service is a quasi-moderator, while public service exerts only a direct negative effect on research performance. In light of the emergent interplay between research and service, the necessity to boost reflection on academic citizenship is discussed and suggestions for its acknowledgement and advancement are formulated

The B-Cell Specific Transcription Factor, Oct-2, Promotes Epstein-Barr Virus Latency by Inhibiting the Viral Immediate-Early Protein, BZLF1

The Epstein-Barr virus (EBV) latent-lytic switch is mediated by the BZLF1 immediate-early protein. EBV is normally latent in memory B cells, but cellular factors which promote viral latency specifically in B cells have not been identified. In this report, we demonstrate that the B-cell specific transcription factor, Oct-2, inhibits the function of the viral immediate-early protein, BZLF1, and prevents lytic viral reactivation. Co-transfected Oct-2 reduces the ability of BZLF1 to activate lytic gene expression in two different latently infected nasopharyngeal carcinoma cell lines. Furthermore, Oct-2 inhibits BZLF1 activation of lytic EBV promoters in reporter gene assays, and attenuates BZLF1 binding to lytic viral promoters in vivo. Oct-2 interacts directly with BZLF1, and this interaction requires the DNA-binding/dimerization domain of BZLF1 and the POU domain of Oct-2. An Oct-2 mutant (Δ262–302) deficient for interaction with BZLF1 is unable to inhibit BZLF1-mediated lytic reactivation. However, an Oct-2 mutant defective for DNA-binding (Q221A) retains the ability to inhibit BZLF1 transcriptional effects and DNA-binding. Importantly, shRNA-mediated knockdown of endogenous Oct-2 expression in several EBV-positive Burkitt lymphoma and lymphoblastoid cell lines increases the level of lytic EBV gene expression, while decreasing EBNA1 expression. Moreover, treatments which induce EBV lytic reactivation, such as anti-IgG cross-linking and chemical inducers, also decrease the level of Oct-2 protein expression at the transcriptional level. We conclude that Oct-2 potentiates establishment of EBV latency in B cells

Benign external hydrocephalus: a review, with emphasis on management

Benign external hydrocephalus in infants, characterized by macrocephaly and typical neuroimaging findings, is considered as a self-limiting condition and is therefore rarely treated. This review concerns all aspects of this condition: etiology, neuroimaging, symptoms and clinical findings, treatment, and outcome, with emphasis on management. The review is based on a systematic search in the Pubmed and Web of Science databases. The search covered various forms of hydrocephalus, extracerebral fluid, and macrocephaly. Studies reporting small children with idiopathic external hydrocephalus were included, mostly focusing on the studies reporting a long-term outcome. A total of 147 studies are included, the majority however with a limited methodological quality. Several theories regarding pathophysiology and various symptoms, signs, and clinical findings underscore the heterogeneity of the condition. Neuroimaging is important in the differentiation between external hydrocephalus and similar conditions. A transient delay of psychomotor development is commonly seen during childhood. A long-term outcome is scarcely reported, and the results are varying. Although most children with external hydrocephalus seem to do well both initially and in the long term, a substantial number of patients show temporary or permanent psychomotor delay. To verify that this truly is a benign condition, we suggest that future research on external hydrocephalus should focus on the long-term effects of surgical treatment as opposed to conservative management