UCL University College London Eprints
UCL Eprints collects the work of UCL researchers and makes it freely available over the web, helping the worldwide scholarly community to discover UCL research. Institutional repositories like UCL Eprints complement the traditional academic publishing and scholarly communications processes. They raise the visibility of research and help to maximise its impact. UCL researchers are encouraged to deposit a copy of each journal article, conference paper, working paper, and any other research output, in the UCL Eprints at the earliest opportunity, ensuring that their research reaches as wide an audience as possible.
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Pathogenic Mechanisms of Neurodegeneration in Parkinson Disease. - Mullin, S; Schapira, AH
The last 2 decades represent a period of unparalleled advancement in the understanding of the pathogenesis of Parkinson disease (PD). The discovery of several forms of familial parkinsonism with mendelian inheritance has elucidated insights into the mechanisms underlying the degeneration of dopaminergic neurons of the substantia nigra that histologically characterize PD. α-Synuclein, the principal component of Lewy bodies, remains the presumed pathogen at the heart of the current model; however, concurrently, a diverse range of other mechanisms have been implicated. The creation of a coherent disease model will be crucial to the development of effective disease modifying therapies for sporadic...
A revised mechanism for the activation of complement C3 to C3b: a molecular explanation of a disease-associated polymorphism. - Rodriguez, E; Nan, R; Li, K; Gor, J; Perkins, SJ
The solution structure of complement C3b is crucial for the understanding of complement activation and regulation. C3b is generated by the removal of C3a from C3. Hydrolysis of the C3 thioester produces C3u, an analogue of C3b. C3b cleavage results in C3c and C3d (TED). To resolve functional questions in relation to C3b and C3u, analytical ultracentrifugation and X-ray and neutron scattering studies were used with C3, C3b, C3u, C3c and C3d, using the wild-type allotype with R102. In 50 mM NaCl buffer, atomistic scattering modelling showed that both C3b and C3u adopted a compact structure, similar to the C3b...
A positive diagnosis of functional (psychogenic) tics. - Demartini, B; Ricciardi, L; Parees, I; Ganos, C; Bhatia, KP; Edwards, MJ
Functional tics, also called psychogenic tics or pseudo-tics, are difficult to diagnose because of the lack of diagnostic criteria and their clinical similarities to organic tics. The aim of the present study was to report a case series of patients with documented functional tics and to describe their clinical characteristics, risk factors and psychiatric comorbidity. Also clinical tips are suggested which might help the differential diagnosis in clinical practice.
Oculoleptomeningeal Amyloidosis associated with transthyretin Leu12Pro in an African patient. - McColgan, P; Viegas, S; Gandhi, S; Bull, K; Tudor, R; Sheikh, F; Pinney, J; Fontana, M; Rowczenio, D; Gillmore, JD; Gilbertson, JA; Whelan, CJ; Shah, S; Jaunmuktane, Z; Holton, JL; Schott, JM; Werring, DJ; Hawkins, PN; Reilly, MM
Oculoleptomeningeal amyloidosis is a rare manifestation of hereditary transthyretin (TTR) amyloidosis. Here, we present the first case of leptomeningeal amyloidosis associated with the TTR variant Leu12Pro mutation in an African patient. A 43-year-old right-handed Nigerian man was referred to our centre with rapidly progressive neurological decline. He presented initially with weight loss, confusion, fatigue, and urinary and erectile dysfunction. He then suffered recurrent episodes of slurred speech with right-sided weakness. He went on to develop hearing difficulties and painless paraesthesia. Neurological examination revealed horizontal gaze-evoked nystagmus, brisk jaw jerk, increased tone, brisk reflexes throughout and bilateral heel-shin ataxia. Magnetic resonance...
Ophthalmic statistics note 5: diagnostic tests-sensitivity and specificity. - Saunders, LJ; Zhu, H; Bunce, C; Doré, CJ; Freemantle, N; Crabb, DP; This fifth note from the Ophthalmic Statistics Group illustrates the utility of measurements of sensitivity and specificity in assessing the usefulness of a test for predicting the presence of pathology,; on behalf of the Ophthalmic Statistics Group,; This fifth note from the Ophthalmic Statistics Group illustrates the utility of measurements of sensitivity and specificity in assessing the usefulness of a test for predicting the presence of pathology,
This is the fifth statistics note produced by the Ophthalmic Statistics Group (OSG) which is designed to be a simple guide to ophthalmic researchers on a statistical issue with an applied ophthalmic example. The OSG is a collaborative group of statisticians who have come together with a desire to raise the statistical standards of ophthalmic researcher by increasing statistical awareness of common issues.
Auditory Pattern Detection - Barascud, N
The work presented in this doctoral thesis uses behavioural methods and neuroimaging to investigate how human listeners detect patterns and statistical regularities in complex sound sequences. Temporal pattern analysis is essential to sensory processing, especially listening, since most auditory signals only have meaning as sequences over time. Previous evidence suggests that the brain is sensitive to the statistics of sensory stimulation. However, the process through which this sensitivity arises is largely unknown. This dissertation is organised as follows: Chapter 1 reviews fundamental principles of auditory scene analysis and existing models of regularity processing to constrain the scientific questions being addressed....
Effects of early childhood trauma on hypothalamic-pituitary-adrenal (HPA) axis function in patients with Chronic Fatigue Syndrome. - Kempke, S; Luyten, P; De Coninck, S; Van Houdenhove, B; Mayes, LC; Claes, S
There is a paucity of studies that have investigated the assumption that early childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction in Chronic Fatigue Syndrome (CFS). The current study is the first to simultaneously investigate relationships among early childhood trauma, cortisol activity, and cortisol stress reactivity to psychosocial stress in a sample of well-screened CFS patients. We also examined whether self-critical perfectionism (SCP) plays a mediating role in the potential relationship between early trauma and neurobiological stress responses.
Sixty-five common genetic variants and prediction of type 2 diabetes. - Talmud, PJ; Cooper, JA; Morris, RW; Dudbridge, F; Shah, T; Engmann, J; Dale, C; White, J; McLachlan, S; Zabaneh, D; Wong, A; Ong, KK; Gaunt, T; Holmes, MV; Lawlor, DA; Richards, M; Hardy, R; Kuh, D; Wareham, N; Langenberg, C; Ben-Shlomo, Y; Wannamethee, SG; Strachan, MW; Kumari, M; Whittaker, JC; Drenos, F; Kivimaki, M; Hingorani, AD; Price, JF; Humphries, SE; on behalf of the UCLEB Consortium,
We developed a 65-T2D variant weighted gene score to examine the impact on T2D risk assessment in a UK-based consortium of prospective studies, initially free from type 2 diabetes (T2D) (N=13,294; 37.3% women; mean age 58.5 (38-99) years). We compared the performance of the gene score with the phenotypically-derived Framingham Offspring Study T2D risk model, and then the two in combination. Over the median 10 years follow-up, 804 participants developed T2D. The odds ratio for T2D (top vs. bottom quintiles of gene score) was 2.70 (95%CI 2.12-3.43). With a 10% false positive rate, the genetic score alone detected 19.9% incident...
Stratification by Smoking Status Reveals an Association of CHRNA5-A3-B4 Genotype with Body Mass Index in Never Smokers. - Taylor, AE; Morris, RW; Fluharty, ME; Bjorngaard, JH; Asvold, BO; Gabrielsen, ME; Campbell, A; Marioni, R; Kumari, M; Hällfors, J; Männistö, S; Marques-Vidal, P; Kaakinen, M; Cavadino, A; Postmus, I; Husemoen, LL; Skaaby, T; Ahluwalia, TS; Treur, JL; Willemsen, G; Dale, C; Wannamethee, SG; Lahti, J; Palotie, A; Räikkönen, K; Kisialiou, A; McConnachie, A; Padmanabhan, S; Wong, A; Dalgård, C; Paternoster, L; Ben-Shlomo, Y; Tyrrell, J; Horwood, J; Fergusson, DM; Kennedy, MA; Frayling, T; Nohr, EA; Christiansen, L; Ohm Kyvik, K; Kuh, D; Watt, G; Eriksson, J; Whincup, PH; Vink, JM; Boomsma, DI; Davey Smith, G; Lawlor, D; Linneberg, A; Ford, I; Jukema, JW; Power, C; Hyppönen, E; Jarvelin, MR; Preisig, M; Borodulin, K; Kaprio, J; Kivimaki, M; Smith, BH; Hayward, C; Romundstad, PR; Sørensen, TI; Munafò, MR; Sattar, N
We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00×10-10), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38×10-5). An interaction test confirmed that...
Preventing Unintended Pregnancy and HIV Transmission: Effects of the HIV Treatment Cascade on Contraceptive Use and Choice in Rural KwaZulu-Natal. - Raifman, J; Chetty, T; Tanser, F; Mutevedzi, T; Matthews, P; Herbst, K; Pillay, D; Bärnighausen, T
For women living with HIV, contraception using condoms is recommended because it prevents not only unintended pregnancy but also acquisition of other sexually transmitted infections and onward transmission of HIV. Dual-method dual-protection contraception (condoms with other contraceptive methods) is preferable over single-method dual-protection contraception (condoms alone) because of its higher contraceptive effectiveness. We estimate the effect of progression through the HIV treatment cascade on contraceptive use and choice among HIV-infected women in rural South Africa.
SOD1 Function and Its Implications for Amyotrophic Lateral Sclerosis Pathology: New and Renascent Themes. - Bunton-Stasyshyn, RK; Saccon, RA; Fratta, P; Fisher, EM
The canonical role of superoxide dismutase 1 (SOD1) is as an antioxidant enzyme protecting the cell from reactive oxygen species toxicity. SOD1 was also the first gene in which mutations were found to be causative for the neurodegenerative disease amyotrophic lateral sclerosis (ALS), more than 20 years ago. ALS is a relentless and incurable mid-life onset disease, which starts with a progressive paralysis and usually leads to death within 3 to 5 years of diagnosis; in the majority of cases, the intellect appears to remain intact while the motor system degenerates. It rapidly became clear that when mutated SOD1 takes...
Task-Dependent and Distinct Roles of the Temporoparietal Junction and Inferior Frontal Cortex in the Control of Imitation. - Hogeveen, J; Obhi, SS; Banissy, MJ; Santiesteban, I; Press, C; Catmur, C; Bird, G
The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: 1) a naturalistic social interaction during which increased imitation is known to improve rapport, 2)...
Probing short-term face memory in developmental prosopagnosia. - Shah, P; Gaule, A; Gaigg, SB; Bird, G; Cook, R
It has recently been proposed that the face recognition deficits seen in neurodevelopmental disorders may reflect impaired short-term face memory (STFM). For example, introducing a brief delay between the presentation of target and test faces seems to disproportionately impair matching or recognition performance in individuals with Autism Spectrum Disorders. The present study sought to determine whether deficits of STFM contribute to impaired face recognition seen in Developmental Prosopagnosia. To determine whether developmental prosopagnosics exhibit impaired STFM, the present study used a six-alternative-forced-choice match-to-sample procedure. Memory demand was manipulated by employing a short or long delay between the presentation of the...
The self to other model of empathy: Providing a new framework for understanding empathy impairments in psychopathy, autism, and alexithymia. - Bird, G; Viding, E
Despite increasing empirical and theoretical work on empathy, particularly on the content of empathic representations, there is a relative lack of consensus regarding the information processing necessary for empathy to occur. Here we attempt to delineate a mechanistic cognitive model of empathy in order to provide a framework within which neuroimaging work on empathy can be located, and which may be used in order to understand various disorders characterised by atypical levels of empathy. To this end data from individuals with psychopathy, autism, and alexithymia inform the model, and the model is used to provide a unifying framework for any...
Structure of the ribosomal interacting GTPase YjeQ from the enterobacterial species Salmonella typhimurium - Nichols, CE; Johnson, C; Lamb, HK; Lockyer, M; Charles, IG; Hawkins, AR; Stammers, DK
The YjeQ class of P-loop GTPases assist in ribosome biogenesis and also bind to the 30S subunit of mature ribosomes. YjeQ ribosomal binding is GTP-dependent and thought to specifically direct protein synthesis, although the nature of the upstream signal causing this event in vivo is as yet unknown. The attenuating effect of YjeQ mutants on bacterial growth in Escherichia coli makes it a potential target for novel antimicrobial agents. In order to further explore the structure and function of YjeQ, the isolation, crystallization and structure determination of YjeQ from the enterobacterial species Salmonella typhimurium (StYjeQ) is reported. Whilst the overall...