A5078366623- interferon and immune responses
- Ubiquitin and proteasome pathways
- Nutritional Studies and Diet
- Pituitary Gland Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Glycosylation and Glycoproteins Research
- Nutrition, Genetics, and Disease
- Electrolyte and hormonal disorders
- Vitamin D Research Studies
- Diet and metabolism studies
- Blood Pressure and Hypertension Studies
- RNA regulation and disease
- Alcoholism and Thiamine Deficiency
- Adrenal Hormones and Disorders
- Retinal Imaging and Analysis
- Glaucoma and retinal disorders
- Adrenal and Paraganglionic Tumors
- Porphyrin Metabolism and Disorders
- Hormonal Regulation and Hypertension
- Cardiac electrophysiology and arrhythmias
- NF-κB Signaling Pathways
- Consumer Attitudes and Food Labeling
- Lysosomal Storage Disorders Research
- Retinal and Optic Conditions
- Urinary Bladder and Prostate Research
University of Dundee
2023-2024
MRC Protein Phosphorylation and Ubiquitylation Unit
2023-2024
Medical Research Council
2023
Age UK
2023
Royal Victoria Hospital
2010-2017
University of Ulster
2010-2017
Queen's University Belfast
1958-2016
Victoria Hospital
2015
Royal Victoria Hospital
2012
Craigavon Area Hospital
2012
Abstract Branched ubiquitin (Ub) chains constitute a sizable fraction of Ub polymers in human cells. Despite their abundance, our understanding branched function cell signaling has been stunted by the absence accessible methods and tools. Here we identify cellular branched-chain-specific binding proteins devise approaches to probe K48–K63-branched function. We establish method monitor cleavage linkages within complex unveil ATXN3 MINDY as debranching enzymes. engineer K48–K63 branch-specific...
Branched ubiquitin (Ub) chains make up a significant proportion of Ub polymers in human cells and are formed when two or more sites on single molecule modified with creating bifurcated architectures. Despite their abundance, we have poor understanding the cellular functions branched signals that stems from lack facile tools methods to study them. Here develop comprehensive pipeline define function, using K48-K63-branched as case study. We discover branch-specific binders and, by developing...
Accidental hypothermia is generally thought to be uncommon in this country (Rees, 1958).It seen most often the elderly and infirm, patients with myxoedema (Summers, 1953; Maiden, 1955;Macdonald, 1958), hypopituitarism (Sheehan Summers, 1952), newborn (Mann Elliott, 1957).Recent interest accidental prompts report of nine cases admitted general medical wards a small hospital within period four months.This relatively high incidence (2.5% acute admissions during that period) suggests condition...
Macroprolactinemia is a common finding in patients with hyperprolactinemia. There are no published long-term follow-up studies.The aim of this study was to describe findings after prolonged previously cohort macroprolactinemia.We studied 51 identified as having macroprolactinemia polyethylene glycol precipitation.Clinical assessment and serum prolactin assay were repeated median 9.9 yr (range, 9-11 yr).Median age at presentation 41 18-55 yr). Mean concentration 1885 mU/liter, 1370 mU/liter....
Cardiovascular toxicity is an important cause of drug failures in the later stages development, early clinical safety assessment, and even postmarket withdrawals. Early-stage vitro assessment potential cardiovascular liabilities pharmaceutical industry involves interactions with cardiac ion channels, as well induced pluripotent stem cell-derived cardiomyocyte-based functional assays, such calcium flux multielectrode-array assays. These methods are appropriate for identification acute...
We describe a 16-year-old boy with juvenile metachromatic leukodystrophy who was treated bone marrow transplantation. Follow-up over 8 years showed no increase in symptoms, progression of neurological signs, and neuropsychological deterioration. conclude that transplantation may brain levels arylsulfatase A enough to prevent deterioration patients leukodystrophy.
Children with attention deficit hyperactivity disorder (ADHD) may have a component of sleep apnea causing arousal and contributing to ADHD behavior during the day. Twenty non-ADHD children between 4 16 years age were compared 18 use nocturnal polysomnography (PSG) psychometric tests. The testing confirmed that control group normal fulfilled diagnostic criteria for ADHD. PSG showed indexes (9.8 ± 3.9/hr) controls (10.2 3.1/hr), apnea/hypnea (1.0 2.4/hr) (0.6 0.9/hr). architecture was not...
SUMMARY Seventeen boys and thirty‐four girls were investigated because of persistent or recurrent urinary infection. The investigation these patients is discussed in detail the limitations various radiological techniques are considered. importance intravenous pyelography micturition cystography initial stressed. It was noted that boys, congenital anomalies causing obstructions stasis present 65 per cent., whereas obstructive rare. However, latter, abnormal widening internal vesical sphincter...
Abstract The attachment of the ubiquitin-like protein ISG15 to substrates by specific E1-E2-E3 enzymes is a well-established signalling mechanism innate immune response. Here, we present 3.45 Å cryo-EM structure chemically trapped UBE1L-UBE2L6 complex bound activated ISG15. This reveals details first steps recognition and UBE2L6 recruitment UBE1L (also known as UBA7). Taking advantage viral effector proteins from severe acute respiratory coronavirus 2 (SARS-CoV-2) influenza B virus (IBV),...
Type 1 interferon stimulation highly up-regulates all elements of a ubiquitin-like conjugation system that leads to ISGylation target proteins. An ISG15-specific member the deubiquitylase family, USP18, is up-regulated in co-ordinated manner. USP18 can also provide negative feedback by inhibiting JAK-STAT signalling through protein interactions independently DUB activity. Here, we an acute example this phenomenon, whereby early expression post-interferon treatment HCT116 colon cancer cells...
Summary TSH-secreting pituitary adenomas are rare and the optimal investigation management is uncertain. We describe a case of 43 year-old woman with adenoma, highlighting diagnostic testing our use, pre-operatively somatostatin analogue therapy, which induced biochemical euthyroidism reduction in tumour size. Learning points The differential diagnosis syndrome inappropriate TSH secretion non-thyroidal illness, medications, assay interference due to heterophilic antibodies, thyroid hormone...
A 28-year-old gentleman was referred to our medical department from the psychiatry department, with problems of confusion, disorientation and inappropriate behaviour. He apyrexic physical examination unremarkable. denied hallucinations, delusions or mood disturbance had no insight his current problems. Mini-Mental State Examination (MMSE)1 score 6/30. Two years previously he started use cocaine heroin episodically. consumed more than 40 units alcohol each week. Five weeks prior transfer,...
Abstract The attachment of the ubiquitin-like protein ISG15 to substrates is a well-established antiviral signalling mechanism innate immune response. However, despite identification thousands and clear roles in immunity, molecular understanding selection transfer through its cognate E1-E2- E3 enzyme cascade largely unknown. Here, we present 3.45 Å cryo-EM structure chemically trapped UBE1L-UBE2L6 complex bound activated ISG15. This reveals details first steps recognition UBE2L6 recruitment...
Summary Context In observational studies, low serum 25‐hydroxyvitamin D (25‐ OHD ) concentration is associated with an increased risk of type 2 diabetes mellitus ( DM ). Increasing 25‐ may have beneficial effects on insulin resistance or beta‐cell function. Cross‐sectional studies utilizing suboptimal methods for assessment sensitivity and provide conflicting results. Objective This study examined the relationship between in healthy overweight individuals at cardiovascular disease, using...
A 60-year-old lady with type 2 diabetes mellitus was admitted apparent bilateral papilloedema, detected by her optician. Fundoscopic findings on admission are shown in Figure 1A and B. Figure 1. ( B ) Optic discs showing marked swelling superficial flame haemorrhages the left eye. Note absence of significant diabetic retinopathy. ( C D Swelling gradually resolving without atrophy 3 months later. She diagnosed 1992 treated metformin, acarbose gliclazide. She had no …
An 8-year-old girl presented with a hypoglycaemic seizure and dark cutaneous pigmentation (Figure 1A B). Response to synacthen stimulation was inadequate adrenocorticotropic hormone (ACTH) elevated [basal cortisol 174 nmol/l, stimulated 173 nmol/l (reference range >500 nmol/l), ACTH 2980 ng/l <55 ng/l)]. However renin, aldosterone electrolytes were normal. She had no postural drop in blood pressure. commenced on hydrocortisone resolving her pigmentation. A Schirmer's test 1C) shows tear...
We report a case of autoimmune polyglandular syndrome type 1 (APS1) complicated by severe vascular insufficiency due to diffuse calcification. APS1 is characterised clinically multiple conditions and development at least two components the triad mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency. highlight problems in current serum calcium monitoring methods suggest that fluctuations concentrations difficulties treating hypoparathyroidism may have contributed calcification...
An 85-year-old lady with decreased mood and low energy was found to have an elevated serum corrected calcium concentration of 2.8 mmol/L (reference range: 2.1–2.6 mmol/L). Plasma parathyroid hormone at 390 pg/mL 10–85 pg/mL). She had a past history renal calculi. Renal function, full blood picture, erythrocyte sedimentation rate, 24-h urinary excretion, immunoglobulins, chest X-ray angiotensin converting enzyme concentrations were all normal. Myeloma screening negative. Serum-corrected fell...
The effect of increased fruit and vegetable consumption on systolic diastolic blood pressure in six randomized controlled intervention trials: a pooled analysis - Volume 76 Issue OCE3
“Alcohol detox” is a common presentation to acute medical services and usually managed via standardised guidelines protocols. We present case of chlordiazepoxide toxicity, requiring repeated bolus doses subsequently 24 hours an intravenous infusion flumazenil in response guideline directed management alcohol withdrawal state. The use prolonged infusions treat benzodiazepine toxicity infrequently described. Chlordiazepoxide metabolised the hepatic microsomal pathway impairment can lead...