bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of a Novel Transcription Factor through Phosphorylation by WIPK, a Wound-Induced Mitogen-Activated Protein Kinase in Tobacco Plants
Authors: Yap Yun-Kiam , Kodama Yutaka , Waller Frank , Chung Kwi Mi , Ueda Hirokazu , Nakamura Kimiyo , Oldsen Maren , Yoda Hiroshi , Yamaguchi Yube , Sano Hiroshi
Published: August 2005

Wound-induced protein kinase (WIPK) is a tobacco (Nicotiana tabacum) mitogen-activated protein kinase known to play an essential role in defense against wounding and pathogens, although its downstream targets have yet to be clarified. This study identified a gene encoding a protein of 648 amino acids, which directly interacts with WIPK, designated as N. tabacum WIPK-interacting factor (NtWIF). The N-terminal region with approximately 250 amino acids showed a high similarity to the plant-specific DNA binding domain, B3, but no other similarity with known proteins. The C terminus of approximately 200 amino acids appeared to be essential for the interaction with WIPK, and a Luciferase-reporter gene assay using Bright Yellow 2 cells indicated the full-length protein to possess trans-activation activity, located to the middle region of approximately 200 amino acids. In vitro phosphorylation assays indicated that WIPK efficiently phosphorylates the full-length protein and the N terminus but not the C terminus. When full-length NtWIF was coexpressed with WIPK in Bright Yellow 2 cells, the Luciferase transcriptional activity increased up to 5-fold that of NtWIF alone, whereas no effect was observed with a kinase-deficient WIPK mutant. Transcripts of NtWIF began to simultaneously accumulate with those of WIPK 30 min after wounding and 1 h after the onset of hypersensitive response upon tobacco mosaic virus infection. These results suggest that NtWIF is a transcription factor that is directly phosphorylated by WIPK, thereby being activated for transcription of target gene(s) involved in wound and pathogen responses.
Enhancing Arabidopsis Salt and Drought Stress Tolerance by Chemical Priming for Its Abscisic Acid Responses
Authors: Jakab Gabor , Ton Jurriaan , Flors Victor , Zimmerli Laurent , Métraux Jean-Pierre , Mauch-Mani Brigitte
Published: August 2005

Drought and salt stress tolerance of Arabidopsis (Arabidopsis thaliana) plants increased following treatment with the nonprotein amino acid β-aminobutyric acid (BABA), known as an inducer of resistance against infection of plants by numerous pathogens. BABA-pretreated plants showed earlier and higher expression of the salicylic acid-dependent PR-1 and PR-5 and the abscisic acid (ABA)-dependent RAB-18 and RD-29A genes following salt and drought stress. However, non-expressor of pathogenesis-related genes 1 and constitutive expressor of pathogenesis-related genes 1 mutants as well as transgenic NahG plants, all affected in the salicylic acid signal transduction pathway, still showed increased salt and drought tolerance after BABA treatment. On the contrary, the ABA deficient 1 and ABA insensitive 4 mutants, both impaired in the ABA-signaling pathway, could not be protected by BABA application. Our data demonstrate that BABA-induced water stress tolerance is based on enhanced ABA accumulation resulting in accelerated stress gene expression and stomatal closure. Here, we show a possibility to increase plant tolerance for these abiotic stresses through effective priming of the preexisting defense pathways without resorting to genetic alterations.
Chlorophyll Breakdown in Senescent Arabidopsis Leaves. Characterization of Chlorophyll Catabolites and of Chlorophyll Catabolic Enzymes Involved in the Degreening Reaction
Authors: Pružinská Adriana , Tanner Gaby , Aubry Sylvain , Anders Iwona , Moser Simone , Müller Thomas , Ongania Karl-Hans , Kräutler Bernhard , Youn Ji-Young , Liljegren Sarah J. , Hörtensteiner Stefan
Published: August 2005

During senescence, chlorophyll (chl) is metabolized to colorless nonfluorescent chl catabolites (NCCs). A central reaction of the breakdown pathway is the ring cleavage of pheophorbide (pheide) a to a primary fluorescent chl catabolite. Two enzymes catalyze this reaction, pheide a oxygenase (PAO) and red chl catabolite reductase. Five NCCs and three fluorescent chl catabolites (FCCs) accumulated during dark-induced chl breakdown in Arabidopsis (Arabidopsis thaliana). Three of these NCCs and one FCC (primary fluorescent chl catabolite-1) were identical to known catabolites from canola (Brassica napus). The presence in Arabidopsis of two modified FCCs supports the hypothesis that modifications, as present in NCCs, occur at the level of FCC. Chl degradation in Arabidopsis correlated with the accumulation of FCCs and NCCs, as well as with an increase in PAO activity. This increase was due to an up-regulation of Pao gene expression. In contrast, red chl catabolite reductase is not regulated during leaf development and senescence. A pao1 knockout mutant was identified and analyzed. The mutant showed an age- and light-dependent cell death phenotype on leaves and in flowers caused by the accumulation of photoreactive pheide a. In the dark, pao1 exhibited a stay-green phenotype. The key role of PAO in chl breakdown is discussed.
A Comprehensive Analysis of the NADP-Malic Enzyme Gene Family of Arabidopsis
Authors: Wheeler Mariel C. Gerrard , Tronconi Marcos A. , Drincovich María F. , Andreo Carlos S. , Flügge Ulf-Ingo , Maurino Verónica G.
Published: August 2005

The Arabidopsis (Arabidopsis thaliana) genome contains four genes encoding putative NADP-malic enzymes (MEs; AtNADP-ME1–ME4). NADP-ME4 is localized to plastids, whereas the other three isoforms do not possess any predicted organellar targeting sequence and are therefore expected to be cytosolic. The plant NADP-MEs can be classified into four groups: groups I and II comprising cytosolic and plastidic isoforms from dicots, respectively; group III containing isoforms from monocots; and group IV composed of both monocots and dicots, including AtNADP-ME1. AtNADP-MEs contained all conserved motifs common to plant NADP-MEs and the recombinant isozymes showed different kinetic and structural properties. NADP-ME2 exhibits the highest specific activity, while NADP-ME3 and NADP-ME4 present the highest catalytic efficiency for NADP and malate, respectively. NADP-ME4 exists in equilibrium of active dimers and tetramers, while the cytosolic counterparts are present as hexamers or octamers. Characterization of T-DNA insertion mutant and promoter activity studies indicates that NADP-ME2 is responsible for the major part of NADP-ME activity in mature tissues of Arabidopsis. Whereas NADP-ME2 and -ME4 are constitutively expressed, the expression of NADP-ME1 and NADP-ME3 is restricted by both developmental and cell-specific signals. These isoforms may play specific roles at particular developmental stages of the plant rather than being involved in primary metabolism.
The Arabidopsis PEX12 Gene Is Required for Peroxisome Biogenesis and Is Essential for Development
Authors: Fan Jilian , Quan Sheng , Orth Travis , Awai Chie , Chory Joanne , Hu Jianping
Published: August 2005

Peroxisomes perform diverse and vital functions in eukaryotes, and abnormalities in peroxisomal function lead to severe developmental disorders in humans. Peroxisomes are also involved in a wide array of physiological and metabolic functions unique to plants, yet many aspects of this important organelle are poorly understood. In yeast and mammals, various steps in peroxisome biogenesis require the function of peroxin (PEX) proteins, among which PEX12 is a RING finger peroxisomal membrane protein involved in the import of matrix proteins. To investigate the role of PEX12 in plants, we identified a T-DNA knockout allele of PEX12 and generated partial loss-of-function pex12 mutants using RNA interference. We show that pex12 null mutants are developmentally arrested during early embryogenesis, and that the embryo-lethal phenotype can be rescued by overexpression of the PEX12-cyan fluorescent protein fusion protein, which targets to the peroxisome. Using virus-induced gene-silencing techniques, we demonstrate that peroxisomal number and fluorescence of the yellow fluorescent protein-peroxisome targeting signal type 1 protein are greatly reduced when PEX12 is silenced. RNA interference plants with partial reduction of the PEX12 transcript exhibit impaired peroxisome biogenesis and function, inhibition of plant growth, and reduced fertility. Our work provides evidence that the Arabidopsis (Arabidopsis thaliana) PEX12 protein is required for peroxisome biogenesis and plays an essential role throughout plant development.
Dissociable memory effects after medial thalamus lesions in the rat
Authors: Mitchell Anna S. , Dalrymple‐Alford John C.
Published: August 2005

Variable neuropathology in cases of diencephalic amnesia has led to uncertainty in identifying key thalamic nuclei and their potential role in learning and memory. Based on the principal neural connections of the medial thalamus, the current study tested the hypothesis that different aggregates of thalamic nuclei contribute to separate memory systems. Lesions of the anterior thalamic aggregate (AT), which comprises the anterodorsal, anteromedial and anteroventral nuclei produced substantial deficits in both working and reference spatial memory in a radial arm maze task in rats, supporting the view that the AT is an integral part of a hippocampal memory system. Lesions to the lateral thalamic aggregate (LT), which comprises the intralaminar nuclei (centrolateral, paracentral and rostral central medial nuclei) and lateral mediodorsal thalamic nuclei (lateral and paralamellar nuclei) produced a mild working memory impairment only, while lesions to the posteromedial thalamic aggregate (MT), which comprises the central and medial mediodorsal thalamic nuclei and the intermediodorsal nucleus had no effect on radial arm maze performance. In contrast, only MT lesions impaired learning associated with memory for reward value, consistent with the idea that the MT contributes to an amygdala memory system. Compared with chance discrimination, the control and AT groups, but not MT or LT groups, showed evidence for temporal order memory for two recently presented objects; all groups showed intact object recognition for novel vs. familiar objects. These new dissociations show that different medial thalamic aggregates participate in multiple memory systems and reinforce the idea that memory deficits in diencephalic amnesics may vary as a function of the relative involvement of different thalamic regions.
Similarities in the phenotype of the auditory neural substrate in children with Asperger syndrome and their parents
Authors: Jansson‐Verkasalo E. , Kujala T. , Jussila K. , Mattila M. L. , Moilanen I. , Näätänen R. , Suominen K. , Korpilahti P.
Published: August 2005

Asperger syndrome (AS) is a developmental disorder of brain function characterized by deficits in social interaction including difficulties in understanding emotional expressions. Children with AS share some of the behavioural characteristics with their parents and AS seems to run particularly in the male members of the same families. The aim of the present study was to determine whether similarities could be found between children with AS and their parents at central auditory processing. It was found that in children with AS the sound encoding, as reflected by the exogenous components of event‐related potentials, was similarly abnormal as in both their mothers and fathers. However, their abnormal cortical auditory discrimination, as indexed by the prolonged latency of the mismatch negativity, resembled that of their fathers but not that of their mothers. The present results suggest that complex genetic mechanisms may contribute to auditory abnormalities encountered in children with AS.
Nicotine‐induced switch in the nicotinic cholinergic mechanisms of facilitation of long‐term potentiation induction
Authors: Yamazaki Yoshihiko , Jia Yousheng , Hamaue Naoya , Sumikawa Katumi
Published: August 2005

Nicotine facilitates the induction of long‐term potentiation (LTP) in the hippocampal CA1 region. The present study reveals the potential mechanisms underlying this effect of nicotine. Timed ACh‐mediated activation of α7 nicotinic acetylcholine receptors (nAChRs) on pyramidal cells is known to promote LTP induction. Nicotine could suppress this timing‐dependent mechanism by desensitizing nAChRs. Timed ACh‐mediated activation of α7 nAChRs on feedforward interneurons can prevent LTP induction by inhibiting pyramidal cells. Nicotine diminished this ACh‐mediated inhibition by desensitizing α7 nAChRs, thereby reducing the inhibitory influence on pyramidal cells. In addition to these desensitizing effects, nicotine activated presynaptic non‐α7 nAChRs on feedforward interneurons to decrease the evoked release of γ‐aminobutyric acid (GABA) onto pyramidal cells. Furthermore, nicotine increased the frequency of spontaneous inhibitory postsynaptic currents (IPSCs) in pyramidal cells, and concomitantly caused a reduction in the size of responses to focal GABA application onto the dendrites of pyramidal cells, suggesting that the nicotine‐induced increase in interneuronal activity leads ultimately to a use‐dependent depression of evoked IPSCs in pyramidal cells. These nicotine‐induced suppressions of inhibition of pyramidal cells were accompanied by enhanced N‐methyl‐d‐aspartate (NMDA) responses in pyramidal cells. Thus, our results suggest that nicotine promotes the induction of LTP by diminishing inhibitory influences on NMDA responses while suppressing the ACh‐mediated mechanisms. These ACh‐independent mechanisms probably contribute to the nicotine‐induced cognitive enhancement observed in the presence of cholinergic deficits, such as those in Alzheimer's disease patients.
Roles of mineralocorticoid and glucocorticoid receptors in the regulation of progenitor proliferation in the adult hippocampus
Authors: Wong Edmund Y. H. , Herbert Joe
Published: August 2005

New neurons are produced continually in the dentate gyrus of the hippocampus. Numerous factors modulate the rate of neuron production. One of the most important is the adrenal‐derived corticoids. Raised levels of corticoids suppress proliferation of progenitor cells, while removal of corticoids by adrenalectomy reverses this. The exact mechanisms by which corticoids mediate such regulation are unknown, but corticoids are believed to act through the receptors for mineralocorticoids (MR) and glucocorticoids (GR). Previous reports regarding the roles of these receptors in regulating cell proliferation came to contrasting conclusions. Here we use both agonists and antagonists to these receptors in adult male rats to investigate and clarify their roles. Blockade of MR with spironolactone in adrenalectomised male rats implanted with a corticosterone pellet to reproduce basal levels enhanced proliferation, whereas treatment with the GR antagonist mifepristone had no effect. However, mifepristone reversed the suppressive effect of additional corticosterone in intact rats. Both aldosterone and RU362, agonists of MR and GR, respectively, reduced proliferation in adrenalectomised rats, and combined treatment with both agonists had an additional suppressive action. These results clearly show that occupancies of both receptors act in the same direction on progenitor proliferation. The existence of two receptors with different affinities for corticoids may ensure that proliferation of progenitor cells in the adult dentate gyrus is regulated across the range of adrenal corticoid activity, including both basal and stressful contexts. Although a small proportion of newly formed cells may express GR and MR, corticosterone probably regulates proliferation indirectly through other local cells.
Spatial tuning of reaching activity in the medial parieto‐occipital cortex (area V6A) of macaque monkey
Authors: Fattori Patrizia , Kutz Dieter F. , Breveglieri Rossella , Marzocchi Nicoletta , Galletti Claudio
Published: August 2005

We recorded neural activity from the medial parieto‐occipital area V6A while three monkeys performed an instructed‐delay reaching task in the dark. Targets to be reached were in different spatial positions. Neural discharges were recorded during reaching movements directed outward from the body (towards visual objects), during the holding phase (when the hand was on the target) and during inward movements of the hand towards the home button (which was near the body and outside the field of view). Reach‐related activity was observed in the majority of 207 V6A cells, during outward (78%) and inward (65%) movements as well as during the holding phase (62%). Most V6A reaching neurons (84%) were modulated in more than one phase of the task. The reach‐related activity in V6A could depend on somatosensory inputs and/or on corollary discharges from the dorsal premotor cortex. Although visual and oculomotor inputs are known to have a strong influence on V6A activity, we excluded the possibility that the reach‐related activity which we observed was due to visual stimulation and/or oculomotor activity. Reach‐related activity for movements towards different locations was spatially modulated during outward (40%) and inward (47%) reaching movements. The position of the hand/arm in space modulated about 40% of V6A cells. Preferred reach directions and spatial locations were represented uniformly across the workspace. These data suggest that V6A reach‐related neurons are able to code the direction of movement of the arm and the position of the hand/arm in space. We suggest that the V6A reach‐related neurons are involved in the guidance of goal‐directed arm movements, whether these actions are visually guided or not.
Linking moose habitat selection to limiting factors
Authors: Dussault Christian , Ouellet Jean‐Pierre , Courtois Réhaume , Huot Jean , Breton Laurier , Jolicoeur Hélène
Published: August 2005

It has been suggested that patterns of habitat selection of animals across spatial scales should reflect the factors limiting individual fitness in a hierarchical fashion. Animals should thus select habitats that permit avoidance of the most important limiting factor at large spatial scales while the influence of less important factors should only be evident at fine scales. We tested this hypothesis by investigating moose Alces alces habitat selection using GPS telemetry in an area where the main factors limiting moose numbers were likely (in order of decreasing importance) predation risk, food availability and snow. At the landscape scale, we predicted that moose would prefer areas where the likelihood of encountering wolves was low or areas where habitats providing protection from predation were dominant. At the home‐range scale, we predicted that moose selection would be driven by food availability and snow depth. Wolf territories were delineated using telemetry locations and the study area was divided into 3 sectors that differed in terms of annual snowfall. Vegetation surveys yielded 6 habitat categories that differed with respect to food availability, and shelter from predation or snow. Our results broadly supported the hypothesis because moose reacted to several factors at each scale. At the landscape scale, moose were spatially segregated from wolves by avoiding areas receiving the lowest snowfall, but they also preferentially established their home range in areas where shelter from snow bordered habitat types providing abundant food. At the home‐range scale, moose also traded off food availability with avoidance of deep snow and predation risk. During winter, moose increased use of stands providing shelter from snow along edges with stands providing abundant food. Habitat selection patterns of females with calves differed from that of solitary moose, the former being associated primarily with habitats providing protection from predation. Animals should attempt to minimize detrimental effects of the main limiting factors when possible at the large scale. However, when the risk associated with several potential limiting factors varies with scale, we should expect animals to make trade‐offs among these.
The implications of different species concepts for describing biodiversity patterns and assessing conservation needs for African birds
Authors: Dillon Shaun , Fjeldså Jon
Published: August 2005

It has been suggested that switching from the widely used Biological Species Concept to a Phylogenetic Species Concept, would result in the appearance of hitherto neglected patterns of endemism. The problem has mainly been analyzed with respect to endemic taxa and for rather limited geographical regions, but will here be analysed for the entire resident avifauna of sub‐Saharan Africa. A database of African bird distributions was re‐edited to create two new datasets representing 1572 biological species and 2098 phylogenetic species. Species richness patterns were virtually identical with the two taxonomies, and only subtle changes were found in the geographical variation in range‐size rarity sum. However, there were some differences in the most range‐restricted species, with increased complexity of long‐recognized centres of endemism. Overall, then, the large‐scale biogeographic patterns are robust to changes in species concepts. This reflects the aggregated nature of endemism, with certain areas acting as “species pumps” and large intervening areas being characterised by a predominance of widespread species which distribute themselves in accordance with contemporary environmental conditions. The percentages of phylogenetic and threatened species captured in a BSC near‐minimum set of 64 grid‐cells and a PSC near‐maximum set, with the same number of grid‐cells, are very similar.
Effect of targeted deletions of β1- and β2-adrenergic-receptor subtypes on heart rate variability
Authors: Ecker Phillip M. , Lin Chu-Chuan , Powers Jennifer , Kobilka Brian K. , Dubin Anne M. , Bernstein Daniel
Published: August 2005

β-Adrenergic receptors (β-ARs) play a major role in regulating heart rate (HR) and contractility in the intact cardiovascular system. Three subtypes (β1, β2, and β3) are expressed in heart tissue, and the role of each subtype in regulating cardiac function has previously been determined by using both pharmacological and gene-targeting approaches. However, previous studies have only examined the role of β-ARs in the macrolevel regulation of HR. We employed three knockout (KO) mouse lines, β1-KO, β2-KO, and β1/β2double KO (DL-KO), to examine the role that β-AR subtypes play in HR variability (HRV) and in the sympathetic and parasympathetic inputs into HR control. Fast Fourier transformation (FFT) in frequency domain methods of ECG spectral analysis was used to resolve HRV into high- and low-frequency (HF and LF) powers. Resting HR (in beats/min) was decreased in β1-KO [488 (SD 27)] and DL-KO [495 (SD 12)] mice compared with wild-type [WT; 638 (SD 30)] or β2-KO [656 (SD 51)] ( P < 0.0005) mice. Mice lacking β1-ARs (β1-KO and DL-KO) had increased HRV (as illustrated by the standard deviation of normal R-R intervals) and increased normalized HF and LF powers compared with mice with intact β1-ARs (WT and β2-KO). These results demonstrate the differential role of β-AR subtypes in regulating autonomic signaling.
Functional hierarchy of coronary circulation: direct evidence of a structure-function relation
Authors: Kassab Ghassan S.
Published: August 2005

The heart muscle is nourished by a complex system of blood vessels that make up the coronary circulation. Here we show that the design of the coronary circulation has a functional hierarchy. A full anatomic model of the coronary arterial tree, containing millions of blood vessels down to the capillary vessels, was simulated based on previously measured porcine morphometric data. A network analysis of blood flow through every vessel segment was carried out based on the laws of fluid mechanics and appropriate boundary conditions. Our results show an abrupt change in cross-sectional area that demarcates the transition from epicardial (EPCA) to intramyocardial (IMCA) coronary arteries. Furthermore, a similar pattern of blood flow was observed with a corresponding transition from EPCA to IMCA. These results suggest functional differences between the two types of vessels. An additional abrupt change occurs in the IMCA in relation to flow velocity. The velocity is fairly uniform proximal to these vessels but drops significantly distal to those vessels toward the capillary branches. This finding suggests functional differences between large and small IMCA. Collectively, these observations suggest a novel functional hierarchy of the coronary vascular tree and provide direct evidence of a structure-function relation.
Angiogenic effects of long-term enhanced external counterpulsation in a dog model of myocardial infarction
Authors: Wu Guifu , Du Zhimin , Hu Chenghen , Zheng Zhensheng , Zhan Chengyang , Ma Hong , Fang Dianqiu , Ahmed Khan Tanveer , Laham Roger J. , Hui John C. K. , Lawson William E.
Published: August 2005

Enhanced external counterpulsation (EECP) is an effective noninvasive treatment of coronary artery disease. Its mechanism of action remains unknown. An acute coronary occlusion dog model was created to explore the angiogenic effect of EECP. After coronary occlusion, 12 dogs were randomly assigned to either EECP ( n = 6) or control ( n = 6). Immunohistochemical studies of α-actin and von Willebrand factor (vWF) were used to detect newly developed microvessels. Systemic and local vascular endothelial growth factor (VEGF) were identified by ELISA and reverse transcriptase PCR analysis. There was a significant increase in the density of microvessels per squared millimeter in the infarcted regions of the EECP group compared with the control group (vWF, 15.2 ± 6.3 vs. 4.9 ± 2.1, P < 0.05; α-actin, 11.8 ± 5.3 vs. 3.4 ± 1.2, P < 0.05). The positive-stained area per squared micrometer also increased significantly (α-actin, 6.6 × 103 ± 2.9 × 103 μm2 vs. 0.6 × 103 ± 0.5 × 103 μm2, P < 0.05; vWF, 5.7 × 103 ± 1.9 × 103 μm2 vs. 1.7 × 103 ± 1.4 × 103 μm2, P < 0.05). Immunohistochemical staining and reverse transcriptase PCR analysis documented a significant increase in VEGF expression. These factors associated with angiogenesis corresponded to improved myocardial perfusion by 99mTc-sestamibi single-photon emission computed tomography. Angiogenesis may be a mechanism of action for the improved myocardial perfusion demonstrated after EECP therapy.
Pulmonary vascular iNOS induction participates in the onset of chronic hypoxic pulmonary hypertension
Authors: Hampl Václav , Bíbová Jana , Baňasová Alena , Uhlík Jiří , Miková Dana , Hniličková Olga , Lachmanová Věra , Herget Jan
Published: August 2005

Pathogenesis of hypoxic pulmonary hypertension is initiated by oxidative injury to the pulmonary vascular wall. Because nitric oxide (NO) can contribute to oxidative stress and because the inducible isoform of NO synthase (iNOS) is often upregulated in association with tissue injury, we hypothesized that iNOS-derived NO participates in the pulmonary vascular wall injury at the onset of hypoxic pulmonary hypertension. An effective and selective dose of an iNOS inhibitor, l- N6-(1-iminoethyl)lysine (l-NIL), for chronic peroral treatment was first determined (8 mg/l in drinking water) by measuring exhaled NO concentration and systemic arterial pressure after LPS injection under ketamine+xylazine anesthesia. A separate batch of rats was then exposed to hypoxia (10% O2) and given l-NIL or a nonselective inhibitor of all NO synthases, NG-nitro-l-arginine methyl ester (l-NAME, 500 mg/l), in drinking water. Both inhibitors, applied just before and during 1-wk hypoxia, equally reduced pulmonary arterial pressure (PAP) measured under ketamine+xylazine anesthesia. If hypoxia continued for 2 more wk after l-NIL treatment was discontinued, PAP was still lower than in untreated hypoxic controls. Immunostaining of lung vessels showed negligible iNOS presence in control rats, striking iNOS expression after 4 days of hypoxia, and return of iNOS immunostaining toward normally low levels after 20 days of hypoxia. Lung NO production, measured as NO concentration in exhaled air, was markedly elevated as early as on the first day of hypoxia. We conclude that transient iNOS induction in the pulmonary vascular wall at the beginning of chronic hypoxia participates in the pathogenesis of pulmonary hypertension.
Hypoxia-induced skeletal muscle fiber dysfunction: role for reactive nitrogen species
Authors: Ottenheijm Coen A. C. , Heunks Leo M. A. , Geraedts Maartje C. P. , Dekhuijzen P. N. Richard
Published: August 2005

Hypoxia impairs skeletal muscle function, but the precise mechanisms are incompletely understood. In hypoxic rat diaphragm muscle, generation of peroxynitrite is elevated. Peroxynitrite and other reactive nitrogen species have been shown to impair contractility of skinned muscle fibers, reflecting contractile protein dysfunction. We hypothesized that hypoxia induces contractile protein dysfunction and that reactive nitrogen species are involved. In addition, we hypothesized that muscle reoxygenation reverses contractile protein dysfunction. In vitro contractility of rat soleus muscle bundles was studied after 30 min of hyperoxia (Po2 ∼90 kPa), hypoxia (Po2 ∼5 kPa), hypoxia + 30 μM NG-monomethyl-l-arginine (l-NMMA, a nitric oxide synthase inhibitor), hyperoxia + 30 μM l-NMMA, and hypoxia (30 min) + reoxygenation (15 min). One part of the muscle bundle was used for single fiber contractile measurements and the other part for nitrotyrosine detection. In skinned single fibers, maximal Ca2+-activated specific force (Fmax), fraction of strongly attached cross bridges (αfs), rate constant of force redevelopment ( ktr), and myofibrillar Ca2+ sensitivity were determined. Thirty minutes of hypoxia reduced muscle bundle contractility. In the hypoxic group, single fiber Fmax, αfs, and ktr were significantly reduced compared with hyperoxic, l-NMMA, and reoxygenation groups. Myofibrillar Ca2+ sensitivity was not different between groups. Nitrotyrosine levels were increased in hypoxia compared with all other groups. We concluded that acute hypoxia induces dysfunction of skinned muscle fibers, reflecting contractile protein dysfunction. In addition, our data indicate that reactive nitrogen species play a role in hypoxia-induced contractile protein dysfunction. Reoxygenation of the muscle bundle partially restores bundle contractility but completely reverses contractile protein dysfunction.
Self-Organized Modularization in Evolutionary Algorithms
Authors: Dauscher Peter , Uthmann Thomas
Published: August 2005

The principle of modularization has proven to be extremely successful in the field of technical applications and particularly for Software Engineering purposes. The question to be answered within the present article is whether mechanisms can also be identified within the framework of Evolutionary Computation that cause a modularization of solutions. We will concentrate on processes, where modularization results only from the typical evolutionary operators, i.e. selection and variation by recombination and mutation (and not, e.g., from special modularization operators). This is what we call Self-Organized Modularization.

Based on a combination of two formalizations by Radcliffe and Altenberg, some quantitative measures of modularity are introduced. Particularly, we distinguish Built-in Modularityas an inherent property of a genotype and Effective Modularity, which depends on the rest of the population. These measures can easily be applied to a wide range of present Evolutionary Computation models.

It will be shown, both theoretically and by simulation, that under certain conditions, Effective Modularity (as defined within this paper) can be a selection factor. This causes Self-Organized Modularization to take place. The experimental observations emphasize the importance of Effective Modularityin comparison with Built-in Modularity. Although the experimental results have been obtained using a minimalist toy model, they can lead to a number of consequences for existing models as well as for future approaches.

Furthermore, the results suggest a complex self-amplification of highly modular equivalence classes in the case of respected relations. Since the well-known Holland schemata are just the equivalence classes of respected relations in most Simple Genetic Algorithms, this observation emphasizes the role of schemata as Building Blocks (in comparison with arbitrary subsets of the search space).
Evolving Evolutionary Algorithms Using Linear Genetic Programming
Authors: Oltean Mihai
Published: August 2005

A new model for evolving Evolutionary Algorithms is proposed in this paper. The model is based on the Linear Genetic Programming (LGP) technique. Every LGP chromosome encodes an EA which is used for solving a particular problem. Several Evolutionary Algorithms for function optimization, the Traveling Salesman Problem and the Quadratic Assignment Problem are evolved by using the considered model. Numerical experiments show that the evolved Evolutionary Algorithms perform similarly and sometimes even better than standard approaches for several well-known benchmarking problems.
Race, Class and the Global Politics of Environmental Inequality
Authors: Newell Peter
Published: August 2005

The politics of natural resource access, control and exploitation assume fundamental relations of social power; they imply them and consolidate them. Environmental issues reflect broader patterns of domination and social exclusion at work in global politics which enable us to understand who benefits from the current distribution of environmental benefits and which social groups shoulder a disproportionate amount of the burden of pollution. The task, however, is not merely to identify those global structures that produce environmental inequities and injustices, but to show how, in some cases, those structures are supported and entrenched by the institutional configurations that we continue to assume are generating the solutions to environmental degradation. Towards this end, I connect debates about the global managerial class and critiques of the prevailing sustainable development historical bloc with more localized studies of the consequences of organized inequality and the strategies adopted by marginalized groups to contest their fate as victims of environmental injustice. Such an approach builds upon the project which Marian Miller began with her enquiries into the Third World in global environmental politics, emphasizing the importance of the global political economy in shaping those political relations. Political and social cleavages of race, class and gender are shown to be key to understanding the global organization of environmental inequality and justice, though it is the neglect of the first two dimensions, in particular, that forms the core concern of this paper. Their importance in understanding patterns of causation (distribution of benefit), process (access, voice, representation) and distribution (of harm) is highlighted through reference to a range of contemporary case studies in the global North and South.
Capacity Development for the Environment: Broadening the Scope
Authors: Sagar Ambuj D. , VanDeveer Stacy D.
Published: August 2005

The notion of capacity development is very much in vogue as an integral element of environmental management in developing countries. We contend that current capacity development for the environment (CDE) efforts are limited in focus, emphasizing mainly implementation while paying insufficient attention to problem recognition and analysis as well as designing and assessing potential management strategies. At the same time, CDE programs and practitioners tend to assume that improving the environment in developing countries (or globally) requires building capacity in these countries, and not in their industrialized counterparts. This view overlooks the role of Northern consumption patterns with significant global footprints and Northern policies (such as agricultural subsidies) that drive unsustainable practices around the world. We suggest that “turning the lens around” and building capacity to examine and re-shape relevant Northern policies and institutions might correct this lacuna. Such a broadened scope can be expected to increase the effectiveness of CDE efforts and programs.
Dying of Consumption: Accidents or Sacrifices of Global Morality?
Authors: Dauvergne Peter
Published: August 2005

Private consumption expenditures are now more than 4 times higher than in 1960. The globalization of ever-more growth and consumption has come, however, at a price: global chains of cause-and-effect that obscure social, environmental and ethical responsibility. The result in practice is a global order that accepts the deaths of millions of young people in dangerous and unhealthy environments as tragic, but largely unavoidable, accidents of economic progress. The history of what most call traffic “accidents” is revealing. The hope at the 1896 inquest into the first “accidental death” was this would never happen again. But hope is not action. Today, traffic injures as many as 50 million and kills over one million people ever year. It is, however, no accident that tragedies like these are “accidents” rather than “sacrifices,” as such language softens criticism of the moral, social and ecological crises arising from the current global consumptive order.
Global Environmental Governance for Corporate Responsibility and Accountability
Authors: Clapp Jennifer
Published: August 2005

Recent years have seen a growing movement toward externally imposed regulations directed specifically at improving TNCs' environmental and social performance. This movement draws on a long history, and its most recent incarnation is largely a reaction to disappointment on the part of many with the results of private voluntary initiatives among global firms. A number of international level initiatives have emerged, including the UN's Global Compact and the inclusion of an environment chapter in the OECD Guidelines for Multinational Enterprises. Because these efforts, while externally driven, are voluntary on the part of firms, there have been growing calls for a binding international treaty on corporate accountability. Industry has been extremely resistant to this idea. Many see such a treaty as vital for developing countries, as it could bolster their ability and willingness to monitor and enforce environmental regulations. This is especially important in the Global South, as these countries have seen the bulk of the negative environmental impacts of TNCs in recent decades.
Herpes simplex virus interferes with amyloid precursor protein processing
Authors: Shipley Suzanne J , Parkin Edward T , Itzhaki Ruth F , Dobson Curtis B
Published: August 2005

Background

The early events underlying Alzheimer's disease (AD) remain uncertain, although environmental factors may be involved. Work in this laboratory has shown that the combination of herpes simplex virus type 1 (HSV1) in brain and carriage of the APOE-ε4 allele of the APOE gene strongly increases the risk of developing AD. The development of AD is thought to involve abnormal aggregation or deposition of a 39–43 amino acid protein – β amyloid (Aβ) – within the brain. This is cleaved from the much larger transmembranal protein 'amyloid precursor protein' (APP). Any agent able to interfere directly with Aβ or APP metabolism may therefore have the capacity to contribute towards AD. One recent report showed that certain HSV1 glycoprotein peptides may aggregate like Aβ; a second study described a role for APP in transport of virus in squid axons. However to date the effects of acute herpesvirus infection on metabolism of APP in human neuronal-type cells have not been investigated. In order to find if HSV1 directly affects APP and its degradation, we have examined this protein from human neuroblastoma cells (normal and transfected with APP 695) infected with the virus, using Western blotting.

Results

We have found that acute HSV1 (and also HSV2) infection rapidly reduces full length APP levels – as might be expected – yet surprisingly markedly increases levels of a novel C-terminal fragment of APP of about 55 kDa. This band was not increased in cells treated with the protein synthesis inhibitor cycloheximide

Conclusion

Herpes virus infection leads to rapid loss of full length APP from cells, yet also causes increased levels of a novel 55 kDa C-terminal APP fragment. These data suggest that infection can directly alter the processing of a transmembranal protein intimately linked to the aetiology of AD.
Acute bronchiolitis in infancy as risk factor for wheezing and reduced pulmonary function by seven years in Akershus County, Norway
Authors: Fjærli Hans-Olav , Farstad Teresa , Rød Gisle , Ufert Gunn Kristin , Gulbrandsen Pål , Nakstad Britt
Published: August 2005

Background

Acute viral bronchiolitis is one of the most common causes of hospitalisation during infancy in our region with respiratory syncytial virus (RSV) historically being the major causative agent. Many infants with early-life RSV bronchiolitis have sustained bronchial hyperreactivity for many years after hospitalisation and the reasons for this are probably multifactorial. The principal aim of the present study was to investigate if children hospitalised for any acute viral bronchiolitis during infancy in our region, and not only those due to RSV, had more episodes of subsequent wheezing up to age seven years and reduced lung function at that age compared to children not hospitalised for acute bronchiolitis during infancy. A secondary aim was to compare the hospitalised infants with proven RSV bronchiolitis (RS+) to the hospitalised infants with non-RSV bronchiolitis (RS-) according to the same endpoints.

Methods

57 infants hospitalised at least once with acute viral bronchiolitis during two consecutive winter seasons in 1993–1994 were examined at age seven years. An age-matched control group of 64 children, who had not been hospitalised for acute viral bronchiolitis during infancy, were recruited from a local primary school. Epidemiological and clinical data were collected retrospectively from hospital discharge records and through structured clinical interviews and physical examinations at the follow-up visit.

Results

The children hospitalised for bronchiolitis during infancy had decreased lung function, more often wheezing episodes, current medication and follow-up for asthma at age seven years than did the age matched controls. They also had lower average birth weight and more often first order family members with asthma. We did not find significant differences between the RSV+ and RSV- groups.

Conclusion

Children hospitalised for early-life bronchiolitis are susceptible to recurrent wheezing and reduced pulmonary function by seven years compared to age-matched children not hospitalised for early-life bronchiolitis. We propose that prolonged bronchial hyperreactivity could follow early-life RSV negative as well as RSV positive bronchiolitis.
A simplified immunoprecipitation method for quantitatively measuring antibody responses in clinical sera samples by using mammalian-produced Renillaluciferase-antigen fusion proteins
Authors: Burbelo Peter D , Goldman Radoslav , Mattson Thomas L
Published: August 2005

Background

Assays detecting human antigen-specific antibodies are medically useful. However, the usefulness of existing simple immunoassay formats is limited by technical considerations such as sera antibodies to contaminants in insufficiently pure antigen, a problem likely exacerbated when antigen panels are screened to obtain clinically useful data.

Results

We developed a novel and simple immunoprecipitation technology for identifying clinical sera containing antigen-specific antibodies and for generating quantitative antibody response profiles. This method is based on fusing protein antigens to an enzyme reporter,Renillaluciferase (Ruc), and expressing these fusions in mammalian cells, where mammalian-specific post-translational modifications can be added. After mixing crude extracts, sera and protein A/G beads together and incubating, during which the Ruc-antigen fusion become immobilized on the A/G beads, antigen-specific antibody is quantitated by washing the beads and adding coelenterazine substrate and measuring light production.

We have characterized this technology with sera from patients having three different types of cancers. We show that 20–85% of these sera contain significant titers of antibodies against at least one of five frequently mutated and/or overexpressed tumor-associated proteins. Five of six colon cancer sera tested gave responses that were statistically significantly greater than the average plus three standard deviations of 10 control sera. The results of competition experiments, preincubating positive sera with unmodifiedE. coli-produced antigens, varied dramatically.

Conclusion

This technology has several advantages over current quantitative immunoassays including its relative simplicity, its avoidance of problems associated withE. coli-produced antigens and its use of antigens that can carry mammalian or disease-specific post-translational modifications. This assay should be generally useful for analyzing sera for antibodies recognizing any protein or its post-translational modifications.
The effect of a monetary incentive on return of a postal health and development questionnaire: a randomised trial [ISRCTN53994660]
Authors: Kenyon Sara , Pike Katie , Jones David , Taylor David , Salt Alison , Marlow Neil , Brocklehurst Peter
Published: August 2005

Background

Postal questionnaires are widely used to collect data in healthcare research but a poor response rate may reduce the validity and reliability of results. There was a lack of evidence available relating to use of a monetary incentive to improve the response rate in the healthcare setting.

Methods

The MRC ORACLE Children Study is assessing the health and development of nearly 9000 seven year old children whose mothers' joined the MRC ORACLE Trial. We carried out a randomised controlled trial of inclusion of monetary incentive (five pound voucher redeemable at many high street stores) with the reminder questionnaire to parents. This trial took place between April 2002 and November 2003. When the parents were sent the reminder questionnaire about their child's health and development they were randomly assigned by concealed computer-generated allocation stratified by week of birthday to receive a five pound voucher or no incentive. The population were 722 non-responders to the initial mailing of a 12-page questionnaire. Main outcome measures: Difference in response rate between the two groups.

Results

Inclusion of the voucher with the reminder questionnaire resulted in a 11.7%(95% CI 4.7% to 18.6%) improvement in the response rate between the two groups.

Conclusion

This improvement in response rate and hence the validity and reliability of results obtained appears to be justified ethically and financially.