bluuebunny/crossref_metadata_2025 huggingface dataset:
Impairment of hippocampal long‐term depression and defective spatial learning and memory in p35–/– mice
Authors: Ohshima Toshio , Ogura Hiroo , Tomizawa Kazuhito , Hayashi Kanehiro , Suzuki Hiromi , Saito Taro , Kamei Hirotsugu , Nishi Akinori , Bibb James A. , Hisanaga Shin‐ichi , Matsui Hideki , Mikoshiba Katsuhiko
Published: July 2005

Cdk5 (cyclin‐dependent kinase 5) activity is dependent upon association with one of two neuron‐specific activators, p35 or p39. Genetic deletion of Cdk5 causes perinatal lethality with severe defects in corticogenesis and neuronal positioning. p35–/– mice are viable with milder histological abnormalities. Although substantial evidence implicates Cdk5 in synaptic plasticity, its role in learning and memory has not been evaluated using mutant mouse models. We report here that p35–/– mice have deficiencies in spatial learning and memory. Close examination of hippocampal circuitry revealed subtle histological defects in CA1 pyramidal cells. Furthermore, p35–/– mice exhibit impaired long‐term depression and depotentiation of long‐term potentiation in the Schaeffer collateral CA1 pathway. Moreover, the Cdk5‐dependent phosphorylation state of protein phosphatase inhibitor‐1 was increased in 4‐week‐old mice due to increased levels of p39, which co‐localized with inhibitor‐1 and Cdk5 in the cytoplasm. These results demonstrate that p35‐dependent Cdk5 activity is important to learning and synaptic plasticity. Deletion of p35 may shift the substrate specificity of Cdk5 due to compensatory expression of p39.
Chronic hyperammonemia in vivo impairs long‐term potentiation in hippocampus by altering activation of cyclic GMP‐dependent‐protein kinase and of phosphodiesterase 5
Authors: Monfort Pilar , Muñoz María‐Dolores , Felipo Vicente
Published: July 2005

Long‐term potentiation (LTP) is impaired in the CA1 area of hippocampal slices from rats with chronic moderate hyperammonemia. We studied the mechanisms by which hyperammonemia in vivo impairs LTP. This process requires sequential activation of soluble guanylate cyclase, cyclic GMP‐dependent protein kinase (PKG) and cyclic GMP‐degrading phosphodiesterase. Application of the tetanus induced a rapid increase of cyclic GMP in slices from control or hyperammonemic rats, which is followed in control slices by a sustained decrease in cyclic GMP due to sustained activation of cyclic GMP‐degrading phosphodiesterase, which in turn is due to sustained activation of PKG. In slices from rats with chronic hyperammonemia tetanus‐induced decrease in cyclic GMP was delayed and transient due to lower and transient activation of PKG and of the phosphodiesterase. Hyperammonemia‐induced impairment of LTP may be involved in the alterations of cognitive function in patients with hepatic encephalopathy.
Why do Nogo/Nogo‐66 receptor gene knockouts result in inferior regeneration compared to treatment with neutralizing agents?
Authors: Teng Felicia Yu Hsuan , Tang Bor Luen
Published: July 2005

IN‐1, the monoclonal antibody against the exon 3‐encoded N‐terminal domain of Nogo‐A, and the Nogo‐66 receptor (NgR) antagonist NEP1‐40 have both shown efficacy in promoting regeneration in animal spinal cord injury models, the latter even when administered subcutaneously 1 week after injury. These results are supportive of the hypothesis that the Nogo–NgR axis is a major path for inhibition of spinal cord axonal regeneration and uphold the promises of these neutralizing agents in clinical applications. However, mice with targeted disruption of Nogo and NgR have, surprisingly, only modest regenerative capacity (if any) compared with treatment with IN‐1 or NEP1‐40. Disruption of the Nogo gene by various groups yielded results ranging from significant regenerative improvement in young mice to no improvement. Likewise, knockout of NgR produced some improvement in raphespinal and rubrospinal axonal regeneration, but not that of corticospinal neurons. Other than invoking possible differences in genetic background, we suggest here some possible and testable explanations for the above phenomena. These possibilities include effects of IN‐1 and NEP1‐40 on the CNS beyond neutralization of Nogo and NgR functions, and the latter's possible role in the CNS beyond that of neuronal growth inhibition.
Activation of calcium‐independent phospholipase A2 (iPLA2) in brain mitochondria and release of apoptogenic factors by BAX and truncated BID
Authors: Brustovetsky Tatiana , Antonsson Bruno , Jemmerson Ronald , Dubinsky Janet M. , Brustovetsky Nickolay
Published: July 2005

Cleaved or truncated BID (tBID) is known to oligomerize both BAK and BAX. Previously, BAK and BAX lacing the C‐terminal fragment (BAXΔC) were shown to induce modest cytochrome c (Cyt c) release from rat brain mitochondria when activated by tBID. We now show that tBID plus monomeric full‐length BAX induce extensive release of Cyt c, Smac/DIABLO, and Omi/HtrA2 (but not endonuclease G and the apoptosis inducing factor) comparable to the release induced by alamethicin. This occurs independently of the permeability transition without overt changes in mitochondrial morphology. The mechanism of the release may involve formation of reactive oxygen species (ROS) and activation of calcium‐independent phospholipase A2 (iPLA2). Indeed, increased ROS production and activated iPLA2 were observed prior to massive Cyt c release. Furthermore, the extent of inhibition of Cyt c release correlated with the degree of suppression of iPLA2 by the inhibitors propranolol, dibucaine, 4‐bromophenacyl bromide, and bromenol lactone. Consistent with a requirement for iPLA2 in Cyt c release from brain mitochondria, synthetic liposomes composed of lipids mimicking the outer mitochondrial membrane (OMM) but lacing iPLA2 failed to release 10 kDa fluorescent dextran (FD‐10) in response to tBID plus BAX. We propose that tBID plus BAX activate ROS generation, which subsequently augments iPLA2 activity leading to changes in the OMM that allow translocation of certain mitochondrial proteins from the intermembrane space.
α‐Linolenic acid does not contribute appreciably to docosahexaenoic acid within brain phospholipids of adult rats fed a diet enriched in docosahexaenoic acid
Authors: DeMar James C. , Ma Kaizong , Chang Lisa , Bell Jane M. , Rapoport Stanley I.
Published: July 2005

Adult male unanesthetized rats, reared on a diet enriched in both α‐linolenic acid (α‐LNA) and docosahexaenoic acid (DHA), were infused intravenously for 5 min with [1‐14C]α‐LNA. Timed arterial samples were collected until the animals were killed at 5 min and the brain was removed after microwaving. Plasma and brain lipid concentrations and radioactivities were measured. Within plasma lipids, > 99% of radioactivity was in the form of unchanged [1‐14C]α‐LNA. Eighty‐six per cent of brain radioactivity at 5 min was present as β‐oxidation products, whereas the remainder was mainly in ‘stable’ phospholipid or triglyceride as α‐LNA or DHA. Equations derived from kinetic modeling demonstrated that unesterified unlabeled α‐LNA rapidly enters brain from plasma, but that its incorporation into brain phospholipid and triglyceride, as in the form of synthesized DHA, is ≤ 0.2% of the amount that enters the brain. Thus, in rats fed a diet containing large amounts of both α‐LNA and DHA, the α‐LNA that enters brain from plasma largely undergoes β‐oxidation, and is not an appreciable source of DHA within brain phospholipids.
High‐affinity peripheral benzodiazepine receptor ligand, PK11195, regulates protein phosphorylation in rat brain mitochondria under control of Ca2+
Authors: Azarashvili T. , Krestinina O. , Yurkov I. , Evtodienko Y. , Reiser G.
Published: July 2005

The effects of PK11195, a high‐affinity peripheral benzodiazepine receptor (PBR) ligand, on protein phosphorylation in isolated purified rat brain mitochondria were investigated. The isoquinoline carboxamide ligand of PBR, PK11195, but not the benzodiazepine ligand Ro5–4864, in the nanomolar concentration range strongly increased the phosphorylation of 3.5 and 17 kDa polypeptides. The effect of PK11195 was seen in the presence of elevated Ca2+ levels (3 × 10−7 to 10−6 m), but not at very low Ca2+ levels (10‐8 to 3 × 10−8 m). This indicates that PBR involves Ca2+ as a second messenger in the regulation of protein phosphorylation. Staurosporine, an inhibitor of protein kinase activity was able to suppress the PK11195‐promoted protein phosphorylation. When the permeability transition pore (PTP) was opened by threshold Ca2+ load, phosphorylation of the 3.5‐kDa polypeptide was diminished, but strong phosphorylation of the 43‐kDa protein was revealed. The 43‐kDa protein appears to be a PTP‐specific phosphoprotein. If PTP was opened, PK11195 did not increase the phosphorylation of the 3.5 and 17‐kDa proteins but suppressed the phosphorylation of the PTP‐specific 43‐kDa phosphoprotein. The ability of PK11195 to increase the protein phosphorylation, which was lost under Ca2+‐induced PTP opening, was restored again in the presence of calmidazolium, an antagonist of calmodulin and inhibitor of protein phosphatase PP2B. These results show a tight interaction of PBR with the PTP complex in rat brain mitochondria. In conclusion, a novel function of PBR in brain mitochondria has been revealed, and the PBR‐mediated protein phosphorylation has to be considered an important element of the PBR‐associated signal transducing cascades in mitochondria and cells.
Transforming growth factor‐β1, Th1 responses, and autoimmune liver disease
Authors: Gorham James D.
Published: July 2005

Transforming growth factor‐β1 (TGF‐β1) is released during the storage of blood components, particularly platelet concentrates, and transfusion recipients are exposed to high levels of TGF‐β1. Because TGF‐β1 is one of the most potent immunosuppressive cytokines known, understanding the immunobiologic functions of TGF‐β1 may be relevant for understanding the immunobiologic effects of transfusion. Our laboratory studies the biologic effects of TGF‐β1 in the immune system. Mice deficient in TGF‐β1 spontaneously develop autoimmunity, confirming the important role of this cytokinean an immune regulator. A few years ago, my laboratory made the observation that genetic background strongly affects the phenotype of TGF‐β1–/– mice. TGF‐β1–/– mice on the BALB/c background rapidly develop an aggressive T‐cell–mediated hepatitis, whereas TGF‐β1–/– mice on the 129/CF‐1 background do not. In this review, I summarize findings published or in press from our laboratory on disease pathogenesis in TGF‐β1–/– mice and then discuss some of the exciting (as‐yet‐unpublished) directions our laboratory is currently taking.
Protective human immunity as a vaccine discovery tool for falciparum malaria
Authors: Nixon Christian P. , Friedman Jennifer F. , Knopf Paul M. , Duffy Patrick E. , Kurtis Jonathan D.
Published: July 2005

BACKGROUND:  Plasmodium falciparum malaria remains a leading cause of morbidity and mortality in developing countries, and malaria‐associated severe anemia is the major factor driving the high transfusion requirements in pediatric populations living in endemic areas.

STUDY DESIGN AND METHODS:  In this report, we identify and evaluate the targets of naturally acquired protective antibody responses in a cohort of n = 143 male volunteers residing in a P. falciparum holoendemic area of western Kenya. Volunteers were drug‐cured of current malaria infection, blood was collected 2 weeks after treatment, and blood smears were collected weekly for 18 weeks. We identified and pooled plasma from the 10 most resistant (RP) and the 7 most susceptible individuals (SP) and utilized these pools in a differential screen of a P. falciparum cDNA expression library. We screened 550,000 clones and identified 7 clones that were uniquely recognized by RP but not by SP. Two clones encoded a C‐terminal region polypeptide from rhoptery‐associated membrane antigen (RAMA‐pr), a recently described rhoptry‐associated membrane antigen.

RESULTS:  We measured RAMA‐pr antibody levels in plasma obtained 2 weeks after treatment. Individuals with detectable immunoglobulin G1 anti‐RAMA‐pr (n = 24) had fewer positive blood films (p < 0.003) and 43 percent lower density of parasitemia (p < 0.02) than individuals with undetectable (n = 115) antibody levels.

CONCLUSION:  RAMA‐pr is a rationally identified vaccine candidate preferentially recognized by antibodies produced by humans with a high level of naturally acquired resistance to P. falciparum infection. Our results demonstrate that naturally acquired protective antibody responses are useful tools to identify vaccine candidates for falciparum malaria.
The importance of National Blood Foundation funding
Authors: Krause Diane S.
Published: July 2005

The research award that I received from the National Blood Foundation (NBF) was very important to me early in my career for several reasons. The funding itself was important for performing the experiments proposed, and the data obtained have played a role in much of the research that has been performed in my laboratory since that time. Also, receiving the award was a very important vote of confidence by the grant review committee at an early time in my career as an independent research scientist. Finally, because it is essential that a junior faculty member secure independent research funding, receiving this award from the NBF also represented a critical step in my career. The work that was funded by the NBF has led my laboratory down many new avenues of research, all of which have been exciting and rewarding.
Post‐National Voices
Authors: GARDELS NATHAN
Published: July 2005

Why didThe Statanic Verses, Salman Rushdie's novel about self‐doubting Muslims in London and Bombay written almost two decades ago, so resonate continents away in the corner minimalls and polylingual schools of the City of Angels?
Oral precancerous disorders associated with areca quid chewing, smoking, and alcohol drinking in southern Taiwan
Authors: Chung Ching‐Hung , Yang Yi‐Hsin , Wang Tung‐Yiu , Shieh Tien‐Yu , Warnakulasuriya Saman
Published: July 2005

Objective:  To investigate the prevalence and the associated risk factors of oral precancerous disorders in southern Taiwan.

Methods:  We conducted a cross‐sectional community survey interviewing 1075 adult subjects, 15 years of age and over, gathered from randomly selected 591 households, and spanning five villages in southern Taiwan. The study protocol included a visual oral soft tissue examination and a questionnaire‐based interview. The chi‐square test was used to test the differences in prevalence of oral precancerous lesions and conditions by different ‘life styles’ relating to current risk habits of current areca quid chewing, smoking, and alcohol drinking. To control for possible confounding, a logistic regression model was used to estimate the Odds Ratios (OR) for leukoplakia and oral submucous fibrosis (OSF).

Results:  136 precancerous lesions and conditions were detected among 1075 subjects (12.7%). The analysis of the spectrum of oral precancerous disorders detected, leukoplakia (n = 80), OSF (n = 17) and verrucous lesions (n = 9), demonstrated an association with gender (P < 0.001). There were statistically significant associations among leukoplakia (P < 0.01), OSF (P < 0.0001), and verrucous lesions (P < 0.0001) and the life style of current areca quid chewing, smoking, and alcohol drinking. The synergistic effect of smoking and areca quid chewing habit on leukoplakia and OSF was demonstrated.

Conclusion:  This study reinforces the association of current areca quid chewing without tobacco, cigarette smoking, and alcohol drinking to leukoplakia, OSF, and verrucous lesions in Taiwan.
A clinical study of 674 patients with oral lichen planus in China
Authors: Xue Jing‐Ling , Fan Ming‐Wen , Wang Shuo‐Zhi , Chen Xin‐Ming , Li Yuan , Wang Li
Published: July 2005

Background:  Oral lichen planus (OLP) is a chronic inflammatory disease with different clinical presentations that can be classified as reticular, atrophic or erosive. Although OLP is a relatively common disorder, the reports comprising large numbers of OLP patients with specific character are lacking in the literature. The purpose of this paper was to describe the clinical characteristics of OLP in 674 Chinese patients.

Methods:  A total of 674 charts of patients with histologically confirmed OLP were collected from Stomatological Hospital of Wuhan University between 1963 and 2003.

Results:  Of the 674 patients, 65.9% were women and 34.1% were men. The most common clinical presentation was the reticular type (51.3%), and symptomatic OLP was noted in 67.5% of the patients, mainly in those with the erosive form. The erosive presentations showed significantly longer duration, more sites affected and a much greater old patients predominance than reticular or atrophic ones. About 90.9% of the patients had multiple oral sites of involvement and isolated lower lip lichen planus were observed in 60 cases (8.9%) and isolated gingiva lichen in only one case (0.2%). Skin involvement of lichen planus was found in 11.4% of patients. No statistically significant differences could be identified between OLP and diabetes, cardiovascular disease, smoking or alcohol use. Precipitating factors that resulted in an exacerbation of the disease were frequently noted and included foods, stress, dental cusp and poor oral hygiene. The transformation of OLP into malignancy was observed in four patients at sites previously diagnosed by clinical examination as erosive or atrophic lichen planus.

Conclusions:  Patients with OLP in China usually present with distinctive clinical morphology and characteristic distribution and few may display lesions with a confusing array of forms mimicking other diseases. A long time follow up is of utmost importance to detect its malignant transformation.
Association of GST genotypes with age of onset and lymph node metastasis in oral squamous cell carcinoma
Authors: Liu Chung‐Ji , Chang Che‐Shoa , Lui Man‐Tin , Dang Ching‐Wen , Shih Yin‐Hua , Chang Kuo‐Wei
Published: July 2005

Background:  Environment–gene interaction in oral carcinogenesis is well demonstrated by phase I and II enzymes that are involved in the metabolism of carcinogens. This study investigated the association of glutathione S‐transferase (GST)T1 and GSTM1 genotypes of phase II enzyme genes with risk for, age of onset, and neck lymph node metastasis (LNM) in areca‐associated oral squamous cell carcinoma (OSCC).

Methods:  A total of 114 OSCC male patients and 100 male controls were recruited. All subjects were areca users and tobacco smokers. DNA was obtained from peripheral blood samples. Genotyping of GSTT1 (non‐null/null) and GSTM1 (non‐null/null) was determined by polymerase chain reaction (PCR) analysis using specific primers that only amplify non‐null alleles.

Results:  No association was found between GST genotype and the risk of OSCC based on case–controls. Patients with the GSTT1 null genotype were older at onset (P = 0.03). Those with the GSTM1 null genotype had a higher incidence of neck LNM than those with the GSTM1 non‐null genotype (P = 0.01). Patients with the GSTM1/GSTT1 null genotype appeared to have later onset and a higher incidence of neck LNM than those carrying the opposite genotype.

Conclusion:  The GST genotypes may be important markers for the age of onset and risk of metastasis in OSCC. The data also suggest that the various GST isoforms may be differentially involved in development or progression of OSCC.
Cleavage of nucleolin and AgNOR proteins during apoptosis induced by anticancer drugs in human salivary gland cells
Authors: Kito S. , Morimoto Y. , Tanaka T. , Haneji T. , Ohba T.
Published: July 2005

Background:  To investigate the behavior of nuclear proteins in apoptosis induced by anticancer drugs in cultured human salivary gland (HSG) cells.

Methods:  Dynamic alternations of nucleolin and argyrophilic nucleolar organizer region (AgNOR) proteins in anticancer drug‐induced apoptosis of HSG cells and in a cell‐free apoptotic system were examined using Western blot analysis and immunocytochemical method.

Results:  The 110‐kDa form of nucleolin and AgNOR protein decreased and the 80‐ and 95‐kDa forms appeared during apoptosis in HSG cells and in a cell‐free apoptotic system. In addition, the induction of DNA ladder formation coincided with the appearance of alternation of nucleolin and AgNOR proteins in a cell‐free apoptosis. Nucleolin diffusely spread out into the nuclear material in the apoptotic body of HSG cells.

Conclusions:  The present results indicate that alternations of nucleolin and AgNOR proteins are associated with the induction of DNA fragmentation and the final active phase of apoptosis induced by anticancer drugs in malignant salivary gland cells.
Pesticide Regulation and Pesticide Prices
Authors: Freshwater David , Short Cameron
Published: July 2005

Pesticides are an increasingly important input in crop production. In North America there has been a longstanding concern by farmers in close proximity to the Canada–U.S. border that either differences in access to compounds or price differentials adversely affect competitive positions. Past analysis of this issue has tended to assume a simple arbitrage process, if borders are opened, that leads to prices falling to the lower price. By contrast, we examine the possibility for systematic price discrimination by pesticide manufacturers. Under this model an open border may lead to price arbitrage, but not at the lower price. Further, we show that while aggregate social welfare gains from removing price discrimination are possible, they may be small. Further, component welfare changes to manufacturers and farmers in each country are large and conflicting, which suggests there will likely be opposition from some groups to more open borders.
Spatial Yield Risk Across Region, Crop and Aggregation Method
Authors: Popp Michael , Rudstrom Margot , Manning Patrick
Published: July 2005

A researcher interested in crop yield risk analysis often has to contend with a lack of field‐ or farm‐level data. While spatially aggregated yield data are often readily available from various agencies, aggregation distortions for farm‐level analysis may exist. This paper addresses how much aggregation distortion might be expected and whether findings are robust across wheat, canola and flax grown in two central Canadian production regions, differing mainly by rainfall, frost‐free growing days and soil type. Using Manitoba Crop Insurance Corporation data from 1980 to 1990, this research, regardless of crop or region analyzed, indicates that (i) spatial patterns in risk are absent; (ii) use of aggregate data overwhelmingly under‐estimates field‐level yield risk; and (iii) use of a relative risk measure compared to an absolute risk measure leads to slightly less aggregation distortion. Analysts interested in conducting farm‐level analysis using aggregate data are offered a range of adjustment factors to adjust for potential bias.
Price Relationships in Processors' Input Market Areas: Testing Theories for Corn Prices Near Ethanol Plants
Authors: Gallagher Paul , Wisner Robert , Brubacker Heather
Published: July 2005

This study examines corn pricing in the vicinity of processing plants. We develop and test several price‐distance models for cargo, insurance and freight (CIF) plant pricing in the presence of varying degrees of exporter competition, and for discriminatory free‐on‐board (FOB) pricing at the farm. The price‐distance functions describing spatial prices near processing plants all depend on local transport costs. But the pricing system (CIF or FOB) and the extent of local competition define the level and spatial rate of change in prices.Estimations of an empirical price‐location function for Iowa during the spring of 2003 suggest that prices near the plants of four conventional businesses conform to the CIF pricing model. But prices near producer‐owned firms or farmer cooperatives failed to show any statistically significant effect on nearby prices. One plant had a price‐distance function that resembled FOB pricing.
Systematic Variation in Willingness to Pay for Aquatic Resource Improvements and Implications for Benefit Transfer: A Meta‐Analysis
Authors: Johnston Robert J. , Besedin Elena Y. , Iovanna Richard , Miller Christopher J. , Wardwell Ryan F. , Ranson Matthew H.
Published: July 2005

Researchers are increasingly considering benefit transfer approaches that allow welfare measures to be adjusted for characteristics of the policy context. The validity and reliability of such adjustments, however, depends on the presence of systematic variation in underlying WTP. This paper describes a meta‐analysis conducted to identify systematic components of WTP for aquatic resource improvements. Model results reveal systematic patterns in WTP unapparent from stated preference models considered in isolation, and suggest that observable attributes account for a substantial proportion of the variance in WTP estimates across studies. The analysis also exposes challenges faced in development, estimation, and interpretation of meta‐models for benefit transfer and welfare guidance. These challenges remain salient even in cases where the statistical performance of meta‐models is satisfactory.
A Spatial Equilibrium Analysis of U.S.–Canadian Disputes on the World Softwood Lumber Market
Authors: Devadoss Stephen , Aguiar Angel H. , Shook Steven R. , Araji Jim
Published: July 2005

This paper utilizes a world spatial equilibrium model to examine the effects of U.S.–Canadian softwood lumber disputes on U.S., Canadian, and other exporters' and importers' lumber markets. Results show that the U.S. import tariff on Canadian softwood lumber impacts prices, supply, demand and trade flows not only in the United States and Canada but also in the other countries. Though the goal of U.S. trade restriction is to limit imports from Canada and protect its producers, the United States cannot fully accomplish this goal as non‐Canadian exporters fill the void left by the reduced imports from Canada. Canadian producers lose from the U.S. policy, but their loss is mitigated as Canada redirects its exports to other importers. Importing countries such as Japan and the European Union benefit from the U.S. trade restrictions as Canada seeks to sell its softwood lumber to these countries.
Evidence for parasympathetic vasodilator fibres in the rat masseter muscle
Authors: Ishii Hisayoshi , Niioka Takeharu , Sudo Emi , Izumi Hiroshi
Published: July 2005

The present study was designed to examine (1) whether there are vasodilator fibres in the masseter muscle, and (2) if there are, to establish the neural pathways mediating these responses in urethane‐anaesthetized rats. Electrical stimulation of the central cut end of the lingual nerve (LN) elicited intensity‐ and frequency‐dependent increases of the blood flow in the masseter muscle (MBF) and lower lip (LBF). Increases in both the MBF and LBF evoked by the LN stimulation were reduced by hexamethonium in a dose‐dependent manner (1–10 mg kg−1). Pretreatment with phentolamine or propranolol at a dose of 100 μg kg−1 had no effect on the increases in either MBF or LBF evoked by LN stimulation. Pretreatment with atropine (100 μg kg−1) significantly reduced the MBF increase induced by LN stimulation, but not that in the LBF. The sectioning of the superior cervical sympathetic trunk did not affect the responses. MBF increases occurred with electrical stimulation of the trigeminal ganglion, and these increases were significantly reduced by the administration of hexamethonium and atropine. Lidocaine microinjection into the trigeminal spinal nucleus or salivatory nuclei caused a significant attenuation of the LN‐induced MBF increases. When wheat germ agglutinin–horseradish peroxidase (WGA–HRP) was injected into the masseter muscle, labelled neurones were abundantly observed in the otic ganglion. The present study indicates that there are parasympathetic cholinergic and noncholinergic vasodilator fibres originating from cell bodies in the otic ganglion in the rat masseter muscle. The MBF increase evoked by activation of the parasympathetic fibres occurred via the trigeminal mediated reflex, suggesting that the novel parasympathetic vasodilator response may play an important role in the regulation of the haemodynamics of jaw muscles.
The mechanism of pneumolysin‐induced cochlear hair cell death in the rat
Authors: Beurg Maryline , Hafidi Aziz , Skinner Liam , Cowan Graeme , Hondarrague Yannick , Mitchell Tim J. , Dulon Didier
Published: July 2005

Streptoccocus pneumoniae infection can result in local and systemic diseases such as otitis media, pneumonia and meningitis. Sensorineural hearing loss associated with this infection is mediated by the release of an exotoxin, pneumolysin. The goal of the present study was to characterize the mechanisms of pneumolysin toxicity in cochlear hair cells in vitro. Pneumolysin induced severe damage in cochlear hair cells, ranging from stereocilia disorganization to total cell loss. Surprisingly, pneumolysin‐induced cell death preferentially targeted inner hair cells. Pneumolysin triggered in vitro cell death by an influx of calcium. Extracellular calcium appeared to enter the cell through a pore formed by the toxin. Buffering intracellular calcium with BAPTA improved hair cell survival. The mitochondrial apoptotic pathway involved in pneumolysin‐induced cell death was demonstrated by the use of bongkrekic acid. Binding of pneumolysin to the hair cell plasma membrane was required to induce cell death. Increasing external calcium reduced cell toxicity by preventing the binding of pneumolysin to hair cell membranes. These results showed the significant role of calcium both in triggering pneumolysin‐induced hair cell apoptosis and in preventing the toxin from binding to its cellular target.
Fasted‐state skeletal muscle protein synthesis after resistance exercise is altered with training
Authors: Kim Paul L. , Staron Robert S. , Phillips Stuart M.
Published: July 2005

The purpose of the present investigation was to determine how fasted‐state protein synthesis was affected, acutely, by resistance training. Eight men (24.8 ± 1.7 years, body mass index = 23.2 ± 1.0 kg m−2; means ±s.e.m.) undertook an 8 week programme of unilateral resistance exercise training (3 sessions week−1, progression from two to four sets; intensity was 80% of the subjects' single repetition maximum (1RM): knee extension and leg press). Following training, subjects underwent two primed constant infusions of l‐[ring‐13C6]phenylalanine to determine mixed and myofibrillar muscle protein synthesis (MPS) at rest and 12 h after an acute bout of resistance exercise at the same exercise intensity – each leg 80% of 1RM. Biopsies (vastus lateralis) were taken to measure incorporation of labelled phenylalanine into mixed and myofibrillar skeletal muscle proteins and yield fractional MPS. Training resulted in significant dynamic strength gains that were greater (P < 0.001) in the trained leg. Hypertrophy of type IIa and IIx fibres (P < 0.05) was observed following training. After training, resting mixed MPS rate was elevated (+48%; P < 0.05). Acutely, resistance exercise stimulated mixed MPS only in the untrained leg (P < 0.05). Myofibrillar MPS was unchanged at rest following training (P= 0.61). Myofibrillar MPS increased after resistance exercise (P < 0.05), but was not different between the trained and untrained legs (P= 0.36). We observed divergent changes in resting mixed versus myofibrillar protein synthesis with training. In addition, resistance training modified the acute response of MPS to resistance exercise by dampening the increased synthesis of non‐myofibrillar proteins while maintaining the synthesis of myofibrillar proteins.
Fe-Mg Interdiffusion in (Mg,Fe)SiO
3
Perovskite and Lower Mantle Reequilibration
Authors: Holzapfel Christian , Rubie David C. , Frost Daniel J. , Langenhorst Falko
Published: July 2005

Fe-Mg interdiffusion coefficients for (Mg,Fe)SiO
3
perovskite have been measured at pressures of 22 to 26 gigapascals and temperatures between 1973 and 2273 kelvin. Perovskite Fe-Mg interdiffusion is as slow as Si self-diffusion and is orders of magnitude slower than Fe-Mg diffusion in other mantle minerals. Length scales over which chemical heterogeneities can homogenize, throughout the depth range of the lower mantle, are limited to a few meters even on time scales equivalent to the age of Earth. Heterogeneities can therefore only equilibrate chemically when they are stretched and thinned by intense deformation.
HST2
Mediates
SIR2
-Independent Life-Span Extension by Calorie Restriction
Authors: Lamming Dudley W. , Latorre-Esteves Magda , Medvedik Oliver , Wong Stacy N. , Tsang Felicia A. , Wang Chen , Lin Su-Ju , Sinclair David A.
Published: July 2005

Calorie restriction (CR) extends the life span of numerous species, from yeast to rodents. Yeast Sir2 is a nicotinamide adenine dinucleotide (NAD
+
-dependent histone deacetylase that has been proposed to mediate the effects of CR. However, this hypothesis has been challenged by the observation that CR can extend yeast life span in the absence of Sir2. Here, we show that Sir2-independent life-span extension is mediated by Hst2, a Sir2 homolog that promotes the stability of repetitive ribosomal DNA, the same mechanism by which Sir2 extends life span. These findings demonstrate that the maintenance of DNA stability is critical for yeast life-span extension by CR and suggest that, in higher organisms, multiple members of the Sir2 family may regulate life span in response to diet.
COLLECTIVE DYNAMICS IN AN ENSEMBLE OF GLOBALLY COUPLED FHN SYSTEMS
Authors: SAILER X. , ZAKS M. , SCHIMANSKY-GEIER L.
Published: July 2005

We examine an ensemble of globally coupled FitzHugh–Nagumo systems with Gaussian, white noise. In the case of spatially uncorrelated noise, at high and at low noise levels the mean of the ensemble is steady. In between it exhibits a complex behavior. Depending on the noise intensity we find small scale oscillations, period doubling, chaos, and spiking. We derive equations of motion for the cumulants of the ensemble distribution. The results of the cumulant dynamics analysis are in good qualitative agreement with results from the Langevin dynamics. Once we additionally apply correlated noise but keep the sum of both noise intensities constant, the mean starts spiking where it did not spike with uncorrelated noise. For increasing correlation strength a minimum of the coefficient of variation appears.
NONMONOTONIC PATTERN FORMATION IN THREE SPECIES LOTKA–VOLTERRA SYSTEM WITH COLORED NOISE
Authors: FIASCONARO A. , VALENTI D. , SPAGNOLO B.
Published: July 2005

A coupled map lattice of generalized Lotka–Volterra equations in the presence of colored multiplicative noise is used to analyze the spatiotemporal evolution of three interacting species: one predator and two preys symmetrically competing each other. The correlation of the species concentration over the grid as a function of time and of the noise intensity is investigated. The presence of noise induces pattern formation, whose dimensions show a nonmonotonic behavior as a function of the noise intensity. The colored noise induces a greater dimension of the patterns with respect to the white noise case and a shift of the maximum of its area towards higher values of the noise intensity.
GLASSY DYNAMICS AT THE ONSET OF CHAOS WITH ADDITIVE NOISE
Authors: BALDOVIN FULVIO , ROBLEDO ALBERTO
Published: July 2005

After recalling key phenomenological properties of glass formation, we point out that similar features are exhibited by the dynamical properties of the noise-perturbed iterates of the logistic map at the onset of chaos. The analysis includes two-step relaxation, aging, subdiffusion and arrest, as well as an expression analogous to the Adam–Gibbs relation connecting dynamical and thermodynamic properties of a glass former. The dynamical properties of the logistic map in the presence of external noise are seen to be comparable to those of a supercooled liquid above a glass transition temperature, whereas the noiseless attractor displays typical nonequilibrium aspects like loss of time translation invariance (aging). Reference is made to connections between the noiseless dynamics at the chaos threshold and the nonextensive formalism.
TRANSIENT PATTERN FORMATION IN A STOCHASTIC MODEL OF CANCER GROWTH
Authors: OCHAB-MARCINEK ANNA
Published: July 2005

We study a spatially inhomogeneous model of cancer growth based on Michaelis–Menten kinetics, subjected to additive Gaussian noise and multiplicative dichotomous noise. In presence of the latter, we can observe a transition between two stationary states of the system, The transient behaviour generates a spatial pattern of two phases, where cancer cells or immune cells predominate.
ROLE OF THE COLORED NOISE IN SPATIO-TEMPORAL BEHAVIOR OF TWO COMPETING SPECIES
Authors: VALENTI D. , FIASCONARO A. , SPAGNOLO B.
Published: July 2005

We study the spatial distributions of two randomly interacting species, in the presence of an external multiplicative colored noise. The dynamics of the ecosystem is described by a coupled map lattice model. We find a nonmonotonic behavior in the formation of large scale spatial correlations as a function of the multiplicative colored noise intensity. This behavior is shifted towards higher values of the noise intensity for increasing correlation time of the noise.
CYCLIC FLUCTUATIONS, CLIMATIC CHANGES AND ROLE OF NOISE IN PLANKTONIC FORAMINIFERA IN THE MEDITERRANEAN SEA
Authors: CARUSO A. , GARGANO M. E. , VALENTI D. , FIASCONARO A. , SPAGNOLO B.
Published: July 2005

The study of Planktonic Foraminifera abundances permits to obtain climatic curves on the basis of percentage ratio between tropical and temperate/polar forms. Climatic changes were controlled by several phenomena as: (i) Milankovitch's cycles, produced by variations of astronomical parameters such as precession, obliquity and eccentricity; (ii) continental geodynamic evolution and orogenic belt; (iii) variations of atmospheric and oceanic currents; (iv) volcanic eruptions; (v) meteor impacts. But while astronomical parameters have a quasi-regular periodicity, the other phenomena can be considered as "noise signal" in natural systems. The interplay between cyclical astronomical variations, the "noise signal" and the intrinsic nonlinearity of the ecologic system produces strong glacial or interglacial period according to the stochastic resonance phenomenon.
COMMENT ON "EXPERIMENTAL DEMONSTRATION OF VIOLATIONS OF THE SECOND LAW OF THERMODYNAMICS FOR SMALL SYSTEMS AND SHORT TIME SCALES"
Authors: NIEUWENHUIZEN THEO M. , ALLAHVERDYAN ARMEN E.
Published: July 2005

In a recent paper Wang et al. [1] report for a colloidal system the entropy production in individual particle trajectories. Some of the trajectories have a negative production, and this is claimed to violate the second law. We stressed that the second law only demands the entropy production averaged over all trajectories to be positive, and this is the case for the data of Wang et al.
TOWARD AN UNDERSTANDING OF ARAB WOMEN ENTREPRENEURS IN BAHRAIN AND OMAN
Authors: DECHANT KATHLEEN , LAMKY ASYA AL
Published: July 2005

Entrepreneurship has become a defining business trend in many countries throughout the world. The ranks of entrepreneurs contain a sizable contingent of women. As a result, research into the pathways of entrepreneurship as a general phenomenon as well as a career option for women has flourished in recent years. However, very little of this research has focused on women entrepreneurs in Arab countries, particularly those around the Gulf of Arabia, where private enterprise is viewed as a way for these nations to reduce their reliance on oil and their dependence on expatriate (foreign) workers. This study of the business start-up experiences of ten Arab women from Bahrain and Oman can serve as a starting point for such research. Although based on a non-representative sample, it suggests that the experiences of the Arab women entrepreneurs studied generally parallel those of their counterparts from other parts of the world with a few distinct differences. These differences relate to securing start-up capital and other resources, networking, and work/family balance. Infused with Arab and Islamic values, the unique cultural milieu played a major role in shaping the entrepreneurial experiences of the Bahraini and Omani business owners studied.
IN AWE OF SUBCELLULAR COMPLEXITY: 50 Years of Trespassing Boundaries Within the Cell
Authors: Sabatini David D.
Published: July 2005

In this review I describe the several stages of my research career, all of which were driven by a desire to understand the basic mechanisms responsible for the complex and beautiful organization of the eukaryotic cell. I was originally trained as an electron microscopist in Argentina, and my first major contribution was the introduction of glutaraldehyde as a fixative that preserved the fine structure of cells, which opened the way for cytochemical studies at the EM level. My subsequent work on membrane-bound ribosomes illuminated the process of cotranslational translocation of polypeptides across the ER membrane and led to the formulation, with Gunter Blobel, of the signal hypothesis. My later studies with many talented colleagues contributed to an understanding of ER structure and function and aspects of the mechanisms that generate and maintain the polarity of epithelial cells. For this work my laboratory introduced the now widely adopted Madin-Darby canine kidney (MDCK) cell line, and demonstrated the polarized budding of envelope viruses from those cells, providing a powerful new system that further advanced the field of protein traffic.
Evolutionary History of Poales
Authors: Linder H. Peter , Rudall Paula J.
Published: July 2005

▪ Abstract  The predominantly wind-pollinated order Poales includes about one third of all monocot (Angiosperm) species, with c. 20,000 species dominating modern savanna and steppe vegetation. Recent improvements in understanding relationships within the order allow phylogenetic optimizations of habitat preferences and adaptive character states, enabling exploration of the factors that have influenced evolution in this successful order. Poales probably originated in the late Cretaceous in wet nutrient–poor sunny habitats. By the Paleogene the lineage had diversified into swamps, the forest understory, epiphytic habitats, and nutrient-poor heathlands. The Neogene saw major diversifications of the grasses and possibly the sedges into fire-adapted vegetation in seasonal climates and low atmospheric CO2. Diversification into these habitats was facilitated by morphological features such as the sympodial habit and physiological factors that allowed frequent evolution of CO2-concentrating mechanisms.
IL-28A and IL-29 mediate antiproliferative and antiviral signals in intestinal epithelial cells and murine CMV infection increases colonic IL-28A expression
Authors: Brand Stephan , Beigel Florian , Olszak Torsten , Zitzmann Kathrin , Eichhorst Sören T. , Otte Jan-Michel , Diebold Joachim , Diepolder Helmut , Adler Barbara , Auernhammer Christoph J. , Göke Burkhard , Dambacher Julia
Published: July 2005

Human cytomegalovirus virus (CMV) is a major cause of morbidity and mortality in immunocompromised individuals. Recently, a novel group of cytokines [interleukin (IL)-28A/B and IL-29, also termed interferon (IFN)-λs] has been described. Here, we demonstrate that intestinal epithelial cell (IEC) lines as well as murine and human colonic tissue express the IFN-λ receptor subunits IL-28R and IL-10R2. IL-28A and IL-29 binding to their receptor complex activates ERK-1/2 and stress-activated protein kinase/c-Jun NH2-terminal kinase MAPKs and Akt, resulting in increased IL-8 protein expression. IFN-λs also induce phosphorylation of signal transducer and activator of transcription 1 and significantly increase mRNA expression of suppressor of cytokine signaling 3 and the antiviral proteins myxovirus resistance A and 2′,5′-oligoadenylate synthetase. These signals result in an up to 83% reduction of cells positive for human CMV immediate-early protein after human CMV infection. In mice, IL-28A mRNA expression is upregulated after infection with murine CMV in vivo. Both IL-28A and IL-29 significantly decrease cell proliferation but have no effect on Fas-induced apoptosis. In conclusion, IECs express functional receptors for IFN-λs, which mediate antiviral and antiproliferative signals in IECs, suggesting a potential for therapeutic use in certain viral infections and as (antiproliferative) anticancer therapy.
Hindbrain chemical mediators of reflex-induced inhibition of gastric tone produced by esophageal distension and intravenous nicotine
Authors: Ferreira Manuel , Sahibzada Niaz , Shi Min , Niedringhaus Mark , Wester Matthew R. , Jones Allison R. , Verbalis Joseph G. , Gillis Richard A.
Published: July 2005

The purpose of this study was to activate a vagovagal reflex by using esophageal distension and nicotine and test whether hindbrain nitric oxide and norepinephrine are involved in this reflex function. We used double-labeling immunocytochemical methods to determine whether esophageal distension (and nicotine) activates c-Fos expression in nitrergic and noradrenergic neurons in the nucleus tractus solitarii (NTS). We also studied c-Fos expression in the dorsal motor nucleus of the vagus (DMV) neurons projecting to the periphery. Esophageal distension caused 19.7 ± 2.3% of the noradrenergic NTS neurons located 0.60 mm rostral to the calamus scriptorius (CS) to be activated but had little effect on c-Fos in DMV neurons. Intravenous administration of nicotine caused 19.7 ± 4.2% of the noradrenergic NTS neurons 0.90 mm rostral to CS to be activated and, as reported previously, had no effect on c-Fos expression in DMV neurons. To determine whether norepinephrine and nitric oxide were central mediators of esophageal distension-induced decrease in intragastric pressure (balloon recording), NG-nitro-l-arginine methyl ester microinjected into the NTS ( n = 5), but not into the DMV, blocked the vagovagal reflex. Conversely, α2-adrenergic blockers microinjected into the DMV ( n = 7), but not into the NTS, blocked the vagovagal reflex. These data, in combination with our earlier pharmacological microinjection data with nicotine, indicate that both esophageal distension and nicotine produce nitric oxide in the NTS, which then activates noradrenergic neurons that terminate on and inhibit DMV neurons.
Are transcription factors NF-κB and AP-1 involved in the ANG II-stimulated production of proinflammatory cytokines induced by LPS in dehydrated rats?
Authors: Sasaki Kumiko , Taniguchi Makoto , Miyoshi Michio , Goto Osamu , Sato Kenzo , Watanabe Tatsuo
Published: July 2005

We recently reported an involvement of ANG II and the ANG II type 1 (AT1) receptor in the hepatic expression of IL-1β induced in dehydrated rats by LPS. Here, we first confirmed that ANG II and AT1receptors contribute to the LPS-induced increase in the splenic concentration of IL-1β in dehydrated rats. We then investigated whether ANG II contributes to IL-1 production through a modulating effect on the activation of proinflammatory transcription factors (NF-κB and AP-1) that is induced in the dehydrated rat's liver and spleen by intravenous injection of LPS. Surprisingly, LPS markedly increased the hepatic activation of NF-κB, an effect that was significantly enhanced (rather than reduced) by pretreatment with an ANG-converting-enzyme (ACE) inhibitor or AT1-receptor antagonist. Furthermore, the same ACE inhibitor and AT1-receptor antagonist each increased the resting NF-κB activity in the liver and spleen, although they had no effect on the LPS-induced splenic expression of NF-κB. Both hepatic and splenic AP-1 expressions were enhanced by LPS. This response was significantly augmented by pretreatment with the AT1-receptor antagonist (but not with the ACE inhibitor) in the spleen, while in the liver, neither drug had any effect. These results suggest that the endogenous ANG II or AT1receptor suppresses the activation of hepatic or splenic transcription factors in dehydrated rats given LPS. Our results seem not to support the idea that NF-κB and AP-1 play key roles in the ANG II-induced enhancement of the production of proinflammatory cytokines that is induced by LPS in dehydrated rats.