Mycoinsecticides for aphid management: a biorational approach

This study considered a novel approach to selecting isolates of Hyphomycete fungi as mycoinsecticides for biological control of aphids in arable crops in the UK. The approach was designed to select isolates which were compatible with both the biotic and abiotic environment. Aphis fabae was chosen as a representative target aphid for bioassays, based on results of preliminary experiments. Eighteen isolates of fungi were screened at a single concentration of 1x 10⁸ conidia ml⁻¹ against apterous adult A. fabae, which were incubated at 23°C. Spray applications were made using an electrostatic rotary atomiser in both laboratory and field experiments. Isolates that originated from aphid hosts were most pathogenic to A. fabae. Four isolates were selected for further studies; ARSEF 2879 (Beauveria bassiana), HRI 1.72 (Verticillium lecanii), Mycotrol strain GHA (B. bassiana) and Z11 (Paecilomyces fumosoroseus). Isolate HRI 1.72 was most virulent to A. fabae in dose-response assays compared to other isolates; at concentrations of 1x 105 conidia ml⁻¹ and above, mortality of aphids due to infection by HRI 1.72 was 100%. Isolates of P. fumosoroseus and V. lecanii were able to grow and germinate better in vitro at low temperatures (10 & 15°C), than isolates of B. bassiana and Metarhizium anisopliae. Aphis fabae and Myzus persicae, inoculated with isolate HRI 1.72 and incubated at 10°C, succumbed to infection after a significantly shorter period of time compared to other isolates. Rhopalosiphum padi was most resistant to infection by the four isolates compared to five other species of aphid. Aphis fabae, Acyrthosiphon pisum, Sitobion avenae, Metopolophium dirhodum, R. padi and M. persicae were most susceptible to infection by isolate HRI 1.72. Aphids infected with isolates of V. lecanii often had fungal sporulation on their legs and died attached to leaves on which they were feeding. The isolates Mycotrol strain GHA and ARSEF 2879 were pathogenic to the 7-spot ladybird Coccinella septempunctata and the generalist parasitoid Praon volucre. The isolates HRI 1.72 and Z11 had very little impact on these natural enemies tested. When aphids of A. fabae were co-inoculated with isolates of Hyphomycete fungi and Erynia neoaphidis, most individuals succumbed to infection with E. neoaphidis. A significant number of aphids died within 24 hours of inoculation and showed no signs of external sporulation. The potential interactions between these natural enemies in the biocontrol of aphids are discussed. The spatial and temporal distribution of aphids and their natural enemies, in field bean and wheat crops, was determined in two field seasons (1997 & 1998). Aphids sampled from the field, after application of Hyphomycete fungi in 1998, mostly succumbed to infection with E. neoaphidis. Epizootics of E. neoaphidis were recorded in both years. Greater numbers of healthy laboratory aphids succumbed to infection with Hyphomycete fungi when they were bioassayed on leaves sampled immediately following spraying (51 - 100%) compared to 24 hours later (8 - 65%). Microclimate recordings showed humidity in both crops was generally >90% overnight and differences were as great as 15% between the top and bottom of crop canopies. Temperature differences were as great as 5-7°C between individual sensors. The implications of using a biorational approach as part of the development of Hyphomycete fungi as mycoinsecticides for the control of aphids is discussed

Mycoinsecticides for aphid management: a biorational approach

This study considered a novel approach to selecting isolates of Hyphomycete fungi as mycoinsecticides for biological control of aphids in arable crops in the UK. The approach was designed to select isolates which were compatible with both the biotic and abiotic environment. Aphis fabae was chosen as a representative target aphid for bioassays, based on results of preliminary experiments. Eighteen isolates of fungi were screened at a single concentration of 1x 10⁸ conidia ml⁻¹ against apterous adult A. fabae, which were incubated at 23°C. Spray applications were made using an electrostatic rotary atomiser in both laboratory and field experiments. Isolates that originated from aphid hosts were most pathogenic to A. fabae. Four isolates were selected for further studies; ARSEF 2879 (Beauveria bassiana), HRI 1.72 (Verticillium lecanii), Mycotrol strain GHA (B. bassiana) and Z11 (Paecilomyces fumosoroseus). Isolate HRI 1.72 was most virulent to A. fabae in dose-response assays compared to other isolates; at concentrations of 1x 105 conidia ml⁻¹ and above, mortality of aphids due to infection by HRI 1.72 was 100%. Isolates of P. fumosoroseus and V. lecanii were able to grow and germinate better in vitro at low temperatures (10 & 15°C), than isolates of B. bassiana and Metarhizium anisopliae. Aphis fabae and Myzus persicae, inoculated with isolate HRI 1.72 and incubated at 10°C, succumbed to infection after a significantly shorter period of time compared to other isolates. Rhopalosiphum padi was most resistant to infection by the four isolates compared to five other species of aphid. Aphis fabae, Acyrthosiphon pisum, Sitobion avenae, Metopolophium dirhodum, R. padi and M. persicae were most susceptible to infection by isolate HRI 1.72. Aphids infected with isolates of V. lecanii often had fungal sporulation on their legs and died attached to leaves on which they were feeding. The isolates Mycotrol strain GHA and ARSEF 2879 were pathogenic to the 7-spot ladybird Coccinella septempunctata and the generalist parasitoid Praon volucre. The isolates HRI 1.72 and Z11 had very little impact on these natural enemies tested. When aphids of A. fabae were co-inoculated with isolates of Hyphomycete fungi and Erynia neoaphidis, most individuals succumbed to infection with E. neoaphidis. A significant number of aphids died within 24 hours of inoculation and showed no signs of external sporulation. The potential interactions between these natural enemies in the biocontrol of aphids are discussed. The spatial and temporal distribution of aphids and their natural enemies, in field bean and wheat crops, was determined in two field seasons (1997 & 1998). Aphids sampled from the field, after application of Hyphomycete fungi in 1998, mostly succumbed to infection with E. neoaphidis. Epizootics of E. neoaphidis were recorded in both years. Greater numbers of healthy laboratory aphids succumbed to infection with Hyphomycete fungi when they were bioassayed on leaves sampled immediately following spraying (51 - 100%) compared to 24 hours later (8 - 65%). Microclimate recordings showed humidity in both crops was generally >90% overnight and differences were as great as 15% between the top and bottom of crop canopies. Temperature differences were as great as 5-7°C between individual sensors. The implications of using a biorational approach as part of the development of Hyphomycete fungi as mycoinsecticides for the control of aphids is discussed

A suggested approach to the diagnosis of urinary tract infection and empiric use of antibiotics among hospitalized older adults with acute confusion and or underlying cognitive and communication deficits

BackgroundThe true incidence of urinary tract infection (UTI) among hospitalized older adults remains unknown.AimsWe aim to present an approach to improve correct identification of UTI diagnosis and empiric use of antibiotics among those who are unable to provide history.Methods A comprehensive review of the literature was undertaken.Results Our suggested approach appears safe and likely to enhance diagnostic accuracy and judicious use of antibiotics among hospitalized older adults.ConclusionOur suggested approach is based on best available literature evidence but requires validation in clinical studies

Heritage Quay: What Will You Discover? Transforming the Archives of the University of Huddersfield, Yorkshire, UK

The Heritage Quay project is changing how archive services at the University of Huddersfield are delivered. This article examines how the Staff/Space/Collections dependency model and Customer Service Excellence framework have been used, and what lessons can be drawn for other archives

DKK1 expression by synovial fibroblasts in very early rheumatoid arthritis associates with lymphocyte adhesion in an in vitro flow co-culture system

BACKGROUND: Synovial fibroblasts play a key role in joint destruction and regulation of the inflammatory infiltrate in established rheumatoid arthritis (RA). The mechanisms by which this occurs in the earliest stages of RA are largely unknown. We investigated the role of Dickkopf-related protein 1 (DKK1) produced by synovial fibroblasts of patients with very early rheumatoid arthritis (VeRA). METHODS: Fibroblasts were isolated from the disease-modifying anti-rheumatic drug–naive Birmingham early arthritis cohort of patients with new onset of clinically apparent arthritis and inflammatory symptoms of ≤12 weeks’ duration, who at follow-up had either resolving arthritis or RA. Endothelial fibroblast co-cultures were formed using porous filters, and lymphocyte adhesion to co-cultures was assessed using phase-contrast microscopy. DKK1 gene expression and secretion were quantified by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Synovial fibroblasts from patients with VeRA expressed significantly higher levels of DKK1 messenger RNA than those from patients with resolving arthritis. A similar trend was observed for DKK1 protein secretion. In co-culture constructs, more DKK1 tended to be secreted in co-cultures incorporating fibroblasts from VeRA than in co-cultures from non-inflamed joints and resolving arthritis. DKK1 secretion during co-culture positively correlated with lymphocyte adhesion. CONCLUSIONS: Alterations in DKK1 could be involved in the pathogenesis and perpetuation of the inflammatory response in the earliest clinically apparent stages of RA

Natural history of epilepsy in argininosuccinic aciduria provides new insights into pathophysiology: A retrospective international study

OBJECTIVE: Argininosuccinate lyase (ASL) is integral to the urea cycle, which enables nitrogen wasting and biosynthesis of arginine, a precursor of nitric oxide. Inherited ASL deficiency causes argininosuccinic aciduria, the second most common urea cycle defect and an inherited model of systemic nitric oxide deficiency. Patients present with developmental delay, epilepsy, and movement disorder. Here we aim to characterize epilepsy, a common and neurodebilitating comorbidity in argininosuccinic aciduria. METHODS: We conducted a retrospective study in seven tertiary metabolic centers in the UK, Italy, and Canada from 2020 to 2022, to assess the phenotype of epilepsy in argininosuccinic aciduria and correlate it with clinical, biochemical, radiological, and electroencephalographic data. RESULTS: Thirty-seven patients, 1-31 years of age, were included. Twenty-two patients (60%) presented with epilepsy. The median age at epilepsy onset was 24 months. Generalized tonic-clonic and focal seizures were most common in early-onset patients, whereas atypical absences were predominant in late-onset patients. Seventeen patients (77%) required antiseizure medications and six (27%) had pharmacoresistant epilepsy. Patients with epilepsy presented with a severe neurodebilitating disease with higher rates of speech delay (p = .04) and autism spectrum disorders (p = .01) and more frequent arginine supplementation (p = .01) compared to patients without epilepsy. Neonatal seizures were not associated with a higher risk of developing epilepsy. Biomarkers of ureagenesis did not differ between epileptic and non-epileptic patients. Epilepsy onset in early infancy (p = .05) and electroencephalographic background asymmetry (p = .0007) were significant predictors of partially controlled or refractory epilepsy. SIGNIFICANCE: Epilepsy in argininosuccinic aciduria is frequent, polymorphic, and associated with more frequent neurodevelopmental comorbidities. We identified prognostic factors for pharmacoresistance in epilepsy. This study does not support defective ureagenesis as prominent in the pathophysiology of epilepsy but suggests a role of central dopamine deficiency. A role of arginine in epileptogenesis was not supported and warrants further studies to assess the potential arginine neurotoxicity in argininosuccinic aciduria

Liver transplantation in ornithine transcarbamylase deficiency: A retrospective multicentre cohort study

Ornithine transcarbamylase deficiency (OTCD) is an X-linked defect of ureagenesis and the most common urea cycle disorder. Patients present with hyperammonemia causing neurological symptoms, which can lead to coma and death. Liver transplantation (LT) is the only curative therapy, but has several limitations including organ shortage, significant morbidity and requirement of lifelong immunosuppression. This study aims to identify the characteristics and outcomes of patients who underwent LT for OTCD. // We conducted a retrospective study for OTCD patients from 5 UK centres receiving LT in 3 transplantation centres between 2010 and 2022. Patients' demographics, family history, initial presentation, age at LT, graft type and pre- and post-LT clinical, metabolic, and neurocognitive profile were collected from medical records.// A total of 20 OTCD patients (11 males, 9 females) were enrolled in this study. 6/20 had neonatal and 14/20 late-onset presentation. 2/20 patients had positive family history for OTCD and one of them was diagnosed antenatally and received prospective treatment. All patients were managed with standard of care based on protein-restricted diet, ammonia scavengers and supplementation with arginine and/or citrulline before LT. 15/20 patients had neurodevelopmental problems before LT. The indication for LT was presence (or family history) of recurrent metabolic decompensations occurring despite standard medical therapy leading to neurodisability and quality of life impairment. Median age at LT was 10.5 months (6–24) and 66 months (35–156) in neonatal and late onset patients, respectively. 15/20 patients had deceased donor LT (DDLT) and 5/20 had living related donor LT (LDLT). Overall survival was 95% with one patient dying 6 h after LT. 13/20 had complications after LT and 2/20 patients required re-transplantation. All patients discontinued dietary restriction and ammonia scavengers after LT and remained metabolically stable. Patients who had neurodevelopmental problems before LT persisted to have difficulties after LT. 1/5 patients who was reported to have normal neurodevelopment before LT developed behavioural problems after LT, while the remaining 4 maintained their abilities without any reported issues. // LT was found to be effective in correcting the metabolic defect, eliminates the risk of hyperammonemia and prolongs patients' survival

Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management.

OBJECTIVE: In adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary centre over a thirteen-year period. DESIGN: Clinical, biochemical, radiological and histological data were reviewed from all confirmed cases of adult-onset hyperinsulinaemic hypoglycaemia at our centre between 2003 and 2016. In a subset of patients with stage I insulinoma, whole-exome sequencing of tumour DNA was performed. RESULTS: Twenty-nine patients were identified (27 insulinoma, including 6 subjects with metastatic disease; 1 pro-insulin/GLP-1 co-secreting tumour; 1 activating glucokinase mutation). In all cases, hypoglycaemia (glucose ≤2.2 mmol/L) was achieved within 48 h of a supervised fast. At fast termination, subjects with stage IV insulinoma had significantly higher insulin, C-peptide and pro-insulin compared to those with insulinoma staged I-IIIB. Preoperative localisation of insulinoma was most successfully achieved with EUS. In two patients with inoperable, metastatic insulinoma, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE rapidly restored euglycaemia and lowered fasting insulin. Finally, in a subset of stage I insulinoma, whole-exome sequencing of tumour DNA identified the pathogenic Ying Yang-1 (YY1) somatic mutation (c.C1115G/p.T372R) in one tumour, with all tumours exhibiting a low somatic mutation burden. CONCLUSION: Our study highlights, in particular, the utility of the 48-h fast in the diagnosis of insulinoma, EUS for tumour localisation and the value of PRRT therapy in the treatment of metastatic disease

Cytoplasmic location of factor-inhibiting hypoxia-inducible factor is associated with an enhanced hypoxic response and a shorter survival in invasive breast cancer

INTRODUCTION: Hypoxia-inducible factor (HIF)-1alpha levels in invasive breast carcinoma have been shown to be an adverse prognostic indicator. Cellular HIF-1alpha activity is regulated by factor-inhibiting hypoxia-inducible factor 1 (FIH-1). In hypoxia, FIH-1 hydroxylation of Asn803 within the C-terminal transactivation domain does not occur and HIF-1alpha forms a fully active transcriptional complex. The present study investigates the role of FIH-1 in invasive breast carcinoma and its correlation with hypoxia. METHODS: Microarrayed tissue cores from 295 invasive carcinomas were stained for FIH-1, for HIF-1alpha and for carbonic anhydrase 9. FIH-1 expression was correlated with standard clinicopathological parameters and with the expression of the surrogate hypoxic markers HIF-1alpha and carbonic anhydrase 9. RESULTS: FIH-1 was positive in 239/295 (81%) tumours, 42/295 (14%) exclusively in the nucleus and 54/295 (18%) exclusively in the cytoplasm. Exclusive nuclear FIH-1 expression was significantly inversely associated with tumour grade (P = 0.02) and risk of recurrence (P = 0.04), whereas exclusive cytoplasmic FIH-1 was significantly positively associated with tumour grade (P = 0.004) and carbonic anhydrase 9 expression (P = 0.02). Patients with tumours that excluded FIH-1 from the nucleus had a significantly shorter survival compared with those with exclusive nuclear expression (P = 0.02). Cytoplasmic FIH-1 expression was also an independent poor prognostic factor for disease-free survival. CONCLUSION: FIH-1 is widely expressed in invasive breast carcinoma. As with other HIF regulators, its association between cellular compartmentalization and the hypoxic response and survival suggests that tumour regulation of FIH-1 is an additional important mechanism for HIF pathway activation