bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors affecting fluid flow in strike–slip fault systems: coupled deformation and fluid flow modelling with application to the western Mount Isa Inlier, Australia
Authors: FORD A. , BLENKINSOP T.G. , McLELLAN J.G. 
Published: December 2008

AbstractDeformation and focused fluid flow within a mineralized system are critical in the genesis of hydrothermal ore deposits. Dilation and integrated fluid flux due to coupled deformation and fluid flow in simple strike–slip fault geometries were examined using finite difference analysis in three dimensions. A series of generic fault bend and fault jog geometries consistent with those seen in the western Mount Isa Inlier were modelled in order to understand how fault geometry parameters influence the dilation and integrated fluid flux. Fault dip, fault width, bend/jog angle, and length were varied, and a cross‐cutting fault and contrasting rock types were included. The results demonstrate that low fault dips, the presence of contrasts in rock type, and wide faults produce highest dilation and integrated fluid flux values. Increasing fault bend lengths and angles increases dilation and integrated fluid flux, but increasing fault jog length or angle has the opposite effect. There is minimal difference between the outputs from the releasing and restraining fault bend and jog geometries. Model characteristics producing greater fluid flows and/or gradients can be used in a predictive capacity in order to focus exploration on regions with more favorable fault geometries, provided that the mineralized rocks had Mohr–Coulomb rheologies similar to the ones used in the models.
PKG activity causes photoreceptor cell death in two retinitis pigmentosa models
Authors: Paquet‐Durand François , Hauck Stefanie M. , Van Veen Theo , Ueffing Marius , Ekström Per 
Published: December 2008

AbstractPhotoreceptor degeneration in retinitis pigmentosa is one of the leading causes of hereditary blindness in the developed world. Although causative genetic mutations have been elucidated in many cases, the underlying neuronal degeneration mechanisms are still unknown. Here, we show that activation of cGMP‐dependent protein kinase (PKG) hallmarks photoreceptor degeneration inrd1andrd2human homologous mouse models. When induced in wild‐type retinae, PKG activity was both necessary and sufficient to trigger cGMP‐mediated photoreceptor cell death. Target‐specific, pharmacological inhibition of PKG activity in bothrd1andrd2retinae strongly reduced photoreceptor cell death in organotypic retinal explants. Likewise, inhibition of PKGin vivo,using three different application paradigms, resulted in robust photoreceptor protection in therd1retina. These findings suggest a pivotal role for PKG activity in cGMP‐mediated photoreceptor degeneration mechanisms and highlight the importance of PKG as a novel target for the pharmacological intervention in RP.
Interleukin‐6 is required for the early induction of glial fibrillary acidic protein in Schwann cells during Wallerian degeneration
Authors: Lee Hyun Kyoung , Seo In Ae , Suh Duk Joon , Hong Jeong‐In , Yoo Young Hyun , Park Hwan Tae 
Published: December 2008

AbstractSignal transducer and activator of transcription 3 (STAT3) regulates gene transcription in response to cytokines and growth factors. In the central nervous system, STAT3 plays a role in neuroprotection and reactive gliosis after lesions. During peripheral nerve regeneration, a nerve injury‐induced up‐regulation of cytokines and growth factors accompanies STAT3 activation in sensory neurons and Schwann cells (SCs) even though its molecular details and functions are unknown. We then analyzed the ligands and functions of STAT3 activation in RT4 schwannoma cells and adult SCs in vitro and in vivo. We have identified that interleukin‐6 (IL‐6), but not ciliary neurotrophic factor, leukemia inhibitory factor, or ligands for receptor tyrosine kinases, activates STAT3 in SCs. The IL‐6/STAT3 signaling in primary SCs and RT4 cells induced the gene expression of glial fibrillary acidic protein (GFAP), which is known to be required for the proper regeneration of the injured nerves. Finally, the GFAP induction in the sciatic nerves after injury was significantly delayed in IL‐6‐deficient mice. These findings indicate that IL‐6 plays an important role in STAT3‐dependent GFAP induction in SCs during peripheral nerve regeneration.
Acetylcholine‐induced neuronal differentiation: muscarinic receptor activation regulates EGR‐1 and REST expression in neuroblastoma cells
Authors: Salani Monica , Anelli Tonino , Tocco Gabriella Augusti , Lucarini Elena , Mozzetta Chiara , Poiana Giancarlo , Tata Ada Maria , Biagioni Stefano 
Published: December 2008

AbstractNeurotransmitters are considered part of the signaling system active in nervous system development and we have previously reported that acetylcholine (ACh) is capable of enhancing neuronal differentiation in cultures of sensory neurons and N18TG2 neuroblastoma cells. To study the mechanism of ACh action, in this study, we demonstrate the ability of choline acetyltransferase‐transfected N18TG2 clones (e.g. 2/4 clone) to release ACh. Analysis of muscarinic receptors showed the presence of M1–M4 subtypes and the activation of both IP3 and cAMP signal transduction pathways. Muscarinic receptor activation increases early growth response factor‐1 (EGR‐1) levels and treatments with agonists, antagonists, and signal transduction enzyme inhibitors suggest a role for M3 subtype in EGR‐1 induction. The role of EGR‐1 in the enhancement of differentiation was investigated transfecting in N18TG2 cells a construct for EGR‐1. EGR‐1 clones show increased neurite extension and a decrease in Repressor Element‐1 silencing transcription factor (REST) expression: both these features have also been observed for the 2/4 clone. Transfection of this latter with EGR zinc‐finger domain, a dominant negative inhibitor of EGR‐1 action, increases REST expression, and decreases fiber outgrowth. The data reported suggest that progression of the clone 2/4 in the developmental program is dependent on ACh release and the ensuing activation of muscarinic receptors, which in turn modulate the level of EGR‐1 and REST transcription factors.
Communication between neurons and astrocytes: relevance to the modulation of synaptic and network activity
Authors: Fellin Tommaso 
Published: December 2008

AbstractNeuromodulation is a fundamental process in the brain that regulates synaptic transmission, neuronal network activity and behavior. Emerging evidence demonstrates that astrocytes, a major population of glial cells in the brain, play previously unrecognized functions in neuronal modulation. Astrocytes can detect the level of neuronal activity and release chemical transmitters to influence neuronal function. For example, recent findings show that astrocytes play crucial roles in the control of Hebbian plasticity, the regulation of neuronal excitability and the induction of homeostatic plasticity. This review discusses the importance of astrocyte‐to‐neuron signaling in different aspects of neuronal function from the activity of single synapses to that of neuronal networks.
l‐DOPA activates ERK signaling and phosphorylates histone H3 in the striatonigral medium spiny neurons of hemiparkinsonian mice
Authors: Santini Emanuela , Alcacer Cristina , Cacciatore Silvia , Heiman Myriam , Hervé Denis , Greengard Paul , Girault Jean‐Antoine , Valjent Emmanuel , Fisone Gilberto 
Published: December 2008

AbstractIn the dopamine‐depleted striatum, extracellular signal‐regulated kinase (ERK) signaling is implicated in the development of l‐DOPA‐induced dyskinesia. To gain insights on its role in this disorder, we examined the effects of l‐DOPA on the state of phosphorylation of ERK and downstream target proteins in striatopallidal and striatonigral medium spiny neurons (MSNs). For this purpose, we employed mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoters for the dopamine D2 receptor (Drd2‐EGFP mice) or the dopamine D1 receptor (Drd1a‐EGFP mice), which are expressed in striatopallidal and striatonigral MSNs, respectively. In 6‐hydroxydopamine‐lesioned Drd2‐EGFP mice, l‐DOPA increased the phosphorylation of ERK, mitogen‐ and stress‐activated kinase 1 and histone H3, selectively in EGFP‐negative MSNs. Conversely, a complete co‐localization between EGFP and these phosphoproteins was observed in Drd1a‐EGFP mice. The effect of l‐DOPA was prevented by blockade of dopamine D1 receptors. The same pattern of activation of ERK signaling was observed in dyskinetic mice, after repeated administration of l‐DOPA. Our results demonstrate that in the dopamine‐depleted striatum, l‐DOPA activates ERK signaling specifically in striatonigral MSNs. This regulation may result in ERK‐dependent changes in striatal plasticity leading to dyskinesia.
Cellular senescence in pretransplant renal biopsies predicts postoperative organ function
Authors: McGlynn Liane M. , Stevenson Karen , Lamb Kelly , Zino Samer , Brown Michaela , Prina Alberto , Kingsmore David , Shiels Paul G. 
Published: December 2008

SummaryOlder and marginal donors have been used to meet the shortfall in available organs for renal transplantation. Post‐transplant renal function and outcome from these donors are often poorer than chronologically younger donors. Some organs, however, function adequately for many years. We have hypothesized that such organs are biologically younger than poorer performing counterparts. We have tested this hypothesis in a cohort of pre‐implantation human renal allograft biopsies (n = 75) that have been assayed by real‐time polymerase chain reaction for the expression of known markers of cellular damage and biological aging, including CDKN2A, CDKN1A, SIRT2 and POT1. These have been investigated for any associations with traditional factors affecting transplant outcome (donor age, cold ischaemic time) and organ function post‐transplant (serum creatinine levels). Linear regression analyses indicated a strong association for serum creatinine with pre‐transplant CDKN2A levels (p = 0.001) and donor age (p = 0.004) at 6 months post‐transplant. Both these markers correlated significantly with urinary protein to creatinine ratios (p = 0.002 and p = 0.005 respectively), an informative marker for subsequent graft dysfunction. POT1 expression also showed a significant association with this parameter (p = 0.05). Multiple linear regression analyses for CDKN2A and donor age accounted for 24.6% (p = 0.001) of observed variability in serum creatinine levels at 6 months and 23.7% (p = 0.001) at 1 year post‐transplant. Thus, these data indicate that allograft biological age is an important novel prognostic determinant for renal transplant outcome.
Debate: When does a seizure imply epilepsy?
Authors: Fisher Robert S. , Leppik Ilo 
Published: December 2008

SummaryEpilepsy recently has been defined conceptually as a condition of at least one seizure, with an enduring predisposition to have seizures. It is not yet clear how to make this definition operational and practical. A diagnosis of epilepsy has potentially serious consequences for health, psychosocial well‐being, and economics, and, therefore, it should be made with a high level of certainty. A definite diagnosis of epilepsy can be made with two unprovoked seizures at least 24 h apart. This method has the benefit of simplicity and consistency with past epidemiologic studies. Nevertheless, certain circumstances suggest a high likelihood of having a second seizure, as evidenced by common clinical practice of considering treatment after a first unprovoked seizure in conjunction with additional risk factors (surrogate markers). One unifying approach is an operational definition of “definite epilepsy” after two unprovoked seizures at least 24 h apart. An operational definition of “probable epilepsy” can be established with one unprovoked seizure and clinical, electroencephalography (EEG), neuroimaging, genetic, or other information to suggest greater than a 50% chance of having another seizure. “Possible epilepsy” operationally would exist with a single unprovoked seizure and insufficient evidence to predict a high likelihood of recurrence. Future clinical and epidemiologic evidence would allow refinements of the operational definitions.
Antiepileptic drugs during pregnancy: What is known and which AEDs seem to be safest?
Authors: Pennell Page B. 
Published: December 2008

SummaryMost infants born to women with epilepsy are healthy, but there are increased risks related to in utero antiepileptic drug (AED) exposure and seizures. Emerging data from pregnancy registries and other studies allow us to better balance the anatomic teratogenic and neurodevelopmental effects of AEDs against the need to maintain maternal seizure control. Several large prospective pregnancy registries demonstrate a consistent pattern of increased risk for major congenital malformations (MCMs) with valproate (VPA) use as monotherapy, compared to nonexposed populations and to other AEDs used in monotherapy. AED polytherapy likely increases risk for MCMs, but the risk is more pronounced if VPA is included. Reduced cognitive outcomes have been reported with AED polytherapy, and with use of VPA, phenobarbital (PB), and PHT as monotherapy. Dose‐dependent risk has been demonstrated with VPA for MCMs and cognitive consequences. CBZ groups show normal neurodevelopment. Increased clearance of most of the AEDs occurs during pregnancy. Use of therapeutic drug monitoring during pregnancy with LTG reduces the risk for seizure worsening. The consistent findings of increased teratogenic risk for VPA should discourage use of this medication as first‐line treatment in women of childbearing age.
Hippocampal epileptogenesis in animal models of mesial temporal lobe epilepsy with hippocampal sclerosis: The importance of the “latent period” and other concepts
Authors: Sloviter Robert S. 
Published: December 2008

SummaryProlonged chemoconvulsant‐induced status epilepticus in rats has long been promoted as an animal model of mesial temporal lobe epilepsy with hippocampal sclerosis, under the assumption that these animals involve: (1) pathology similar to that of the human neurologic condition; (2) a seizure‐free, “preepileptic” latent period of several weeks duration after injury, during which a secondary epileptogenic process gradually develops; and (3) a chronic epileptic state in which the hippocampus, in general, and the dentate gyrus, in particular, becomes a source of the spontaneous behavioral seizures that define these animals as “epileptic.” Retrospective analysis suggests that all of these assumptions are in doubt. Neuropathologic studies have shown that prolonged status epilepticus causes greater extrahippocampal than hippocampal damage, and does not produce classic hippocampal sclerosis. In vivo electrophysiologic studies suggest that the hippocampus of these animals may not be “epileptic.” Most importantly, studies using continuous video monitoring to detect spontaneous behavioral seizures indicate that these rats become epileptic soon after insult, before any delayed secondary processes have time to develop. High mortality, significant variability, and the lack of an extended “therapeutic window” after brain injury suggest the need to develop animal models that more closely resemble the human neurologic condition.
Should all patients be told about sudden unexpected death in epilepsy (SUDEP)? Pros and Cons
Authors: Brodie Martin J. , Holmes Gregory L. 
Published: December 2008

SummaryDespite being a relatively rare event, sudden unexpected death in epilepsy (SUDEP) can tragically cut short a young person’s life, particularly if seizures are not well controlled or when concordance with the antiepileptic drug regimen is less than optimal. Both the Scottish Intercollegiate Guidelines Network (SIGN) and the UK National Institute of Clinical Excellence (NICE) recommend universal discussion of SUDEP and support the view of one of the authors (MJB) and that of the Joint Epilepsy Council of UK charities that patients and their families have the right to know about the risks of epilepsy and the reasons for treatment. However, the risk of SUDEP is not uniform across all patient populations. Most people with newly diagnosed epilepsy will stop having seizures, and SUDEP is very rare among them. The highest risk groups are those with a young age of onset, frequent generalized tonic–clonic seizures, and medical intractability. The mechanisms underlying SUDEP are unclear, and there are no effective preventative therapies. It is the contention of the other author (GLH) that it is not necessary, or advisable, to discuss SUDEP with all patients. Rather, he contends that SUDEP should be discussed only with those patients who are at high risk. In particular, patients who have generalized tonic–clonic seizures and who are non‐compliant with antiepileptic drugs should be counseled about their risk‐taking behavior. Both authors agree that additional studies into the pathophysiology and prevention of SUDEP are urgently needed.
Knowledge, Skill, and the Inculcation of the Anthropologist: Reflections on Learning to Sew in the Field
Authors: Prentice Rebecca 
Published: December 2008

AbstractThis article explores employment as a mode of participant observation, by analyzing the complex relationship between skill acquisition, embodiment, and anthropological analysis. It highlights the importance of thinking critically about the body, including the ethnographer's own body in the field. I describe working in a garment factory and learning to sew as part of my doctoral research on the garment industry in Trinidad, West Indies. I argue that disciplining the body into a particular craft is also a process of incorporating (or “taking into the body”) the ideologies of work that structure skill's meaning and practice. By describing my own difficulties “disembodying” what I learned in the field (in order to intellectualize the experience) I show how learning practical skills and enacting them everyday can be both a vigorous and perilous form of ethnographic research.
Combination of DNA methylation inhibitor 5‐azacytidine and arsenic trioxide has synergistic activity in myeloma
Authors: Chen Guanghua , Wang Yi , Huang Haiwen , Lin Fengru , Wu Depei , Sun Aining , Chang Huirong , Feng Yufeng 
Published: December 2008

AbstractXAF1 is a newly identified candidate tumour‐suppressor gene that can antagonise XIAP and sensitise cells to cell death triggers. This study was undertaken to study the effect of 5‐azacytidine (AZA) on XAF1 expression in myeloma cells and efficacy of 5‐AZA and arsenic trioxide (ATO) combination treatment in myeloma in vivo and in vitro. XAF1 expression was analysed by semi‐quantitative PCR and western blotting. Methylation specific PCR was used to detect methylation status of XAF1 promoter CpG islands. RPMI 8226 and XG‐7 cells were treated with various concentrations of 5‐AZA and ATO. Expression of XAF1 mRNA variants were confirmed by gel electrophoresis and sequencing. Untreated RPMI 8226 cell expresses two variants of XAF1 mRNA. Untreated XG‐7 cell has no expression of XAF1. Hypermethylation of XAF1 promoter CpG islands was detected in both cell lines. Both cell lines express full‐length XAF1 transcript after treated with 2.5 μmol/L 5‐AZA for 72 h. Our studies demonstrated that 5‐AZA exhibits anti‐myeloma synergy with ATO. In addition, ATO alone, 5‐AZA alone, or combination of 5‐AZA and ATO was effective in slowing myeloma growth and prolonging survival of myeloma‐loaded nude mice. The findings suggested that 5‐AZA and ATO may be an effective combination in the therapy of myeloma patients.
Echocardiographic finding in beta‐thalassemia intermedia and major: absence of pulmonary hypertension following hydroxyurea treatment in beta‐thalassemia intermedia
Authors: Karimi Mehran , Borzouee Mohammad , Mehrabani Alireza , Cohan Nader 
Published: December 2008

AbstractObjectives:  The aim of this study was to investigate the echocardigraphic finding in β‐thalassemia intermedia (TI) and β‐thalassemia major (TM) and to compare this finding together and with healthy control subjects.Methods:  Fifty TI, who have been treated with hydroxyurea (HU) for 7 yrs and 51 transfusion dependent TM were compared with 50 age and sex matched healthy control subjects. Left and right ventricular parameters, systolic and diastolic functions, stroke volume, cardiac index and indices of pulmonary hypertension (PHT) were determined by two‐dimensional, M‐mode echocardiography and Doppler echocardiography.Results:  Left ventricular parameters such as left ventricular end diastolic diameter, left ventricular end systolic diameter and also interventricular septal diameter in systole and diastole were significantly higher in TI patients compared with TM and control group (P < 0.05). There was elevated left ventricular mass (LV mass) in TI and TM patients compared with controls (P < 0.05). Regarding the LV diastolic function indices, E and A were significantly higher in TI patients compared with TM patients and control which were compatible with high output state. Measurement of pulmonary acceleration time and tricuspid and pulmonary valve continuous‐wave Doppler tracing in patients with tricuspid regurgitation and pulmonary insufficiency showed no difference between TI, TM and control group.Conclusion:  Both TI and TM patients who have no clinical signs of cardiac involvement have significant abnormalities in volume, mass and shape of the LV which may be the consequence of chronic anemia. We found the unexpected absence of PHT in TI patients who have been treated with HU. In conclusion Low dose HU treatment of TI patients may prevent the devastating complication of PHT.
Retiring in an Australian Country Town
Authors: Dempsey Ken 
Published: December 2008

ABSTRACTFindings from an enquiry into retirement in an Australian country town show that whilst there was often some sense of loss associated with retirement in the great majority of cases it proved a positive experience. It is argued that a satisfactory transition from work to retirement was facilitated by the small size of the community, the presence of lifelong friends, and opportunities for substitutionary or new sources of pleasure and usefulness.
TRANSIENT IMPROVEMENT OF MEMORY IN SENILE DEMENTIA FOLLOWING MNEMONIC TRAINING
Authors: Koch Carol , Luszcz Mary A. , Overstreet David H. , Henschke Philip J. 
Published: December 2008

ABSTRACTThe effect of Levodopa administration and mnemonic strategy training in the treatment of memory deficits associated with denile dementia of the Alzheimer type was investigated in a short‐term longitudinal study. Levodopa administration exerted no significant effect upon memory functioning whereas training in the chunking of information and in visual association led to a significant, but temporary, improvement in memory functioning. Training raised performance of demented subjects to about 58% of that of non‐demented controls, compared to the 38% observed at baseline. No significant interactions between the drug and training manipulation were indicated.
HEALTH AND AUTONOMY IN OLD AGE
Authors: Vanclay F. M. , Selby J. , Hall A. 
Published: December 2008

ABSTRACTThis paper examines theories on the health status of aged people by reference lo a survey of healthy, active, mobile elderly in Brisbane. In particular, theories relating to relationships between the aged person's self perception of health, their actual state of health, their subjective well being, and their autonomy and independence are considered.
IMPROVING EFFICIENCY AND COVERAGE IN SURVEY RESEARCH ON THE AGED
Authors: Rowland D. T. , Kendig H. L. , Jones R. G. 
Published: December 2008

ABSTRACTThis paper discusses approaches to survey design applied in a large scale study of the aged in Sydney. The subject matter concerns methods of (i) achieving an adequate coverage of topics and rare sub‐populations while minimising the need for prolonged interviews and sample weighting; (ii) locating a widely dispersed target population economically, (iii) maintaining control over respondent selection and (iv) ensuring the attainment of objectives despite cost constraints and uncertainty.