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Gareth Jones

Publications and source records attributed to Gareth Jones.

At least 19 recordsLinked to original sources
PubMed2006

Sensory neuropathy in human immunodeficiency virus/acquired immunodeficiency syndrome patients: protease inhibitor-mediated neurotoxicity.

OBJECTIVE: Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) is a common and disabling disorder, often associated with antiretroviral therapy (ART) use. We investigated the clinical features and associated pathogenic determinants of HIV-SN in a neurological cohort of HIV-infected patients, together with a novel model of HIV-SN. METHODS: HIV-infected patients with neurological disease were investigated in terms of clinical and laboratory aspects together with ART exposure focusing on symptomatic HIV-SN. Rat-derived dorsal root ganglion (DRG) cultures, transgenic for human CD4 and CCR5 treated with ARTs or HIV infected, or both, were studied with respect to quantitative neuronal injury. RESULTS: Among 221 patients assessed from 1998 to 2004, 120 had no sensory neuropathy, whereas 101 displayed HIV-SN, including 64 with distal sensory neuropathy and 37 with antiretroviral toxic neuropathy. HIV-SN patients exhibited significantly greater mean age, peak plasma viral loads, and exposure to neurotoxic dideoxynucleosides and protease inhibitors, including indinavir, saquinavir, or ritonavir. HIV-infected DRG cultures exposed to indinavir or didanosine showed significant neuronal atrophy, neurite retraction, and process loss, compared with controls. Indinavir was selectively cytotoxic to DRG macrophages compared with other ARTs. INTERPRETATION: Protease inhibitor exposure is an unrecognized risk factor for the development of HIV-SN, which may potentiate neuronal damage in HIV-infected DRGs, possibly through the loss of macrophage-derived trophic factors.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Population genetic structure and demographic history of the endemic Formosan lesser horseshoe bat (Rhinolophus monoceros).

Intraspecific phylogenies can provide useful insights into how populations have been shaped by historical and contemporary processes. Taiwan formed around 5 million years ago from tectonic uplift, and has been connected to mainland Asia several times since its emergence. A central mountain range runs north to south, bisecting the island, and potentially impedes gene flow along an east-west axis. The Formosan lesser horseshoe bat (Rhinolophus monoceros) is endemic to Taiwan, where it is found mainly at low altitude. To determine the population structure and the demographic and colonization history of this species, we examined variation in the mitochondrial DNA control region in 203 bats sampled at 26 sites. We found very high haplotype and nucleotide diversity, which decreased from the centre to the south and north. Population differentiation followed a pattern of isolation by distance, though most regional genetic variance was attributable to differences between the relatively isolated southern population and those from other regions. A haplotype network was consistent with these findings and also suggested a southward colonization, followed by subsequent secondary contact between the south and other regions. Mismatch distributions were used to infer a past population expansion predating the last glacial maximum, and a neighbour-joining tree showed that R. monoceros formed a monophyletic grouping with respect to its sister taxa. Taken together, our results suggest that this taxon arose from a single period of colonization, and that demographic growth followed in the late Pleistocene. Current genetic structure reflects limited gene flow, probably coupled with stepwise colonization in the past. We consider explanations for the persistence of the species through multiple glacial maxima.

Animals↗
PubMed2006

Flight and echolocation behaviour of whiskered bats commuting along a hedgerow: range-dependent sonar signal design, Doppler tolerance and evidence for 'acoustic focussing'.

Echolocating bats obtain three-dimensional images of their surroundings in complete darkness by emitting sonar signals and evaluating returning echoes. When flying close to objects, bats risk collision and therefore depend on the accuracy of images--particularly in the perceived distance of obstacles, which is coded by the time delay between call and echo. Yet, during flight, such accuracy is perturbed first because bats call and receive echoes at different positions and second because echoes are modified by Doppler shifts. Certain call designs avoid both sources of ranging error, but only for a limited range of distances [the 'distance of focus' (DOF)]. Here, we show that whiskered bats (Myotis mystacinus) using broadband echolocation calls adjust call design in a range-dependent manner so that nearby obstacles are localised accurately. Such behaviour is adaptive because it reduces collision risk. The bats also reduced call duration to some extent as they approached obstacles so that most returning echoes arrived after they finished calling. This reduction in call duration during the approach to obstacles was neither the only nor the main factor that influenced DOF. Indeed, both duration and bandwidth of calls influenced DOF independently, with lower bandwidths and longer durations giving greater DOF. Our findings give a new perspective on the adaptive significance of echolocation call design in nature and have implications for sonar engineering.

Animals↗
PubMed2005

Regulation of neural cell survival by HIV-1 infection.

Infection by the lentivirus, human immunodeficiency virus type 1 (HIV-1), results in a variety of syndromes involving both the central (CNS) and the peripheral (PNS) nervous systems. Productive HIV-1 infection of the CNS is chiefly detectable in perivascular macrophages and microglia. HIV-1 encoded transcripts and proteins have also been detected in the PNS; however, productive viral replication appears to be sparse and restricted to the macrophage cell population. Despite the absence of productive infection of neurons, HIV-1 infection has been associated with neuronal loss in distinct regions of the brain. Neuronal cell loss may occur through both necrosis and apoptosis, although neuronal apoptosis appears to be a feature of AIDS, as only rare apoptotic neurons have been demonstrated in a few pre-AIDS cases. Although there is no clear consensus as to the underlying mechanism of HIV-induced neuropathogenesis, two complementary concepts predominate. Firstly, HIV-1 encoded proteins injure neurons directly without requiring the intermediary functions of nonneuronal cells. Alternatively, neuronal apoptosis may result indirectly from the secretion of neurotoxic host molecules by resident brain macrophages or microglia in response to HIV-1 infection, stimulation by viral proteins or immune activation. Herein, we review the neurological disorders and their underlying mechanisms associated with HIV infection, focusing on HIV-associated dementia (HAD) and HIV sensory neuropathy (HIV-SN). The evidence that neuronal loss in HIV-1-infected individuals may be due to neuronal apoptosis is then discussed. This review also summarizes the current data supporting both the direct and indirect mechanisms by which neuronal death may occur during infection with HIV-1 or the closely related lentiviruses SIV and FIV. Lastly, strategies are examined for treating or preventing HAD by targeting specific neurotoxic mechanisms.

AIDS Dementia Complex↗
PubMed2005

Mate fidelity and intra-lineage polygyny in greater horseshoe bats.

Mating strategies that lead to increased kinship within socially cooperative groups may offer inclusive fitness benefits to individuals, but can also result in higher levels of inbreeding. Here we show in a sexually segregated bat species that females avoid this conflict through two mating behaviours. First, most females revisit and breed with specific, individual males across years, so that their single offspring born in different years are full siblings. Second, relatives in the maternal line, including mothers and daughters, share breeding partners (intra-lineage polygyny) more often than expected by chance. Although these behaviours increased levels of co-ancestry among colony members, there was no concomitant rise in inbreeding. We suggest that when females engage in mate fidelity and intra-lineage polygyny, kin ties among female roost mates will be strengthened, thereby potentially contributing to social group cohesiveness. Our findings reveal the hidden complexity that can underlie polygynous breeding, and highlight a new potential route by which female mate choice could influence social evolution.

Animals↗
PubMed2005

Lentivirus infection causes neuroinflammation and neuronal injury in dorsal root ganglia: pathogenic effects of STAT-1 and inducible nitric oxide synthase.

Distal sensory polyneuropathy (DSP) is currently the most common neurological complication of HIV infection in the developed world and is characterized by sensory neuronal injury accompanied by inflammation, which is clinically manifested as disabling pain and gait instability. We previously showed that feline immunodeficiency virus (FIV) infection of cats caused DSP together with immunosuppression in cats, similar to that observed in HIV-infected humans. In this study, we investigated the pathogenic mechanisms underlying the development of FIV-induced DSP using feline dorsal root ganglia (DRG) cultures, consisting of neurons, Schwann cells, and macrophages. FIV-infected cultures exhibited viral Ags (p24 and envelope) in macrophages accompanied by neuronal injury, indicated by neurite retraction, neuronal loss and decreased soma size, compared with mock-infected (control) cultures. FIV infection up-regulated inducible NO synthase (iNOS), STAT-1, and TNF-alpha mRNA levels in DRG cultures. Increased STAT-1 and iNOS mRNA levels were also observed in DRGs from FIV-infected animals relative to mock-infected controls. Similarly, immunolabeling studies of DRGs from FIV-infected animals showed that macrophages were the principal sources of STAT-1 and iNOS protein production. The iNOS inhibitor aminoguanidine reduced nitrotyrosine and protein carbonyl levels, together with preventing neuronal injury in FIV-infected DRG cultures. The present studies indicate that FIV infection of DRGs directly contributes to axonal and neuronal injury through a mechanism involving macrophage immune activation, which is mediated by STAT-1 and iNOS activation.

Animals↗
PubMed2005

Echolocation.

Explore the source record for details and available documents.

Animals↗
PubMed2005

Peripheral nerve-derived HIV-1 is predominantly CCR5-dependent and causes neuronal degeneration and neuroinflammation.

HIV-related peripheral neuropathy is a major neurological complication of HIV infection, although little is known about its pathogenesis. We amplified HIV-1 C2V3 envelope sequences from peroneal nerves obtained from HIV/AIDS patients. Sequence analysis and infectious recombinant viruses containing peripheral nerve-derived C2V3 sequences indicated a predominance of CCR5-dependent and macrophage-tropic HIV-1, although dual tropic viruses using both CCR5 and CXCR4 were identified. The neuropathogenic effects of recombinant HIV-1 clones were investigated using a novel dorsal root ganglion culture system that was comprised of sensory neurons, macrophages and Schwann cells from transgenic rats expressing human CD4 and CCR5 on monocytoid cells. Despite restricted viral replication, HIV-1 infection caused a reduction in the percentage of neurons with neuritic processes together with significant neurite retraction, which was accompanied by induction of IL-1beta and TNF-alpha expression, depending on the individual virus. Our results suggest that HIV-1 infection of the peripheral nervous system causes axonal degeneration, possibly through the induction of pro-inflammatory cytokines.

Adult↗
PubMed2005

Isolation and characterization of CXC receptor genes in a range of elasmobranchs.

The CXC group of chemokines exert their cellular effects via the CXCR group of G-protein coupled receptors. Six CXCR genes have been identified in humans (CXCR1-6), and homologues to some of these have been isolated from a range of vertebrate species. Here we isolate and characterize CXCR genes from a range of elasmobranch species. One CXCR1/2 gene fragment isolated from Scyliorhinus caniculus (lesser spotted catshark), and two CXCR1/2 copies from each of the elasmobranchs, Cetorhinus maximus (basking shark), Carcharodon carcharias (great white shark), and Raja naevus (cuckoo ray), exhibit high similarity to both CXCR1 and CXCR2. The two copies evident in the cuckoo ray and lamniform sharks provide strong evidence of CXCR1/2 lineage specific duplication in rays and sharks. A CXCR fragment isolated from Lamna ditropis (salmon shark) shows high similarity to a range of CXCR4 genes and strong clustering with CXCR4 gene homologues was apparent during phylogenetic reconstruction.

Amino Acid Sequence↗
PubMed2005

Echolocation call intensity in the aerial hawking bat Eptesicus bottae (Vespertilionidae) studied using stereo videogrammetry.

Aerial hawking bats use intense echolocation calls to search for insect prey. Their calls have evolved into the most intense airborne animal vocalisations. Yet our knowledge about call intensities in the field is restricted to a small number of species. We describe a novel stereo videogrammetry method used to study flight and echolocation behaviour, and to measure call source levels of the aerial hawking bat Eptesicus bottae (Vespertilionidae). Bats flew close to their predicted minimum power speed. Source level increased with call duration; the loudest call of E. bottae was at 133 dB peSPL. The calculated maximum detection distance for large flying objects (e.g. large prey, conspecifics) was up to 21 m. The corresponding maximum echo delay is almost exactly the duration of one wing beat in E. bottae and this also is its preferred pulse interval. These results, obtained by using videogrammetry to track bats in the field, corroborate earlier findings from other species from acoustic tracking methods.

Animals↗
PubMed2005

Managing authenticity: the paradox of great leadership.

Leaders and followers both associate authenticity with sincerity, honesty, and integrity. It's the real thing--the attribute that uniquely defines great managers. But while the expression of a genuine self is necessary for great leadership, the concept of authenticity is often misunderstood, not least by leaders themselves. They often assume that authenticity is an innate quality--that a person is either genuine or not. In fact, the authors say, authenticity is largely defined by what other people see in you and, as such, can to a great extent be controlled by you. In this article, the authors explore the qualities of authentic leadership. To illustrate their points, they recount the experiences of some of the authentic leaders they have known and studied, including the BBC's Greg Dyke, Nestlé's Peter Brabeck-Letmathe, and Marks & Spencer's Jean Tomlin. Establishing your authenticity as a leader is a two-part challenge. You have to consistently match your words and deeds; otherwise, followers will never accept you as authentic. But it is not enough just to practice what you preach. To get people to follow you, you also have to get them to relate to you. This means presenting different faces to different audiences--a requirement that many people find hard to square with authenticity. But authenticity is not the product of manipulation. It accurately reflects aspects of the leader's inner self, so it can't be an act. Authentic leaders seem to know which personality traits they should reveal to whom, and when. Highly attuned to their environments, authentic leaders rely on an intuition born of formative, sometimes harsh experiences to understand the expectations and concerns of the people they seek to influence. They retain their distinctiveness as individuals, yet they know how to win acceptance in strong corporate and social cultures and how to use elements of those cultures as a basis for radical change.

Commerce↗
PubMed2004

Treatment of idiopathic membranoproliferative glomerulonephritis with mycophenolate mofetil and steroids.

BACKGROUND: Treatment of adults with idiopathic membranoproliferative glomerulonephritis (IMPGN) is often unrewarding with approximately 60% of patients progressing to end-stage renal failure within 10 years. Although children with IMPGN may respond to steroid therapy, there is no significant benefit to treating adult IMPGN patients with immunosuppression. METHODS: Outcome measures in five patients with IMPGN who were treated with oral prednisolone and mycophenolate mofetil (MMF) (treatment group) were compared with six patients with IMPGN who did not receive immunosuppression (control group). RESULTS: There was no significant difference between either group in baseline clinical characteristics or systolic and diastolic blood pressure during observation. In the treatment group, there was a significant reduction in proteinuria from a baseline of 5.09 to 1.97 g/24 h (P = 0.003) at 6 months, 1.96 g/24 h (P = 0.003) at 12 months and 2.59 g/24 h (P = 0.015) at 18 months. There was no significant change in proteinuria over 18 months in the control group. Serum creatinine concentration and creatinine clearance did not change significantly over 18 months in the treatment group. In the control group, there were significant changes in serum creatinine and creatinine clearance over 18 months [baseline 103 to 159 micromol/l (P = 0.004) and baseline 108 to 67 ml/min (P > 0.001), respectively] when compared to baseline, although the differences were not significant when the two groups were compared directly. CONCLUSIONS: This preliminary study suggests that in the short term, the combination of MMF and prednisolone can significantly reduce proteinuria and may preserve renal function in patients with IMPGN.

Adrenal Cortex Hormones↗
PubMed2004

CD12: a new high-flux beamline for ultraviolet and vacuum-ultraviolet circular dichroism on the SRS, Daresbury.

This paper describes the commissioning and characterization of an SRS bending-magnet beamline constructed for the measurement of vacuum-ultraviolet circular dichroism on biological and other materials. The beamline provides photon fluxes of many orders of magnitude greater than commercial instruments or beamlines at other synchrotron radiation facilities. The beamline uses the conventional approach of utilizing the plane polarized light emitted from the bending magnet which is subsequently converted into circularly polarized light using a photoelastic modulator with a switching frequency of 50 kHz. The beamline has a best wavelength resolution of 0.5 nm and stray light levels better than 0.01%. The latter may be predicted to give improved performance over other beamlines at synchrotron radiation sources especially when short-wavelength CD spectra are to be collected. An example spectrum and submillisecond time-resolved CD profile are given and the impact that the new beamline is likely to have is speculated on. The ultimate flux limitations of the technique with regard to the avoidance of the effects of radiation damage are also discussed.

Circular Dichroism↗
PubMed2004

HIV type 1-specific inter- and intrasubtype cellular immune responses in HIV type 1-infected Ugandans.

Investigations concerning the extent and nature of subtype-specific and intersubtype immune responses in HIV-1-infected persons are necessary for the development of appropriate candidate vaccines. In the cross-sectional study described here, 26 HIV-1-positive Ugandan patients were tested for their ability to mount HIV antigen-specific cellular immune responses. Subjects were infected with either HIV-1 subtypes A, C, or D. Recombinant vaccinia virus (rVV)-based and peptide-based enzyme-linked immunospot (Elispot) assays were used to evaluate HIV-1-specific gamma-interferon (IFN-gamma) cellular responses. rVV expressing gag, pol, or env proteins derived from HIV-1 subtypes A, B, and D were evaluated for their ability to induce whole HIV-1-protein-specific IFN-gamma responses in 14 patients. A panel of previously identified HLA class I-restricted peptides based on representative sequences from HIV-1 subtypes A, B, C, and D and restricted through HLA-A2, -A29, -B42, -B53, and -B57 alleles were used to evaluate the presence of HIV-1-peptide-specific T cells in 19 patients. Using rVV, 27 of a possible 38 subtype-specific responses (71%) and 56 of a possible 110 intersubtype responses (51%) were observed. When appropriate peptides were used 18 of 39 (46.2%) subtype-specific and 13 of 39 (33.3%) intersubtype responses were observed. Peptide responses were higher quantitatively than those seen when rVV were used. In 7 patients, both rVV and specific peptides were evaluated; in 3 of 7 individuals, global responses were seen despite a lack of measurable HLA-restricted peptide-specific responses demonstrating the need to evaluate a broader range of HIV-specific immune responses.

Acquired Immunodeficiency Syndrome↗
PubMed2003

How many child deaths can we prevent this year?

This is the second of five papers in the child survival series. The first focused on continuing high rates of child mortality (over 10 million each year) from preventable causes: diarrhoea, pneumonia, measles, malaria, HIV/AIDS, the underlying cause of undernutrition, and a small group of causes leading to neonatal deaths. We review child survival interventions feasible for delivery at high coverage in low-income settings, and classify these as level 1 (sufficient evidence of effect), level 2 (limited evidence), or level 3 (inadequate evidence). Our results show that at least one level-1 intervention is available for preventing or treating each main cause of death among children younger than 5 years, apart from birth asphyxia, for which a level-2 intervention is available. There is also limited evidence for several other interventions. However, global coverage for most interventions is below 50%. If level 1 or 2 interventions were universally available, 63% of child deaths could be prevented. These findings show that the interventions needed to achieve the millennium development goal of reducing child mortality by two-thirds by 2015 are available, but that they are not being delivered to the mothers and children who need them.

Child, Preschool↗