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1.
Nat Commun ; 11(1): 2126, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32358532

ABSTRACT

Many inland waters exhibit complete or partial desiccation, or have vanished due to global change, exposing sediments to the atmosphere. Yet, data on carbon dioxide (CO2) emissions from these sediments are too scarce to upscale emissions for global estimates or to understand their fundamental drivers. Here, we present the results of a global survey covering 196 dry inland waters across diverse ecosystem types and climate zones. We show that their CO2 emissions share fundamental drivers and constitute a substantial fraction of the carbon cycled by inland waters. CO2 emissions were consistent across ecosystem types and climate zones, with local characteristics explaining much of the variability. Accounting for such emissions increases global estimates of carbon emissions from inland waters by 6% (~0.12 Pg C y-1). Our results indicate that emissions from dry inland waters represent a significant and likely increasing component of the inland waters carbon cycle.

2.
Mol Neurobiol ; 56(3): 1628-1636, 2019 Mar.
Article in English | MEDLINE | ID: mdl-29911254

ABSTRACT

The regulation of Trk receptors is critical for orchestrating multiple signalling pathways required for developing and maintaining neuronal networks. Activation of Trk receptors results in signalling, internalisation and subsequent degradation of the protein. Although ubiquitination of TrkA by Nedd4-2 has been identified as an important degradation pathway, much less is known about the pathways regulating the degradation of TrkB and TrkC. Critical to the interaction between TrkA and Nedd4-2 is a PPxY motif present within TrkA but absent in TrkB and TrkC. Given the absence of this interaction motif, it remains to be determined how TrkB and TrkC are ubiquitinated. Here we report that the adaptor protein Ndfip1 can interact with all three Trk receptors and show for TrkB the recruitment of Nedd4-2 through PPxY motifs present in Ndfip1. Ndfip1 mediates the ubiquitination of TrkB, resulting in receptor trafficking predominantly on Rab7 containing late endosomes, highlighting a pathway for TrkB degradation at the lysosome. In vitro, overexpression of Ndfip1 increased TrkB ubiquitination and decreased viability of BDNF-dependent primary neurons. In vivo, conditional genetic deletion of Ndfip1 increased TrkB in the brain and resulted in enlargement of the granular cell layer of the dentate gyrus.


Subject(s)
Hippocampus/metabolism , Neurons/metabolism , Receptor, trkA/metabolism , Receptor, trkB/metabolism , Ubiquitins/metabolism , Animals , COS Cells , Carrier Proteins/metabolism , Cell Survival/physiology , Chlorocebus aethiops , Endosomes/metabolism , HEK293 Cells , Humans , Membrane Proteins/metabolism , Mice , Mice, Transgenic , Protein Transport , Proteolysis , Ubiquitination
3.
Mar Pollut Bull ; 63(5-12): 86-90, 2011.
Article in English | MEDLINE | ID: mdl-21592532

ABSTRACT

Hepatic lipidosis is a non-specific biomarker of effect from pollution exposure in fish. Fatty liver is often misdiagnosed or overlooked in histological assessments due to the decreasing application of specific fat procedures and stains. For example, ethanol dehydration in standard paraffin processing removes lipids, leaving vacuoles of which the precise nature is unknown. Lipids can be identified using osmium post-fixation in semi-thin resin sections or transmission electron microscopy. However, both are expensive and technically demanding procedures, often not available for routine environmental risk assessment and monitoring programs. The current emphasis to reduce and refine animal toxicity testing, requires refinement of the suite of histopathological techniques currently available to maximize information gained from using fish for toxicity testing and as bio-indicators of environmental quality. This investigation has successfully modified an osmium post-fixation technique to conserve lipids in paraffin-embedded tissues using medaka (Oryzias latipes) eleutheroembryos and eggs (embryos) as lipid rich models.


Subject(s)
Embryo, Nonmammalian/metabolism , Lipid Metabolism , Liver/metabolism , Osmium/chemistry , Ovum/metabolism , Paraffin Embedding/methods , Animals , Embryo, Nonmammalian/pathology , Liver/pathology , Models, Biological , Oryzias
4.
Prosthet Orthot Int ; 32(1): 84-92, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18330807

ABSTRACT

The Adaptive knee joint is a microprocessor-controlled prosthetic knee that incorporates both pneumatic and hydraulic control in one electronic unit. Pneumatic control is said to provide control during swing phase and the hydraulic control during the stance phase of the gait. This hybrid controller is triggered by a computer contained within the knee that responds to input from force, time and angle sensors. The microprocessor then selects an appropriate speed and stability setting. The Catech knee joint is a conventional hydraulic knee joint. The aim of this study was to compare the Adaptive and Catech knee joints in established trans-femoral amputees. The patients meeting the inclusion criteria were all established trans-femoral amputees using the Catech knee joint. The study was carried out by performing gait analysis, assessing energy requirements using the Physiological Cost Index (PCI) and using questionnaires. There was no significant benefit gained from the use of the Adaptive knee over the Catech knee joint in our small study group.


Subject(s)
Amputation, Surgical/rehabilitation , Joint Prosthesis , Knee Joint , Microcomputers , Adult , Gait , Heart Rate , Humans , Middle Aged , Patient Satisfaction , Prosthesis Design
5.
Biochem Soc Trans ; 34(Pt 3): 418-21, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16709176

ABSTRACT

Slits are large secreted glycoproteins characterized by an unusual tandem of four LRR (leucine-rich repeat) domains in their N-terminal half. Slit proteins were initially described as repulsive guidance cues in neural development, but it has become clear that they have additional important functions, for instance in the vasculature and immune system. Genetic studies have identified two types of cellular receptors for Slits: Robos (Roundabout) and the HS (heparan sulphate) proteoglycan syndecan. The intracellular signalling cascade downstream of Robo activation is slowly being elucidated, but the mechanism of transmembrane signalling by Robo has remained obscure. No active signalling role for syndecan has yet been demonstrated. Slit-HS interactions may be important for shaping the presumed Slit gradient or presenting Slit at its target cell surface. Recent studies have mapped the binding sites for Robos and HS/heparin to discrete Slit domains. Robos bind to the second LRR domain of Slit, whereas HS/heparin binds with very high affinity to the C-terminal portion of Slit. Slit activity is likely to be modulated by physiological proteolytic cleavage in the region separating the Robo and HS/heparin-binding sites.


Subject(s)
Cell Movement/physiology , Glycoproteins/metabolism , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Animals , Drosophila Proteins/metabolism , Humans
6.
Prosthet Orthot Int ; 28(2): 115-20, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15382805

ABSTRACT

The ICEX system (Ossur, Iceland), allows a socket to be manufactured directly onto the stump and is thought to provide improved comfort due to better pressure distribution whilst being easier to fit and manufacture. The aims of this project were to a) compare gait performance by measuring several gait characteristics, b) compare production and fitting times, c) investigate financial implications and d) attempt to gauge the amputees' subjective opinions of socket comfort. A randomised, controlled trial was conducted on 27 trans-tibial amputees with an existing patellar tendon bearing (PTB) socket on the Endolite system (Chas A. Blatchford, UK). Twenty one (21) subjects completed the study. Of these, 10 in the control group received new PTB sockets while 11 in the experimental group received ICEX. Gait analysis wearing existing sockets was performed and kinetic data obtained from a force plate. This was repeated with the new sockets after a 6 week period of adjustment. Mann-Whitney tests were used in statistical evaluations with a significance level of 5%. Subjects were asked to score their prosthesis for comfort using the Socket Comfort Score (Hanspal et al., 2003) and the frequency of visits for socket adjustments over a three-month period post-delivery of the sockets was recorded. This study demonstrates no significant difference in any of the gait parameters measured. Though the time required to manufacture a PTB prosthesis was found to be considerably longer than the ICEX, the overall cost for producing the ICEX was significantly greater. Subjects showed only minor comfort preference for the ICEX design and there was no significant difference in the mean number of visits for socket adjustments. In view of the considerable additional cost of providing ICEX and the lack of evidence of improvement in any parameter tested, the routine provision of ICEX prostheses to unselected trans-tibial amputees cannot be recommended.


Subject(s)
Artificial Limbs/economics , Direct Service Costs , Gait/physiology , Prosthesis Fitting/economics , Adolescent , Adult , Aged , Amputation Stumps/physiopathology , Female , Humans , Leg , Male , Middle Aged , Patient Satisfaction , Prosthesis Design , Time Factors
7.
Curr Top Microbiol Immunol ; 272: 331-64, 2003.
Article in English | MEDLINE | ID: mdl-12747555

ABSTRACT

Representative adenoviruses from four of the five major virus subgroups have been shown to interact with the 46-kDa coxsackievirus and adenovirus receptor (CAR) that is widely expressed on many human cell types, suggesting that the ability to bind CAR may be a conserved feature of many of the approximately 50 known adenovirus serotypes. Receptor binding is a function of the distal 'knob' domain of the trimeric viral fiber protein. Here we review recent structural characterizations of knob, CAR and knob-CAR complexes, and we discuss how knob architecture may have evolved to accommodate opposing selective pressures to vary antigenic structure while conserving receptor binding specificity. In contrast to the hypervariability of the solvent-exposed surface of knob, the CAR receptor was found to be non-polymorphic.


Subject(s)
Adenoviruses, Human/metabolism , Receptors, Virus/metabolism , Adenoviruses, Human/chemistry , Adenoviruses, Human/genetics , Capsid/chemistry , Capsid/metabolism , Coxsackie and Adenovirus Receptor-Like Membrane Protein , Genetic Vectors/genetics , Humans , Models, Molecular , Protein Binding , Protein Conformation , Receptors, Virus/chemistry , Receptors, Virus/genetics
8.
Nat Struct Biol ; 8(10): 874-8, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11573093

ABSTRACT

Group B coxsackieviruses (CVB) utilize the coxsackievirus-adenovirus receptor (CAR) to recognize host cells. CAR is a membrane protein with two Ig-like extracellular domains (D1 and D2), a transmembrane domain and a cytoplasmic domain. The three-dimensional structure of coxsackievirus B3 (CVB3) in complex with full length human CAR and also with the D1D2 fragment of CAR were determined to approximately 22 A resolution using cryo-electron microscopy (cryo-EM). Pairs of transmembrane domains of CAR associate with each other in a detergent cloud that mimics a cellular plasma membrane. This is the first view of a virus-receptor interaction at this resolution that includes the transmembrane and cytoplasmic portion of the receptor. CAR binds with the distal end of domain D1 in the canyon of CVB3, similar to how other receptor molecules bind to entero- and rhinoviruses. The previously described interface of CAR with the adenovirus knob protein utilizes a side surface of D1.


Subject(s)
Adenoviridae/metabolism , Enterovirus B, Human/metabolism , Receptors, Virus/metabolism , Adenoviridae/chemistry , HeLa Cells , Humans , Microscopy, Electron/methods , Models, Molecular , Receptors, Virus/chemistry , Viral Plaque Assay
9.
Clin Rehabil ; 14(5): 518-22, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11043877

ABSTRACT

OBJECTIVE: To compare the cognitive demand of walking when using a conventional prosthesis with that using a microprocessor-controlled prosthesis. DESIGN: Ten unilateral transfemoral amputees wearing conventional pneumatic swing phase control (conventional prosthesis) prostheses walked on a treadmill which enforced a pattern of constantly varying speeds. The subjects simultaneously performed a simple or a complex distracting task. Following a period of accustomization, the subjects performed the same test wearing a prosthesis with microprocessor control of swing phase damping (the Intelligent Prosthesis). OUTCOME MEASURES: The three-dimensional trajectory (sway) of a retroreflective marker attached to the forehead was measured by a video-based motion analysis system, and used as a measure of gait quality. The ratio of the sway for the complex task over the simple task (the 'automation index') was used as a measure of the degree of automation of gait. RESULTS: No significant differences were found in the automation index between the two devices. However, the total sway for the conventional prosthesis was significantly higher. Sway during the complex distracting task was significantly higher than during the simple task. CONCLUSIONS: The microprocessor-controlled prosthesis was not found to be less cognitively demanding than a conventional prosthesis.


Subject(s)
Amputees/rehabilitation , Artificial Limbs/classification , Automation/methods , Cognition/physiology , Gait/physiology , Walking/physiology , Adult , Artificial Intelligence , Artificial Limbs/standards , England , Female , Humans , Knee Prosthesis , Male , Microcomputers
10.
J Clin Forensic Med ; 7(1): 61, 2000 Mar.
Article in English | MEDLINE | ID: mdl-15274995
11.
Prosthet Orthot Int ; 22(2): 129-35, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9747997

ABSTRACT

A questionnaire survey of 22 selected transfemoral amputees who were switched from pneumatic swing phase control knee joints (PSPC) to microprocessor controlled intelligent knee joints (IP) is presented. On overall rating all respondents considered the IP to be an improvement or a great improvement compared to the PSPC and none decided to revert back or wished to use their previous PSPC prosthesis on a regular basis. However the IP was not rated to be superior in every area of the questionnaire. Walking at different speeds, walking further, reduction of energy consumption were the main areas where subjective improvements were perceived by the amputees themselves. It is strongly believed that patients' own views should be an important and integral part of the evaluation of new prosthetic technology.


Subject(s)
Amputees/rehabilitation , Artificial Limbs , Adult , Aged , Computers , Female , Femur , Gait , Humans , Leg , Male , Middle Aged , Patient Satisfaction , Prosthesis Design
12.
J Clin Forensic Med ; 4(2): 59-63, 1997 Jun.
Article in English | MEDLINE | ID: mdl-15335580

ABSTRACT

The role of the forensic physician in domestic violence incidents in South London was investigated over a 6-month period. The aim of the study was to identify the nature of domestic violence, to determine whether the individuals involved had previously been in contact with the primary health care team or other agencies and whether direct communication between the examining forensic physician and the patient's general practitioner was of assistance to the latter. We concluded that there is a definite role for the forensic physician in documenting injuries in victims and assailants (although most were minor injuries), providing appropriate medical treatment, supplying information regarding support agencies and passing the relevant information, with the patient's consent, to the primary health care team.

13.
Prosthet Orthot Int ; 20(2): 111-5, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8876004

ABSTRACT

A report of the outcome of fitting ICEROSS prostheses to trans-tibial amputees from a subregional amputee rehabilitation centre is presented. This work has mainly concentrated on obtaining patients' own views to judge advantages and disadvantages of ICEROSS compared to their previous patellar-tendon-bearing (PTB) prostheses. Sixty-nine patients were entered for this study, but the results of the study are based on 54 patients who responded. Fifteen patients (27.7%) had rejected their ICEROSS prosthesis at the time of the study. Provision of ICEROSS prostheses did not improve indoor and outdoor walking abilities in terms of distance or use of other walking aids, nor were they more comfortable to wear. An increase in sweating in the first 3 months of wearing ICEROSS was significant, but settled afterwards. The amputees considered that the rate of stump skin breakdown with ICEROSS compared to their PTB prostheses was significantly less. Walking up and down stairs was more comfortable and in general overall rating of ICEROSS prostheses they were scored significantly higher by the amputees themselves. It is concluded that appropriate patient selection is vital and in certain cases ICEROSS will provide considerable benefits to the amputees.


Subject(s)
Amputees/psychology , Amputees/rehabilitation , Artificial Limbs/adverse effects , Artificial Limbs/standards , Attitude to Health , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Humans , Leg , Middle Aged , Patient Selection , Prosthesis Fitting , Surveys and Questionnaires , Walking
14.
J Clin Forensic Med ; 2(4): 177-83, 1995 Dec.
Article in English | MEDLINE | ID: mdl-15335630

ABSTRACT

Forensic physicians are at times required to provide a professional opinion on a person's degree of intoxication through alcohol, particularly with regard to fitness for interview by the police. Inherent to these assessments is an estimation of the blood alcohol concentration (BAC). Most forensic physicians rely on taking a history regarding recent alcohol consumption and a clinical assessment to estimate the BAC. We report a study in which the BAC of 118 detainees was estimated and compared with the BAC measured by an alcometer. Our estimations were accurate in 66% of cases. Most errors resulted from underestimating the BAC. Additionally, we attempted to determine fitness for interview using a single measurement of the BAC without a clinical assessment. 19% of those who were assessed as unfit for interview had a BAC of less than the UK legal limit for driving (currently 80 mg%) and 37% considered fit, had a BAC above that level. We conclude that the routine use of alcometers would enhance the practice of forensic medicine but could not replace its role in the assessment of levels of alcohol intoxication.

15.
J Clin Forensic Med ; 2(1): 17-24, 1995 Mar.
Article in English | MEDLINE | ID: mdl-15335662

ABSTRACT

A personal comparison and contrast of the differences between two geographical areas following a unique opportunity to experience working in clinical forensic medicine in both London and Melbourne.

17.
Br J Gen Pract ; 40(334): 214-5, 1990 May.
Article in English | MEDLINE | ID: mdl-2114139
18.
Aviat Space Environ Med ; 49(10): 1197-202, 1978 Oct.
Article in English | MEDLINE | ID: mdl-708348

ABSTRACT

Continuous recordings were made of the EEG and ECG of one pilot during a series of instrument flights in a feeder-type transport aircraft. The flights were arranged to contain epochs of distinctly differing levels of workload. In addition, some flights were made after a night of sleep deprivation and others were made as the second and third flights of the day. Subjectively, there appeared to be marked differences in performance between the two types of tired flight. The EEG analyses showed changes that correlated well with differences in workload. In the highest workload areas during fresh flights, EEG activity increased by approximately a factor of 4 over that of the preflight resting values. This large increase did not occur in the tired flights. Further experiments are planned using flights in aircraft and in simulators using several subjects.


Subject(s)
Aerospace Medicine , Electroencephalography , Fatigue/physiopathology , Work , Electrocardiography , Humans , Male , Middle Aged
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