bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rheumatic heart disease in pregnancy: cardiac and obstetric outcomes
Authors: Sartain J. B. , Anderson N. L. , Barry J. J. , Boyd P. T. , Howat P. W. 
Published: January 2012

AbstractBackground:  Rheumatic heart disease (RHD) remains an important health issue for indigenous women of child‐bearing age in northern Australia. However, the influence of RHD on maternal outcomes with current clinical practice is unclear.Aims:  To determine maternal cardiac complications and obstetric outcomes in patients with RHD.Methods:  Retrospective case note analysis of women with RHD who received obstetric care between July 1999 and May 2010 at Cairns Base Hospital in north Queensland. Outcome measures were obstetric interventions and outcomes, cardiac interventions and complications, stratified according to a cardiac risk score (CRS).Results:  Ninety‐five confinements occurred in 54 patients, of whom 52 were Indigenous Australians. There were no maternal or neonatal deaths. With a CRS of 0, cardiac complications occurred in 0 of 70 confinements; with a CRS of 1, complications occurred in 5 of 17 confinements (29%); with a CRS of >1, complications occurred in 2 of 4 confinements (50%). Another four patients were first diagnosed with RHD after developing acute pulmonary oedema during the peripartum period.Conclusions:  RHD has a major impact on maternal cardiac outcomes. However, with current management practices, maternal and fetal mortality are low, and the incidence of complications is predictable based on known risk factors.
Effects of methylnaltrexone in patients with narcotic bowel syndrome: a pilot observational study
Authors: Gibson P. R. , Morrison G. 
Published: January 2012

AbstractBackground:  Narcotic bowel syndrome (NBS) describes disabling chronic severe abdominal pain that worsens despite continuing or escalating doses of opiates. Therapy is very limited.Aim:  To examine effects of blocking peripheral µ‐opioid receptors on the symptomatology of patients with NBS and its safety.Methods:  An open‐label observational study was performed in four women with NBS. After a 2‐week run‐in period, patients were treated for 12 weeks with 8–12 mg methylnaltrexone bromide subcutaneously every other day, increasing to daily if there was poor response. Patient and physician assessment was documented, and patients completed an eight‐symptom visual analogue scale weekly and the Functional Assessment of Chronic Illnesses Therapy‐Fatigue questionnaire for fatigue. Patients were observed for 4 weeks following withdrawal of the drug.Results:  One patient was unable to tolerate the study medication because of worsening pain after injection, and withdrew. Two showed clear benefit with reduction of symptoms overall, pain, bloating, distension, nausea and tiredness, with improved satisfaction and consistency of bowel actions and fatigue scores. Both reduced analgesic usage. The third had improved ileostomy output and had no episodes of severe bloating, but pain scores remained high. All three worsened after drug withdrawal and requested retreatment. Three experienced abdominal pains of moderate severity for 30–60 min consistently within 5 min of each injection. No other adverse events were experienced.Conclusions:  Methylnaltrexone has a positive impact on symptoms in women with NBS, although treatment does induce transient pain following its administration. Larger studies are required to examine its efficacy and longer term safety in this patient group.
Cysteine‐ and glycine‐rich protein 1a is involved in spinal cord regeneration in adult zebrafish
Authors: Ma Liping , Yu Young‐Mi , Guo Yuji , Hart Ronald P. , Schachner Melitta 
Published: January 2012

AbstractIn contrast to mammals, adult zebrafish have the ability to regrow descending axons and gain locomotor recovery after spinal cord injury (SCI). In zebrafish, a decisive factor for successful spinal cord regeneration is the inherent ability of some neurons to regrow their axons via (re)expressing growth‐associated genes during the regeneration period. The nucleus of the medial longitudinal fascicle (NMLF) is one of the nuclei capable of regenerative response after SCI. Using microarray analysis with laser capture microdissected NMLF, we show that cysteine‐ and glycine‐rich protein (CRP)1a (encoded by the csrp1a gene in zebrafish), the function of which is largely unknown in the nervous system, was upregulated after SCI. In situ hybridization confirmed the upregulation of csrp1a expression in neurons during the axon growth phase after SCI, not only in the NMLF, but also in other nuclei capable of regeneration, such as the intermediate reticular formation and superior reticular formation. The upregulation of csrp1a expression in regenerating nuclei started at 3 days after SCI and continued to 21 days post‐injury, the longest time point studied. In vivo knockdown of CRP1a expression using two different antisense morpholino oligonucleotides impaired axon regeneration and locomotor recovery when compared with a control morpholino, demonstrating that CRP1a upregulation is an important part of the innate regeneration capability in injured neurons of adult zebrafish. This study is the first to demonstrate the requirement of CRP1a for zebrafish spinal cord regeneration.
IRS2 signalling is required for the development of a subset of sensory spinal neurons
Authors: Chirivella Laura , Cano‐Jaimez Marifé , Pérez‐Sánchez Francisco , Herraez Luis , Carretero José , Fariñas Isabel , Burks Deborah J. , Kirstein Martina 
Published: January 2012

AbstractInsulin and insulin‐like growth factor‐I play important roles in the development and maintenance of neurons and glial cells of the nervous system. Both factors activate tyrosine kinase receptors, which signal through adapter proteins of the insulin receptor substrate (IRS) family. Although insulin and insulin‐like growth factor‐I receptors are expressed in dorsal root ganglia (DRG), the function of IRS‐mediated signalling in these structures has not been studied. Here we address the role of IRS2‐mediated signalling in murine DRG. Studies in cultured DRG neurons from different embryonic stages indicated that a subset of nerve growth factor‐responsive neurons is also dependent on insulin for survival at very early time points. Consistent with this, increased apoptosis during gangliogenesis resulted in a partial loss of trkA‐positive neurons in DRG of Irs2 mutant embryos. Analyses in adult Irs2−/− mice revealed that unmyelinated fibre afferents, which express calcitonin gene‐related peptide/substance P and isolectin B4, as well as some myelinated afferents to the skin were affected by the mutation. The diminished innervation of glabrous skin in adult Irs2−/− mice correlated with longer paw withdrawal latencies in the hot‐plate assay. Collectively, these findings indicate that IRS2 signalling is required for the proper development of spinal sensory neurons involved in the perception of pain.
Brain‐derived neurotrophic factor‐mediated effects on mitochondrial respiratory coupling and neuroprotection share the same molecular signalling pathways
Authors: Markham Anthony , Cameron Ian , Bains Rasneer , Franklin Paul , Kiss Janos P. , Schwendimann Leslie , Gressens Pierre , Spedding Michael 
Published: January 2012

AbstractIntracerebral injection of ibotenate into mouse pups induced grey matter lesions and white matter cysts; co‐administration of brain‐derived neurotrophic factor (BDNF) produced a dose‐dependent reduction in these lesions. In contrast, glial cell line‐derived neurotrophic factor (GDNF) had no significant effect, whereas nerve growth factor (NGF) or interleukin‐1β (IL‐1β) resulted in dose‐dependent exacerbation. The neuroprotective effects of BDNF were abolished by co‐administration of anti‐BDNF antibody or MEK inhibitors, or ABT‐737, a BH3 mimetic and Bcl‐2 antagonist. The actions of BDNF, GDNF and NGF were measured in a parallel in vitro study on the oxidative metabolism of mouse brain mitochondria. BDNF produced a concentration‐dependent increase in the respiratory control index (RCI, a measure of respiratory coupling efficiency, ATP synthesis, and organelle integrity) when co‐incubated with synaptosomes containing signal transduction pathways; but GDNF failed to modify RCI, and NGF had only weak effects. BDNF had no effect on pure mitochondria, and enhanced oxidation only when complex I substrates were used. The effect of BDNF was inhibited by anti‐BDNF antibody, MEK inhibitors or ABT‐737, and also by IL‐1β, indicating that the mitochondrial effects are mediated via the same MEK–Bcl‐2 pathway as the neuroprotection. The complex I inhibitor rotenone, a compound implicated in the aetiology of Parkinson’s disease, inhibited both the in vitro mitochondrial and in vivo neuroprotective effects of BDNF. The ability of BDNF to modify brain metabolism and the efficiency of oxygen utilization via a MEK–Bcl‐2 pathway may be an important component of the neuroprotective action observed with this neurotrophin.
Increased stress reactivity is associated with reduced hippocampal activity and neuronal integrity along with changes in energy metabolism
Authors: Knapman Alana , Kaltwasser Sebastian F. , Martins‐de‐Souza Daniel , Holsboer Florian , Landgraf Rainer , Turck Christoph W. , Czisch Michael , Touma Chadi 
Published: January 2012

AbstractPatients suffering from major depression have repeatedly been reported to have dysregulations in hypothalamus–pituitary–adrenal (HPA) axis activity along with deficits in cognitive processes related to hippocampal and prefrontal cortex (PFC) malfunction. Here, we utilized three mouse lines selectively bred for high (HR), intermediate, or low (LR) stress reactivity, determined by the corticosterone response to a psychological stressor, probing the behavioral and functional consequences of increased vs. decreased HPA axis reactivity on the hippocampus and PFC. We assessed performance in hippocampus‐ and PFC‐dependent tasks and determined the volume, basal activity, and neuronal integrity of the hippocampus and PFC using in vivo manganese‐enhanced magnetic resonance imaging and proton magnetic resonance spectroscopy. The hippocampal proteomes of HR and LR mice were also compared using two‐dimensional gel electrophoresis and mass spectrometry. HR mice were found to have deficits in the performance of hippocampus‐ and PFC‐dependent tests and showed decreased N‐acetylaspartate levels in the right dorsal hippocampus and PFC. In addition, the basal activity of the hippocampus, as assessed by manganese‐enhanced magnetic resonance imaging, was reduced in HR mice. The three mouse lines, however, did not differ in hippocampal volume. Proteomic analysis identified several proteins that were differentially expressed in HR and LR mice. In accordance with the notion that N‐acetylaspartate levels, in part, reflect dysfunctional mitochondrial metabolism, these proteins were found to be involved in energy metabolism pathways. Thus, our results provide further support for the involvement of a dysregulated HPA axis and mitochondrial dysfunction in the etiology and pathophysiology of affective disorders.
Archer fish fast hunting maneuver may be guided by directionally selective retinal ganglion cells
Authors: Tsvilling Vadim , Donchin Opher , Shamir Maoz , Segev Ronen 
Published: January 2012

AbstractArcher fish are known for their unique hunting method, where one fish in a group shoots down an insect with a jet of water while all the other fish are observing the prey’s motion. To reap its reward, the archer fish must reach the prey before its competitors. This requires fast computation of the direction of motion of the prey, which enables the fish to initiate a turn towards the prey with an accuracy of 99%, at about 100 ms after the prey is shot. We explored the hypothesis that direction‐selective retinal ganglion cells may underlie this rapid processing. We quantified the degree of directional selectivity of ganglion cells in the archer fish retina. The cells could be categorized into three groups: sharply (5%), broadly (37%) and non‐tuned (58%) directionally selective cells. To relate the electrophysiological data to the behavioral results we studied a computational model and estimated the time required to accumulate sufficient directional information to match the decision accuracy of the fish. The computational model is based on two direction‐selective populations that race against each other until one reaches the threshold and drives the decision. We found that this competition model can account for the observed response time at the required accuracy. Thus, our results are consistent with the hypothesis that the fast response behavior of the archer fish relies on retinal identification of movement direction.
Applying developed‐country regulation in emerging markets: an analysis of Thai insider trading
Authors: Budsaratragoon Pornanong , Hillier David , Lhaopadchan Suntharee 
Published: January 2012

AbstractThis paper undertakes an out‐of‐sample test of developed‐country insider trading regulation in an emerging market environment (Thailand), where severe information asymmetry, lax enforcement and poor pricing efficiency are endemic. Thai insider trading regulation, which mimics developed market rules, fails on all three measures of success. Insiders trade with impunity during a regulated trading ban. Their trading performance outperforms other investors at all times, and they continue to exploit their privileged position with respect to information flow. Our study suggests it is inappropriate for emerging market regulators to adopt developed market regulation without first considering the unique characteristics of their own environment.
Occupational and Locational Substitution: Measuring the Effect of Occupational and Regional Mobility
Authors: Aldashev Alisher 
Published: January 2012

AbstractThe paper analyses the effects of occupational and regional mobility on the matching rate using monthly panel data disaggregated at the regional and occupational level. The main contribution of the paper is to measure the effect of substitutability between vacancies in different occupations, and vacancies in different regions on the matching rate. The estimates indicate higher regional mobility in West Germany but higher occupational mobility in East Germany. The results show that if occupations were perfect substitutes, then the number of matches could increase by 5–9 per cent. Perfect regional mobility would increase matchings by 5–15 per cent. It is also shown that partial aggregation causes a downward bias in substitutability estimates.
Sunlight is associated with decreased multiple sclerosis risk: no interaction with human leukocyte antigen‐DRB1*15
Authors: Bäärnhielm M. , Hedström A. K. , Kockum I. , Sundqvist E. , Gustafsson S. A. , Hillert J. , Olsson T. , Alfredsson L. 
Published: January 2012

Background:  Both insufficient exposure to sunlight and vitamin D deficiency have been associated with an increased risk for multiple sclerosis (MS). An interaction between human leukocyte antigen HLA‐DRB1*15 and vitamin D in MS was recently proposed. We investigated the association between previous exposure to ultraviolet radiation (UVR), vitamin D status at inclusion in the study, and MS risk including the interaction of these factors with HLA‐DRB1*15.Methods:  A population‐based case–control study involving 1013 incident cases of MS and 1194 controls was performed in Sweden during 2005–2010. Subjects were classified according to their UVR exposure habits, vitamin D status, and HLA genotypes. The associations between different sun exposure habits/vitamin D levels and MS were calculated as odds ratios (OR) with 95% confidence intervals (CI) using logistic regression. Potential interaction was evaluated by calculating the attributable proportion due to interaction.Results:  Subjects with low UVR exposure had a significantly increased risk of MS compared with those who reported the highest exposure (OR 2.2, 95% CI 1.5–3.3). Similarly, subjects who had 25‐hydroxy‐vitamin D levels less than 50 nM/l had an increased risk for MS (OR 1.4, 95% CI 1.2–1.7). The association between UVR exposure and MS risk persisted after adjustment for vitamin D status. There was no interaction with HLA‐DRB1*15 carriage.Conclusions:  UVR and vitamin D seem to affect MS risk in adults independently of HLA‐DRB1*15 status. UVR exposure may also exert a protective effect against developing MS via other pathways than those involving vitamin D.
Telomere length shortening in patients with dementia with Lewy bodies
Authors: Kume K. , Kikukawa M. , Hanyu H. , Takata Y. , Umahara T. , Sakurai H. , Kanetaka H. , Ohyashiki K. , Ohyashiki J. H. , Iwamoto T. 
Published: January 2012

Background and purpose:  Shortened telomere length has been considered to be associated with various age‐related diseases, especially in dementia such as Alzheimer’s disease and vascular dementia. However, changes in telomere length in dementia with Lewy bodies (DLB) remain unclear. To elucidate these changes, we set out to determine telomere length in peripheral leukocytes as well as the level of urinary 8‐hydroxy‐deoxyguanosine (8‐OHdG) as a marker of oxidative stress in DLB.Methods:  Blood samples were obtained from 33 patients with a clinical diagnosis of probable DLB and 35 age‐matched, non‐demented elderly controls (NEC). Telomere length was assessed by quantitative real‐time polymerase chain reaction of genomic DNA extracted from leukocytes, whereas oxidative stress was assessed on the basis of urine 8‐OHdG level, which was measured using high‐performance liquid chromatography.Results:  Telomere length was significantly shorter in the DLB group than in the NEC group. Urinary 8‐OHdG levels were significantly higher in the DLB group than in the NEC group. There was a negative correlation between telomere length and age in the DLB group; however, there were no significant relationships between telomere length and clinical findings including disease duration, severity of cognitive decline, presence or absence of fluctuation in cognitive function, visual hallucinations, and Parkinsonism. In both groups, the correlation between telomere length and urinary 8‐OHdG levels was not significant.Conclusions:  These findings indicate that the etiopathology of DLB is considered to be an accelerated aging process.
Activated human hydroxy‐carboxylic acid receptor‐3 signals to MAP kinase cascades via the PLC‐dependent PKC and MMP‐mediated EGFR pathways
Authors: Zhou Q , Li G , Deng XY , He XB , Chen LJ , Wu C , Shi Y , Wu KP , Mei LJ , Lu JX , Zhou NM 
Published: January 2012

BACKGROUND AND PURPOSE 3‐Hydroxy‐octanoate, recently identified as a ligand for, the orphan GPCR, HCA3, is of particular interest given its ability to treat lipid disorders and atherosclerosis. Here we demonstrate the pathway of HCA3‐mediated activation of ERK1/2.EXPERIMENTAL APPROACH Using CHO‐K1 cells stably expressing HCA3 receptors and A431 cells, a human epidermoid cell line with high levels of endogenous expression of functional HCA3 receptors, HCA3‐mediated activation of ERK1/2 was measured by Western blot.KEY RESULTS HCA3‐mediated activation of ERK1/2 was rapid, peaking at 5 min, and was Pertussis toxin sensitive. Our data, obtained by time course analyses in combination with different kinase inhibitors, demonstrated that on agonist stimulation, HCA3 receptors evoked ERK1/2 activation via two distinct pathways, the PLC/PKC pathway at early time points (≤2 min) and the MMP/ epidermal growth factor receptor (EGFR) transactivation pathway with a maximum response at 5 min. Furthermore, our present results also indicated that the βγ‐subunits of the Gi protein play a critical role in HCA3‐activated ERK1/2 phosphorylation, whereas β‐arrestins and Src were not required for ERK1/2 activation.CONCLUSIONS AND IMPLICATIONS We have described the molecular mechanisms underlying the coupling of human HCA3 receptors to the ERK1/2 MAP kinase pathway in CHO‐K1 and A431 cells, which implicate the Gi protein‐initiated, PLC/PKC‐ and platelet‐derived growth factor receptor/EGFR transactivation‐dependent pathways. These observations may provide new insights into the pharmacological effects and the physiological functions modulated by the HCA3‐mediated activation of ERK1/2.
Effects of temperature on the development of overwintering immature stages of the near‐threatened butterfly Leptalina unicolor (Bremer & Grey) (Lepidoptera: Hesperiidae)
Authors: INOUE Takenari 
Published: January 2012

AbstractOverwintering larvae of multivoltine and univoltine populations of Leptalina unicolor were reared under various constant and fluctuating temperatures superimposed on a photoperiod of either 12 h of light and 12 h of darkness (LD 12:12) or LD 15:9. Diapause of the larvae terminated in midwinter (by early February). All the larvae of both populations pupated after two molts without feeding and the head capsule width of the final instar larvae was smaller than that of the penultimate instar ones. The photoperiod did not significantly affect larval development, but long‐day conditions (LD 15:9) hastened pupal development. The thermoperiod had a significant effect on the development of the multivoltine population. When multivoltine population larvae were kept under a low fluctuating temperature regime (cryophase/thermophase = 14/20°C), the period until adult eclosion was shorter than that under a constant temperature of 17°C. On the contrary, when larvae were kept under a high fluctuating temperature regime (24/30°C), the period until adult eclosion was longer than that under a constant temperature of 27°C. However, the univoltine population did not show such a reaction to the fluctuating temperature. The durations of final instar larva and pupa of the multivoltine population were shorter than those of the univoltine population. The developmental zeros of penultimate and final instar larvae and pupae of the univoltine population were lower than those of the multivoltine population. The head capsule width of penultimate instar larvae and the forewing length of adults of the univoltine population were larger than those of the multivoltine population for both sexes.
Identification of new epilepsy treatments: Issues in preclinical methodology
Authors: Galanopoulou Aristea S. , Buckmaster Paul S. , Staley Kevin J. , Moshé Solomon L. , Perucca Emilio , Engel Jerome , Löscher Wolfgang , Noebels Jeffrey L. , Pitkänen Asla , Stables James , White H. Steve , O’Brien Terence J. , Simonato for the American Epilepsy Society Basic Science Com Michele 
Published: January 2012

SummaryPreclinical research has facilitated the discovery of valuable drugs for the symptomatic treatment of epilepsy. Yet, despite these therapies, seizures are not adequately controlled in a third of all affected individuals, and comorbidities still impose a major burden on quality of life. The introduction of multiple new therapies into clinical use over the past two decades has done little to change this. There is an urgent demand to address the unmet clinical needs for: (1) new symptomatic antiseizure treatments for drug‐resistant seizures with improved efficacy/tolerability profiles, (2) disease‐modifying treatments that prevent or ameliorate the process of epileptogenesis, and (3) treatments for the common comorbidities that contribute to disability in people with epilepsy. New therapies also need to address the special needs of certain subpopulations, that is, age‐ or gender‐specific treatments. Preclinical development in these treatment areas is complex due to heterogeneity in presentation and etiology, and may need to be formulated with a specific seizure, epilepsy syndrome, or comorbidity in mind. The aim of this report is to provide a framework that will help define future guidelines that improve and standardize the design, reporting, and validation of data across preclinical antiepilepsy therapy development studies targeting drug‐resistant seizures, epileptogenesis, and comorbidities.