Improving Aquatic Habitat Representation in Utah Using Large Spatial Scale Environmental Datasets

Rivers provide habitat for aquatic species, but widespread human water development degrades aquatic habitat, fragments stream networks, and threatens native fish populations. Habitat suitability models are commonly used to identify current instream habitat conditions, but are often species-specific, data-intensive, and rarely suitable to the large spatial scales required in conservation and water resources management. Thus, there is need to develop and validate habitat suitability models that provide ecologically-meaningful estimations of aquatic habitat, but are simple enough to apply at large geographic areas and flexible to incorporate different species. I tested the accuracy of 15 habitat suitability models estimating Bonneville Cutthroat Trout and Bluehead Sucker monthly habitat suitability in Utah perennial streams using unique combinations of four modeled environmental variables; percent mean annual discharge, velocity, gradient, and stream temperature. Modeled discharge and stream temperature matched observed values well, explaining 78-89% of variability in the observed data. Habitat suitability model accuracy varied considerably, but simple models including fewer variables than considered in this study most accurately predicted Bonneville Cutthroat Trout and Bluehead Sucker habitat suitability. Temperature best predicted Bonneville Cutthroat Trout habitat suitability, while gradient and percent mean annual discharge best predicted Bluehead Sucker habitat suitability. Utah stream networks were highly fragmented by instream barriers, but connectivity decreased significantly in May and June when habitat suitability was considered. This work demonstrates that habitat suitability models can accurately estimate habitat suitability when generalized for multiple species and large spatial scales, and that additional variables do not necessarily improve model accuracy. The modeling approach expands current methods for quantifying aquatic habitat conditions for use in conservation and water resources planning

Getting evidence into policy: The need for deliberative strategies?

Getting evidence into policy is notoriously difficult. In this empirical case study we used document analysis and key informant interviews to explore the Australian federal government’s policy to implement a national bowel cancer screening programme, and the role of evidence in this policy. Our analysis revealed a range of institutional limitations at three levels of national government: within the health department, between government departments, and across the whole of government. These limitations were amplified by the pressures of the 2004 Australian federal election campaign. Traditional knowledge utilisation approaches, which rely principally on voluntarist strategies and focus on the individual, rather than the institutional level, are often insufficient to ensure evidence-based implementation. We propose three alternative models, based on deliberative strategies which have been shown to work in other settings: review of the evidence by a select group of experts whose independence is enshrined in legislation and whose imprimatur is required before policy can proceed; use of an advisory group of experts who consult widely with stakeholders and publish their review findings; or public discussion of the evidence by the media and community groups who act as more direct conduits to the decision-makers than researchers. Such deliberative models could help overcome the limitations on the use of evidence by embedding public review of evidence as the first step in the institutional decision-making processes. Highlights  Achieving evidence-based policy implementation is much harder than the rhetoric suggests.  Our case study showed traditional voluntarist approaches are not enough to overcome institutional filtering of the evidence.  Deliberative strategies open up the decision-making processes to greater expert and public scrutiny.  Our framework illustrates the potential for deliberative strategies to increase the relative weight of evidence in policy.  This article challenges researchers and policy-makers to acknowledge and address the institutional context of decision-making. Keywords: Australia; Health policy; Decision-making; Evidence; Knowledge utilisation; Bowel cancer; Screening; DeliberativeNHMR

A Novel Human Cytomegalovirus Locus Modulates Cell Type-Specific Outcomes of Infection

Clinical strains of HCMV encode 20 putative ORFs within a region of the genome termed ULb′ that are postulated to encode functions related to persistence or immune evasion. We have previously identified ULb′-encoded pUL138 as necessary, but not sufficient, for HCMV latency in CD34+ hematopoietic progenitor cells (HPCs) infected in vitro. pUL138 is encoded on polycistronic transcripts that also encode 3 additional proteins, pUL133, pUL135, and pUL136, collectively comprising the UL133-UL138 locus. This work represents the first characterization of these proteins and identifies a role for this locus in infection. Similar to pUL138, pUL133, pUL135, and pUL136 are integral membrane proteins that partially co-localized with pUL138 in the Golgi during productive infection in fibroblasts. As expected of ULb′ sequences, the UL133-UL138 locus was dispensable for replication in cultured fibroblasts. In CD34+ HPCs, this locus suppressed viral replication in HPCs, an activity attributable to both pUL133 and pUL138. Strikingly, the UL133-UL138 locus was required for efficient replication in endothelial cells. The association of this locus with three context-dependent phenotypes suggests an exciting role for the UL133-UL138 locus in modulating the outcome of viral infection in different contexts of infection. Differential profiles of protein expression from the UL133-UL138 locus correlated with the cell-type dependent phenotypes associated with this locus. We extended our in vitro findings to analyze viral replication and dissemination in a NOD-scid IL2Rγcnull-humanized mouse model. The UL133-UL138NULL virus exhibited an increased capacity for replication and/or dissemination following stem cell mobilization relative to the wild-type virus, suggesting an important role in viral persistence and spread in the host. As pUL133, pUL135, pUL136, and pUL138 are conserved in virus strains infecting higher order primates, but not lower order mammals, the functions encoded likely represent host-specific viral adaptations

Primary demyelination induced by exposure to tellurium alters Schwann cell gene expression: a model for intracellular targeting of NGF receptor

Exposure of developing rats to tellurium results in a highly synchronous segmental demyelination of peripheral nerves with sparing of axons; this demyelination is followed closely by a period of rapid remyelination. Demyelination occurs subsequent to a tellurium-induced block in the synthesis of cholesterol, the major myelin lipid. We utilized the techniques of Northern blotting, in situ hybridization, and immunocytochemistry to examine temporal alterations in Schwann cell gene expression related to demyelination and remyelination. Tellurium- induced demyelination is associated with downregulation of myelin protein expression and a corresponding upregulation of NGF receptor (NGF-R) and glial fibrillary acidic protein (GFAP) expression. Steady- state mRNA levels (expressed on a “per nerve” basis) for P0, the major myelin protein, were decreased by about 50% after 5 d of tellurium exposure, while levels of mRNA for NGF-R and GFAP were markedly increased (about 15-fold). In situ hybridization of teased fibers suggested that the increase in steady-state mRNA levels for NGF-R was primarily associated with demyelinated internodes and not with adjacent unaffected internodes. Although P0 message was almost totally absent from demyelinating internodes, it was also reduced in normal-appearing internodes as well. This suggests that limiting the supply of a required membrane component (cholesterol) may lead to partial downregulation of myelin gene expression in all myelinating Schwann cells. In partially demyelinated internodes, NGF-R and GFAP immunofluorescence appeared largely confined to the demyelinated regions. This suggests specific targeting of these proteins to local areas of the Schwann cell where there is myelin loss. These results demonstrate that demyelination is associated with reversion of the affected Schwann cells to a precursor cell phenotype. Because axons remain intact, our results suggest that these changes in Schwann cell gene expression do not require input from a degenerating axon, but instead may depend on whether concerted synthesis of myelin is occurring

Field Research Is Essential to Counter Virological Threats

The interface between humans and wildlife is changing and, with it, the potential for pathogen introduction into humans has increased. Avian influenza is a prominent example, with an ongoing outbreak showing the unprecedented expansion of both geographic and host ranges. Research in the field is essential to understand this and other zoonotic threats. Only by monitoring dynamic viral populations and defining their biology in situ can we gather the information needed to ensure effective pandemic preparation.</p

Alternative promoters drive human cytomegalovirus reactivation from latency

Reactivation from latency requires reinitiation of viral gene expression and culminates in the production of infectious progeny. The major immediate early promoter (MIEP) of human cytomegalovirus (HCMV) drives the expression of crucial lytic cycle transactivators but is silenced during latency in hematopoietic progenitor cells (HPCs). Because the MIEP has poor activity in HPCs, it is unclear how viral transactivators are expressed during reactivation. It has been presumed that viral gene expression is reinitiated via de-repression of the MIEP. We demonstrate that immediate early transcripts arising from reactivation originate predominantly from alternative promoters within the canonical major immediate early locus. Disruption of these intronic promoters results in striking defects in re-expression of viral genes and viral genome replication in the THP-1 latency model. Furthermore, we show that these promoters are necessary for efficient reactivation in primary CD34+ HPCs. Our findings shift the paradigm for HCMV reactivation by demonstrating that promoter switching governs reactivation from viral latency in a context-specific manner

Learning to Teach About Ideas and Evidence in Science : The Student Teacher as Change Agent

A collaborative curriculum development project was set up to address the lack of good examples of teaching about ideas and evidence and the nature of science encountered by student teachers training to teach in the age range 11-16 in schools in England. Student and teacher-mentor pairs devised, taught and evaluated novel lessons and approaches. The project design required increasing levels of critique through cycles of teaching, evaluation and revision of lessons. Data were gathered from interviews and students' reports to assess the impact of the project on student teachers and to what extent any influences survived when they gained their first teaching posts. A significant outcome was the perception of teaching shifting from the delivery of standard lessons in prescribed ways to endeavours demanding creativity and decision-making. Although school-based factors limited newly qualified teachers' chances to use new lessons and approaches and therefore act as change-agents in schools, the ability to critique curriculum materials and the recognition of the need to create space for professional dialogue were durable gains

Human cytomegalovirus latency-associated proteins elicit immune-suppressive IL-10 producing CD4⁺ T cells.

Human cytomegalovirus (HCMV) is a widely prevalent human herpesvirus, which, after primary infection, persists in the host for life. In healthy individuals, the virus is well controlled by the HCMV-specific T cell response. A key feature of this persistence, in the face of a normally robust host immune response, is the establishment of viral latency. In contrast to lytic infection, which is characterised by extensive viral gene expression and virus production, long-term latency in cells of the myeloid lineage is characterised by highly restricted expression of viral genes, including UL138 and LUNA. Here we report that both UL138 and LUNA-specific T cells were detectable directly ex vivo in healthy HCMV seropositive subjects and that this response is principally CD4⁺ T cell mediated. These UL138-specific CD4⁺ T cells are able to mediate MHC class II restricted cytotoxicity and, importantly, show IFNγ effector function in the context of both lytic and latent infection. Furthermore, in contrast to CDCD4⁺ T cells specific to antigens expressed solely during lytic infection, both the UL138 and LUNA-specific CD4⁺ T cell responses included CD4⁺ T cells that secreted the immunosuppressive cytokine cIL-10. We also show that cIL-10 expressing CD4⁺ T-cells are directed against latently expressed US28 and UL111A. Taken together, our data show that latency-associated gene products of HCMV generate CD4⁺ T cell responses in vivo, which are able to elicit effector function in response to both lytic and latently infected cells. Importantly and in contrast to CD4⁺ T cell populations, which recognise antigens solely expressed during lytic infection, include a subset of cells that secrete the immunosuppressive cytokine cIL-10. This suggests that HCMV skews the T cell responses to latency-associated antigens to one that is overall suppressive in order to sustain latent carriage in vivo

Potentiation of radiation therapy by the oncolytic adenovirus dl1520 (ONYX-015) in human malignant glioma xenografts

In spite of aggressive surgery, irradiation and/or chemotherapy, treatment of malignant gliomas remains a major challenge in adults and children due to high treatment failure. We have demonstrated significant cell lysis and antitumour activity of the E1B-55 kDa-gene-deleted adenovirus ONYX-015 (dl1520, CI-1042; ONYX Pharmaceuticals) in subcutaneous human malignant glioma xenografts deriving from primary tumours. Here, we show the combined efficacy of this oncolytic therapy with radiation therapy. Total body irradiation (5 Gy) of athymic nude mice prior to intratumoral injections of ONYX-015 1 x 10(8) PFU daily for 5 consecutive days yielded additive tumour growth delays in the p53 mutant xenograft IGRG88. Radiation therapy was potentiated in the p53 functional tumour IGRG121 with a 'subtherapeutic' dose of 1 x 10(7) PFU daily for 5 consecutive days, inducing significant tumour growth delay, 90% tumour regression and 50% tumour-free survivors 4 months after treatment. These potentiating effects were not due to increased adenoviral infectivity or replication. Furthermore, cell lysis and induction of apoptosis, the major mechanisms for adenoviral antitumour activity, did not play a major role in the combined treatment strategy. Interestingly, the oncolytic adenovirus seemed to accelerate radiation-induced tumour fibrosis. Potentiating antitumour activity suggests the development of this combined treatment for these highly malignant tumours