bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clone clusters in autoreactive CD4 T‐cell lines from probable multiple sclerosis patients form disease‐characteristic signatures
Authors: Mandel Mathilda , Achiron Anat , Tuller Tamir , Barliya Tilda , Rechavi Gideon , Amariglio Ninette , Loewenthal Ron , Lavie Gad 
Published: May 2009

SummaryWe developed a method for selectively propagating disease‐related autoreactive T‐cell lines (auTCLs) based on their increased resistance to apoptosis. The generated auTCLs homogeneously co‐express CD45RO and CD49a, adhere strongly to extracellular matrix proteins and express high interleukin‐17 (IL‐17) messenger RNA levels, resembling a T‐cell subset proposed to transmigrate into tissues and induce systemic and local inflammation in rheumatoid arthritis. The combinations of T‐cell oligoclones that comprise probable multiple sclerosis (pMS) disease‐related lines use a unique portfolio of T‐cell receptor β‐chain variable allele (BV genes) combinations forming ‘disease‐specific cluster patterns’. The auTCL derived from different patients and from different myelin epitopes display striking similarities in BV gene allele clusters and are derived primarily from a disease‐prone hotspot residing in the BV gene locus between Vβ6 and Vβ9. Conversely, healthy subject TCLs use different BV gene allele sets, forming ‘healthy responder usage formats’. These formats were absent from the pMS patient V‐β gene allele combinations evaluated in this study. Hierarchical clustering of the BV gene combinations, distinguish three pMS auTCL groups, implying existence of up to three disease‐related immune response patterns. These subgroup patterns may reflect different disease subclasses or alternatively they may suggest immune reactivity to different aetiological agents. Analyses of clonal‐clustering patterns may potentially aid in subclassification of MS or in characterizing aetiological agents of this disease.
Response of macrophage Toll‐like receptor 4 to a Sporothrix schenckii lipid extract during experimental sporotrichosis
Authors: Sassá Micheli F. , Saturi Ana E. T. , Souza Lucas F. , De Abreu Ribeiro Livia C. , Da Graça Sgarbi Diana B. , Carlos Iracilda Z. 
Published: May 2009

SummaryToll‐like receptors have been implicated in the recognition of various pathogens, including bacteria, viruses, protozoa and fungi. However, no information is available about Toll‐like receptor 4 (TLR4) participation in Sporothrix schenckii recognition and the consequent triggering of the immune response to this fungal pathogen. Following activation of TLRs by ligands of microbial origin, several responses are provoked, including reactions in immune cells that may lead them to produce signalling factors that trigger inflammation. The present study was designed to elucidate the role of TLR4 during the host response to S. schenckii. TLR4‐deficient (C3H/HeJ) and control mice (C3H/HePas) were infected with S. schenckii yeast cells and immune response was assessed over 10 weeks by assaying production of pro‐inflammatory mediator (nitric oxide and tumour necrosis factor‐α) and anti‐inflammatory cytokine (interleukin‐10) by peritoneal macrophages and their correlation with apoptosis in peritoneal exudate cells. We found that both pro‐inflammatory and anti‐inflammatory mediators are reduced in TLR4‐deficient mice, suggesting the involvement of this receptor in the recognition of this infectious agent. Translocation into the nucleus of nuclear transcription factor, nuclear factor‐κB, was also evaluated and showed higher levels in TLR‐4 normal mice, consistent with the results found for cytokine production. We are showing here, for the first time, the involvement of TLR4 in S. schenckii recognition. Taken together, our results demonstrate that the activation of peritoneal macrophages in response to S. schenckii lipid extracts has different responses in these two mouse strains which differ in TLR4 expression, suggesting an important role for TLR4 in governing the functions of macrophages in this fungal infection.
Natural killer cell cytotoxicity: how do they pull the trigger?
Authors: Topham Nicola J. , Hewitt Eric W. 
Published: May 2009

SummaryNatural killer (NK) cells target and kill aberrant cells, such as virally infected and tumorigenic cells. Killing is mediated by cytotoxic molecules which are stored within secretory lysosomes, a specialized exocytic organelle found in NK cells. Target cell recognition induces the formation of a lytic immunological synapse between the NK cell and its target. The polarized exocytosis of secretory lysosomes is then activated and these organelles release their cytotoxic contents at the lytic synapse, specifically killing the target cell. The essential role that secretory lysosome exocytosis plays in the cytotoxic function of NK cells is highlighted by immune disorders that are caused by the mutation of critical components of the exocytic machinery. This review will discuss recent studies on the molecular basis for NK cell secretory lysosome exocytosis and the immunological consequences of defects in the exocytic machinery.
IL‐10 and TGF‐β1 are associated with variations in fluke burdens following experimental fasciolosis in sheep
Authors: HAÇARIZ O. , SAYERS G. , FLYNN R. J. , LEJEUNE A. , MULCAHY G. 
Published: May 2009

SummaryInfection with Fasciola hepatica causes an economically important disease in ruminants. Variability in parasite load may indicate innate differences in the host immune system. This study aimed to investigate the immunological mechanisms that are associated with variability in parasite burden following experimental F. hepatica infection in cross‐bred sheep. Of a total of 16 animals, four were randomly chosen as uninfected controls, and the remainder infected with 100 viable metacercariae. Uninfected animals were used as the control group for evaluation of cytokine gene expression levels. For comparative analysis, specific animals were selected on the basis of extremes of fluke burdens, and were categorised into light (n = 4) and heavy burdened (n = 3) cohorts. Serum antibody levels, haematological parameters, and expression of IL‐4 and IFN‐γ genes in hepatic lymph nodes were equivalent in both groups. However, significant differences in mitogen‐specific lymphocyte proliferation in vitro and in expression of TGF‐β1 and IL‐10 genes in hepatic lymph nodes were observed at acute and chronic phases of infection, respectively. These results provide useful information in developing further understanding of natural resistance to fasciolosis in sheep.
Gaps and nodes between fossil and extant insects
Authors: BÉTHOUX O. 
Published: May 2009

Abstract.Traditional contributions of the insect fossil record are listed. Fossil material indicates the earliest occurrence of a group, which in turn is useful for inferring clade divergence dates and net diversification rates. Fossil material provides complementary information on the dynamics of taxonomic diversity. Geographical occurrences outside the extant range of a taxon can be used to infer climatic macro‐fluctuations. In short, the fossil record of insects is essential for pointing out the major factors responsible for the mega‐diversity of the group, and of some of its internal lineages. Reliable taxonomic assignments and phylogenetic hypotheses underpin broader generalizations. In that respect, a problem is the inadequate integration of data from fossil and extant insect taxa in phylogenetic investigations. Stumbling blocks lie at various systematic levels. Unreliability of specimen‐based data, of species delimitation, and of homology assumptions, might have been responsible for a disdain by some entomologists for palaeoentomological literature. Idiosyncratic (and in cases flawed) methods aimed at investigating phylogenetic relationships used by a fraction of the palaeoentomological community might also have contributed to this situation. Concurrently, the traditional nomenclatural procedure might prevent effective communication between neo‐ and palaeoentomologists. Augmenting the available information on the wing venation of extant taxa would significantly advance palaeoentomology, and provide a relevant broad‐scale character system. Furthermore, the entomological community should contribute to experimentations of various nomenclatural procedures, with the aim of developing an optimal approach in terms of communication and information retrieval.
The frontline and the ivory tower: A case study of service and professional‐driven curriculum
Authors: Lenthall Sue , Wakerman John , Knight Sabina 
Published: May 2009

AbstractObjective:  To describe the development of a postgraduate, multidisciplinary program designed to meet the needs of remote health professionals, present formative evaluation findings and to offer an analysis of the difficulties and lessons learnt. Design:  Case study. Setting:  University Department of Rural Health in a remote region. Participants:  University staff, students and stakeholders involved in the development of the remote health practice program.Results:  Formative evaluation suggests that a curriculum driven by service and professional groups, such as the Flinders University Remote Health Practice program, is able to better prepare remote health practitioners and improve their effectiveness. Difficulties in development included a lack of recognition by some university academics of the value of practitioner knowledge and a reluctance to accept a clinical component in a masters program. Lessons learnt included the importance of: (i) respect for practitioner knowledge; (ii) explicit and appropriate values; (iii) high‐quality academics with strong service links; (iv) appropriate length of lead time; (v) institutional links between university and both relevant professional organisations and health services; (vi) a receptive university; (vii) location; and (viii) ongoing engagement with services and professional responsive development.Conclusion:  The success of the program was due in large part to the relationship with professional bodies and close links with remote health services. We have described a number of lessons learnt from this experience that can be useful to other educational groups developing or revising their educational programs.
Scale‐dependent trait correlations in a temperate tree community
Authors: BURNS K. C. , BEAUMONT SAM 
Published: May 2009

AbstractRecent investigations of relationships among plant traits have generated important insights into plant form and function. However, relationships involving leaf area, leaf shape and plant height remain poorly resolved. Previous work has also focused on correlations between average trait values for individual species. It is unclear whether similar relationships occur within species. We searched for novel plant trait correlations by comparing leaf area, leaf circularity, specific leaf area (SLA) and plant height among 16 common woody plant species from a temperate forest in New Zealand. Analyses were conducted both within species (intra‐specifically) and among species (inter‐specifically) to determine whether trait correlations were scale dependent. Leaf area was unrelated to other leaf traits inter‐specifically. However, leaf area declined with plant height and increased with SLA intra‐specifically. Leaf circularity decreased with plant height inter‐specifically, but increased with plant height intra‐specifically. SLA increased with plant height both inter‐ and intra‐specifically. Leaf circularity increased with SLA inter‐specifically, but decreased with SLA intra‐specifically. Overall results showed that leaf shape, SLA and plant height are interrelated. However, intra‐specific relationships often differed substantially from inter‐specific relationships, suggesting that the processes shaping relationships between this suite of plant traits are scale‐dependent.
Impacts of grazing, selective logging and hyper‐aggressors on diurnal bird fauna in intact forest landscapes of the Brigalow Belt, Queensland
Authors: EYRE TERESA J. , MARON MARTINE , MATHIESON MICHAEL T. , HASELER MURRAY 
Published: May 2009

AbstractThe impact of forest management on diurnal bird assemblages and abundance was investigated in contiguous tracts of eucalypt forest in the Brigalow Belt Bioregion, south central Queensland. Sites were located across three levels of livestock grazing intensity and three levels of selective logging intensity within the most extensive habitat type, Corymbia citriodora‐dominant forest. We recorded a high rate of incidence and large numbers of the hyper‐aggressive noisy miner Manorina melanocephala (Passeriformes: Meliphagidae) at the majority of our survey sites, a phenomenon rarely reported in non‐cleared landscapes. As shown by numerous studies in fragmented landscapes, the distribution of this species in our study had a substantial negative effect upon the distribution of small passerine species. Noisy miners exerted the strongest influence upon small passerine abundance, and masked any forest management effects. However, key habitat features important for small passerines were identified, including a relatively high density of large trees and stems in the midstorey. Selective logging appeared to exert a minimal effect upon noisy miner abundance, whereas grazing intensity had a profound, positive influence. Noisy miners were most abundant in intensively grazed forest with minimal midstorey and a low volume of coarse woody debris. Higher road density in the forest landscape also corresponded with increased numbers of noisy miners. Reduction in grazing pressure in Brigalow Belt forests has the potential to benefit small passerine assemblages across large areas through moderating noisy miner abundance. The strong relationship between noisy miners and small passerines suggests that noisy miner abundance could act as an easily measured indicator of forest condition, potentially contributing to monitoring of forest management outcomes.
Morphological variation and floral abnormalities in a trigger plant across a narrow altitudinal gradient
Authors: HOFFMANN ARY A. , GRIFFIN PHILIPPA C. , MACRAILD ROGER D. 
Published: May 2009

AbstractLocal adaptation in alpine plants has been demonstrated across wide altitudinal gradients, but has rarely been examined across the alpine‐to‐montane transition that often encompasses only a few hundred metres. Here we characterize morphological variation in leaf and floral characteristics of the trigger plant Stylidium armeria along a narrow altitudinal gradient in the Bogong High Plains in Victoria. Across this gradient, which encompasses the high‐elevation limit of this species, linear changes were found for floral scape height, leaf length and flower number. All these traits decreased with increasing altitude, whereas the frequency of abnormal flowers increased. When plants were grown in a common garden environment, an altitudinal pattern for flower abnormalities was no longer detected. However, altitudinal patterns for leaf length and scape height were maintained, albeit weaker than in the field. This indicates heritable variation for these morphological traits; the altitudinal patterns are likely to reflect the effects of selection by environmental factors that vary with altitude. Selection pressures remain to be identified but have generated both cogradient and countergradient patterns of variation.
The four horsemen: clinicopathological correlation in 407 hospital autopsies
Authors: Heriot G. S. , Pitman A. G. , Gonzales M. , McKelvie P. 
Published: May 2009

AbstractBackground:  Few previous papers comparing clinical diagnoses with autopsy findings present sensitivities and positive predictive values for individual conditions. The aim of this study is to determine the sensitivity and positive predictive value of current clinical diagnosis both overall and for individual conditions.Methods:  Retrospective review of hospital records of a consecutive series of patients undergoing hospital autopsy at two metropolitan teaching hospitals over a 7‐year period (407 patients). Comparison was made with autopsy reports to allocate one of three outcome measures (true‐positive, false‐positive, false‐negative) to each condition.Results:  The overall sensitivity and positive predictive value of clinical diagnosis were 0.74 and 0.93 respectively. Pneumonia, acute myocardial infarction, bowel ischaemia and pulmonary embolism were each present in greater than 10% of patients and had sensitivities below 0.70 and positive predictive values below 0.90.Conclusion:  There exists a large burden of clinically undiagnosed and incorrectly diagnosed disease in hospital. Pneumonia, acute myocardial infarction, bowel ischaemia and pulmonary embolism represent important and difficult diagnostic challenges.
Predictors of clinic non‐attendance: opportunities to improve patient outcomes in colorectal cancer
Authors: Kosmider S. , Shedda S. , Jones I. T. , McLaughlin S. , Gibbs P. 
Published: May 2009

AbstractAim: Colorectal cancer is one of the few tumour types, where routine patient follow up has been demonstrated to impact significantly on survival. Patients who fail to attend regular clinic reviews may compromise their outcome, but the frequency at which this occurs is unknown. Identifying the extent of this problem, and the factors that predict non‐attendance, may provide opportunities to improve patient outcomes.Methods: Utilizing the Australian Comprehensive Cancer Outcomes and Research Database (ACCORD) colorectal database at Royal Melbourne and Western Hospitals and the Hospital Patient Management System (HOMER) we collected attendance data for colorectal surgical and oncology outpatient clinic appointments.Results: A total of 619 patients (368 men and 251 women) with curatively treated Australian ClinicoPathological Staging System (ACPS) Stage A, B and C colorectal cancer was identified from the two sites over 1988–2008. Twenty‐one per cent (n= 130) of patients failed to attend one or more appointments. Patients who failed to attend were more likely to require the services of an interpreter (25% vs 18%; P= 0.007), to have a smoking history and to have not received adjuvant therapy. Tumour site, patient age, sex and comorbidities were not associated with non‐attendance.Conclusion: A significant percentage of patients fail to attend routine clinic visits to colorectal speciality clinics. Patients at risk of non‐attendance can be identified. More research is needed to identify barriers as to why patients do not attend appointments and to develop measures that may improve patient attendance.
Scleroderma lung disease, variation in screening, diagnosis and treatment practices between rheumatologists and respiratory physicians
Authors: Mangat P. , Conron M. , Gabbay E. , Proudman S. M. ,   on behalf of the Pulmonary Interstitial Vascular Organisational Taskforce (PIVOT)
Published: May 2009

AbstractBackground:  Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) represent the leading causes of death in systemic sclerosis (SSc). Screening for these complications has assumed greater importance, but is not universal. The aim of this study is to determine the self‐reported screening, diagnosis and treatment practices of rheumatologists and respiratory physicians for SSc‐related lung disease.Methods:  Email survey of 270 rheumatologists and 600 respiratory physicians.Results:  Responses were received from 42 (16%) rheumatologists and 68 (11%) respiratory physicians. Of SSc patients seen by rheumatologists, 17% had ILD and 7.5% had a diagnosis of PAH compared with 31% and 21% for respiratory physicians. Forty per cent of all physicians screened asymptomatic SSc patients without a known diagnosis of ILD or PAH less than annually or not at all. The most commonly used screening investigations were pulmonary function tests (PFT) (95%) and transthoracic echocardiogram (TTE) (78%). In suspected ILD, both groups used high‐resolution computed tomography scans and PFT in >90% of patients. In suspected PAH, both used TTE and PFT (>90%); right heart catheterisation was used by only 50% of physicians. In treatment of ILD, rheumatologists used intravenous (IV) cyclophosphamide more often (CYC) (59% vs 28%, P= 0.003) and more respiratory physicians used oral CYC (44% vs 28%, P= 0.012). In PAH, more respiratory physicians used warfarin (68% vs 40%, P= 0.006). Only approximately 65% of physicians had used specific PAH therapy, which may reflect lack of access to a designated PAH treatment centre.Conclusion:  The heterogeneity of responses revealed in this study raises the importance of screening, diagnosis and treatment algorithms in the management of this potentially life‐threatening disease.
WIN55,212‐2, a cannabinoid receptor agonist, protects against nigrostriatal cell loss in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine mouse model of Parkinson’s disease
Authors: Price David A. , Martinez Alex A. , Seillier Alexandre , Koek Wouter , Acosta Yolanda , Fernandez Elizabeth , Strong Randy , Lutz Beat , Marsicano Giovanni , Roberts James L. , Giuffrida Andrea 
Published: May 2009

AbstractParkinson’s disease (PD) is characterized by the progressive loss of nigrostriatal dopamine neurons leading to motor disturbances and cognitive impairment. Current pharmacotherapies relieve PD symptoms temporarily but fail to prevent or slow down the disease progression. In this study, we investigated the molecular mechanisms by which the non‐selective cannabinoid receptor agonist WIN55,212‐2 (WIN) protects mouse nigrostriatal neurons from 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced neurotoxicity and neuroinflammation. Stereological analyses showed that chronic treatment with WIN (4 mg/kg, intraperitoneal), initiated 24 h after MPTP administration, protected against MPTP‐induced loss of tyrosine hydroxylase‐positive neurons in the substantia nigra pars compacta independently of CB1cannabinoid receptor activation. The neuroprotective effect of WIN was accompanied by increased dopamine and 3,4‐dihydroxyphenylacetic acid levels in the substantia nigra pars compacta and dorsal striatum of MPTP‐treated mice. At 3 days post‐MPTP, we found significant microglial activation and up‐regulation of CB2cannabinoid receptors in the ventral midbrain. Treatment with WIN or the CB2receptor agonist JWH015 (4 mg/kg, intraperitoneal) reduced MPTP‐induced microglial activation, whereas genetic ablation of CB2receptors exacerbated MPTP systemic toxicity. Furthermore, chronic WIN reversed MPTP‐associated motor deficits, as revealed by the analysis of forepaw step width and percentage of faults using the inverted grid test. In conclusion, our data indicate that agonism at CB2cannabinoid receptors protects against MPTP‐induced nigrostriatal degeneration by inhibiting microglial activation/infiltration and suggest that CB2receptors represent a new therapeutic target to slow the degenerative process occurring in PD.