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Neil Smith

Publications and source records attributed to Neil Smith.

10 recordsLinked to original sources
PubMed2026

Pathogen Species-Specific Differences in Induction of the Maize Polyubiquitin Gene Promoter in Transgenic Wheat.

The maize polyubiquitin promoter (ZmUbi) is a mainstay in molecular biology for transgene expression and is used for constitutive expression of defense-related gene products. Transgenic wheat lines were produced expressing a ZmUbi-RUBY reporter gene that produces the red pigment betalain. Some lines showed transgene silencing with reduced RUBY transcript accumulation and chimeric sectors of betalain. Infection of these plants with Blumeria graminis, Puccinia graminis f. sp. tritici (Pgt), or P. triticina (Pt) each resulted in localized betalain accumulation at infection sites and increased RUBY transcript accumulation. In contrast, two isolates of P. striiformis f. sp. tritici (Pst) caused no detectable RUBY transcript accumulation and no visible betalain accumulation at infection sites, although a modest betalain increase was detected in infected tissue extracts. Compared with Pst, Pgt more strongly induced host genes involved in transcriptional and post-transcriptional regulatory processes, although no obvious pathogen-induced changes in ZmUbi promoter methylation were observed. ZmUbi-GUS transgenic wheat plants were also pathogen challenged, and, unlike Pst, both Pgt and Pt induced localized GUS staining at infection sites. Database mining showed that the endogenous maize polyubiquitin gene from which ZmUbi is derived was pathogen inducible, albeit in a species-specific fashion. These pathogen differences in ZmUbi induction have implications when using this regulatory element to express defense-related transgenes in wheat. Comparing the resistance efficacy of transgenes against different pathogens using this promoter is potentially influenced by significant, localized expression differences occurring at infection sites of different pathogen species. [Formula: see text] Copyright © 2026 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Promoter Regions, Genetic↗
PubMed2026

Effect of long-term sepiapterin treatment on dietary phenylalanine tolerance in patients with phenylketonuria: Interim results from the phase 3 APHENITY Extension Study.

PURPOSE: To report interim results from the ongoing, open-label, phase 3 APHENITY Extension Study (NCT05166161), evaluating long-term treatment with sepiapterin in patients with phenylketonuria. METHODS: Participants received an age-based dose of oral sepiapterin daily; those with mean blood phenylalanine (Phe) levels <360 &#x3bc;mol/L (<5.95 mg/dL) after 2 weeks underwent a 26-week dietary Phe tolerance assessment, wherein dietary Phe intake was adjusted and blood Phe levels monitored. Other participants continued treatment with optional diet liberalization. Primary endpoints included change from baseline to week 26 in dietary Phe intake and treatment-emergent adverse events (TEAEs). RESULTS: As of September 2, 2024, 169 participants received sepiapterin (median [minimum, maximum] age: 14.0 [0.2, 55.0] years, median exposure: 72.9 weeks); 102 participants underwent dietary Phe tolerance assessments. Mean (SD) dietary Phe intake increased from 27.6 (18.0) mg/kg/day at baseline to 62.5 (41.5) mg/kg/day at week 26 (least-squares mean change [SE]: 36.4 [2.8] mg/kg/day from baseline) (P < .0001 from post hoc analysis). The incidence of treatment-related TEAEs was 29.0%; 3 participants (1.8%) discontinued treatment owing to treatment-related TEAEs. There were no treatment-related serious TEAEs or deaths. CONCLUSION: Interim results support the long-term safety of sepiapterin and demonstrate the potential for diet liberalization in adults and children with phenylketonuria. GOV IDENTIFIER: NCT05166161 (https://www. CLINICALTRIALS: gov/study/NCT05166161; date of registration, December 8, 2021).

Humans↗
PubMed2004

Dysfunctional assumptions in bipolar disorder.

BACKGROUND: Despite the initial encouraging outcome in developing CBT for bipolar affective disorder [Arch. Gen. Psychiatry 2002 (in press); Psychol. Med. 31 (2001) 459-467], very little is known about whether there are any differences in dysfunctional attitudes between unipolar and bipolar patients. Both the behavioural activation system theory [J. Pers. Soc. Psychol. 67 (1994) 488-498; Major Theories of Personality Disorder, Guilford Press, New York, 1996; Psychol. Bull. 117 (1995) 434-449] and the cognitive model for bipolar affective disorder [Cognitive Therapy for Bipolar Disorder: A Therapist's Guide to Concepts, Methods and Practise, Wiley, New York, 1999] postulate high goal striving as a risk factor for bipolar disorder. However, the existing subscales in the dysfunctional attitude scale (DAS) were derived from patients and relatives of patients suffering from unipolar depression, patients with a mixed psychiatric diagnosis or normal controls. None of the existing subscales reflects high goal striving beliefs. Using a sample of bipolar patients may yield different factors. METHODS: A total of 143 bipolar 1 patients filled in the short version of DAS 24. Principal component analysis was carried out to derive factors. The scores of these factors were compared with those of 109 unipolar patients to investigate if these factors distinguish bipolar patients from unipolar patients. RESULTS: Three factors were derived: factor 1 'Goal-attainment' accounted for 25.0% of the total variance. Factor 2 'Dependency' accounted for 11.0% of the total variance. Factor 3 'Achievement' accounted for 8.2% of the total variance. However, factor 1 appeared to consist of items that made a coherent theoretical construct. No significant differences were found when the validation sample was compared with 109 patients suffering from unipolar depression in any of the three factors. When subjects who were likely to be in a major depressive episode were excluded, the scores of bipolar patients (n=49) were significantly higher than euthymic unipolar patients (n=25) in factor 1 'Goal attainment'. Goal-attainment also correlated with the number of past hospitalisations due to manic episodes and to bipolar episodes as a whole. CONCLUSIONS: The Goal-attainment subscale captures the risky attitudes described by the behavioural activation system theory and the cognitive model for bipolar affective disorder. It is postulated that these beliefs may interact with the illness and predispose bipolar patients to have a more severe course of the illness.

Adult↗
PubMed2004

Antenatal screening for HIV; are those who refuse testing at higher risk than those who accept testing?

BACKGROUND: The UK Department of Health recommends that all pregnant women are offered screening for infection with human immunodeficiency virus (HIV) and had encouraged maternity units to achieve uptake targets of 90 per cent by the end of 2002. Many maternity units fail to meet this target and there is concern that those women who are still refusing testing may include a higher proportion of women at high risk of infection. In consequence, those infected with HIV are not being identified and are not receiving the antiviral treatment, which would be of benefit to them and reduce the risk of transmission of HIV to their babies. METHODS: A retrospective audit of HIV screening uptake in women who were found to be infected with hepatitis B virus (HBV) and in those who were not infected with HBV was carried out in order to explore further the characteristics of 'acceptors' and 'refusers' of HIV screening. RESULTS: The overall uptake rate of HIV screening in the West Midlands population served by the National Blood Service was 60 per cent in 2001 and 74 per cent in 2002. The prevalence of HBV infection was found to be twice as high (0.39 per cent) in those who had refused an HIV test compared with those who had accepted a test (0.21 per cent) (p = 0.022). CONCLUSION: There is good evidence that women refusing HIV antenatal screening have a higher prevalence of another blood-borne virus, indicating clearly that further effort must be made to increase the screening uptake and fully integrate HIV screening with other antenatal tests.

AIDS Serodiagnosis↗
PubMed2003

Response style, interpersonal difficulties and social functioning in major depressive disorder.

BACKGROUND: It is postulated that depressed patients who engaged in self-focused rumination on their depressive symptoms may experience more hopelessness, more interpersonal distress and poorer social functioning while patients who distract themselves may experience less severe hopelessness and better social functioning. METHOD: One-hundred and nine outpatients suffering from DSM-IV (APA, 1994) major depressive disorders filled in questionnaires that mapped into their response style to depression, hopelessness and interpersonal style. They were also interviewed for their levels of social functioning. RESULTS: Rumination was associated with higher levels of depression and distraction was associated with lower levels of depression. Furthermore when levels of depression and gender were controlled for, rumination contributed to higher levels of hopelessness and distraction contributed to lower levels of hopelessness. Both rumination and levels of depression contributed significantly to higher levels of interpersonal distress when gender was controlled for. Ruminators were rated to have significantly more severe problems in intimate relationships while distractors were rated to have significantly higher social functioning. CONCLUSION: Our study suggests the importance of teaching patients techniques to distract themselves. This could prevent patients from getting into a vicious cycle of self-absorption and increased levels of hopelessness, finding it hard to interact with people in their social network and neglecting their intimate relationships.

Adult↗
PubMed2003

Custom knock-outs with hairpin RNA-mediated gene silencing.

Hairpin (hpRNA)-mediated gene silencing exploits a cellular mechanism that recognizes double-stranded RNA (dsRNA) and subjects it and its corresponding mRNA to a sequence-specific degradation. This phenomenon is known as posttranscriptional gene silencing (PTGS) in plants and RNA interference (RNAi) in animals. dsRNA, when introduced into plant cells through hpRNA constructs, results in severe reduction of the target mRNA-the silencing effect being stably inherited over many generations. While hpRNA constructs can be made using conventional plasmids, use of generic vectors such as pHANNIBAL makes it more convenient to silence a number of genes simultaneously. Vectors, such as pHELLSGATE, that are based on the Gateway(R) technology are suitable for high-throughput gene silencing. The specificity of dsRNA silencing, it's ability to simultaneously silence multiple genes combined with the availability of high-throughput silencing vectors enables the researcher to generate custom knockout plants.

Base Sequence↗
PubMedDate not supplied

T-cell responses and previous exposure to hepatitis C virus in indeterminate blood donors.

Blood donors are routinely screened for hepatitis C virus infection. Some individuals have weak or restricted virus-specific antibody responses, and are classed as indeterminate. Such donors are almost always negative for viral RNA in blood. We postulated that previous transient virus exposure might account for some of these cases. With sensitive ex-vivo analyses of T-cell responses, we identified virus-specific responses in 15 of 30 indeterminate blood donors tested, compared with none in controls (p=0.0013). Additionally, these responses were typically focused on core-derived peptides. These findings suggest previous exposure to the virus in many indeterminate blood donors.

Adult↗