Biomedical subjects

R Noad

Publications and source records attributed to R Noad.

5 recordsLinked to original sources

PubMed2006

Bluetongue virus assembly and morphogenesis.

Like other members of the Reoviridae, bluetongue virus faces the same constraints on structure and assembly that are imposed by a large dsRNA genome. However, since it is arthropod-transmitted, BTV must have assembly pathways that are sufficiently flexible to allow it to replicate in evolutionarily distant hosts. With this background, it is hardly surprising that BTV interacts with highly conserved cellular pathways during morphogenesis and trafficking. Indeed, recent studies have revealed striking parallels between the pathways involved in the entry and egress of nonenveloped BTV and those used by enveloped viruses. In addition, recent studies with the protein that is the major component of the BTV viroplasm have revealed how the assembly and, as importantly, the disassembly of this structure may be achieved. This is a first step towards resolving the interactions that occur in these virus 'assembly factories'. Overall, this review demonstrates that the integration of structural, biochemical and molecular data is necessary to fully understand the assembly and replication of this complex RNA virus.

Animals↗

PubMed2004

Evaluation of the effect of radiotherapy for pituitary tumours on cognitive function and quality of life.

AIMS: Pituitary tumours are often treated with radiotherapy, which can cause cognitive impairment when given in high doses. It is assumed that current regimens do not cause damage, but this has not been established. The aim was to determine whether radiotherapy given to people with pituitary tumours was associated with cognitive impairment and reduced quality of life. MATERIAL AND METHODS: We retrospectively compared two outcome groups (patients with pituitary tumours who had undergone radiotherapy and surgery and patients with pituitary tumours who had surgery alone), and carried out standardised tests of cognitive function and quality of life. RESULTS: The data suggested that patients with pituitary tumours treated with surgery, with or without radiotherapy, had cognitive impairment compared with the normal population. Patients receiving radiotherapy performed significantly worse than those receiving only surgery on the Stroop test, a measure of executive function. They also scored significantly lower on the Physical Health composite of the SF36, although this difference was no longer significant when account was taken of baseline differences between the groups. There were no significant differences in other cognitive functions, mood, general well-being or the Mental Health Composite of the SF36. CONCLUSIONS: Patients treated for pituitary disease may have cognitive impairment. A decrease in cognitive function was found regardless of treatment type. The decrease seemed to be greater in the radiotherapy group and was mainly on executive function. This impairment of executive function could affect daily life. Further prospective studies are required to assess the effect of pituitary disease on cognitive function and the safety of radiotherapy.

Adult↗

PubMed2000

Nitric oxide and salicylic acid signaling in plant defense.

Salicylic acid (SA) plays a critical signaling role in the activation of plant defense responses after pathogen attack. We have identified several potential components of the SA signaling pathway, including (i) the H(2)O(2)-scavenging enzymes catalase and ascorbate peroxidase, (ii) a high affinity SA-binding protein (SABP2), (iii) a SA-inducible protein kinase (SIPK), (iv) NPR1, an ankyrin repeat-containing protein that exhibits limited homology to IkappaBalpha and is required for SA signaling, and (v) members of the TGA/OBF family of bZIP transcription factors. These bZIP factors physically interact with NPR1 and bind the SA-responsive element in promoters of several defense genes, such as the pathogenesis-related 1 gene (PR-1). Recent studies have demonstrated that nitric oxide (NO) is another signal that activates defense responses after pathogen attack. NO has been shown to play a critical role in the activation of innate immune and inflammatory responses in animals. Increases in NO synthase (NOS)-like activity occurred in resistant but not susceptible tobacco after infection with tobacco mosaic virus. Here we demonstrate that this increase in activity participates in PR-1 gene induction. Two signaling molecules, cGMP and cyclic ADP ribose (cADPR), which function downstream of NO in animals, also appear to mediate plant defense gene activation (e.g., PR-1). Additionally, NO may activate PR-1 expression via an NO-dependent, cADPR-independent pathway. Several targets of NO in animals, including guanylate cyclase, aconitase, and mitogen-activated protein kinases (e.g., SIPK), are also modulated by NO in plants. Thus, at least portions of NO signaling pathways appear to be shared between plants and animals.

Adenosine Diphosphate Ribose↗

PubMed2000

Genetic dissection of tomato bushy stunt virus p19-protein-mediated host-dependent symptom induction and systemic invasion.

The plus-sense single-stranded RNA of tomato bushy stunt virus (TBSV) encodes a 19-kDa protein, which is translated from a 3' proximal open reading frame (p19) that is entirely nested within the cell-to-cell movement gene (p22). Expression of the cytosolic p19-protein induces either a systemic lethal collapse in Nicotiana benthamiana and N. clevelandii, or necrotic local lesions on resistant N. tabacum. In spinach, the p19-protein is required at high abundance for efficient systemic invasion. This study aimed to determine whether these seemingly different host-dependent biological activities are governed by the same or separate regions on the 172 amino acid p19-protein. For this purpose, codons for charged amino acids predicted to be exposed on the surface of the polypeptide and presumably available for host-specific interactions, were targeted for mutagenesis. A total of 12 mutants were generated, which had no deficiencies in replication or cell-to-cell movement, and substitution of amino acids at the extreme N-terminal end or within the carboxyl 70 amino acids failed to cause a noticeable biological effect on plants. However, mutations dispersed between positions 43 and 85 on the N-terminal half prevented the onset of a systemic lethal necrosis on N. benthamiana and N. clevelandii. With one exception, the same mutants elicited mostly chlorotic, rather than necrotic, local lesions on N. tabacum. Mutations in the central region, which substituted Arg with Gly at positions 72 or 75-78, impaired the ability of TBSV to systemically invade spinach plants. However, substitution with Ala instead of Gly at position 72 had minimal effects on systemic spread in spinach, suggesting the possible influence of protein structure effects. The implications are that regions on the N-terminal portion of the p19-protein mediate interactions in a host-dependent manner and that a central region is required for all activities either by a direct effect of the amino acids or through maintenance of structural integrity.

Mutagenesis, Site-Directed↗

PubMed2000

Nitric oxide modulates the activity of tobacco aconitase.

Recent evidence suggests an important role for nitric oxide (NO) signaling in plant-pathogen interactions. Additional elucidation of the role of NO in plants will require identification of NO targets. Since aconitases are major NO targets in animals, we examined the effect of NO on tobacco (Nicotiana tabacum) aconitase. The tobacco aconitases, like their animal counterparts, were inhibited by NO donors. The cytosolic aconitase in animals, in addition to being a key redox and NO sensor, is converted by NO into an mRNA binding protein (IRP, or iron-regulatory protein) that regulates iron homeostasis. A tobacco cytosolic aconitase gene (NtACO1) whose deduced amino acid sequence shared 61% identity and 76% similarity with the human IRP-1 was cloned. Furthermore, residues involved in mRNA binding by IRP-1 were conserved in NtACO1. These results reveal additional similarities between the NO signaling mechanisms used by plants and animals.

Aconitate Hydratase↗