bluuebunny/crossref_metadata_2025 huggingface dataset:
Six degrees of Apodemus separation
Authors: McCallum Hamish
Published: July 2009

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S.E. Perkins, F. Cagnacci, A. Stradiotto, D. Arnoldi & P.J. Hudson (2009) A comparison of social networks derived from ecological data: implications for inferring infectious disease dynamics. Journal of Animal Ecology, 78, 1015–1022.

Social network analysis has been widely used to help understand the transmission of human diseases. Its application to wildlife disease is very much in its infancy, largely because of the difficulty of recording contacts between wild animals. Sarah Perkins et al. have constructed contact networks for yellow‐necked mice (Apodemus flavicollis) in the Italian Alps, comparing networks derived from radio‐tracking and mark–recapture data. They found that the method producing the most informative data depended on population density. However, all networks had aggregated contact distributions, which is important for understanding disease transmission.
Genetic and biochemical analyses of the Pseudomonas aeruginosa Psl exopolysaccharide reveal overlapping roles for polysaccharide synthesis enzymes in Psl and LPS production
Authors: Byrd Matthew S. , Sadovskaya Irina , Vinogradov Evgueny , Lu Haiping , Sprinkle April B. , Richardson Stephen H. , Ma Luyan , Ralston Brad , Parsek Matthew R. , Anderson Erin M. , Lam Joseph S. , Wozniak Daniel J.
Published: July 2009

Exopolysaccharides contribute significantly to attachment and biofilm formation in the opportunisitc pathogen Pseudomonas aeruginosa. The Psl polysaccharide, which is synthesized by the polysaccharide synthesis locus (psl), is required for biofilm formation in non‐mucoid strains that do not rely on alginate as the principal biofilm polysaccharide. In‐frame deletion and complementation studies of individual psl genes revealed that 11 psl genes, pslACDEFGHIJKL, are required for Psl production and surface attachment. We also present the first structural analysis of the psl‐dependent polysaccharide, which consists of a repeating pentasaccharide containing d‐mannose, d‐glucose and l‐rhamnose:

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In addition, we identified the sugar nucleotide precursors involved in Psl generation and demonstrated the requirement for GDP‐d‐mannose, UDP‐d‐glucose and dTDP‐l‐rhamnose in Psl production and surface attachment. Finally, genetic analyses revealed that wbpW restored Psl production in a pslB mutant and pslB promoted A‐band LPS synthesis in a wbpW mutant, indicating functional redundancy and overlapping roles for these two enzymes. The structural and genetic data presented here provide a basis for further investigation of the Psl proteins and potential roles for Psl in the biology and pathogenesis of P. aeruginosa.
Partial functional redundancy of MreB isoforms, MreB, Mbl and MreBH, in cell morphogenesis of Bacillus subtilis
Authors: Kawai Yoshikazu , Asai Kei , Errington Jeffery
Published: July 2009

MreB proteins are bacterial actin homologues thought to have a role in cell shape determination by positioning the cell wall synthetic machinery. Many bacteria, particularly Gram‐positives, have more than one MreB isoform. Bacillus subtilis has three, MreB, Mbl and MreBH, which colocalize in a single helical structure. We now show that the helical pattern of peptidoglycan (PG) synthesis in the cylindrical part of the rod‐shaped cell is governed by the redundant action of the three MreB isoforms. Single mutants for any one of mreB isoforms can still incorporate PG in a helical pattern and generate a rod shape. However, after depletion of MreB in an mbl mutant (or depletion of all three isoforms) lateral wall PG synthesis was impaired and the cells became spherical and lytic. Overexpression of any one of the MreB isoforms overcame the lethality as well as the defects in lateral PG synthesis and cell shape. Furthermore, MreB and Mbl can associate with the peptidoglycan biosynthetic machinery independently. However, no single MreB isoform was able to support normal growth under various stress conditions, suggesting that the multiple isoforms are used to allow cells to maintain proper growth and morphogenesis under changing and sometimes adverse conditions.
Confirmation of the novel association at the BTNL2 locus with ulcerative colitis
Authors: Pathan S. , Gowdy R. E. , Cooney R. , Beckly J. B. , Hancock L. , Guo C. , Barrett J. C. , Morris A. , Jewell D. P.
Published: July 2009

Linkage in families and association in population case–control investigations have clearly shown that genes within the major histocompatibility complex region on chromosome 6p are relevant to the susceptibility and pathogenesis of ulcerative colitis (UC) and Crohn’s disease. However, identifying the causative variants by fine mapping has not been conclusive. In this study using 58 single nucleotide polymorphisms (SNPs) with 616 UC cases, there was significant association with SNP rs2294881 of the (butyrophilin‐like 2) BTNL2 gene with odds ratio (OR) = 2.80, confidence interval (CI) = 1.62–4.84 and P = 5.69 × 10−4 (PBonferroni = 3.3 × 10−2) and replication of SNP rs9268480. The missense SNP rs2076523 (K196E) showed novel association with a subset of UC cases with colectomy (n = 126), OR = 0.25, CI = 0.11–0.58 and P = 4.42 × 10−4 (PBonferroni = 2.56 × 10−2). These three associated variants within the BTNL2 gene were neither in linkage disequilibrium with each other nor correlated with the SNPs tagging the human leukocyte antigen (HLA)‐DRB1*1502 and HLA‐DRB1*0301 alleles.
Transmission of chromosomally integrated human herpesvirsus 6 (HHV‐6) variant A from a parent to children leading to misdiagnosis of active HHV‐6 infection
Authors: Mori T. , Tanaka‐Taya K. , Satoh H. , Aisa Y. , Yamazaki R. , Kato J. , Ikeda Y. , Okamoto S.
Published: July 2009

Abstract: Only a handful of cases of chromosomally integrated human herpesvirus 6 (CI‐HHV‐6) have been reported, suggesting that this phenomenon is rare. We here present a familial case of HHV‐6 variant A (HHV‐6A) transmission through a generation, which was identified in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). A 31‐year‐old man with myelodysplastic syndrome underwent allogeneic HSCT from a human leukocyte antigen‐identical sibling, and was found to be continuously yielding high copy numbers of HHV‐6A DNA in plasma evaluated by real‐time polymerase chain reaction (PCR). Antiviral therapy with ganciclovir or foscarnet failed to decrease the copy numbers. HHV‐6A DNA was detected in the patient's buccal mucosa and hair follicles, and was also detected in the plasma, whole blood, and buccal mucosa of the patient's father and 2 siblings, but not in his mother. The sequences of HHV‐6A DNA isolated from all family members were identical. Since monitoring of HHV‐6 by PCR has been widely introduced to the field of HSCT, transplant physicians should be aware of such an alternative form of HHV‐6 transmission, particularly when HHV‐6A is detected.
Mycobacterium genavense duodenitis following allogeneic peripheral blood stem cell transplantation
Authors: Lu K.J. , Grigg A. , Leslie D. , Finlay M. , Sasadeusz J.
Published: July 2009

Abstract: A 56‐year‐old man was diagnosed with Mycobacterium genavense duodenitis 21 months after an allogeneic peripheral stem cell transplant complicated by graft‐versus‐host disease requiring intense immunosuppression. This duodenitis responded to prolonged therapy with clarithromycin, ciprofloxacin, and rifabutin and reduction of immunosuppression.
Prosthetic joint infection with Mycobacterium avium complex in a solid organ transplant recipient
Authors: Gupta A. , Clauss H.
Published: July 2009

Abstract: Prosthetic joint infection (PJI) occurs with significant morbidity and health care expenditure. Transplant recipients on immunosuppressive medications are at increased risk for infections caused by less common organisms at unusual sites. Here we report a case of isolated PJI with Mycobacterium avium complex (MAC) in an immunosuppressed failed kidney transplant recipient and review the literature on this unique infection. We discuss the likely pathogenesis of PJI with MAC including the role of biofilm formation by non‐tuberculous mycobacteria. The possible role of cytokine milieu alteration by immunosuppressive therapy, particularly the reduction in interferon‐gamma levels, as a predisposing factor for non‐tuberculous mycobacterial infections in transplant recipients is explored. Lastly, we review the role of immune cell function assay in predicting the susceptibility to infection in our patient specifically and in solid organ transplant recipients in general.
Long‐lasting infiltration anaesthesia by lidocaine‐loaded biodegradable nanoparticles in hydrogel in rats
Authors: YIN Q.‐Q. , WU L. , GOU M.‐L. , QIAN Z.‐Y. , ZHANG W.‐S. , LIU J.
Published: July 2009

Background: Infiltration of a long‐lasting anaesthetic is helpful during the post‐operative period. The recently developed local drug delivery system, biodegradable nanoparticles in a thermo‐sensitive hydrogel (nanogel system), may possibly provide an extended duration of drugs. Therefore, we evaluated whether prolonged infiltration anaesthesia could be achieved by loading lidocaine into this delivery system.

Methods: Thirty male rats were randomized into five groups of six rats each: saline; 2% hydrochloride lidocaine solution; lidocaine‐loaded nanogel system and its compositing formulations, namely lido–nano gel; lido–nano; and lidogel. Durations of local anaesthesia with subcutaneously injected agents were measured by tail flick latency tests in a randomized, blind fashion.

Results: Lido–nano gel produced effective anaesthesia for 360±113 min, compared with 150±33 min by lidogel, 180±37 min by lido–nano, and 110±45 min by lidocaine solution (P<0.001, means±SD), and elicited complete sensory blockade for 300±114 min, compared with 75±37 min by lidogel, 105±53 min by lido–nano, and 60±33 min by lidocaine solution (P<0.001, means±SD) without severe skin/systemic toxicity.

Conclusion: Lidocaine‐loaded biodegradable nanoparticles in hydrogel produced prolonged infiltration anaesthesia in rats without severe toxicity, indicating a possible way to develop long‐lasting local anaesthetics.
The Effect of Late‐terminal Drought Stress on Yield Components of Four Barley Cultivars
Authors: Samarah N. H. , Alqudah A. M. , Amayreh J. A. , McAndrews G. M.
Published: July 2009

Barley (Hordeum vulgare L.) is an important winter cereal crop grown in the semiarid Mediterranean, where late‐terminal drought stress during grain filling has recently become more common. The objectives of this study were to investigate the growth performance and grain yield of four barley cultivars under late‐terminal drought stress under both glasshouse and field conditions. At grain filling, four barley cultivars (Rum, ACSAD176, Athroh and Yarmouk) were exposed to three watering treatments: (1) well‐watered [soil maintained at 75 % field capacity (FC)], (2) mild drought stress at 50 % FC, (3) severe drought stress at 25 % FC in the glasshouse experiment and (1) well‐watered (irrigated once a week), (2) mild drought (irrigated once every 2 weeks), (3) severe drought (non‐irrigated; rainfed) in the field. As drought stress severity increased, gross photosynthetic rate, water potential, plant height, grain filling duration, spike number per plant, grain number per spike, 1000‐grain weight, straw yield, grain yield and harvest index decreased. In the glasshouse experiment, the six‐row barley cultivars (Rum, ACSAD176, and Athroh) had higher grain yield than the two‐row barley cultivar (Yarmouk), but the difference was not significant among the six‐row cultivars under all treatments. In the field experiment, Rum had the highest grain yield among all cultivars under the mild drought stress treatment. The two‐row cultivar (Yarmouk) had the lowest grain yield. In general, the traditional cultivar Rum had either similar or higher grain yield than the other three cultivars under all treatments. However, the yield response to drought differed between the cultivars. Those, Rum and ACSAD176, that were capable of maintaining a higher proportion of their spikes and grains per spike during drought also maintained a higher proportion of their yield compared with those in well‐watered treatment. In conclusion, cultivar differences in grain yield were related to spike number per plant and grain number per spike, but not days to heading or grain filling duration.
Relationships of PpACS1 and PpACS2 genotypes, internal ethylene concentration and fruit softening in European (Pyrus communis) and Japanese (Pyrus pyrifolia) pears during cold air storage
Authors: Oraguzie N. C. , Whitworth C. J. , Brewer L. , Hall A. , Volz R. K. , Bassett H. , Gardiner S. E.
Published: July 2009

With 3 figures and 3 tables

Previous studies have demonstrated that genotypes of PpACS1 and PpACS2 genes are associated with certain levels of ethylene production in Japanese pears (Pyrus pyrifolia Nakai). This study was undertaken to examine further the relationships of PpACS1 and PpACS2 genotypes and internal ethylene concentration (IEC) with fruit firmness/softening in both European (P. communis L.) and Japanese pears (P. pyrifolia Nakai). Our data showed that P. communis L. lacked genotypes ‘AB’/‘Ab’ and ‘aB’, for high and medium IEC respectively, irrespective of high levels of IEC found in the European pear cultivars/selections. PpACS1 and PpACS2 genotypes were related to IEC at 20 days after harvest (DAH) in P. pyrifolia Nakai but IEC did not have any significant relationship with fruit firmness at 50DAH in either P. communis L. or P. pyrifolia Nakai. Harvest firmness was a better predictor of postharvest firmness than IEC across both species and genotypes, explaining 46% of the variation in fruit firmness at 50DAH. We recommend breeding for higher harvest firmness within low ethylene cultivars in order to extend the shelf life/storage potential of Japanese pears.
A model of the genetic differences in malting quality between European and North American barley cultivars based on a QTL study of the cross Triumph × Morex
Authors: Elía M. , Swanston J. S. , Moralejo M. , Casas A. , Pérez‐Vendrell A.‐M. , Ciudad F. J. , Thomas W. T. B. , Smith P. L. , Ullrich S. E. , Molina‐Cano J.‐L.
Published: July 2009

With 2 figures and 2 tables

To study the genetic control of malting quality, in North American and European barley varieties, over five contrasting environments, 106 doubled haploid (DH) lines, from the cross ‘Triumph’ × ‘Morex’, were grown at Pullman (Washington State, USA) in 2002, Dundee (Scotland) in 2003 and 2005 and Lleida and Valladolid (Northern Spain) in 2006. The vrs locus, associated with two‐row vs. six‐row ear type, had a significant effect, as two‐row lines had higher grain protein content at all sites. This had variable effects on other malting parameters, but hot water extract (EXT) was not significantly affected at the two Spanish sites. Quantitative trait loci associated with malting characters were distributed across all seven chromosomes, but the most influential, with effects on EXT and alcohol yield, at more than one site, were on 1H, with ‘Morex’ providing the increasing allele and 5H, with the increasing allele from ‘Triumph’. Transgressive segregation, in both directions, occurred at all sites. It was concluded that crosses between European and North American germplasm could enhance quality attributes in barley cultivated across diverse environments.
The risk of iatrogenic Creutzfeldt‐Jakob disease through medical and surgical procedures
Authors: Hamaguchi Tsuyoshi , Noguchi‐Shinohara Moeko , Nozaki Ichiro , Nakamura Yosikazu , Sato Takeshi , Kitamoto Tetsuyuki , Mizusawa Hidehiro , Yamada Masahito
Published: July 2009

There have been more than 400 patients who contracted Creutzfeldt‐Jakob disease (CJD) via a medical procedure, that is, through the use of neurosurgical instruments, intracerebral electroencephalographic electrodes (EEG), human pituitary hormone, dura mater grafts, corneal transplant, and blood transfusion. The number of new patients with iatrogenic CJD has decreased; however, cases of variant CJD that was transmitted via blood transfusion have been reported since 2004. Clearly, iatrogenic transmission of CJD remains a serious problem. Recently, we investigated medical procedures (any surgery, neurosurgery, ophthalmic surgery, and blood transfusion) performed on patients registered by the CJD Surveillance Committee in Japan during a recent 9‐year period. In a case‐control study comprising 753 sporadic CJD (sCJD) patients and 210 control subjects, we found no evidence that prion disease was transmitted via the investigated medical procedures before onset of sCJD. In a review of previously reported case‐control studies, blood transfusion was never shown to be a significant risk factor for CJD; our study yielded the same result. Some case‐control studies reported that surgery was a significant risk factor for sCJD. However, when surgical procedures were categorized by type of surgery, the results were conflicting, which suggests that there is little possibility of prion transmission via surgical procedures. In our study, 4.5% of sCJD patients underwent surgery after onset of sCJD, including neurosurgeries in 0.8% and ophthalmic surgeries in 1.9%. The fact that some patients underwent surgery, including neurosurgery, even after the onset of sCJD indicates that we cannot exclude the possibility of prion transmission via medical procedures. We must remain vigilant against prion diseases to reduce the risk of iatrogenesis.
Time to death and mast cell degranulation in fatal asthma
Authors: ELLIOT John G. , ABRAMSON Michael J. , DRUMMER Olaf H. , WALTERS E. Haydn , JAMES Alan L.
Published: July 2009

Background and objective:  Attacks of fatal asthma have been shown to be either of short duration or long duration and associated with differing degrees of smooth muscle contraction, luminal mucus deposition and ratios of eosinophils to neutrophils in the airway wall. We hypothesized that this bimodal distribution might be related to airway mast cell degranulation.

Methods:  Airway sections from cases of fatal asthma in the second Victorian asthma mortality study and from cases coming to coronial autopsy in Perth were examined. Tryptase‐positive mast cells, numbers of intact and degranulated mast cells, post‐mortem blood salbutamol levels and airway dimensions were measured.

Results:  Although the total number of mast cells were similar, the ratio of degranulated to intact mast cells (D/I) was significantly increased in the smooth muscle (P < 0.05) and outer airway wall (P < 0.001), in short‐duration cases compared with long‐duration cases. Proportional muscle shortening was significantly increased (P < 0.05) in short‐duration cases (17 ± 7%) compared with long‐duration cases (11 ± 7%). Blood salbutamol levels were related to the total airway wall mast cell D/I ratio for all cases combined (r = 0.57, P = 0.01).

Conclusions:  The duration of a fatal attack of asthma may be partly determined by the degranulation of mast cells.
Choice of spirometric reference values for compensation assessment
Authors: LEUNG Chi Chiu , YEW Wing Wai , LAW Wing Sze , WONG Man Yee , TAM Cheuk Ming , LEUNG Simon K.F. , TSUI Dennis P.W.
Published: July 2009

Background and objective:  Two sets of local reference values are available for spirometry in Hong Kong, but it is uncertain how well they work in the assessment of occupational lung diseases. This study examined their relative performance in the compensational assessment of silicosis.

Methods:  Local reference values published in 1982 and 2006 were compared in two different populations comprising normal construction/quarry workers and silicosis patients. Only men aged 20–74 years were included.

Results:  The FVC results of 93 normal workers were significantly higher than those predicted by either the 1982 or the 2006 reference values. Compared with the 1982 reference values, the mean FEV1% or FVC% was age‐dependent and 5.2% higher in the normal workers. Smoking decreased the forced expiratory ratio, but did not show a major effect on FEV1 or FVC among asymptomatic subjects. Despite their derivation largely from never‐smokers, the 2006 reference values better predicted FEV1 and FVC among all smoking categories. Among the 357 silicosis patients, the 1982 reference values also gave 8.8% higher FEV1% and 7.4% higher FVC%. These spirometric values differed by more than 10% in patients aged 60 years or more. Despite the presence of disease, the mean FVC% was still significantly above 100%.

Conclusions:  Both the 1982 and 2006 local reference values underestimated the FVC of normal construction and quarry workers, reflecting possible occupational selection factors. The 2006 reference values outperformed the 1982 ones, especially among older subjects. Careful calibration with similar occupational groups in the same laboratory is highly desirable in the choice of spirometric reference values for compensation assessment. Smoking does not appear to affect this choice.
Severe bullous emphysema and hypercapnia successfully treated by bronchoscopic lung volume reduction
Authors: TSUJINO Kazuyuki , SASADA Shinji , KODAMA Masami , ISHIHARA Hideki , KAWASE Ichiro
Published: July 2009

Patients with severe COPD may develop hypercapnic respiratory failure requiring mechanical ventilation and are at risk of becoming ventilator‐dependent. We describe a patient with uncontrollable hypercapnic respiratory failure on mechanical ventilation whose respiratory condition and life were improved after bronchoscopic lung volume reduction. Further discussion of the possibility of bronchoscopic lung volume reduction in patients who require mechanical ventilation due to hypercapnic respiratory failure is warranted.
Panax notoginseng saponins attenuate acute lung injury induced by intestinal ischaemia/reperfusion in rats
Authors: RONG Ling , CHEN Yuqing , HE Mudan , ZHOU Xin
Published: July 2009

Background and objective:  Acute lung injury remains a challenge for both clinicians and scientists. The effects of Panax notoginseng saponins (PNS) on acute lung injury induced by intestinal ischaemia/reperfusion (II/R) were studied in rats.

Methods:  Forty‐eight Wistar rats were randomly assigned to four groups: (1) a sham‐operated group that received laparotomy without II/R (n= 12); (2) a sham + PNS group, which was identical to group 1 except for PNS treatment (n= 12); (3) an II/R group that had 1 h of intestinal ischaemia followed by 3 h of reperfusion (n= 12); and (4) an II/R + PNS group that received 100 mg/kg of PNS, i.v., 15 min before reperfusion (n= 12). The effects of PNS administration on lung tissue histology, activities of oxidant and antioxidant enzymes, levels of malondialdehyde, nitric oxide and inducible nitric oxide synthase activity were examined. Levels of surfactant protein B, cell numbers in BAL fluid and plasma levels of pro‐inflammatory cytokines were also examined.

Results:  Compared with the II/R group, pulmonary parenchymal damage, activities of oxidant enzymes, levels of malondialdehyde and nitric oxide, inducible nitric oxide synthase activity in lung tissue, and plasma levels of pro‐inflammatory cytokines were significantly reduced by PNS treatment. In addition, the decreases in antioxidant enzyme activities were prevented in the II/R + PNS group. Total leukocyte and neutrophil counts were significantly decreased by PNS treatment. The decline in surfactant protein B levels in BAL fluid was reduced in the II/R + PNS group compared with the II/R group.

Conclusions:  Administration of PNS before reperfusion injury alleviates acute lung injury induced by II/R, and this is attributable to the antioxidant and anti‐inflammatory effects of PNS.
Transoesophageal needle aspiration using a convex probe ultrasonic bronchoscope
Authors: HWANGBO Bin , LEE Hee Seok , LEE Geon‐Kook , LIM Kun‐Young , LEE Soo‐Hyun , KIM Hyae‐Young , LEE Jong‐Yeul , ZO Jae Ill
Published: July 2009

Background and objective:  Although endoscopic ultrasound‐guided fine needle aspiration can be helpful when combined with bronchoscopic procedures, endoscopic ultrasound‐guided fine needle aspiration is not available as a conjunctive procedure with bronchoscopy at many institutions. This study evaluated the feasibility and the additional role of transoesophageal fine needle aspiration using a convex probe ultrasonic bronchoscope (EUS‐B‐FNA).

Methods:  We analysed 84 patients who underwent EUS‐B‐FNA between Oct 2007 and May 2008. Bronchoscopy and/or endobronchial ultrasound‐guided transbronchial needle aspiration was performed on 83 patients prior to EUS‐B‐FNA.

Results:  EUS‐B‐FNA was performed on 89 lesions (1.7 aspirations/lesion) including three lung masses and 86 lymph nodes (nodal stations 1, 3P, 4L, 5, 7, 8, 9 and 10L) without complication. Sample adequacy was 95.4% for each aspiration and 100% for each lesion. Of the 89 lesions, 39 malignant lesions were confirmed by EUS‐B‐FNA. EUS‐B‐FNA provided additional diagnostic gain to bronchoscopic procedures in 16 patients (19.0%): 3 lung cancers were upstaged, 11 lung cancers were pathologically confirmed, and 2 patients were diagnosed with mediastinal metastasis from an extrathoracic malignancy. This gain was obtained by the sampling of inaccessible (n = 4) or difficult lesions by endobronchial ultrasound‐guided transbronchial needle aspiration (n = 2) or when bronchoscopy was difficult due to dyspnoea, cough, brain metastasis or other conditions (n = 10).

Conclusions:  EUS‐B‐FNA is a technically feasible and safe procedure, which may be an alternative to endoscopic ultrasound‐guided fine needle aspiration as a procedure that complements bronchoscopy. Additional diagnostic yield can be obtained by combining EUS‐B‐FNA with bronchoscopic procedures.
Identification of the target neuronal elements in electrical deep brain stimulation
Authors: Holsheimer Jan , Demeulemeester Hilde , Nuttin Bart , De Sutter Paul
Published: July 2009

The aim of this study is to identify the primary neuronal target elements in electrical deep‐brain stimulation, taking advantage of the difference in strength–duration time constant (τsd) of large myelinated axons (≈ 30–200 µs), small axons (≈ 200–700 µs) and cell bodies and dendrites (≈ 1–10 ms). Strength–duration data were measured in patients suffering from Parkinson's disease or essential tremor and treated by high‐frequency stimulation in the ventral intermediate thalamic nucleus or the internal pallidum. Threshold voltages for the elimination of tremor were determined at various pulsewidths and a pulse rate of 130 pulses per second. The τsd was calculated using Weiss's linear approximation. Its mean value was 64.6 ± 25.4 µs (SD) for the thalamic nucleus and 75.3 ± 25.5 µs for the internal pallidum. Corrections to the mean values were made because the τsd values were based on voltage–duration measurements using polarizable electrodes. Apart from this systematic error, a resolution error, due to the relatively large increment steps of the pulse amplitude, was taken into account, resulting in mean τsd estimates of 129 and 151 µs for the thalamic nucleus and the internal pallidum, respectively. It is concluded that the primary targets of stimulation in both nuclei are most probably large myelinated axons.
Vitamin E supplementation prevents spatial learning deficits and dendritic alterations in aged apolipoproteinE‐deficient mice
Authors: Veinbergs Isaac , Mallory Margaret , Sagara Yutaka , Masliah Eliezer
Published: July 2009

Recent studies have suggested that altered function of apolipoprotein E might lead to Alzheimer's disease via oxidative stress. In this context, the objective of this study was to determine if antioxidative treatment with vitamin E was neuroprotective in apolipoprotein E‐deficient mice. For this purpose, 1‐month‐old control and apolipoprotein E‐deficient mice received dietary vitamin E for 12 months. We showed that, compared to apolipoprotein E‐deficient mice who received a regular diet, mice treated with vitamin E displayed a significantly improved behavioural performance in the Morris water maze. This improved performance was associated with preservation of the dendritic structure in vitamin E‐treated apolipoprotein E‐deficient mice. In addition, whilst untreated apolipoprotein E‐deficient mice displayed increased levels of lipid peroxidation and glutathione, vitamin E‐treated mice showed near normal levels of both lipid peroxidation and glutathione. These results support the contention that vitamin E prevents the age‐related neurodegenerative alterations in apolipoprotein E‐deficient mice.
Distribution of glycine receptor subunits on primate retinal ganglion cells: a quantitative analysis
Authors: Lin Bin , Martin Paul R. , Solomon Samuel G. , Grünert Ulrike
Published: July 2009

This study investigates the distribution of inhibitory neurotransmitter receptors on sensory neurons. Ganglion cells in the retina of a New World monkey, the common marmoset Callithrix jacchus, were injected with Lucifer yellow and Neurobiotin and subsequently processed with antibodies against one (α1), or against all subunits, of the glycine receptor, or against the anchoring protein gephyrin. Immunoreactive (IR) puncta representing glycine receptor or gephyrin clusters were found on the proximal and the distal dendrites of all ganglion cell types investigated. For both parasol and midget cells, the density of receptor clusters was greater on distal than proximal dendrites for all antibodies tested. In parasol cells the average density for the α1 subunit of the glycine receptor was 0.087 IR puncta/µm of dendrite, and for all subunits it was 0.119 IR puncta/µm of dendrite. Thus, the majority of glycine receptors on parasol cells contain the α1 subunit. For parasol cells, we estimated an average of 1.5 glycinergic synapses/100 µm2 dendritic membrane on proximal dendrites and about 9.4 glycinergic synapses/100 µm2 on distal dendrites. The segregation of receptors to the distal dendrites appears to be a common feature of inhibitory neurotransmitter input to parasol and midget cells, and might be associated with the receptive field surround mechanism.
Clock genes outside the suprachiasmatic nucleus involved in manifestation of locomotor activity rhythm in rats
Authors: Masubuchi Satoru , Honma Sato , Abe Hiroshi , Ishizaki Kouji , Namihira Masakazu , Ikeda Masaaki , Honma Ken‐ichi
Published: July 2009

Chronic treatment of methamphetamine (MAP) in rats desynchronized the locomotor activity rhythm from the light–dark cycle. When the activity rhythm was completely phase‐reversed with respect to a light dark‐cycle, 24 h profiles were examined for the clock gene (rPer1,rPer2,rBMAL1,rClock) expressions in several brain structures byin situhybridization, and for the pineal as well as plasma melatonin levels. In the MAP‐treated rats, therPer1expression in the suprachiasmatic nucleus (SCN) showed a robust circadian rhythm which was essentially identical to that in the control rats. Circadian rhythms in pineal as well as plasma melatonin were not changed significantly in the MAP‐treated rats. However, robust circadian rhythms in therPer1,rPer2 and rBMAL1expressions detected in the caudate‐putamen (CPU) and parietal cortex were completely phase‐reversed in the MAP‐treated rats, compared with those in the control rats, indicating desynchronization from the SCN rhythm. Such desynchronization was not observed in the circadian rhythms of clock gene expression in the nucleus accumbens and cingulate cortex. The circadianrClockexpression rhythm in the MAP‐treated rats was not phase‐reversed in the CPU and parietal cortex. These findings indicate that the locomotor activity rhythm in rats is directly driven by the pacemaker outside the SCN, in whichrPer1,rPer2 and rBMAL1in the CPU and parietal cortex are involved.
Parkin expression in the adult mouse brain
Authors: Stichel Christine C. , Augustin Martin , Kühn Kati , Zhu Xin‐Ran , Engels Peter , Ullmer Christoph , Lübbert Hermann
Published: July 2009

Mutations in a protein designated Parkin were shown to be involved in the pathogenesis of autosomal recessive juvenile parkinsonism. Nothing is known about its regional and subcellular distribution in the mouse. In order to elucidate the Parkin mRNA and protein distribution in the adult mouse, the mouse cDNA was cloned and polyclonal antisera were generated against the N‐terminal part of mouse Parkin. The antibodies were shown to be specific using Western blot analysis, immunostaining of cells transfected with mouse Parkin and pre‐absorption tests. The Parkin protein expression profile was studied using immunohistochemistry and Western blot analysis and was compared with that of the mRNA yielded by in situ hybridization and RT‐PCR analysis. Parkin protein was widely distributed in all subdivisions of the mouse brain. Low levels were found in the telencephalon and diencephalon, while the brainstem contained a large number of cells heavily expressing Parkin. Ultrastructural analysis and double immunohistochemistry revealed that the majority of Parkin‐expressing cells were neurons, while only single glial cells exhibited immunostaining. The protein was distributed nonhomogeneously throughout the entire cytoplasm. A subpopulation of Parkin‐immunopositive cells displayed speckled immunodeposits in the nucleus. Dopaminergic cells of the substantia nigra pars compacta exhibited high levels of Parkin mRNA but no Parkin protein, while the striatum contained immunopositive profiles but no mRNA signals. Our data indicate that Parkin is neither restricted to a single functional system nor associated with a particular transmitter system. The speckled nuclear distribution of Parkin immunoreactivity strongly suggests a role for Parkin in gene expression.
High susceptibility of the anterior and posterior piriform cortex to induction of convulsions by bicuculline
Authors: Ebert Ulrich , Wlaź Piotr , Löscher Wolfgang
Published: July 2009

Accumulating evidence suggests that the piriform cortex (PC) plays a critical role in the development of limbic motor seizures. In the anterior piriform cortex (aPC), a functionally defined, discrete epileptogenic site has been previously identified by unilateral microinjection of bicuculline in Sprague–Dawley (SD) rats and termed the ‘area tempestas’ (AT). Compared to this site in the aPC, more posterior PC sites, particularly a site in the transition zone between the posterior and aPC (central PC) exhibited a greater susceptibility to electrical stimulation. However, it is not known whether central and posterior sites in the PC differ from the aPC, including the AT, with regard to their sensitivity to bicuculline. In the present study, unilateral focal microinfusion of picomole quantities of bicuculline induced behavioural (focal and generalized) seizures in deep layers of all parts of the PC in two rat strains, Wistar and SD. The incidence of generalized seizures was higher in the AT of SD rats, but no such difference was seen in Wistar rats, arguing against the previous proposal that the rat AT is unique in its sensitivity to induction of seizures by bicuculline compared to other locations within or outside of the PC. Injection of biotin–dextran in PC seizure‐sensitive sites in SD rats showed clear differences in anterograde and retrograde labelling between the different PC sites. Therefore, although it was possible to evoke generalized seizures from all parts of the PC, the anatomical connections of the bicuculline injection sites were qualitatively different. The results suggest that the deep layers of the entire PC are highly sensitive to seizure induction by bicuculline, thus substantiating the notion that the PC may be important in seizure generation and propagation.
Cloning, distribution and functional analysis of the type III sodium channel from human brain
Authors: Chen Yu Hua , Dale Timothy J. , Romanos Michael A. , Whitaker William R. J. , Xie Xin Min , Clare Jeffrey J.
Published: July 2009

The type III voltage‐gated sodium channel was cloned from human brain. The full‐length cDNA has 89% identity with rat type III, and the predicted protein (1951 amino acids) has 55 differences. The expression pattern of human type III mRNA was determined in adult brain tissue and, in contrast to rat, was detected in many regions, including caudate nucleus, cerebellum, hippocampus and frontal lobe. The human type III channel was stably expressed in Chinese hamster ovary (CHO) cells and its biophysical properties compared to the human type II channel using identical conditions. The voltage dependence and kinetics of activation were found to be similar to that of type II. The kinetics of inactivation of the two human subtypes were also similar. However, type III channels inactivated at more hyperpolarized potentials and were slower to recover from inactivation than type II. When expressed in human embryonic kidney (HEK293T) cells, type III channels produced currents with a prominent persistent component, which were similar to those reported for rat type II [Ma et al. (1997) Neuron, 19, 443–452]. However, unlike type II, this was prominent even in the absence of coexpressed G‐proteins, suggesting type III may adopt this gating mode more readily. The distinct properties of the channel, together with its wide distribution in adult brain, suggest that in humans, type III may have important physiological roles under normal, and perhaps also pathological conditions.
Increased neuronal damage and apoE immunoreactivity in human apolipoprotein E, E4 isoform‐specific, transgenic mice after global cerebral ischaemia
Authors: Horsburgh Karen , McCulloch James , Nilsen Margaret , Roses Allen D. , Nicoll James A. R.
Published: July 2009

Apolipoprotein E (apoE, protein; APOE, gene) is expressed as three isoforms in humans (E2, E3, E4). The APOE‐ε4 allele is associated with a poor outcome in patients after head injury of which ischaemic brain damage is a contributor of mortality and morbidity. The aim of the study was to determine whether mice expressing human APOE‐ε4 displayed more extensive ischaemic neuronal damage 72 h after transient global ischaemia compared with mice which express human APOE‐ε3. APOE‐ε3 and ‐ε4 transgenic mice, under the control of a human promoter, were used which express human APOE in neurons and glia. Ischaemic neuronal damage in the CA1 pyramidal cell layer in the APOE‐ε4 transgenic mice was significantly greater than in the APOE‐ε3 mice after global ischaemia (36.4 ± 8.9%, 18.2 ± 7.3%; P < 0.05). This was associated with more extensive neuronal apoE immunoreactivity in the CA1 pyramidal cell layer in the APOE‐ε4 transgenic mice compared with APOE‐ε3 transgenic mice. In contrast, in the caudate nucleus, there were similar levels of ischaemic neuronal damage in the APOE‐ε3 and ‐ε4 transgenic mice (39.2 ± 10.1%; 44.6 ± 8.4%, P = 0.32). In the caudate, similar numbers of neurons were immunostained for apoE in the APOE‐ε3 and ‐ε4 transgenic mice. The present study demonstrated that the APOE‐ε4 allele is associated with an increased vulnerability of a specific brain region to the effects of global ischaemia, which is closely associated with an increase in neuronal apoE. The data extend previous work and are consistent with an association of the APOE‐ε4 allele with a poor outcome after acute brain injury in humans.
Electrical stimulation accelerates and increases expression of BDNF and trkB mRNA in regenerating rat femoral motoneurons
Authors: Al‐Majed Abdulhakeem A. , Brushart Thomas M. , Gordon Tessa
Published: July 2009

Electrical stimulation promotes the speed and accuracy of motor axonal regeneration. The positive effects of stimulation are mediated at the cell body. Here we characterize the effect of electrical stimulation on motoneuronal expression of BDNF and its receptor, trkB, two genes whose expression levels in motoneurons correlate with regeneration and are regulated by electrical activity in a variety of neurons. We used semiquantitative in situ hybridization to measure expression of mRNA encoding BDNF and the full‐length trkB receptor at intervals of 8 h, 2 days and 7 days after unilateral femoral nerve cut, suture, and stimulation. Expression in regenerating motoneurons was compared to that of contralateral intact motoneurons. BDNF and trkB signals were not significantly upregulated 8 h and 2 days after femoral nerve suture and sham stimulation. By 7 days, there was a 2‐fold increase in both BDNF and trkB mRNA expression. In contrast, stimulation of cut and repaired nerves for only 1 h led to rapid upregulation of BDNF and trkB mRNA by 3‐fold and 2‐fold, respectively, within the first 8 h. The stimulation effect peaked at 2 days with 6‐fold and 4‐fold increases in the signals, respectively. Thereafter, the levels of BDNF and trkB mRNA expression declined to equal the 2‐fold increase seen at 7 days after nerve repair and sham‐stimulation. We conclude that brief electrical stimulation stimulates BDNF and trkB expression in regenerating motoneurons. Because electrical stimulation is known to accelerate axonal regeneration, we suggest that changes in the expression of BDNF and trkB correlate with acceleration of axonal regeneration.
APP is required during an early phase of memory formation
Authors: Mileusnic R. , Lancashire C. L. , Johnston A. N. B. , Rose S. P. R.
Published: July 2009

The amyloid β/A4 protein precursor (APP) has been shown to be implicated in age‐associated plastic changes at synapses that might contribute to memory loss in Alzheimer's disease. As APP has previously been reported to have multiple functions during normal development, we have employed a one‐trial passive avoidance task in day‐old chicks to study its role in the process of memory formation. Administration of anti‐APP antibodies, injected 30 min pretraining, prevented memory for a one‐trial passive avoidance task in day‐old chicks without effects on general behaviour or initial acquisition. Amnesia was apparent by 30 min post‐training and lasted for at least 24 h. The same result was obtained by down‐regulation of APP expression by APP‐antisense, injected 8–12 h pretraining. However, injections of anti‐APP antibodies or APP antisense at later post‐training time did not cause amnesia for the task. Unlike antibodies and antisense, injection of the APP328–332 pentapeptide, in either orientation, 30 min pretraining, rescued the memory and prevented antisense‐induced amnesia. The post‐training time within which the antibody‐ and antisense‐induced amnesia, and within which the APP peptides prevent amnesia, correspond to that during which memory formation is vulnerable to disruption of the putative signal transduction functions of APP. These results suggest that: (i) APP is required during an early phase of memory formation, and (ii) the memory enhancing effect of secretory APP is localized within a 5‐mer sequence of growth‐promoting domain.
Changes in the firing pattern of globus pallidus neurons after the degeneration of nigrostriatal pathway are mediated by the subthalamic nucleus in the rat
Authors: Ni Zhongge , Bouali‐Benazzouz Rabia , Gao Dongming , Benabid Alim‐Louis , Benazzouz Abdelhamid
Published: July 2009

Changes in the neuronal activity of globus pallidus (GP) have been shown in animal models of parkinsonism. In order to study the implication of the subthalamic nucleus (STN) in these changes, the effects of STN lesions alone or in combination with 6‐hydroxydopamine (6‐OHDA) ‐induced damage to the substantia nigra compacta (SNc) were examined in rats using electrophysiological recordings of GP cells. In normal rats, the firing rate was 22.1 ± 1.4 spikes/s. The pattern was regular in 45%, irregular in 49% and bursty in 6% of the cases. In rats with STN lesions, the firing rate of GP units (20.15 ± 1.25 spikes/s) did not differ from that of normal rats and only regular (46%) and irregular (54%) cells were found; a bursty pattern was not observed. 6‐OHDA lesions of the SNc induced no change in the firing rate of GP neurons (21.5 ± 1.4 spikes/s, P > 0.05) but a significant decrease in the percentage of regular cells (27%, P < 0.001), a significant increase in burst cells (21%, P < 0.001) with no change in the percentage of irregular units (52%) were observed. In rats with combined SNc and STN lesions, the firing pattern did not change from that of normal rats. The present results show that STN lesions induced the disappearance of bursts in normal rats and normalization of firing pattern in the GP units of rats with 6‐OHDA lesions suggesting that the STN plays an important role in the modulation of the pattern of activity of GP neurons which may account for the therapeutic effect of STN lesions in Parkinson's disease.
Cortical cholinergic inputs mediate processing capacity: effects of 192 IgG‐saporin‐induced lesions on olfactory span performance
Authors: Turchi Janita , Sarter Martin
Published: July 2009

An olfactory span task that required rats to discriminate an olfactory stimulus added to an increasing list of such stimuli (nonmatching‐to‐sample; NMTS) was employed to assess the role of the basal forebrain cholinergic system in the animals' olfactory working memory capacity. A separate group of animals was trained in a matching‐to‐sample (MTS) version of this task that did not tax span performance. NMTS animals required significantly more sessions to reach an olfactory span of 18 stimuli than MTS rats. Infusions of the cholino‐immunotoxin 192 IgG‐saporin into the basal forebrain resulted in decreases of cortical acetylcholinesterase (AChE)‐positive fibre density ranging from 80% in frontodorsal and frontoparietal regions to 35% in the pyriform cortex and 24% in the olfactory bulb. Postsurgery span performance was significantly reduced in lesioned NMTS but not MTS animals. Span performance in lesioned NMTS animals recovered following 4 weeks of postoperative training; however, these animals' span remained vulnerable to the effects of increased intertrial intervals. The distribution of errors in lesioned animals indicated a recency effect. In NMTS animals, olfactory span performance during the initial two postoperative weeks correlated significantly with AChE‐positive fibre density in neocortical but not olfactory areas. The privileged, automatic processing of olfactory stimuli in rats may have contributed to the transience of the lesion effect. The results support the crucial role of cortical cholinergic input in the mediation of aspects of processing capacity.
Morphological evidence for selective modulation by serotonin of a subpopulation of dorsal horn cells which possess the neurokinin‐1 receptor
Authors: Stewart W. , Maxwell D. J.
Published: July 2009

Serotonin selectively depresses transmission of nociceptive information through the spinal dorsal horn but the mechanisms of this depression are poorly understood. In this study we report that serotonin‐containing axons form basket‐like clusters which are intimately woven around cell bodies and proximal dendrites of a subpopulation (≈ 50%) of laminae III/IV neurons which possess the neurokinin‐1 receptor. Statistical analysis confirms that cells belonging to this subpopulation have significantly higher numbers of serotoninergic contacts on proximal dendrites when compared with the population of neurokinin‐1 cells that are not associated with clusters (mean ± SD = 13 ± 5.8 and 5 ± 2.9, respectively). Neurokinin‐1 cells in laminae III/IV project to regions of the brain which are involved in nociceptive processing and are likely to be activated predominantly by nociceptive input. The concentration of serotoninergic axons around proximal regions of some of these cells indicates that serotonin may have a powerful influence on transmission through this pathway. This type of arrangement could be a morphological correlate for at least part of the selective antinociceptive actions of serotonin.