bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic Efficacy of High‐Molecular‐Weight Antigenic Fractions of a Recent Clinical Isolate of Leishmania donovani Against Visceral Leishmaniasis
Authors: Tripathi P. , Gupta S. K. , Sinha S. , Sundar S. , Dube A. , Naik S. 
Published: September 2008

AbstractT‐cell mediated immune responses are key determinants to the natural course of infection caused by intracellular parasites such as Leishmania. Thus, T‐cell activating proteins of these microbes continue to generate active interest particularly in view of their possible role in the design and development of newer and more effective vaccines. We have recently reported the presence of T‐cell immunostimulatory antigens with the high‐molecular‐weight (MW) fractions (134–64.2 kDa) of whole Leishmania donovani antigen (strain 2001), which stimulated variable amounts of IFN‐γ, IL‐12 and IL‐10 in exposed immune individuals. The present study was undertaken to further evaluate these high‐MW antigenic fractions (MW range >100–60 kDa) for potential protective efficacy. The high‐MW region of the parasite was resolved into five antigenic fractions (Prep A–E) using continuous elution gel electrophoresis. Prior to in vivo protection studies in hamsters, these fractions were used to evaluate in vitro cellular responses in eight Leishmania‐exposed individuals and treated cured hamsters. The protective efficacy of prep (A + B), C, D and E in combination with BCG was evaluated in inbred hamsters using standard immunization protocol. Proliferative responses were seen in all eight of eight exposed individuals to prep D [median stimulation index (SI): 5.2 (range 3.9–7.1)] and E [median SI: 5.6 (range 4.4–8.2)], five of eight individuals to prep B and prep C and three of eight to prep A [median SI: 0.2 (range 0.1–7.2)]. The median proliferative responses to prep D and prep E were significantly higher than to fraction prep A; (P < 0.05) but not to prep B and prep C. However, prep A–E induced equivalent levels of IFN‐γ, IL‐10 and IL‐12 cytokines. Fractions D and E also exhibited marked parasite inhibition in spleen (52.5% and 73.7%) and liver (65% and 80.2%) as compared with prep (A + B) (23% in spleen and 24% in liver) and prep C (38% in spleen and 24% in liver). Prep D and prep E vaccinated animals showed higher in vitro stimulatory responses (mean SI: 6.6 and 8.8) and nitric oxide (NO) induction (mean NO levels: 6.4 and 10.7 μg/ml) against whole cell extract as compared with other groups. The protection also correlated with presence of suppressed Leishmania‐specific IgG levels in prep D and prep E immunized hamsters. These studies indicate the presence of immunostimulatory and protective molecules in 60–80 kDa region of L. donovani, which may be further exploited for developing a subunit vaccine.
Diagnostic accuracy of a new Leishmania PCR for clinical visceral leishmaniasis in Nepal and its role in diagnosis of disease
Authors: Deborggraeve Stijn , Boelaert Marleen , Rijal Suman , De Doncker Simonne , Dujardin Jean‐Claude , Herdewijn Piet , Büscher Philippe 
Published: September 2008

SummaryObjective  To develop a new PCR for Leishmania detection and to estimate its diagnostic accuracy in a visceral leishmaniasis (VL) endemic area.Methods  After providing the proof‐of‐concept, the diagnostic accuracy was estimated on blood from 247 non‐endemic control persons and on blood and bone marrow from 173 confirmed VL, 39 probable VL and 87 non‐VL patients from south‐eastern Nepal.Results  The PCR showed a specificity of 99.64% [95% confidence interval (CI): 98.93–100%) on non‐endemic controls and a sensitivity of 92.1% (95% CI: 87.6–96.6%) on blood and 92.9% (95% CI: 89–96.8%) on bone marrow from the confirmed VL patients. Leishmania DNA was detected in blood and bone marrow of 67.6% (95% CI: 50.8–80.9%) and 71.8% (95% CI: 56.2–83.5%) of the probable VL patients, respectively, and of 38.2% (95% CI: 28–49.4%) and 29.9% (95% CI: 21.3–40.2%) of the non‐VL patients, respectively. The PCR showed 97% concordance with a positive DAT status while for a negative DAT status this was only 41.3% (kappa‐index 0.416, 95% CI: 0.30–0.53).Conclusions  Our findings indicate that PCR alone rather provides a marker for infection than a marker for disease and its role in VL diagnosis in endemic regions is discussed.
Responses of global plant diversity capacity to changes in carbon dioxide concentration and climate
Authors: Woodward F. I. , Kelly C. K. 
Published: September 2008

AbstractWe model plant species diversity globally by country to show that future plant diversity capacity has a strong dependence on changing climate and carbon dioxide concentration. CO2 increase, through its impact on net primary production and warming is predicted to increase regional diversity capacity, while warming with constant CO2 leads to decreases in diversity capacity. Increased CO2 concentrations are unlikely to counter projected extinctions of endemic species, shown in earlier studies to be more strongly dependent on changing land use patterns than climate per se. Model predictions were tested against (1) contemporary observations of tree species diversity in different biomes, (2) an independent global map of contemporary species diversity and (3) time sequences of plant naturalisation for different locations. Good agreements between model, observations and naturalisation patterns support the suggestion that future diversity capacity increases are likely to be filled from a ‘cosmopolitan weed pool’ for which migration appears to be an insignificant barrier.
Acetophenone superior to verbenone for reducing attraction of western pine beetle Dendroctonus brevicomis to its aggregation pheromone
Authors: Erbilgin Nadir , Gillette Nancy E. , Owen Donald R. , Mori Sylvia R. , Nelson Andrew S. , Uzoh Fabian , Wood David L. 
Published: September 2008

Abstract1 The western pine beetle Dendroctonus brevicomis LeConte (Coleoptera: Scolytidae) is one of the most damaging insect pests of ponderosa pines Pinus ponderosa Douglas ex P. & C. Lawson in Western U.S.A. We compared the effect of verbenone, a well known bark beetle anti‐aggregation pheromone, with that of acetophenone on the attraction of D. brevicomis to its aggregation pheromone in a ponderosa pine forest in northern California. We tested the D. brevicomis aggregation pheromone alone and with three different release ratios of the aggregation pheromone (attractant) to verbenone or acetophenone (1 : 1, 1 : 2 and 1 : 5).2 All treatments containing acetophenone or verbenone resulted in a significant reduction in the catch of D. brevicomis relative to the aggregation pheromone alone. When beetle responses to the three verbenone or three acetophenone treatments were pooled, the pooled verbenone treatment caught more D. brevicomis than the pooled acetophenone treatment.3 There was no significant difference in the number of D. brevicomis caught among the three release rates of verbenone. By contrast, the 1 : 2 attractant : acetophenone ratio attracted significantly more D. brevicomis than the traps with the 1 : 5 attractant : acetophenone ratio.4 Attraction of a major predator, Temnochila chlorodia (Mannerheim) (Coleoptera: Trogositidae), to the aggregation pheromone of D. brevicomis was reduced by verbenone, but not by acetophenone. Moreover, the T. chlorodia : D. brevicomis ratio for the pooled acetophenone treatment was 1.7‐fold greater than that for the attractant alone and two‐fold greater than the ratio for the pooled verbenone treatment, suggesting that acetophenone would not disrupt populations of this natural enemy. The importance of anti‐attractants in the biology of D. brevicomis and other bark beetles is discussed.
Clinical assessment of prognostic factors for long‐term pain and handicap after whiplash injury: a 1‐year prospective study
Authors: Kasch H. , Qerama E. , Kongsted A. , Bendix T. , Jensen T. S. , Bach F. W. 
Published: September 2008

Background and purpose:  Physical mechanisms are the possible factors involved in the development and maintenance of long‐term handicaps after acute whiplash injury. This study prospectively examined the role of active neck mobility, cervical and extra‐cervical pains, as well as non‐painful complaints after a whiplash injury as predictors for subsequent handicap.Methods:  Consecutive acute whiplash patients (n = 688) were interviewed and examined by a study nurse after the median of 5 days after injury, and divided into a high‐ or a low‐risk group by an algorithm based on pain intensity, number of non‐painful complaints and active neck mobility [active cervical range of motion (CROM)]. All 458 high‐risk patients and 230 low‐risk patients received mailed questionnaires after 3, 6 and 12 months. Two examiners examined all high‐risk patients (n = 458) and 41 consecutive low‐risk patients at median 11, 109, 380 days after injury. The main outcome measures were: handicaps, severe headaches, neck pain and neck disability.Results:  The relative risk for a 1‐year disability increased by 3.5 with initial intense neck pain and headaches, by 4.6 times with reduced CROM and by four times with multiple non‐painful complaints.Conclusion:  Reduced active neck mobility, immediate intense neck pain and headaches and the presence of multiple non‐painful complaints are the important prognostic factors for a 1‐year handicap after acute whiplash.
Chondrichthyans have a bulbus arteriosus at the arterial pole of the heart: morphological and evolutionary implications
Authors: Durán Ana C. , Fernández Borja , Grimes Adrian C. , Rodríguez Cristina , Arqué Josep M. , Sans‐Coma Valentín 
Published: September 2008

AbstractIt has been generally assumed that the outflow tract of the chondrichthyan heart consists of the conus arteriosus, characterized by cardiac muscle in its walls. However, classical observations, neglected for many years, indicated that the distal component of the cardiac outflow tract of several elasmobranch species was composed of tissue resembling that of the ventral aorta. The present study was outlined to test the hypothesis that this intrapericardial, non‐myocardial component might be homologous to the actinopterygian bulbus arteriosus. The material consisted of Atlantic catshark adults and embryos, which were examined by means of histochemical and immunohistochemical techniques for light and fluorescence microscopy. In this species, the distal component of the outflow tract differs histomorphologically from both the ventral aorta and the conus arteriosus; it is devoid of myocardium, is covered by epicardium and is crossed by the coronary arterial trunks. In the embryonic hearts examined, this distal component showed positive reactivity for 4,5‐diaminofluorescein 2‐diacetate (DAF‐2DA), a fluorescent nitric oxide indicator. These findings, together with other observations in holocephals and several elasmobranch species, confirm that chondrichthyans possess a bulbus arteriosus interposed between the conus arteriosus and the ventral aorta. Therefore, the primitive heart of gnathostomates consists of five intrapericardial components, sinus venosus, atrium, ventricle, conus arteriosus and bulbus arteriosus, indicating that the bulbus arteriosus can no longer be regarded as an actinopterygian apomorphy. The DAF‐2DA‐positive reactivity of the chondrichthyan embryonic bulbus suggests that this structure is homologous to the base of the great arterial trunks of birds and mammals, which derives from the embryonic secondary heart field.
Nerve growth factor regulates the expression of the cholinergic locus and the high‐affinity choline transporter via the Akt/PKB signaling pathway
Authors: Madziar Beata , Shah Sonia , Brock Martina , Burke Rebecca , Lopez‐Coviella Ignacio , Nickel Ann‐Christin , Cakal Esra Betul , Blusztajn Jan Krzysztof , Berse Brygida 
Published: September 2008

AbstractNerve growth factor (NGF) is a trophic and survival factor for cholinergic neurons, and it induces the expression of several genes that are essential for synthesis and storage of acetylcholine (ACh), specifically choline acetyltransferase, vesicular ACh transporter (VAChT), and choline transporter. We have found previously that the phosphatidylinositol 3′‐kinase pathway, but not the MEK/MAPK pathway, is the mediator of NGF‐induced cholinergic differentiation. Here we demonstrate, in the rat pheochromocytoma cell line PC12 and in primary mouse neuronal cultures, that NGF‐evoked up‐regulation of these three cholinergic‐specific genes is mediated by the anti‐apoptotic signaling molecule Akt/protein kinase B. Inhibition of Akt activation by the pharmacological inhibitor 1L‐6‐hydroxymethyl‐chiro‐inositol 2(R)‐2‐O‐methyl‐3‐O‐octadecylcarbonate (HIMO), or by a peptide fragment derived from the proto‐oncogene TLC1, eliminated NGF‐stimulated increases in cholinergic gene expression, as demonstrated by RT‐PCR and reporter gene assays. Moreover, treatment with HIMO reversed NGF‐evoked increases in choline acetyltransferase activity and ACh production. In co‐transfection assays with the reporter construct, a dominant‐negative Akt plasmid and Akt1‐specific small interfering RNA also attenuated NGF‐induced cholinergic promoter activity. Our data indicate that, in addition to its well‐described role in promoting neuronal survival, Akt can also mediate signals necessary for neurochemical differentiation.
The methylmercury‐l‐cysteine conjugate is a substrate for the L‐type large neutral amino acid transporter
Authors: Yin Zhaobao , Jiang Haiyan , Syversen Tore , Rocha João B. T. , Farina Marcelo , Aschner Michael 
Published: September 2008

AbstractMethylmercury (MeHg) is a potent neurotoxin. The mechanism(s) that governs MeHg transport across the blood‐brain barrier and other biological membranes remains unclear. This study addressed the role of the L‐type large neutral amino acid transporter, LAT1, in MeHg transport. Studies were carried out in CHO‐k1 cells. Over‐expression of LAT1 in these cells was associated with enhanced uptake of [14C]‐MeHg when treated withl‐cysteine, but not with thed‐cysteine conjugate. In the presence of excessl‐methionine, a substrate for LAT1,l‐cysteine‐conjugated [14C]‐MeHg uptake was significantly attenuated. Treatment of LAT‐1 over‐expressing CHO‐k1 cells withl‐cysteine‐conjugated MeHg was also associated with increased leakage of lactate dehydrogenase into the media as well as reduced cell viability measured by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide reduction assay. In contrast, knock‐down of LAT1 decreased the uptake ofl‐cysteine‐conjugated MeHg and attenuated the effects of MeHg on lactate dehydrogenase leakage and CHO‐k1 cell viability. These results indicate that the MeHg‐l‐cysteine conjugate is a substrate for the neutral amino acid transporter, LAT1, which actively transports MeHg across membranes.
c‐Jun Expression, activation and function in neural cell death, inflammation and repair
Authors: Raivich Gennadij 
Published: September 2008

AbstractUp‐regulation of c‐Jun is a common event in the developing, adult as well as in injured nervous system that serves as a model of transcriptional control of brain function. Functional studies employingin vivostrategies using gene deletion, targeted expression of dominant negative isoforms and pharmacological inhibitors all suggest a three pronged role of c‐Jun action, exercising control over neural cell death and degeneration, in gliosis and inflammation as well as in plasticity and repair.In vitro, structural and molecular studies reveal several non‐overlapping activation cascades via N‐terminal c‐Jun phosphorylation at serine 63 and 73 (Ser63, Ser73), and threonine 91 and 93 (Thr91, Thr93) residues, the dephosphorylation at Thr239, the p300‐mediated lysine acetylation of the near C‐terminal region (Lys268, Lys271, Lys 273), as well as the Jun‐independent activities of the Jun N‐terminal family of serine/threonine kinases, that regulate the different and disparate cellular responses. A better understanding of these non‐overlapping rolesin vivocould considerably increase the potential of pharmacological agents to improve neurological outcome following trauma, neonatal encephalopathy and stroke, as well as in neurodegenerative disease.
Pathogenic missense MAPT mutations differentially modulate tau aggregation propensity at nucleation and extension steps
Authors: Chang Edward , Kim Sohee , Yin Haishan , Nagaraja Haikady N. , Kuret Jeff 
Published: September 2008

AbstractMutations in the MAPT gene encoding tau protein lead to neurofibrillary lesion formation, neurodegeneration, and cognitive decline associated with frontotemporal lobar degeneration. While some pathogenic mutations affect MAPT introns, resulting in abnormal splicing patterns, the majority occur in the tau coding sequence leading to single amino acid changes in tau primary structure. Depending on their location within the polypeptide chain, tau missense mutations have been reported to augment aggregation propensity. To determine the mechanisms underlying mutation‐associated changes in aggregation behavior, the fibrillization of recombinant pathogenic mutants R5L, G272V, P301L, V337M, and R406W prepared in a full‐length four‐repeat human tau background was examined in vitro as a function of time and submicromolar tau concentrations using electron microscopy assay methods. Kinetic constants for nucleation and extension phases of aggregation were then estimated by direct measurement and mathematical simulation. Results indicated that the mutants differ from each other and from wild‐type tau in their aggregation propensity. G272V and P301L mutations increased the rates of both filament nucleation and extension reactions, whereas R5L and V337M increased only the nucleation phase. R406W did not differ from wild‐type in any kinetic parameter. The results show that missense mutations can directly promote tau filament formation at different stages of the aggregation pathway.
Amino acids involved in conformational dynamics and G protein coupling of an odorant receptor: targeting gain‐of‐function mutation
Authors: Kato Aya , Katada Sayako , Touhara Kazushige 
Published: September 2008

AbstractThousands of different odorants are recognized and discriminated by odorant receptors (ORs) in the guanine nucleotide‐binding protein (G protein)‐coupled seven‐transmembrane receptor family. Odorant‐bound ORs stimulate Gs‐type G proteins, Gαolf, which in turn activates cAMP‐mediated signaling pathway in olfactory sensory neurons. To better understand the molecular basis for OR activation and G protein coupling, we analyzed the effects of a series of site‐directed mutations of mouse ORs, on function. Mutations of conserved amino acid residues in an intracellular loop or the C‐terminus resulted in loss of activity without impairing ligand‐binding activity, indicating that these residues are involved in Gαs/olf coupling. Moreover, mutation of the serine in KAFSTC, the OR‐specific sequence motif, resulted in a dramatic increase in odorant responsiveness, suggesting that the motif is involved in a conformational change of the receptor that regulates G protein coupling efficiency. Our results provide insights into how ORs switch from an inactive to an active state, as well as where and how activated ORs interact with G proteins.
Extended NO analysis in a healthy subgroup of a random sample from a Swedish population
Authors: Högman Marieann , Lafih Jaroslava , Meriläinen Pekka , Bröms Kristina , Malinovschi Andrei , Janson Christer 
Published: September 2008

SummaryIntroduction:  There is an interest in modelling exhaled nitric oxide (NO). Studies have shown that flow‐independent NO parameters i.e. NO of the alveolar region (CANO), airway wall (CawNO), diffusing capacity (DawNO) and flux (JawNO), are altered in several disease states such as asthma, cystic fibrosis, alveolitis and chronic obsmuctive pulmonary disease (COPD). However, values from a healthy population are missing.Objectives:  To calculate NO parameters in a healthy population by collecting NO values at different exhalation flow rates.Methods:  A random sample from the ECRHS II study was investigated. Among the 281 subjects that had performed a bronchial hyperreactivity (BHR)‐test, FEV1·0, IgE and NO‐analyses 89 were found to be healthy.Results:  There were no differences in FENO0·05 or NO parameters between men and women. There were weak correlations between height and both FENO0·05 (r = 0·23, P = 0·03) and CawNO (r = 0·22, P = 0·04). There was also a correlation between age and CANO (r = 0·28, P = 0·007). When controlled for gender, this correlation was more powerful in women (r = 0·51, P = 0·001) but did not remain for male subjects.Conclusion:  Extended NO analysis is a simple non‐invasive tool that gives by far more information than FENO0·05. Based on our results, we suggest that the values for healthy subjects should be considered to fall between the following ranges: FENO0·05, 10–30 ppb; CawNO, 50–250 ppb; DawNO, 5–15 ml s−1; JawNO, 0·8–1·6 nl s−1; and CANO, 0–4 ppb. Values outside these intervals indicate the need for further investigation to exclude a state of disease.
Interictal rhythmical midline theta differentiates frontal from temporal lobe epilepsies
Authors: Beleza Pedro , Bilgin Özgür , Noachtar Soheyl 
Published: September 2008

SummaryPurpose:  We evaluated the role of interictal rhythmical midline theta (RMT) in the identification of frontal lobe epilepsy (FLE) and its differentiation from temporal lobe epilepsy (TLE) and nonepileptic controls.Methods:  We included 162 individuals in the study: 54 FLE patients, 54 TLE patients, and 54 nonepileptic controls. Continuous electroencephalographic (EEG)‐video monitoring was performed in all individuals. Interictal RMT was included only if it occurred during definite awake states. RMT associated with drowsiness or mental activation and ictal RMT was excluded.Results:  We identified RMT significantly more frequently in FLE patients (48.1%, 26 of 54) than in TLE patients (3.7%, 2 of 54) (p < 0.01), and not in the control group. The average frequency was 6 Hz (range 5–7 Hz), and the average RMT bursts lasted 8 s (3–12 s). Interestingly, all mesial FLE patients (n = 4) (as established by invasive EEG recordings) showed RMT, whereas this was less frequently the case in the other FLE patients (44%, 22 of 50) (p = 0.03). Thirteen of our 54 patients with FLE (24%) did not have any interictal epileptiform discharges (IEDs), but RMT was observed in the majority of these patients (62%, 8 of 13).Conclusion:  Interictal RMT is common and has a localizing value in patients with FLE, provided that conditions such as drowsiness and mental activation as confounding factors for RMT are excluded. RMT should be included in the evaluation of patients considered for resective epilepsy surgery.