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1.
Database (Oxford) ; 20202020 01 01.
Article in English | MEDLINE | ID: mdl-32507889

ABSTRACT

Modern biology produces data at a staggering rate. Yet, much of these biological data is still isolated in the text, figures, tables and supplementary materials of articles. As a result, biological information created at great expense is significantly underutilised. The protein motif biology field does not have sufficient resources to curate the corpus of motif-related literature and, to date, only a fraction of the available articles have been curated. In this study, we develop a set of tools and a web resource, 'articles.ELM', to rapidly identify the motif literature articles pertinent to a researcher's interest. At the core of the resource is a manually curated set of about 8000 motif-related articles. These articles are automatically annotated with a range of relevant biological data allowing in-depth search functionality. Machine-learning article classification is used to group articles based on their similarity to manually curated motif classes in the Eukaryotic Linear Motif resource. Articles can also be manually classified within the resource. The 'articles.ELM' resource permits the rapid and accurate discovery of relevant motif articles thereby improving the visibility of motif literature and simplifying the recovery of valuable biological insights sequestered within scientific articles. Consequently, this web resource removes a critical bottleneck in scientific productivity for the motif biology field. Database URL: http://slim.icr.ac.uk/articles/.


Subject(s)
Amino Acid Motifs , Data Mining/methods , Databases, Protein , Molecular Sequence Annotation , Molecular Sequence Annotation/classification , Molecular Sequence Annotation/methods , Publications/classification
2.
Br Poult Sci ; 59(1): 13-20, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29099622

ABSTRACT

1. The aim of this study was to evaluate the electroencephalographic (EEG) and behavioural responses of turkeys stunned with three different concussive non-penetrative captive-bolt guns prior to slaughter. 2. A total of 31 slaughter weight ex-breeding female turkeys (29 weeks of age; mean body weight 13.32 ± SD 0.65 kg) were stunned with the Cash Poultry Killer (CPK) (n = 10), Turkey Euthanasia Device (TED) (n = 10) and Zephyr EXL (n = 11). 3. Mean peak kinetic energy was highest for the CPK compared to the TED and Zephyr EXL (75.9 ± 4.5, 28.4 ± 0.4 and 24.4 ± 0.7 J, respectively). 4. A total of 29 (94%) of the turkeys were rendered unconscious following captive bolt stunning, with total power of the EEG (Ptot) significantly reduced from baseline values (reductions of 67% CPK, 84% TED and 76% Zephyr EXL, p < 0.01) and waveforms becoming isoelectric after periods of transitional EEG. However, two birds shot with the CPK and Zephyr EXL had periods of behavioural/reflexes (rhythmic respiration, nictitating membrane reflex, neck tension) and EEG activity (43-47 and 36-60 + s after the shot, respectively) indicating incomplete concussion and return of consciousness. In one bird, the shot was incorrectly positioned (Zephyr EXL), while the other appeared to be related to a defective cartridge (CPK). 5. In conclusion, all three captive bolt gun models were effective in producing unconsciousness in turkeys, provided they were positioned correctly and power loads performed according to their specifications.


Subject(s)
Abattoirs , Conducted Energy Weapon Injuries , Electroencephalography/veterinary , Turkeys , Unconsciousness/veterinary , Animal Husbandry , Animal Welfare , Animals , Body Weight , Electroencephalography/methods , Euthanasia , Female , Reflex
3.
Rev Sci Tech ; 36(1): 125-135, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28926021

ABSTRACT

This paper examines four examples of animal welfare issues, demonstrating the interactions between welfare and economic principles. Welfare issues associated with purebred companion animals are examined in terms of predicted inherited diseases, highlighting the power of supply and demand in perpetuating traits in pets that compromise their well-being. The livestock industry is presented from the point of view of pig production and the impact that a major disease (pleurisy) has on production and the animals' welfare. The authors investigate the conflicting and complementary demands of animal welfare and economic gains during the transport and slaughter of livestock and poultry. Finally, wildlife species are considered in terms of their prevalence as pests, and the different types of economic analysis that have been conducted to understand the losses caused by these organisms. Also included in this example are decisions made about cost effectiveness and opportunity costs, and regulatory and financial barriers to the development of humane control agents. In conclusion, animal welfare is illustrated as a central factor in the benefits that humans enjoy from the role played by animals in society. There are, however, tradeoffs between optimal animal welfare and meeting the needs of modern human society.


Les auteurs analysent les effets réciproques du bien-être animal et des principes de l'économie à travers quatre exemples. La problématique du bienêtre des animaux de compagnie de race est examinée en lien avec les maladies à prédisposition génétique, ce qui permet de souligner l'influence de l'offre et de la demande dans la perpétuation de traits génétiques particuliers à ces animaux, au péril de leur bien-être. Le secteur de l'élevage est examiné à travers l'exemple de la production porcine en étudiant l'impact d'une maladie majeure (pleurésie) sur la production et le bien-être des porcs. Les auteurs abordent ensuite les exigences antinomiques ou complémentaires du bien-être animal et de la rentabilité économique dans le domaine du transport et de l'abattage des animaux d'élevage et des volailles. Enfin, les espèces sauvages sont examinées du point de vue de leur rôle en tant que nuisibles, en exposant les différentes manières d'expliquer au moyen d'analyses économiques les pertes causées par les nuisibles. Cet exemple aborde également les décisions en matière de rentabilité et les coûts d'opportunité, ainsi que les obstacles réglementaires et financiers à l'utilisation d'agents pouvant servir à contrôler les maladies par des méthodes respectueuses du bien-être animal. En conclusion, le bien-être animal apparaît comme un facteur central des bénéfices que les humains retirent des animaux et de leur rôle dans la société. Il y a néanmoins des compromis à trouver entre l'optimisation du bien-être animal et les exigences d'une société moderne.


Apoyándose en cuatro ejemplos de bienestar animal, los autores ponen de manifiesto cuán imbricados están entre sí los temas de bienestar y los principios económicos. Ante todo examinan los problemas de bienestar que sufren los animales de compañía de pura raza por lo que respecta a sus previsibles enfermedades hereditarias, subrayando el poder de la ley de la oferta y la demanda para perpetuar en ellos una serie de rasgos que comprometen su bienestar. A continuación se detienen en la ganadería industrial, y más concretamente en la producción porcina y la influencia que ejerce una enfermedad importante (la pleuresía) en el bienestar de los animales y en la propia producción. Después exponen los imperativos antagónicos y complementarios que se plantean en clave de bienestar animal y de beneficio económico durante las operaciones de transporte y sacrificio de ganado y aves de corral. Por último, considerando las especies de animales salvajes desde el punto de vista de su prevalencia como plagas, exponen los distintos tipos de análisis económico que se han realizado para aprehender las pérdidas resultantes de las plagas. Valiéndose de este ejemplo examinan también las decisiones adoptadas en materia de rentabilidad y de costos de oportunidad, así como las barreras reglamentarias y económicas que dificultan un funcionamiento más compasivo de los agentes de control. El bienestar animal, en conclusión, aparece como un factor central de los beneficios que extrae el ser humano de la función que cumplen los animales en la sociedad. Sin embargo, es preciso hallar un compromiso entre los niveles óptimos de bienestar animal y la satisfacción de las necesidades de la sociedad humana moderna.


Subject(s)
Animal Diseases/economics , Animal Welfare/economics , Genetic Diseases, Inborn/veterinary , Livestock , Pets , Abattoirs/economics , Animals , Animals, Wild , Genetic Diseases, Inborn/economics , Pest Control/methods , Pleurisy/economics , Pleurisy/veterinary , Swine , Swine Diseases/economics , Transportation/economics
4.
Br Poult Sci ; 57(3): 295-305, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27023411

ABSTRACT

The study assesses the effectiveness of reversible head-only and back-of-the-head electrical stunning of chickens using 130-950 mA per bird at 50 Hz AC. Three trials were conducted to compare both stunning systems: (a) behavioural assessment of return of consciousness, (b) insensibility to thermal pain, and (c) assessment of return of brain activity with visually evoked potentials (VEPs). Assessment of behaviour suggested that the period of unconsciousness following head-only electrical stunning was shorter in hens compared to broilers. Stunning across the back-of-the-head delayed the time to return of brainstem function compared to stunning with standard head-only electrodes. Additionally, back-of-the-head stunning produced a more prolonged period of electroanalgesia compared to head-only. Based on examination of return of brain function with VEPs in hens, back-of-the-head stunning produced a shorter-lasting stun than standard head-only. However, even for standard head-only, the stun was notably shorter than previously reported. In some birds, brain function had returned within 9 s after the end of stunning. The results suggest that some birds may recover consciousness prior to or during the neck cut. Based on these findings, back-of-the-head stunning and standard head-only stunning of hens should not be recommended without further development.


Subject(s)
Animal Husbandry/methods , Chickens/physiology , Electroshock/veterinary , Abattoirs , Animals , Electroencephalography/veterinary , Female , Head/physiology , Motor Activity , Random Allocation , Restraint, Physical/veterinary , Unconsciousness/veterinary
6.
Bioinformatics ; 28(7): 976-82, 2012 Apr 01.
Article in English | MEDLINE | ID: mdl-22328783

ABSTRACT

MOTIVATION: Eukaryotic proteins are highly modular, containing multiple interaction interfaces that mediate binding to a network of regulators and effectors. Recent advances in high-throughput proteomics have rapidly expanded the number of known protein-protein interactions (PPIs); however, the molecular basis for the majority of these interactions remains to be elucidated. There has been a growing appreciation of the importance of a subset of these PPIs, namely those mediated by short linear motifs (SLiMs), particularly the canonical and ubiquitous SH2, SH3 and PDZ domain-binding motifs. However, these motif classes represent only a small fraction of known SLiMs and outside these examples little effort has been made, either bioinformatically or experimentally, to discover the full complement of motif instances. RESULTS: In this article, interaction data are analysed to identify and characterize an important subset of PPIs, those involving SLiMs binding to globular domains. To do this, we introduce iELM, a method to identify interactions mediated by SLiMs and add molecular details of the interaction interfaces to both interacting proteins. The method identifies SLiM-mediated interfaces from PPI data by searching for known SLiM-domain pairs. This approach was applied to the human interactome to identify a set of high-confidence putative SLiM-mediated PPIs. AVAILABILITY: iELM is freely available at http://elmint.embl.de CONTACT: toby.gibson@embl.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Computational Biology/methods , Databases, Protein , Protein Interaction Domains and Motifs , Proteins/chemistry , Humans , Markov Chains , Protein Binding , Proteins/metabolism , Software
7.
Vet Rec ; 168(19): 511, 2011 May 14.
Article in English | MEDLINE | ID: mdl-21546406

ABSTRACT

The aim of this study was to develop a technique for recording electrical activity of the equine cerebral cortex following application of a noxious electrical stimulus to the maxillary branch of the trigeminal nerve in order to investigate trigeminal nerve neurophysiology in control and headshaking horses. Triphasic somatosensory evoked potentials (SEPs) were recorded using subcutaneous needle electrodes in four control and four headshaking horses under general anaesthesia. Dural electroencephalography electrodes were used to record SEPs in one further control and one further headshaking horse. Headshaking horses appeared to have decreased middle latency and inter-peak intervals following stimulation of the trigeminal nerve compared with control horses, supporting abnormal trigeminal nerve physiology in equine headshaking.


Subject(s)
Evoked Potentials, Somatosensory/physiology , Head Movements/physiology , Head/innervation , Horse Diseases/diagnosis , Trigeminal Nerve/pathology , Anesthesia/veterinary , Animals , Case-Control Studies , Electroencephalography/veterinary , Horse Diseases/pathology , Horses
8.
N Z Vet J ; 57(2): 74-6, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19471324

ABSTRACT

Commercial slaughter of farm livestock usually employs an extensive incision that severs the soft tissues of the neck including the major blood vessels supplying and draining the brain. It is intended to cause a catastrophic decrease in cerebral blood flow with rapid onset of unconsciousness or insensibility. The tissues of the neck are innervated with nociceptive nerve fibres and their transection will cause a barrage of sensory impulses. Consciousness, and therefore the ability of the animal to feel pain and experience distress after the incision, may persist for 60 seconds or longer in cattle. These observations suggest that livestock may experience pain and distress during the period before they become unconscious (insensible). Psychological shock and fear may also be associated with the extensive tissue damage and blood loss. Pre-incision stunning has been adopted as a precautionary measure to prevent suffering. However, the question remains: How intense and noxious are these experiences? Recent methodological developments related to quantitative analysis of the electroencephalogram (EEG) allow the experience of pain to be assessed more directly than has hitherto been possible. This methodology has now been applied to the question of the slaughter of calves by ventral-neck incision. The new information demonstrates clearly for the first time that the act of slaughter by ventral-neck incision is associated with noxious stimulation that would be expected to be perceived as painful in the period between the incision and loss of consciousness. These data provide further support for the value of stunning in preventing pain and distress in animals subjected to this procedure.


Subject(s)
Abattoirs , Cattle/physiology , Neck/surgery , Pain Measurement/veterinary , Pain/veterinary , Abattoirs/standards , Animals , Brain Concussion/veterinary , Carbon Dioxide/administration & dosage , Cattle/surgery , Electroencephalography/veterinary , Electroshock/methods , Electroshock/veterinary , Pain/prevention & control , Pain Measurement/methods , Unconsciousness/veterinary
9.
N Z Vet J ; 57(2): 84-9, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19471326

ABSTRACT

AIM: To identify whether cutting neck tissues or cutting major blood vessels initiates the mechanisms responsible for electroencephalographic (EEG) responses to slaughter by ventral-neck incision without prior stunning in halothane-anaesthetised calves. METHODS: Calves were assigned to two groups, viz transection of neck tissues with intact blood circulation through the brain (n=10), or transection of the major blood vessels of the neck but not most other neck tissues (n=7). They were minimally anaesthetised with halothane, using an established anaesthesia protocol. The animals in the neck-tissue transection group had their carotid arteries and jugular veins exposed and cannulated proximal and distal to the proposed site of subsequent ventral-neck incision; this diverted blood flow through these vessels so that cerebral perfusion and drainage were preserved. In animals in the blood-vessel transection group, the carotid arteries and jugular veins were exposed bilaterally by surgical dissection. They were then transected without further damage to the remaining structures of the neck. Changes in the median frequency (F50), 95% spectral edge frequency (F95), total power of the EEG (Ptot), and arterial blood pressure were compared within each group before and after neck-tissue or blood-vessel transection, and between groups following treatments. RESULTS: Neck-tissue transection resulted in little overall change in the F50, an increase in the F95, and an initial increase in Ptot followed by a transient decrease and eventual return to pre-treatment values. There was between-animal variation in these EEG parameters. Transection of the major blood vessels of the neck resulted in a decrease in F50 in most animals; changes in F95 were highly variable, and there was a decrease in Ptot. CONCLUSIONS: The EEG responses seen following neck-tissue and blood-vessel transection were qualitatively distinct, and suggested that cutting neck tissues caused greater noxious sensory input than transection of only the major blood vessels of the neck. These observations support the conclusion that the EEG responses seen after ventral-neck incision in intact animals are primarily due to noxious stimulation as a result of incision of ventral-neck tissues and not mainly as a result of loss of blood flow through the brain.


Subject(s)
Carotid Arteries/physiology , Cattle/physiology , Electroencephalography/veterinary , Jugular Veins/physiology , Nociceptors/physiology , Abattoirs , Analysis of Variance , Anesthetics, Dissociative/administration & dosage , Anesthetics, Inhalation/administration & dosage , Animals , Brain/blood supply , Carotid Arteries/surgery , Cattle/surgery , Electroencephalography/drug effects , Halothane/administration & dosage , Jugular Veins/surgery , Ketamine/administration & dosage , Neck/surgery , Nociceptors/drug effects
10.
N Z Vet J ; 57(2): 77-83, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19471325

ABSTRACT

AIM: To investigate whether the electroencephalographic (EEG) responses to slaughter by ventral-neck incision without prior stunning may be perceived as painful in halothane-anaesthetised calves. METHODS: Fourteen Angus steers were minimally anaesthetised with halothane, using an established anaesthesia protocol. EEG indices were recorded bilaterally for 5 minutes prior to and 5 minutes following ventral-neck incision. A single incision was made in the ventral aspect of the neck, severing all tissues ventral to the vertebral column including the major blood vessels supplying and draining the head. Changes in the median frequency (F50), 95% spectral edge frequency (F95) and total power of the EEG (Ptot) were used to investigate the effects of ventral-neck incision. At the completion of the experiment, brains of calves were examined histologically. RESULTS: During the 30 seconds following ventral-neck incision, the F95 and Ptot showed significant changes (p<0.05) compared with pre-treatment values. The F50 increased significantly from recordings from the right side of the cranium. No gross or histological abnormalities were detected in the brains following slaughter. CONCLUSIONS: This study is the first investigation of the noxiousness of slaughter by ventral-neck incision, using EEG spectral analysis. It demonstrated that there is a period following slaughter where ventral-neck incision represents a noxious stimulus.


Subject(s)
Abattoirs , Cattle/physiology , Electroencephalography/veterinary , Neck/surgery , Pain Measurement/veterinary , Analysis of Variance , Anesthetics, Inhalation/administration & dosage , Animals , Brain/pathology , Cattle/surgery , Electrocardiography/veterinary , Female , Halothane/administration & dosage , Male , Pain Measurement/methods
11.
N Z Vet J ; 57(2): 90-5, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19471327

ABSTRACT

AIM: To investigate the electroencephalographic (EEG) and cardiovascular responses of halothane-anaesthetised calves to non-penetrative captive-bolt stunning. METHODS: Ten calves were minimally anaesthetised with halothane, using an established anaesthesia protocol. The EEG, blood pressure and electrocardiogram (ECG) were recorded before and after non-penetrative captive-bolt stunning. Visual inspection and alterations in the total power of the EEG (Ptot) were used to investigate the effects of stunning. RESULTS: Captive-bolt stunning significantly altered cerebrocortical function in all animals. In four animals, Ptot decreased immediately following stunning and remained low throughout the recording period. In another five animals, Ptot responded to stunning in a biphasic manner characterised by an immediate decrease followed by a transient increase and then a final decrease to values similar to those of the non-biphasic animals. CONCLUSIONS: Non-penetrative captive-bolt stunning significantly altered cerebrocortical function in halothane-anaesthetised calves. The changes in cerebrocortical function would be sufficient to produce insensibility within 0 to 14 seconds in conscious animals.


Subject(s)
Abattoirs/standards , Brain Concussion/veterinary , Cattle/physiology , Cerebrovascular Circulation/physiology , Electroencephalography/veterinary , Anesthetics, Inhalation/administration & dosage , Animals , Blood Pressure/physiology , Brain Concussion/etiology , Brain Concussion/physiopathology , Electrocardiography/veterinary , Electroencephalography/drug effects , Halothane/administration & dosage
12.
N Z Vet J ; 57(2): 96-101, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19471328

ABSTRACT

AIM: To investigate the ability of non-penetrative captive-bolt stunning delivered after ventral-neck incision to ameliorate responses to noxious stimulation associated with slaughter by ventral-neck incision in halothane-anaesthetised calves. METHODS: Seven calves were minimally anaesthetised with halothane, using an established anaesthesia protocol. Electroencephalographic (EEG) indices of cerebrocortical activity were measured in response to ventral-neck incision followed 5 seconds later by non-penetrative captive-bolt stunning. Changes in heart rate and arterial blood pressure were measured and instances of occlusion of the carotid arteries were also noted. RESULTS: After ventral-neck incision there were periods of an active EEG in some calves, which ceased after non-penetrative captive-bolt stunning in most of the animals. Two calves had periods of active EEG following stunning. Arterial blood pressure decreased significantly after neck incision in all calves, including three with occlusion of the carotid arteries. CONCLUSIONS: Non-penetrative captive-bolt stunning after ventral-neck incision resulted in the cessation of functional cortical activity in the majority of calves. This procedure prevented the development of cerebrocortical responses to ventral-neck incision, demonstrated elsewhere, which would be painful in conscious animals subjected to this procedure. In addition, instances of carotid arterial occlusion had no significant effect on the decrease in arterial blood pressure.


Subject(s)
Abattoirs/standards , Brain/physiology , Cattle/physiology , Electroencephalography/veterinary , Neck/surgery , Anesthetics, Inhalation/administration & dosage , Animals , Blood Pressure/physiology , Cattle/surgery , Electrocardiography/veterinary , Female , Halothane/administration & dosage , Heart Rate/physiology , Male , New Zealand
13.
Bioinformatics ; 23(21): 2947-8, 2007 Nov 01.
Article in English | MEDLINE | ID: mdl-17846036

ABSTRACT

SUMMARY: The Clustal W and Clustal X multiple sequence alignment programs have been completely rewritten in C++. This will facilitate the further development of the alignment algorithms in the future and has allowed proper porting of the programs to the latest versions of Linux, Macintosh and Windows operating systems. AVAILABILITY: The programs can be run on-line from the EBI web server: http://www.ebi.ac.uk/tools/clustalw2. The source code and executables for Windows, Linux and Macintosh computers are available from the EBI ftp site ftp://ftp.ebi.ac.uk/pub/software/clustalw2/


Subject(s)
Algorithms , Computer Graphics , Sequence Alignment/methods , Sequence Analysis, Protein/methods , Software , User-Computer Interface , Amino Acid Sequence , Cluster Analysis , Molecular Sequence Data , Programming Languages
14.
N Z Vet J ; 55(4): 152-7, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17676078

ABSTRACT

AIM: To validate use of the electroencephalogram (EEG) and a minimal anaesthesia model for assessment of noxious sensory input caused by scoop dehorning of calves. METHODS: Twenty Friesian heifers weighing 125-178 kg were maintained under light general anaesthesia using halothane and an established protocol (minimal anaesthesia model). They were then dehorned using a scoop dehorner either with (DH+LA) or without (DH) a lignocaine ring block, and changes in the EEG and electrocardiogram (ECG) recorded. Median frequency (F50), 95% spectral edge frequency (F95) and total power (Ptot) were derived from the EEG data. RESULTS: There were significant increases in the F50 (p<0.01) and F95 (p<0.01), and a decrease in Ptot (p<0.01) following dehorning in the DH group, but there were no changes in the DH+LA group. Transient bradycardia in the first 75 sec following dehorning was recorded in the DH group compared with both pre-treatment values in the same group and with the DH+LA group (p<0.001). Tachycardia was evident by 15 min after dehorning in the DH but not the DH+LA group. CONCLUSIONS: The results validate use of the EEG and a minimal anaesthesia model for assessment of noxious sensory inputs in cattle.


Subject(s)
Anesthesia, General/veterinary , Cattle , Electroencephalography/veterinary , Horns/surgery , Pain Measurement/veterinary , Anesthetics, Local/administration & dosage , Animals , Cattle/physiology , Cattle/surgery , Cautery/methods , Cautery/veterinary , Electrocardiography/methods , Electrocardiography/veterinary , Electroencephalography/methods , Electroencephalography/standards , Female , Lidocaine/administration & dosage , Pain Measurement/methods , Pain Measurement/standards , Tachycardia/epidemiology , Tachycardia/veterinary
15.
Article in English | MEDLINE | ID: mdl-18184500

ABSTRACT

Seat belt interaction with a far-side occupant's shoulder and thorax is critical to governing excursion towards the struck-side of the vehicle in side impact. In this study, occupant-to-belt interaction was simulated using a modified MADYMO human model and finite element belts. Quasi-static tests with volunteers and dynamic sled tests with PMHS and WorldSID were used for model validation and comparison. Parameter studies were then undertaken to quantify the effect of impact direction, seat belt geometry and pretension on occupant-to-seat belt interaction. Results suggest that lowering the D-ring and increasing pretension reduces the likelihood of the belt slipping off the shoulder. Anthropometry was also shown to influence restraint provided by the shoulder belt. Furthermore, the belt may slip off the occupant's shoulder at impact angles greater than 40 degrees from frontal when no pretension is used. However, the addition of pretension allowed the shoulder to engage the belt in all impacts from 30 to 90 degrees.


Subject(s)
Accidents, Traffic/statistics & numerical data , Air Bags/standards , Automobiles/statistics & numerical data , Safety/standards , Seat Belts/standards , Aged , Aged, 80 and over , Air Bags/statistics & numerical data , Anthropometry , Australia , Female , Humans , Male , Models, Theoretical , Pilot Projects , Risk Assessment , Safety/statistics & numerical data , Seat Belts/statistics & numerical data , United States
16.
Hum Mol Genet ; 10(21): 2463-8, 2001 Oct 01.
Article in English | MEDLINE | ID: mdl-11689493

ABSTRACT

Much has been learned about the cellular pathology of Friedreich's ataxia, a recessive neurodegenerative disease resulting from insufficient expression of the mitochondrial protein frataxin. However, the biochemical function of frataxin has remained obscure, hampering attempts at therapeutic intervention. To predict functional interactions of frataxin with other proteins we investigated whether its gene specifically co-occurs with any other genes in sequenced genomes. In 56 available genomes we identified two genes with identical phylogenetic distributions to the frataxin/cyaY gene: hscA and hscB/JAC1. These genes have not only emerged in the same evolutionary lineage as the frataxin gene, they have also been lost at least twice with it, and they have been horizontally transferred with it in the evolution of the mitochondria. The proteins encoded by hscA and hscB, the chaperone HSP66 and the co-chaperone HSP20, have been shown to be required for the synthesis of 2Fe-2S clusters on ferredoxin in proteobacteria. JAC1, an ortholog of hscB, and SSQ1, a paralog of hscA, have been shown to be required for iron-sulfur cluster assembly in mitochondria of Saccharomyces cerevisiae. Combining data on the co-occurrence of genes in genomes with experimental and predicted cellular localization data of their proteins supports the hypothesis that frataxin is directly involved in iron-sulfur cluster protein assembly. They indicate that frataxin is specifically involved in the same sub-process as HSP20/Jac1p.


Subject(s)
Iron-Binding Proteins , Iron-Sulfur Proteins/metabolism , Phosphotransferases (Alcohol Group Acceptor)/genetics , Phylogeny , Saccharomyces cerevisiae Proteins , Animals , Bacteria/genetics , Bacteria/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Buchnera/genetics , Buchnera/metabolism , Eukaryotic Cells/metabolism , Evolution, Molecular , Genome , HSP70 Heat-Shock Proteins , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Humans , Mitochondria/metabolism , Mitochondrial Proteins , Molecular Chaperones/genetics , Molecular Chaperones/metabolism , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Phosphotransferases (Alcohol Group Acceptor)/physiology , Protein Binding , Frataxin
17.
Genome Biol ; 2(7): Preprint 0006, 2001.
Article in English | MEDLINE | ID: mdl-11521680

ABSTRACT

BACKGROUND: Despite decades of research, the agent responsible for transmitting spongiform encephalopathies (TSEs) has not been identified. The Prion hypothesis, which dominates the field, supposes that modified host PrP protein, termed PrPSc, acts as the transmissible agent. This model fits the observation that TSE diseases elicit almost no immune reaction. Prion transmission has not been verified, however, as it has not been possible to produce pure PrPSc aggregates. One long-standing objection to the Prion model is the observation that TSE disease agents show classical genetic behaviours, such as reproducible strain variation, while also responding to selection for novel traits such as adaptation to new hosts. Moreover, evidence has been steadily accumulating that infectious titre is decoupled from the quantity (or even the presence) of PrPSc deposits. Rather awkwardly for the Prion hypothesis, PrP0/0 knockout mice have been found to incubate and transmit TSE agents (despite themselves being refractory to TSE disease). HYPOTHESIS: In this article, a new scheme, RuNAway, is proposed whereby uncontrolled proliferation of a type of parasitic gene, the small dispersed repeat sequences (SINEs), in somatic cells induces overproduction of PrP with pathogenic consequences. The RuNAway scheme involves twin tandem positive feedback loops: triggering the second loop leads to the pathogenic disease. This model is consistent with the long latency period and much shorter visible disease progression typical of TSEs.


Subject(s)
Creutzfeldt-Jakob Syndrome/genetics , PrPSc Proteins/genetics , Short Interspersed Nucleotide Elements/genetics , Animals , Creutzfeldt-Jakob Syndrome/metabolism , Creutzfeldt-Jakob Syndrome/pathology , Humans , Models, Biological , PrPSc Proteins/metabolism
18.
Nat Struct Biol ; 8(7): 626-33, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11427895

ABSTRACT

The SAND domain is a conserved sequence motif found in a number of nuclear proteins, including the Sp100 family and NUDR. These are thought to play important roles in chromatin-dependent transcriptional regulation and are linked to many diseases. We have determined the three-dimensional (3D) structure of the SAND domain from Sp100b. The structure represents a novel alpha/beta fold, in which a conserved KDWK sequence motif is found within an alpha-helical, positively charged surface patch. For NUDR, the SAND domain is shown to be sufficient to mediate DNA binding. Using mutational analyses and chemical shift perturbation experiments, the DNA binding surface is mapped to the alpha-helical region encompassing the KDWK motif. The DNA binding activity of wild type and mutant proteins in vitro correlates with transcriptional regulation activity of full length NUDR in vivo. The evolutionarily conserved SAND domain defines a new DNA binding fold that is involved in chromatin-associated transcriptional regulation.


Subject(s)
Antigens, Nuclear , Autoantigens/chemistry , Autoantigens/metabolism , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/metabolism , DNA/metabolism , Gene Expression Regulation , Nuclear Proteins/chemistry , Nuclear Proteins/metabolism , Transcription, Genetic , Amino Acid Motifs , Amino Acid Sequence , Animals , Autoantigens/genetics , Base Sequence , Binding Sites , Cell Line , Chromatin/genetics , Chromatin/metabolism , Conserved Sequence , DNA/genetics , DNA-Binding Proteins/genetics , Genes, Reporter/genetics , Models, Molecular , Molecular Sequence Data , Nuclear Magnetic Resonance, Biomolecular , Nuclear Proteins/genetics , Point Mutation/genetics , Protein Binding , Protein Structure, Secondary , Protein Structure, Tertiary , Sequence Alignment , Static Electricity
19.
Nucleic Acids Res ; 29(6): 1272-7, 2001 Mar 15.
Article in English | MEDLINE | ID: mdl-11238992

ABSTRACT

Expressed sequence tags (ESTs) are randomly sequenced cDNA clones. Currently, nearly 3 million human and 2 million mouse ESTs provide valuable resources that enable researchers to investigate the products of gene expression. The EST databases have proven to be useful tools for detecting homologous genes, for exon mapping, revealing differential splicing, etc. With the increasing availability of large amounts of poorly characterised eukaryotic (notably human) genomic sequence, ESTs have now become a vital tool for gene identification, sometimes yielding the only unambiguous evidence for the existence of a gene expression product. However, BLAST-based Web servers available to the general user have not kept pace with these developments and do not provide appropriate tools for querying EST databases with large highly spliced genes, often spanning 50 000-100 000 bases or more. Here we describe Gene2EST (http://woody.embl-heidelberg.de/gene2est/), a server that brings together a set of tools enabling efficient retrieval of ESTs matching large DNA queries and their subsequent analysis. RepeatMasker is used to mask dispersed repetitive sequences (such as Alu elements) in the query, BLAST2 for searching EST databases and Artemis for graphical display of the findings. Gene2EST combines these components into a Web resource targeted at the researcher who wishes to study one or a few genes to a high level of detail.


Subject(s)
Databases, Factual , Expressed Sequence Tags , Software , Amino Acid Sequence , Base Sequence , Eukaryotic Cells , Humans , Information Storage and Retrieval , Internet , Molecular Sequence Data , Sequence Alignment , Sequence Homology, Nucleic Acid
20.
Bioinformatics ; 16(7): 628-38, 2000 Jul.
Article in English | MEDLINE | ID: mdl-11038333

ABSTRACT

MOTIVATION: While database activities in the biological area are increasing rapidly, rather little is done in the area of parsing them in a simple and object-oriented way. RESULTS: We present here an elegant, simple yet powerful way of parsing biological flat-file databases. We have taken EMBL, SWISSPROT and GENBANK as examples. EMBL and SWISS-PROT do not differ much in the format structure. GENBANK has a very different format structure than EMBL and SWISS-PROT. Extracting the desired fields in an entry (for example a sub-sequence with an associated feature) for later analysis is a constant need in the biological sequence-analysis community: this is illustrated with tools to make new splice-site databases. The interface to the parser is abstract in the sense that the access to all the databases is independent from their different formats, since parsing instructions are hidden.


Subject(s)
Databases, Factual , Programming Languages , Sequence Analysis/methods
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