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Article ; Online: Gepotidacin, a new first-in-class antibiotic for treating uncomplicated urinary tract infection.

Ali, Ased S M / Anderson, Catriona S

2024 Volume 403, Issue 10428, Page(s) 702–703

MeSH term(s)	Humans ; Anti-Bacterial Agents/therapeutic use ; Urinary Tract Infections/drug therapy ; Acenaphthenes ; Heterocyclic Compounds, 3-Ring
Chemical Substances	Anti-Bacterial Agents ; gepotidacin (DVF0PR037D) ; Acenaphthenes ; Heterocyclic Compounds, 3-Ring
Language	English
Publishing date	2024-02-08
Publishing country	England
Document type	Journal Article
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(23)02697-1
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Article ; Online: Comment on: Nailfold capillaroscopy: a survey of current UK practice and 'next steps' to increase uptake among rheumatologists.

Anderson, Catriona / Leone, Valentina / Pain, Clare

Rheumatology (Oxford, England)

2023 Volume 62, Issue 10, Page(s) e303–e304

MeSH term(s)	Humans ; Microscopic Angioscopy ; Rheumatologists ; Surveys and Questionnaires ; Nails/diagnostic imaging ; United Kingdom ; Capillaries
Language	English
Publishing date	2023-08-01
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kead386
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Article ; Online: Co-option of a conserved host glutamine transporter facilitates aphid/

Duncan, Rebecca P / Anderson, Catriona M H / Thwaites, David T / Luetje, Charles W / Wilson, Alex C C

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 43, Page(s) e2308448120

Abstract: Organisms across the tree of life colonize novel environments by partnering with bacterial symbionts. These symbioses are characterized by intimate integration of host/endosymbiont biology at multiple levels, including metabolically. Metabolic ... ...

Abstract	Organisms across the tree of life colonize novel environments by partnering with bacterial symbionts. These symbioses are characterized by intimate integration of host/endosymbiont biology at multiple levels, including metabolically. Metabolic integration is particularly important for sap-feeding insects and their symbionts, which supplement nutritionally unbalanced host diets. Many studies reveal parallel evolution of host/endosymbiont metabolic complementarity in amino acid biosynthesis, raising questions about how amino acid metabolism is regulated, how regulatory mechanisms evolve, and the extent to which similar mechanisms evolve in different systems. In the aphid/
MeSH term(s)	Animals ; Glutamine/metabolism ; Aphids/microbiology ; Buchnera/genetics ; Buchnera/metabolism ; Amino Acids/metabolism ; Membrane Transport Proteins/metabolism ; Arginine/metabolism ; Symbiosis/physiology
Chemical Substances	Glutamine (0RH81L854J) ; Amino Acids ; Membrane Transport Proteins ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2023-10-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2308448120
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Article ; Online: Reshaping the Binding Pocket of the Neurotransmitter:Solute Symporter (NSS) Family Transporter SLC6A14 (ATB<sup>0,+</sup>) Selectively Reduces Access for Cationic Amino Acids and Derivatives.

Anderson, Catriona M H / Edwards, Noel / Watson, Andrew K / Althaus, Mike / Thwaites, David T

Biomolecules

2022 Volume 12, Issue 10

Abstract: SLC6A14 (ATB ... 0,+ ... ) is unique among SLC proteins in its ability to transport 18 of the 20 proteinogenic (dipolar and cationic) amino acids and naturally occurring and synthetic analogues (including anti-viral prodrugs and nitric oxide synthase ( ... ...

Abstract	SLC6A14 (ATB<sup>0,+</sup>) is unique among SLC proteins in its ability to transport 18 of the 20 proteinogenic (dipolar and cationic) amino acids and naturally occurring and synthetic analogues (including anti-viral prodrugs and nitric oxide synthase (NOS) inhibitors). SLC6A14 mediates amino acid uptake in multiple cell types where increased expression is associated with pathophysiological conditions including some cancers. Here, we investigated how a key position within the core LeuT-fold structure of SLC6A14 influences substrate specificity. Homology modelling and sequence analysis identified the transmembrane domain 3 residue V128 as equivalent to a position known to influence substrate specificity in distantly related SLC36 and SLC38 amino acid transporters. SLC6A14, with and without V128 mutations, was heterologously expressed and function determined by radiotracer solute uptake and electrophysiological measurement of transporter-associated current. Substituting the amino acid residue occupying the SLC6A14 128 position modified the binding pocket environment and selectively disrupted transport of cationic (but not dipolar) amino acids and related NOS inhibitors. By understanding the molecular basis of amino acid transporter substrate specificity we can improve knowledge of how this multi-functional transporter can be targeted and how the LeuT-fold facilitates such diversity in function among the SLC6 family and other SLC amino acid transporters.
MeSH term(s)	Amino Acids/metabolism ; Prodrugs ; Amino Acid Transport Systems/genetics ; Amino Acid Transport Systems/metabolism ; Nitric Oxide Synthase/metabolism ; Neurotransmitter Agents
Chemical Substances	Amino Acids ; Prodrugs ; Amino Acid Transport Systems ; Nitric Oxide Synthase (EC 1.14.13.39) ; Neurotransmitter Agents
Language	English
Publishing date	2022-10-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12101404
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Article ; Online: The British English version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

Martin, Neil / Davidson, Joyce / Anderson, Catriona / Consolaro, Alessandro / Bovis, Francesca / Ruperto, Nicolino

Rheumatology international

2018 Volume 38, Issue Suppl 1, Page(s) 67–73

Abstract: The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the ...

Abstract	The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the British English language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 100 JIA patients (7.0% systemic, 38.0% oligoarticular, 27.0% RF negative polyarthritis, 28% other categories) and 100 healthy children, were enrolled at the Royal Hospital for Sick Children in Glasgow. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the British English version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.
MeSH term(s)	Adolescent ; Age of Onset ; Arthritis, Juvenile/diagnosis ; Arthritis, Juvenile/physiopathology ; Arthritis, Juvenile/psychology ; Arthritis, Juvenile/therapy ; Case-Control Studies ; Child ; Child, Preschool ; Cultural Characteristics ; Disability Evaluation ; Female ; Health Status ; Humans ; Male ; Parents/psychology ; Patient Reported Outcome Measures ; Patients/psychology ; Predictive Value of Tests ; Prognosis ; Psychometrics ; Quality of Life ; Reproducibility of Results ; Rheumatology/methods ; Translating ; United Kingdom
Language	English
Publishing date	2018-04-07
Publishing country	Germany
Document type	Journal Article ; Multicenter Study ; Validation Study
ZDB-ID	8286-7
ISSN	1437-160X ; 0172-8172
ISSN (online)	1437-160X
ISSN	0172-8172
DOI	10.1007/s00296-018-3985-5
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Article ; Online: Chronic non bacterial osteitis- a multicentre study.

Bhat, Chandrika S / Anderson, Catriona / Harbinson, Aoibhinn / McCann, Liza J / Roderick, Marion / Finn, Adam / Davidson, Joyce E / Ramanan, Athimalaipet V

Pediatric rheumatology online journal

2018 Volume 16, Issue 1, Page(s) 74

Abstract: Objective: To understand the demographics, clinical features and treatment outcomes of Chronic Non-bacterial Osteitis (CNO) from three tertiary paediatric rheumatology services in the United Kingdom.: Methods: Children less than 18 years of age ... ...

Abstract	Objective: To understand the demographics, clinical features and treatment outcomes of Chronic Non-bacterial Osteitis (CNO) from three tertiary paediatric rheumatology services in the United Kingdom. Methods: Children less than 18 years of age diagnosed with CNO between 2001 to 2016 from one tertiary service and between 2001 to 2017 from two tertiary services were included. Clinical notes were reviewed and all pertinent data were collected on a pre-defined proforma. One hundred and thirty one patients were included in the study. The Bristol diagnostic criteria were applied retrospectively. Results: Retrospective analysis of the data showed that the disease was more common in girls than boys (2.5:1), median age at onset of symptoms was 9.5 years (IQR 8 to 11 years). Bone pain was the predominant symptom in 118/129 (91.4%) followed by swelling in 50/102 (49.01%). Raised inflammatory markers were present in 39.68% of the patients. Whole body Magnetic Resonance Imaging (MRI) was a useful diagnostic tool. Metaphyses of long bones were most often involved and the distal tibial metaphyses 65/131 (49.6%) was the most common site. Non-steroidal anti-inflammatory drugs were used as first line (81.67%) followed by bisphosphonates (61.79%). Treatment was escalated to a TNF blocker when response to bisphosphonates was suboptimal. The disease was in remission in 82.4% of the patients during the last follow up. Conclusion: Our multicentre study describes features and outcomes of CNO in a large number of patients in the United Kingdom. Significance and innovation: Raised inflammatory markers were present in 39.68% of our patients. Whole body MRI is useful for diagnosis and also determining response to treatment. A greater number of lesions were detected on radiological imaging compared to clinical assessment. Metaphyses of long bones were most often involved and the distal tibial metaphyses (49.6%) were the most common site. Non-steroidal anti-inflammatory drugs were used as first line (81.67%) followed by bisphosphonates (61.79%). There was no difference in number of medications used for management in unifocal versus multifocal disease. TNF blockers were used with good effect in our cohort.
MeSH term(s)	Adolescent ; Bone and Bones/pathology ; Child ; Child, Preschool ; Chronic Disease ; Female ; Humans ; Male ; Osteitis/diagnosis ; Osteitis/drug therapy ; Osteomyelitis/diagnosis ; Osteomyelitis/drug therapy ; Retrospective Studies ; United Kingdom
Language	English
Publishing date	2018-11-22
Publishing country	England
Document type	Journal Article ; Multicenter Study
ZDB-ID	2279468-2
ISSN	1546-0096 ; 1546-0096
ISSN (online)	1546-0096
ISSN	1546-0096
DOI	10.1186/s12969-018-0290-5
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Article ; Online: The SLC36 family of proton-coupled amino acid transporters and their potential role in drug transport.

Thwaites, David T / Anderson, Catriona M H

British journal of pharmacology

2011 Volume 164, Issue 7, Page(s) 1802–1816

Abstract: Members of the solute carrier (SLC) 36 family are involved in transmembrane movement of amino acids and derivatives. SLC36 consists of four members. SLC36A1 and SLC36A2 both function as H(+) -coupled amino acid symporters. SLC36A1 is expressed at the ... ...

Abstract	Members of the solute carrier (SLC) 36 family are involved in transmembrane movement of amino acids and derivatives. SLC36 consists of four members. SLC36A1 and SLC36A2 both function as H(+) -coupled amino acid symporters. SLC36A1 is expressed at the luminal surface of the small intestine but is also commonly found in lysosomes in many cell types (including neurones), suggesting that it is a multipurpose carrier with distinct roles in different cells including absorption in the small intestine and as an efflux pathway following intralysosomal protein breakdown. SLC36A1 has a relatively low affinity (K(m) 1-10 mM) for its substrates, which include zwitterionic amino and imino acids, heterocyclic amino acids and amino acid-based drugs and derivatives used experimentally and/or clinically to treat epilepsy, schizophrenia, bacterial infections, hyperglycaemia and cancer. SLC36A2 is expressed at the apical surface of the human renal proximal tubule where it functions in the reabsorption of glycine, proline and hydroxyproline. SLC36A2 also transports amino acid derivatives but has a narrower substrate selectivity and higher affinity (K(m) 0.1-0.7 mM) than SLC36A1. Mutations in SLC36A2 lead to hyperglycinuria and iminoglycinuria. SLC36A3 is expressed only in testes and is an orphan transporter with no known function. SLC36A4 is widely distributed at the mRNA level and is a high-affinity (K(m) 2-3 µM) transporter for proline and tryptophan. We have much to learn about this family of transporters, but from current knowledge, it seems likely that their function will influence the pharmacokinetic profiles of amino acid-based drugs by mediating transport in both the small intestine and kidney.
MeSH term(s)	Amino Acid Transport Systems/genetics ; Amino Acid Transport Systems/metabolism ; Amino Acids/metabolism ; Animals ; Biological Transport ; Humans ; Intestine, Small/metabolism ; Kidney/metabolism ; Pharmaceutical Preparations/metabolism ; Tissue Distribution
Chemical Substances	Amino Acid Transport Systems ; Amino Acids ; Pharmaceutical Preparations
Language	English
Publishing date	2011-06-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/j.1476-5381.2011.01438.x
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Article ; Online: A randomised controlled trial of time-limited individual placement and support: IPS-LITE trial.

Burns, Tom / Yeeles, Ksenija / Langford, Oliver / Montes, Maria Vazquez / Burgess, Jennifer / Anderson, Catriona

The British journal of psychiatry : the journal of mental science

2015 Volume 207, Issue 4, Page(s) 351–356

Abstract: Background: Individual placement and support (IPS) has been repeatedly demonstrated to be the most effective form of mental health vocational rehabilitation. Its no-discharge policy plus fixed caseloads, however, makes it expensive to provide.: Aims: ...

Abstract	Background: Individual placement and support (IPS) has been repeatedly demonstrated to be the most effective form of mental health vocational rehabilitation. Its no-discharge policy plus fixed caseloads, however, makes it expensive to provide. Aims: To test whether introducing a time limit for IPS would significantly alter its clinical effectiveness and consequently its potential cost-effectiveness. Method: Referrals to an IPS service were randomly allocated to either standard IPS or to time-limited IPS (IPS-LITE). IPS-LITE participants were referred back to their mental health teams if still unemployed at 9 months or after 4 months employment support. The primary outcome at 18 months was working for 1 day. Secondary outcomes comprised other vocational measures plus clinical and social functioning. The differential rates of discharge were used to calculate a notional increased capacity and to model potential rates and costs of employment. Results: A total of 123 patients were randomised and data were collected on 120 patients at 18 months. The two groups (IPS-LITE = 62 and IPS = 61) were well matched at baseline. Rates of employment were equal at 18 months (IPS-LITE = 24 (41%) and IPS = 27 (46%)) at which time 57 (97%) had been discharged from the IPS-LITE service and 16 (28%) from IPS. Only 11 patients (4 IPS-LITE and 7 IPS) obtained their first employment after 9 months. There were no significant differences in any other outcomes. IPS-LITE discharges generated a potential capacity increase of 46.5% compared to 12.7% in IPS which would translate into 35.8 returns to work in IPS-LITE compared to 30.6 in IPS over an 18-month period if the rates remained constant. Conclusions: IPS-LITE is equally effective to IPS and only minimal extra employment is gained by persisting beyond 9 months. If released capacity is utilised with similar outcomes, IPS-LITE results in an increase by 17% in numbers gaining employment within 18 months compared to IPS and will increase with prolonged follow-up. IPS-LITE may be more cost-effective and should be actively considered as an alternative within public services.
MeSH term(s)	Adult ; Cost-Benefit Analysis ; Employment/statistics & numerical data ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Mental Disorders/rehabilitation ; Middle Aged ; Proportional Hazards Models ; Psychiatric Status Rating Scales ; Rehabilitation, Vocational ; Time Factors
Language	English
Publishing date	2015-10
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	218103-4
ISSN	1472-1465 ; 0007-1250
ISSN (online)	1472-1465
ISSN	0007-1250
DOI	10.1192/bjp.bp.114.152082
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Article ; Online: Hijacking solute carriers for proton-coupled drug transport.

Anderson, Catriona M H / Thwaites, David T

Physiology (Bethesda, Md.)

2010 Volume 25, Issue 6, Page(s) 364–377

Abstract: The physiological role of mammalian solute carrier (SLC) proteins is to mediate transmembrane movement of electrolytes, nutrients, micronutrients, vitamins, and endogenous metabolites from one cellular compartment to another. Many transporters in the ... ...

Abstract	The physiological role of mammalian solute carrier (SLC) proteins is to mediate transmembrane movement of electrolytes, nutrients, micronutrients, vitamins, and endogenous metabolites from one cellular compartment to another. Many transporters in the small intestine, kidney, and solid tumors are H(+)-coupled, driven by local H(+)-electrochemical gradients, and transport numerous drugs. These transporters include PepT1 and PepT2 (SLC15A1/2), PCFT (SLC46A1), PAT1 (SLC36A1), OAT10 (SLC22A13), OATP2B1 (SLCO2B1), MCT1 (SLC16A1), and MATE1 and MATE2-K (SLC47A1/2).
MeSH term(s)	Animals ; Antiporters/metabolism ; Biological Transport ; Humans ; Hydrogen-Ion Concentration ; Intestine, Small/metabolism ; Kidney Tubules, Proximal/metabolism ; Neoplasms/metabolism ; Pharmaceutical Preparations/metabolism ; Protons ; Symporters/metabolism
Chemical Substances	Antiporters ; Pharmaceutical Preparations ; Protons ; Symporters
Language	English
Publishing date	2010-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2158667-6
ISSN	1548-9221 ; 1548-9213
ISSN (online)	1548-9221
ISSN	1548-9213
DOI	10.1152/physiol.00027.2010
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Article ; Online: Resculpting the binding pocket of APC superfamily LeuT-fold amino acid transporters.

Edwards, Noel / Anderson, Catriona M H / Conlon, Nichola J / Watson, Andrew K / Hall, Rebecca J / Cheek, Timothy R / Embley, T Martin / Thwaites, David T

Cellular and molecular life sciences : CMLS

2017 Volume 75, Issue 5, Page(s) 921–938

Abstract: Amino acid transporters are essential components of prokaryote and eukaryote cells, possess distinct physiological functions, and differ markedly in substrate specificity. Amino acid transporters can be both drug targets and drug transporters ( ... ...

Abstract	Amino acid transporters are essential components of prokaryote and eukaryote cells, possess distinct physiological functions, and differ markedly in substrate specificity. Amino acid transporters can be both drug targets and drug transporters (bioavailability, targeting) with many monogenic disorders resulting from dysfunctional membrane transport. The largest collection of amino acid transporters (including the mammalian SLC6, SLC7, SLC32, SLC36, and SLC38 families), across all kingdoms of life, is within the Amino acid-Polyamine-organoCation (APC) superfamily. The LeuT-fold is a paradigm structure for APC superfamily amino acid transporters and carriers of sugars, neurotransmitters, electrolytes, osmolytes, vitamins, micronutrients, signalling molecules, and organic and fatty acids. Each transporter is specific for a unique sub-set of solutes, specificity being determined by how well a substrate fits into each binding pocket. However, the molecular basis of substrate selectivity remains, by and large, elusive. Using an integrated computational and experimental approach, we demonstrate that a single position within the LeuT-fold can play a crucial role in determining substrate specificity in mammalian and arthropod amino acid transporters within the APC superfamily. Systematic mutation of the amino acid residue occupying the equivalent position to LeuT V104 titrates binding pocket space resulting in dramatic changes in substrate selectivity in exemplar APC amino acid transporters including PAT2 (SLC36A2) and SNAT5 (SLC38A5). Our work demonstrates how a single residue/site within an archetypal structural motif can alter substrate affinity and selectivity within this important superfamily of diverse membrane transporters.
MeSH term(s)	Amino Acid Transport Systems/chemistry ; Amino Acid Transport Systems/genetics ; Amino Acid Transport Systems/metabolism ; Amino Acids/metabolism ; Animals ; Biological Transport ; Catalytic Domain/genetics ; Humans ; Models, Molecular ; Multigene Family ; Mutagenesis, Site-Directed ; Phylogeny ; Protein Interaction Domains and Motifs/genetics ; Substrate Specificity/genetics
Chemical Substances	Amino Acid Transport Systems ; Amino Acids
Language	English
Publishing date	2017-10-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-017-2677-8
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