Search PubMed⌕ Search

Biomedical subjects

N Bennett

Publications and source records attributed to N Bennett.

At least 19 recordsLinked to original sources
PubMed2026

Addressing the dual-use of antifungals and fungal antimicrobial resistance (fAMR) through a One Health approach.

Fungal antimicrobial resistance (fAMR) is accelerating, driven in part by the dual-use of antifungal modes of action in agriculture and medicine, threatening therapy. Addressing this challenge requires a unified One Health response that balances agricultural productivity, economic stability, and human and animal health. By focusing on the United Kingdom's policy approach, we argue that current efforts are constrained by fragmented governance, surveillance and regulation. To resolve this, we propose three policy recommendations: 1. a cross-government fAMR body, 2. mandatory environmental and clinical surveillance, and 3. for fungicide approvals to look beyond crop pathogens and integrate risk assessments for potential hotspots of resistance selection in human fungal pathogens. These measures will safeguard current and future antifungals while providing much-needed regulatory clarity and will be translatable to other national and regional contexts.

Journal Article↗
PubMed2002

Basis for intracellular retention of a human mutant of the retinal rod channel alpha subunit.

A mutant of the a subunit of the retinal rod cyclic GMP-gated channel, [Arg654(1-bp del)], corresponding to a truncated alphaR654Dstop subunit, was previously described in patients with retinitis pigmentosa: when expressed in HEK-293 cells, this mutated a subunit was retained inside the cell, but had normal channel activity in one case where it reached the plasma membrane, indicating that the mechanism of targeting is altered by the mutation, but not the function of the channel. The corresponding mutants of the bovine rod channel (alphaR656D stop), and of the closely related olfactory neuron channel (alphaR632Dstop) alpha subunits were expressed in Xenopus oocytes and their activity was analyzed by patch-clamp. Like their human homologue, these two channels have no activity, and we show that their GFP fusion proteins are accumulated into intracellular compartments. The truncation alone or the R/D mutation alone do not prevent or modify channel activity, indicating that neither the R656 residue nor the C-terminal domain downstream of R656 is necessary for homomeric channel targeting and function. Several mutations of R656 and of the preceding residues in the R656Dstop mutant disclose that the motif responsible for the absence of channel activity is an endoplasmic reticulum retention signal (KXKXXstop) in which the nature of the residues in positions -1 and -4 is determinant.

Amino Acid Sequence↗
PubMed2001

Interaction of plant protein Ser/Thr phosphatase PP7 with calmodulin.

We have recently identified PP7, a novel group of plant protein Ser/Thr phosphatases, and hypothesized that PP7 may possess a calmodulin-binding site. To test this hypothesis, we assessed the effect of calmodulin on the activity of recombinant Arabidopsis thaliana PP7 and directly tested interaction between PP7 and calmodulin using surface plasmon resonance. Calmodulin exerted a moderate inhibitory effect on the phosphatase activity of PP7 with submicromolar affinity. PP7 specifically interacted with immobilized calmodulin (but not with recoverin, another EF hand Ca(2+)-binding protein) in a strictly Ca(2+)-dependent manner with nanomolar affinity. Deletion of an insert in the catalytic domain of PP7, predicted to function as a calmodulin-binding site, greatly decreased PP7 binding to calmodulin. These findings provide the first evidence for a plant protein phosphatase directly interacting with calmodulin and indicate that PP7 might be regulated by Ca(2+) levels in vivo.

Arabidopsis↗
PubMed2001

Preventing falls in older people: impact of an intervention to reduce environmental hazards in the home.

OBJECTIVES: To evaluate the impact of an intervention to reduce fall hazards in the homes of older people. DESIGN: The intervention was administered to the 570 subjects in the experimental arm of a randomized controlled trial, with follow-up of subjects for 1 year. SETTING: Community-based seniors living in Perth, Australia. PARTICIPANTS: People age 70 and older. INTERVENTION: Registered nurses delivered the intervention. It consisted of a home hazard assessment, an educational strategy on general fall hazard reduction and ways to reduce identified home hazards, and the free installation of safety devices: grab rails, nonslip stripping on steps, and double-sided tape for floor rugs and mats. All intervention subjects received the home hazard assessment, and 96% received the educational strategy. Grab rails were installed in 77% of homes, rugs were stabilized in 8%, and nonslip step stripping was installed in 36%. MEASUREMENTS: Hazard prevalence was assessed at baseline in all homes and 11 months later in a random sample of 51 homes. Action taken in response to the intervention was assessed by a self-completed postal questionnaire completed 11 months after the intervention. RESULTS: All homes had at least one fall hazard. The most prevalent were floor rugs and mats (mean of 14 per home), stepovers (Stepovers are structural changes to the height of the floor that were designed to be stepped over rather than stepped upon, for example, the lip of a shower or a bath side.) (mean of seven per home), steps (mean of four per home), and trailing cords (mean of two per home). The intervention was associated with a small but significant reduction in four of the five most prevalent hazards. The mean number of unsafe rugs and mats was reduced by 1.57 per house (95% confidence interval (CI) = 0.91-2.24); the mean number of unsafe steps was reduced by 0.61 per house (95% CI = 0.28-0.94); the mean number of rooms with trailing cords was reduced by 0.43 per house (95% CI = 0.10-0.76); and the mean number of unsafe chairs was reduced by 0.10 per house (95% CI = 0.02-0.18). Safety devices were installed in 81.9% of homes. Advice on modifying specific hazards identified on the home hazard assessment resulted in over 50% of subjects removing hazards of floor rugs and mats, trailing cords, and obstacles. The general education message prompted less activity to reduce these hazards than did the advice on identified hazards. CONCLUSIONS: Fall hazards are ubiquitous in the homes of older people. The intervention resulted in a small reduction in the mean number of hazards per house, with many study subjects taking action but removing only a few hazards. The impact of the intervention in achieving self-reported action to reduce hazards was high.

Accidental Falls↗
PubMed2001

Preventing falls in older people: outcome evaluation of a randomized controlled trial.

OBJECTIVES: To evaluate the outcome of an intervention to reduce hazards in the home on the rate of falls in seniors. DESIGN: Randomized controlled trial, with follow-up of subjects for 1 year. SETTING: Community-based study in Perth, Western Australia. PARTICIPANTS: People age 70 and older. INTERVENTION: One thousand eight hundred seventy-nine subjects were recruited and randomly allocated by household to the intervention and control groups in the ratio 1:2. Because of early withdrawals, 1,737 subjects commenced the study. All members of both groups received a single home visit from a research nurse. Intervention subjects (n = 570) were offered a home hazard assessment, information on hazard reduction, and the installation of safety devices, whereas control subjects (n = 1,167) received no safety devices or information on home hazard reduction. MEASUREMENTS: Both groups recorded falls on a daily calendar. Reported falls were confirmed by a semistructured telephone interview and were assigned to one of three overlapping categories: all falls, falls inside the home, and falls involving environmental hazards in the home. Analysis was by multivariate modelling of rate ratios and odds ratios for falls, corrected for household clustering, using Poisson regression and logistic regression with robust variance estimation. RESULTS: Overall, 86% of study subjects completed the 1 year of follow-up. The intervention was not associated with any significant reduction in falls or fall-related injuries. There was no significant reduction in the intervention group in the incidence rate of falls involving environmental hazards inside the home (adjusted rate ratio, 1.11; 95% CI = 0.82-1.50), or the proportion of the intervention group who fell because of hazards inside the home (adjusted odds ratio, 0.97; 95% CI = 0.74-1.28). No reduction was seen in the rate of all falls (adjusted rate ratio, 1.02; 95% CI = 0.83-1.27) or the rate of falls inside the home (adjusted rate ratio, 1.17; 95% CI = 0.85-1.60). There was no significant reduction in the rate of injurious falls in intervention subjects (adjusted rate ratio, 0.92; 95% CI = 0.73-1.14). CONCLUSIONS: The intervention failed to achieve a reduction in the occurrence of falls. This was most likely because the intervention strategies had a limited effect on the number of hazards in the homes of intervention subjects. The study provides evidence that a one-time intervention program of education, hazard assessment, and home modification to reduce fall hazards in the homes of healthy older people is not an effective strategy for the prevention of falls in seniors.

Accidental Falls↗
PubMed2000

Coexpression of alpha and beta subunits of the rod cyclic GMP-gated channel restores native sensitivity to cyclic AMP: role of D604/N1201.

Coexpression of the betawt and alphawt subunits of the bovine rod channel restores two characteristics of the native channels: higher sensitivity to cAMP and potentiation of cGMP-induced currents by low cAMP concentrations. To test whether the increased sensitivity to cAMP is due to the uncharged nature of the asparagine residue (N1201) situated in place of aspartate D604 in the beta subunit as previously suggested (, Neuron. 15:619-625), we compared currents from wild-type (alphawt and alphawt/betawt) and from mutated channels (alphaD604N, alphaD604N/betawt, and alphawt/betaN1201D). The results show that the sensitivity to cAMP and cAMP potentiation is partly but not entirely determined by the charge of residue 1201 in the beta subunit. The D604N mutation in the alpha subunit and, to a lesser extent, coexpression of the betawt subunit with the alphawt subunit reduce the open probability for cGMP compared to that of the alphawt channel. Interpretation of the data with the MWC allosteric model (model of Monod, Wyman, Changeux;, J. Mol. Biol. 12:88-118) suggests that the D604N mutation in the alpha subunits and coassembly of alpha and beta subunits alter the free energy of gating by cAMP more than that of cAMP binding.

Amino Acid Substitution↗
PubMed2000

A paired comparison of tuberculin skin test results in health care workers using 5 TU and 10 TU tuberculin.

BACKGROUND: Historically, 10 TU has been employed in Australia and the United Kingdom to perform the tuberculin skin test (TST). However, this makes it difficult to compare the rates of TST positivity with other countries such as the USA who use 5 TU. To assess the impact of the dose of tuberculin on the TST a comparison was made of TST responses in health care workers given a TST with both 5 and 10 TU. METHODS: Two TSTs were performed simultaneously in each health care worker using 5 and 10 TU. Each dose was randomly assigned in a blinded manner to the right or left forearm and read at 48-72 hours by a single nurse who was blinded to the assignment of the 5 and 10 TU doses. RESULTS: A total of 128 health care workers were enrolled, 119 (93%) of whom had a past history of BCG vaccination. The overall mean difference in paired reaction sizes for the two doses was 1.5 mm with 95% limits of agreement of -3.6 to 6.5 mm. CONCLUSION: A slightly larger TST reading was seen with 10 TU than with 5 TU. The mean difference of 1.5 mm between the two doses should be considered when comparing rates of TST positivity between countries who use different doses of tuberculin to perform the tuberculin skin test.

Adult↗
PubMed1999

Hypotension and adrenal insufficiency.

This case conference describes two patients with hypotension who eventually were diagnosed with adrenal insufficiency. The first patient was initially believed to have a cardiac abnormality and the second patient sepsis, which was causing the continued hypotension. Both patients exhibited several clinical similarities; however, neither had the classic symptoms of adrenal insufficiency. This report discusses the causes of postoperative hypotension, diagnostic testing, and treatment for patients with adrenal insufficiency, and briefly reviews the literature.

Adrenal Insufficiency↗
PubMed1999

Glutathione depletion increases brain susceptibility to m-dinitrobenzene neurotoxicity.

To test the hypothesis that glutathione (GSH) status in brain tissue plays an important role in the selective neurotoxicity of m-dinitrobenzene (DNB), the sensitivity to intoxication of three groups of male F344 rats were studied and correlated with brain tissue GSH levels. In Group I were young 6-8 week old rats with normal GSH levels, and in Group II were rats of the same age whose brain GSH levels had been reduced by intracerebroventricular (i.c.v.) injections of L-buthionine-[S,R]-sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase. In Group III were 6 month old rats that, as a result of normal aging, show GSH levels of 16-29% below those seen in younger animals. All three groups were subjected to a 1 to 4 dose schedule of dosing with DNB (7.5 mg/kg/day i.p.) and killed 1 day after the last dose of DNB. It was found that whereas Group I animals developed ataxia and brain stem lesions after 4 doses, Group III animals showed these changes after 3 doses, while Group II animals had brain stem lesions after only 2 doses of DNB. The timing of the onset of these changes correlated closely with the degree of reduction of brain tissue levels of GSH, this being greatest in those animals infused i.c.v. with BSO. This demonstration indicates that GSH status in brain tissue is likely to be an important factor in determining regional sensitivity to gliovascular damage from this agent.

Animals↗
PubMed1998

PP7, a plant phosphatase representing a novel evolutionary branch of eukaryotic protein Ser/Thr phosphatases.

We describe a novel protein Ser/Thr phosphatase from Arabidopsis thaliana, PP7, which is only 27-32% identical in amino acid sequence to the known phosphatases and is the most divergent member of the PPP (PP1/2A/2B) family for today. Some structural features suggest more close relationship of PP7 to the PP5/rdgC subfamily. PP7 contains all of the residues essential for the phosphatase activity and possesses three major insertions in its presumable C-terminal subdomain, which suggest its unique regulation and/or optimisation of its structure for interaction with specific substrates or regulators. A phosphatase structurally related to PP7 is expressed in rice. PP7 conservation between mono- and dicotyledonous plants may point to its essential role in the plant cell.

Amino Acid Sequence↗
PubMed1998

[Ser/Thr-phosphatases from bovine retina: detection of cDNA coding for the catalytic subunit of the gamma-isoform PP2B and two homologs of rdgC/PPEF].

The expression of genes for Ser/Thr phosphatases of the PP1/2A/2B class in the bovine retina was analyzed using PCR on cDNA. The mRNAs were found for the following phosphatases: PP1 (alpha- and gamma-isoforms), PP2A (alpha- and beta-isoforms), PPV, and PP2B (beta- and gamma-isoforms). Earlier, PP2B gamma-isoform was considered testis-specific. cDNAs of two phosphatases related to rdgC/PPEF were also detected. Thus, there are mRNAs of at least four phosphatases in retina that may be regulated by Ca2+.

Amino Acid Sequence↗
PubMed1997

Capacity of rat brain to metabolize m-dinitrobenzene: an in vitro study.

m-dinitrobenzene (m-DNB) is a neurotoxin producing selective brain lesions, but the in situ metabolic fate of m-DNB in brain is unknown. In this study, nitroreductive capacity of brain towards m-dinitrobenzene (m-DNB) has been investigated. Tissue slices from F344 rat brain stem, forebrain, and liver were separately incubated with 0.2 mM m-DNB. m-DNB and its metabolites were detected by HPLC, and identified by either HPLC or Mass Spectrometry (MS). All three types of tissues showed metabolic activity towards m-DNB. Metabolic disposal of m-DNB was 1.05 +/- 0.11 mumol/g wet weight/h in liver, 0.49 +/- 0.05 in brain stem, and 0.44 +/- 0.05 in forebrain (mean +/- SD, n = 4). m-Nitroaniline was found to be the main metabolite produced by both brain and liver slices, representing 57-66% of the disposal of m-DNB. Liver slices also produced 2(or 4)-amino-4(or 2)-nitrophenol, which was not detected in brain slices. We detected nitrosonitrobenzene in the slices from both parts of brain, but not in liver slices. The glucose consumption of brain slices from both areas were significantly increased in the presence of m-DNB: by 26% in the brain stem (p < 0.001) and by 17.9% in cerebral cortex (p < 0.01). This may be considered a pre-cytotoxic effect. The results demonstrate that brain has considerable nitroreductive capacity towards m-DNB, and that in situ reduction of m-DNB may be responsible for its neurotoxicity.

Animals↗
PubMed1996

Calcium-activated opsin phosphatase activity in retinal rod outer segments.

We describe the presence in bovine retinal rod outer segments of a phosphatase which dephosphorylates phosphoopsin with an efficiency similar to that of PP2A, and which is stimulated by submicromolar levels of Ca2+ (half-maximal activation, 0.4-0.5 microM). This enzyme is designated CA2+ -activated opsin phosphatase (CAOP). CAOP has a molecular mass of 70-75 kDa as determined by gel filtration on Superose 12 and exhibits reversible Ca2+ -dependent oligomerization. An unidentified protein of approximately 25 kDa is necessary for full activity of CAOP and for cooperative binding of Ca2+ (h > 2). CAOP does not require Mg2+ and is inhibited by okadaic acid (median inhibitory concentration > 25 microM), which suggests that it is related to the PP1/2A/2b class of protein phosphatases. Like PP2B, CAOP is inhibited by trifluoperazine (median inhibitory concentration 40 microM), but calmodulin has no effect on CAOP activity, and CAOP is inhibited by mastoparan at much higher concentrations than PP2b. This combination of properties suggests that CAOP is not identical to any characterized protein phosphatase. Since the cytoplasmic concentration of Ca2+ -sensitive opsin phosphatase activity suggests that light-dependent Ca2+ levels may control rhodopsin dephosphorylation.

Animals↗