bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression mechanism of mitochondrial ORF79 accumulation by Rf1 protein in BT‐type cytoplasmic male sterile rice
Authors: Kazama Tomohiko , Nakamura Takahiro , Watanabe Masao , Sugita Mamoru , Toriyama Kinya
Published: April 2008

In BT‐type cytoplasmic male sterile rice (Oryza sativa L.) with Chinsurah Boro II cytoplasm, cytoplasmic male sterility (CMS) is caused by an accumulation of the cytotoxic peptide ORF79. The ORF79 protein is expressed from a dicistronic gene atp6‐orf79, which exists in addition to the normal atp6 gene in the BT‐type mitochondrial genome. The CMS is restored by a PPR (pentatricopeptide‐repeat) gene, Rf1, via RNA processing. However, it has not yet been elucidated how the accumulation of ORF79 is reduced by the action of the Rf1 protein. Here, we report that the level of processed orf79 transcripts in the restorer line was reduced to 50% of the unprocessed atp6‐orf79 transcripts in the CMS line. Ninety percent of the processed orf79 transcripts, which remained after degradation, were not associated with the ribosome for translation. Our data suggests that the processing of atp6‐orf79 transcripts diminishes the expression of orf79 by the translational reduction and degradation of the processed orf79 transcripts.
VASCULAR‐RELATED NAC‐DOMAIN7 is involved in the differentiation of all types of xylem vessels in Arabidopsis roots and shoots
Authors: Yamaguchi Masatoshi , Kubo Minoru , Fukuda Hiroo , Demura Taku
Published: April 2008

The Arabidopsis thaliana NAC domain transcription factor, VASCULAR‐RELATED NAC‐DOMAIN7 (VND7), plays a pivotal role in regulating the differentiation of root protoxylem vessels. In order to understand the mechanisms underscoring the function of VND7 in vessel differentiation in more detail, we conducted extensive molecular analyses in yeast (Saccharomyces cerevisiae), Arabidopsis, and Nicotiana tabacum L. cv. Bright Yellow 2 (tobacco BY‐2) cells. The transcriptional activation activity of VND7 was confirmed in yeast and Arabidopsis, and the C‐terminal region was shown to be required for VND7 transcriptional activation. Expression of the C‐terminus‐truncated VND7 protein under the control of the native VND7 promoter resulted in inhibition of the normal development of metaxylem vessels in roots and vessels in aerial organs, as well as protoxylem vessels in roots. The expression pattern of VND7 overlapped that of VND2 to VND5 in most of the differentiating vessels. Furthermore, a yeast two‐hybrid assay revealed the ability of VND7 to form homodimers and heterodimers with other VND proteins via their N‐termini, which include the NAC domain. The heterologous expression of VND7 in tobacco BY‐2 cells demonstrated that the stability of VND7 could be regulated by proteasome‐mediated degradation. Together these data suggest that VND7 regulates the differentiation of all types of vessels in roots and shoots, possibly in cooperation with VND2 to VND5 and other regulatory proteins.
Isoprene emission is not temperature‐dependent during and after severe drought‐stress: a physiological and biochemical analysis
Authors: Fortunati Alessio , Barta Csengele , Brilli Federico , Centritto Mauro , Zimmer Ina , Schnitzler Jörg‐Peter , Loreto Francesco
Published: April 2008

Black poplar (Populus nigra L.) plants grown at 25 and 35°C were subjected to drought stress to assess the combined impact of two consequences of global climate change – rising temperature and drought – on isoprene biosynthesis and emission. At both temperatures, photosynthesis was inhibited by moderate drought, but isoprene emission only decreased when drought was prolonged. The mRNA transcript level, protein concentration and activity of isoprene synthase (ISPS) changed in concert with isoprene emission during drought stress. However, ISPS activity decreased before isoprene emission during drought development, indicating a tighter control of the emission at a transcriptional or post‐transcriptional level under moderate drought stress, and at both temperatures. A residual isoprene emission was measured when photosynthesis was totally inhibited after 35 days of drought. This photosynthesis‐independent emission of isoprene was probably dependent on a cytosolic carbon supply as all the properties of ISPS were drastically inhibited. Isoprene emission was associated with dark respiration during the entire drought stress period, and at both temperatures, indicating that the two processes are sustained by, but do not compete for, the same carbon source. Isoprene emission was directly related to phosphoenolpyruvate carboxylase activity in plants grown at 25°C and inversely related in plants grown at 35°C, suggesting a strong temperature control on the regulation of the pyruvate flowing from the cytosol to the plastidic isoprenoid biosynthetic pathway under drought stress and recovery. In re‐watered plants, the temperature control on isoprene emission was suppressed, despite complete recovery of photosynthesis and ISPS activity similar to levels in plants subjected to mild drought stress. Our results reveal the overriding effects of drought on isoprene emission, possibly affecting protein level or substrate supply. These effects may largely offset the predicted impact of rising temperatures on the emission of isoprene in terrestrial ecosystems.
Treatment of skin swellings with C1‐inhibitor concentrate in patients with hereditary angio‐oedema
Authors: Bork K. , Staubach P. , Hardt J.
Published: April 2008

Background:  Skin swellings are the most frequent symptoms in hereditary angio‐oedema (HAE) arising out of C1‐inhibitor (C1‐INH) deficiency. They may be painful and impact daily activities of patients. Detailed clinical data concerning the treatment of skin swellings by C1‐INH concentrate have not been reported yet.

Methods:  From 1976 through 2007, a total of 2104 skin‐swelling attacks in 47 patients with HAE were treated with the C1‐INH concentrate. Time to relief and duration of the swellings were documented during personal interviews using standardized questionnaires. The results were compared with 9046 untreated skin swellings in the same patients.

Results:  The first clinical sign of efficacy was a slowdown of progress of symptoms accompanied by a decreased feeling of tension and pain in the swollen area. The mean time to the first relief of symptoms was 1.1 ± 1.4 h in treated skin swellings and 50.4 ± 33 h in untreated skin swellings. Improvement of facial skin swellings took longer than swellings of the extremities, genitals or trunk. The duration of treated skin swellings was 1.7 day in treated and 3.2 day in untreated ones. In treated swellings, there was long‐lasting control and no rebound within the 48 h following the drug administration and no laryngeal oedema following facial oedema were observed. No severe side‐effects occurred.

Conclusions:  The C1‐INH concentrate has proven to be highly effective and safe for treating skin swellings in patients with HAE arising out of C1‐INH deficiency.
Identification of a serine protease as a major allergen (Per a 10) of Periplaneta americana
Authors: Sudha V. T. , Arora N. , Gaur S. N. , Pasha S. , Singh B. P.
Published: April 2008

Background:  Cockroach allergens are associated with the development of asthma, but none of these has been characterized for proteolytic activity. This study was undertaken to isolate and characterize a protease from Periplaneta americana and determine its allergenicity.

Methods:  A serine protease was isolated from P. americana extract using benzamidine sepharose column and characterized by immunobiochemical methods. Allergenicity of the protease was assessed by enzyme‐linked immunosorbent assay, immunoblot, intradermal testing, histamine release and peripheral blood mononuclear cells (PBMCs) proliferation.

Results:  Affinity purified protein of ∼28 kDa (Per a 10) showed a single band of activity in gelatin zymogram and agarose plate assay. N‐terminal sequence (IVGGRPAQI) revealed similarity with mite serine protease allergens and insect trypsins. It demonstrated proteolytic activity with azocollagen > gelatin > defatted‐milk > casein including serine protease specific substrate, N‐benzoyl‐arginine‐ethyl‐ester‐hydrochloride. It was inhibited by serine protease inhibitors, namely aprotinin > pefabloc > AEBSF > PMSF > benzamidine > antipain > leupeptin and trypsin‐specific inhibitor (tosyl‐lysyl‐chloromethyl‐ketone) suggesting it to be a trypsin‐like serine protease. Per a 10 was recognized as a major allergen, showing IgE reactivity with >80% of cockroach sensitized patients by skin tests and immunoblot. It could induce significant histamine release (P < 0.05) in blood and secretion of interleukin‐4 (IL‐4) (P < 0.05) and IL‐5 (P < 0.05) in culture supernatant of PBMCs from cockroach hypersensitive patients, suggesting a strong allergenic potency.

Conclusion:  A serine protease isolated from P. americana was demonstrated to be a major allergen (Per a 10). It has a potential for component‐based diagnosis of allergy and will be useful in elucidating the mechanism of allergy.
Characterization of Der p 21, a new important allergen derived from the gut of house dust mites*
Authors: Weghofer M. , Dall’Antonia Y. , Grote M. , Stöcklinger A. , Kneidinger M. , Balic N. , Krauth M.‐T. , Fernández‐Caldas E. , Thomas W. R. , Hage M. van , Vieths S. , Spitzauer S. , Horak F. , Svergun D. I. , Konarev P. V. , Valent P. , Thalhamer J. , Keller W. , Valenta R. , Vrtala S.
Published: April 2008

Background:  The house dust mite (HDM) Dermatophagoides pteronyssinus is a major allergen source eliciting allergic asthma. The aim of the study was to identify new important HDM allergens associated with allergic asthma.

Methods:  A cDNA coding for a new mite allergen, designated Der p 21, was isolated using immunoglobulin E (IgE) antibodies from patients with allergic asthma out of a D. pteronyssinus expression cDNA library and expressed in Escherichia coli.

Results:  Circular dichroism analysis of the purified allergen showed that rDer p 21 (14 726 Da) is one of the few mite allergens with an α‐helical secondary structure. The protein exhibited high thermal stability and refolding capacity, and, as determined by small angle X‐ray scattering, formed a dimer consisting of two flat triangles. rDer p 21 bound high levels of patients’ IgE antibodies and showed high allergenic activity in basophil activation experiments. Rabbit anti‐Der p 21 IgG antibodies inhibited mite‐allergic patients’ IgE binding and allowed the ultrastructural localization of the allergen in the midgut (epithelium, lumen and faeces) of D. pteronyssinus by immunogold electron microscopy. Der p 21 revealed sequence homology with group 5 mite allergens, but IgE and IgG reactivity data and cross‐inhibition studies identified it as a new mite allergen.

Conclusions:  Der p 21 is a new important mite allergen which is liberated into the environment via faecal particles and hence may be associated with allergic asthma.
ARIA‐suggested drugs for allergic rhinitis: what impact on quality of life? A GA2LEN Review
Authors: Baiardini I. , Braido F. , Tarantini F. , Porcu A. , Bonini S. , Bousquet P.‐J. , Zuberbier T. , Demoly P. , Canonica G. W.
Published: April 2008

Allergic diseases constitute a global health problem, as they have an increasing economic and social impact and, especially, they can deeply interfere with the patients’ daily life, being a cause of physical and emotional discomfort. This is why the health‐related quality‐of‐life (HRQoL) has become increasingly important in health care research; in fact, the assessment of the impact the disease and its treatment have on patients, provides a more comprehensive approach in outcome evaluation. Numerous validated questionnaires are available and many studies have been performed evaluating HRQoL in people affected by allergic rhinitis (AR), thus testifying a great interest in this topic. The aims of the present review are: to examine the scientific literature of the last 3 years dealing with the impact of AR treatments suggested by allergic rhinitis and its impact on asthma guidelines on patients’ QoL, and to identify the unexplored or not‐fully‐investigated areas concerning this issue.
House dust mite control measures for asthma: systematic review
Authors: Gøtzsche P. C. , Johansen H. K.
Published: April 2008

The major allergen in house dust comes from mites. We performed a systematic review of the randomized trials that had assessed the effects of reducing exposure to house dust mite antigens in the homes of people with mite‐sensitive asthma, and had compared active interventions with placebo or no treatment. Fifty‐four trials (3002 patients) were included. Thirty‐six trials assessed physical methods (26 mattress covers), 10 chemical methods and eight a combination of chemical and physical methods. Despite the fact that many trials were of poor quality and would be expected to exaggerate the reported effect, we did not find an effect of the interventions. For the most frequently reported outcome, peak flow in the morning (1565 patients), the standardized mean difference was 0.00 (95% confidence interval (CI) −0.10 to 0.10). There were no statistically significant differences in number of patients improved (relative risk 1.01, 95% CI 0.80–1.27), asthma symptom scores (standardized mean difference −0.04, 95% CI −0.15 to 0.07) or in medication usage (standardized mean difference −0.06, 95% CI −0.18 to 0.07). Chemical and physical methods aimed at reducing exposure to house dust mite allergens cannot be recommended.
Finnish Allergy Programme 2008–2018 – time to act and change the course
Authors: Haahtela T. , Von Hertzen L. , Mäkelä M. , Hannuksela M. ,   the Allergy Programme Working Group
Published: April 2008

Background:  The prevalence of allergic diseases has grown in Finland, similarly to many other western countries. Although the origin of allergy remains unresolved, increasing body of evidence indicates that the modern man living in urban built environment is deprived from environmental protective factors (e.g. soil microorganisms) that are fundamental for normal tolerance development. The current dogma of allergen avoidance has not proved effective in halting the ‘epidemic’, and it is the Finnish consensus that restoring and strengthening tolerance should more be in focus.

Aim:  The national 10‐year programme is aimed to reduce burden of allergies. The main goals are to (i) prevent the development of allergic symptoms; (ii) increase tolerance against allergens; (iii) improve the diagnostics; (iv) decrease work‐related allergies; (v) allocate resources to manage and prevent exacerbations of severe allergies and (vi) decrease costs caused by allergic diseases.

Methods:  For each goal, specific tasks, tools and evaluation methods are defined. Nationwide implementation acts through the network of local co‐ordinators (primary care physicians, nurses, pharmacists). In addition, three nongovernmental organizations (NGOs) take care of the programme implementation. The 21 central hospital districts carry out a three step educational process: (i) healthcare personnel; (ii) representatives and educators of NGOs and (iii) patients and the general population. For outcome evaluation, repeated surveys are performed and healthcare registers employed at the beginning, at 5 years, and at the end of the programme. The process will be evaluated by an independent external body.

Conclusion:  The Finnish initiative is a comprehensive plan to reduce burden of allergies. The aim is to increase immunological tolerance and change attitudes to support health instead of medicalizing common and mild allergy symptoms. It is time to act, when allergic individuals are becoming a majority of western populations and their numbers are in rapid increase worldwide. The Programme is associated with the Global Alliance of Chronic Respiratory Diseases (GARD), WHO.
Dysregulation of toll‐like receptor‐2 (TLR‐2)‐induced effects in monocytes from patients with atopic dermatitis: impact of the TLR‐2 R753Q polymorphism
Authors: Niebuhr M. , Langnickel J. , Draing C. , Renz H. , Kapp A. , Werfel T.
Published: April 2008

Background:  Atopic dermatitis (AD) is often complicated by an enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus. Toll‐like receptors (TLR), especially TLR‐2 recognizes cell wall components of S. aureus, e.g. lipoteichoic acid (LTA) and peptidoglycan (PGN). A heterozygous TLR‐2 R753Q polymorphism occurs in a frequency of 11.5% in adult AD patients and has been shown to be associated with a severe phenotype of AD.

Methods:  The aim of this study was to investigate the impact of TLR‐2 agonists (LTA, PGN and Pam3Cys) on cytokine production in human monocytes from AD patients with the TLR‐2 R753Q polymorphism compared with that of AD patients with ‘wild type’ TLR‐2 and control individuals to elucidate the functional role of the TLR‐2 R753Q polymorphism.

Results:  Monocytes from AD patients with the TLR‐2 R753Q mutation produced significantly more IL‐6 and IL‐12 compared with that of AD patients with nonmutated TLR‐2 upon stimulation with TLR‐2 agonists.

Conclusion:  We show for the first time functional differences in TLR‐2 responsiveness of monocytes from AD patients with the TLR‐2 R753Q mutation compared with wild type AD patients in a ligand‐dependent manner.

Clinical implication:  Our data support the emerging concept that AD patients have a dysbalance in innate and aquired immunity. TLR‐2 may be essential in the pathogenesis and maintenance of AD and may be involved in the enhanced susceptibility to skin infections with S. aureus and in a higher inflammatory response in patients with AD carrying the TLR‐2 polymorphism.
Stomatal and non‐stomatal limitations of photosynthesis in trees of a tropical seasonally flooded forest
Authors: Herrera Ana , Tezara Wilmer , Marín Oranys , Rengifo Elizabeth
Published: April 2008

Trees in the flooded forest of the Mapire River in Venezuela suffer a decrease in photosynthetic rate (A) when flood begins, which is reverted at maximum flood. Changes in A are accompanied by similar changes in stomatal conductance (gs), and the possibility of changes in photosynthetic capacity is not ruled out. In order to understand how relative stomatal and non‐stomatal limitations of photosynthesis are affected by flooding, we studied the seasonal changes in A and its response to intercellular CO2 concentration in trees of Campsiandra laurifolia, Symmeria paniculata, Acosmium nitens and Eschweilera tenuifolia. Flooding caused in trees of C. laurifolia and S. paniculata a reduction in A, gs, carboxylation efficiency and total soluble protein (TSP), whereas gas exchange in A. nitens and E. tenuifolia was more sensitive to drought. Under flooding, relative stomatal limitation (Ls) was on average half the highest, and relative non‐stomatal limitation (Lns) increased from the dry season to flooding. Under full flood, A, gs and TSP regained high values. A was positively correlated to light‐saturated electron transport rate, suggesting that part of the decrease in A under flooding was due to impairment of photosynthetic capacity. Under flooding, not only stomatal closure but also increased Lns causes a reduction in photosynthesis of all four species, and a process of acclimation as flooding progresses allows gas exchange and related variables to regain high values.
A growth hormone‐secreting adenoma with incomplete nerve bundle formation
Authors: Ikeda Hidetoshi , Takayasu Shinobu
Published: April 2008

We present a unique case of an adenoma secreting growth hormone (GH), showing incomplete nerve bundle formation without ganglion cells. A 47‐year‐old man presenting with acromegaly was revealed to have high serum GH and IGF‐1 levels. The concentrations of the other adenohypophysial hormones were within the normal range. Histology revealed an unusual pituitary adenoma containing many nerve bundle‐like structures. Adenoma cells with ovoid or round hyperchromatic nuclei and eosinophilic cytoplasms lacked the typical features of ganglion cells. The nerve bundles consisted of slender elongated cells. These fibers were arranged into groups in a roughly parallel fashion. By immunohistochemistry, many adenoma cells were positive for GH, prolactin, thyrotropin beta, synaptophysin and chromogranin. Fibrous bodies revealed by keratin immunostaining were found only in adenoma cells. Scattered star‐shaped adenoma cells showed the same immunoreactivity as folliculo‐satellite cells. Adenoma cells, but not the bundle‐like structures, were also positive for Pit‐1. Immunostaining for neurofilament protein, GFAP, vimentin, and S‐100 protein revealed variable amounts of fibrils within the bundle‐like structures. Scattered immunoreactivity for myelin basic protein and synaptophysin was also found in the bundle area. Our case is the first GH‐secreting pituitary adenoma showing incomplete nerve bundle differentiation and lacking mature ganglion cells.
The pedunculopontine nucleus in developmental disorders of the basal ganglia
Authors: Anzai Yuki , Hayashi Masaharu , Ohya Tatsuo , Yokota Shumpei
Published: April 2008

The pedunculopontine nucleus (PPN), which is located in the upper brainstem, contains cholinergic and non‐cholinergic neurons, and has afferent and efferent connections to the basal ganglia and spinal cord. The PPN is known to be affected in adult‐onset basal ganglia diseases, and we speculated that the PPN might be similarly insulted in developmental basal ganglia disorders. We immunohistochemically examined the expression patterns of acetylcholine esterase and tyrosine hydroxylase, markers of acetylcholinergic and catecholaminergic neurons, respectively, in the PPN pars dissipata (PPNd) of controls and patients with bilirubin encephalopathy (BE) and perinatal hypoxic ischemic encephalopathy with localized basal ganglia lesion (HIEbg). Controls showed an age‐dependent change in the percentages of acetylcholinergic and catecholaminergic neurons. Three out of six BE cases and three out of six HIEbg cases showed a reduction in the percentage of acetylcholinergic neurons in the PPNd. Additionally, three BE cases demonstrated an increase in the percentage of catecholaminergic neurons. It is likely that the relative proportions of acetylcholinergic and catecholaminergic neurons in the PPN can be altered in developmental basal ganglia disorders.
Intratelencephalic corticostriatal neurons equally excite striatonigral and striatopallidal neurons and their discharge activity is selectively reduced in experimental parkinsonism
Authors: Ballion Bérangère , Mallet Nicolas , Bézard Erwan , Lanciego José Luis , Gonon Francois
Published: April 2008

Striatonigral and striatopallidal neurons form distinct populations of striatal projection neurons. Their discharge activity is imbalanced after dopaminergic degeneration in Parkinson's disease. Striatal projection neurons receive massive cortical excitatory inputs from bilateral intratelencephalic (IT) neurons projecting to both the ipsilateral and contralateral striatum and from collateral axons of ipsilateral neurons that send their main axon through the pyramidal tract (PT). Previous anatomical studies in rats suggested that IT and PT inputs preferentially excite striatonigral and striatopallidal neurons, respectively. Here we used electrophysiological criteria to identify them with antidromic stimulations. We show that the spontaneous discharge activity of IT neurons is depressed, whereas that of PT neurons is not affected in the rat cortex ipsilateral to 6‐hydroxydopamine injection. However, our functional experiments do not support the hypothesis of a differential cortical input to striatal pathways. Firstly, although the conduction velocity of PT neurons is 4.6 times faster than that of IT neurons, identified striatopallidal and striatonigral neurons exhibit identical latencies of their spike responses to electrical stimulation of the ipsilateral cortex. Secondly, although PT neurons are ipsilateral, both striatal populations exhibit similar sensitivity to the stimulation of the ipsilateral and contralateral cortex. We suggest that IT neurons provide the main excitatory input to both striatal populations and that the corticostriatal PT input is weaker. Therefore, our functional data do not support our previous hypothesis that the deficit of IT neurons associated with the dopaminergic depletion might contribute to the striatal imbalance. This imbalance might rather result from intrinsic striatal mechanisms.
Medial orbitofrontal cortex codes relative rather than absolute value of financial rewards in humans
Authors: Elliott R. , Agnew Z. , Deakin J. F. W.
Published: April 2008

Functional imaging studies in recent years have confirmed the involvement of orbitofrontal cortex (OFC) in human reward processing and have suggested that OFC responses are context‐dependent. A seminal electrophysiological experiment in primates taught animals to associate abstract visual stimuli with differently valuable food rewards. Subsequently, pairs of these learned abstract stimuli were presented and firing of OFC neurons to the medium‐value stimulus was measured. OFC firing was shown to depend on the relative value context. In this study, we developed a human analogue of this paradigm and scanned subjects using functional magnetic resonance imaging. The analysis compared neuronal responses to two superficially identical events, which differed only in terms of the preceding context. Medial OFC response to the same perceptual stimulus was greater when the stimulus predicted the more valuable of two rewards than when it predicted the less valuable. Additional responses were observed in other components of reward circuitry, the amygdala and ventral striatum. The central finding is consistent with the primate results and suggests that OFC neurons code relative rather than absolute reward value. Amygdala and striatal involvement in coding reward value is also consistent with recent functional imaging data. By using a simpler and less confounded paradigm than many functional imaging studies, we are able to demonstrate that relative financial reward value per se is coded in distinct subregions of an extended reward and decision‐making network.
Altered neurovascular coupling during information‐processing states
Authors: Jones Myles , Devonshire Ian M. , Berwick Jason , Martin Chris , Redgrave Peter , Mayhew John
Published: April 2008

Brain imaging techniques rely on changes in blood flow, volume and oxygenation to infer the loci and magnitude of changes in activity. Although progress has been made in understanding the link between stimulus‐evoked neural activity and haemodynamics, the extent to which neurovascular‐coupling relationships remain constant during different states of baseline cortical activity is poorly understood. Optical imaging spectroscopy, laser Doppler flowmetry and electrophysiology were used to measure haemodynamics and neural activity in the barrel cortex of anaesthetized rats. The responses to stimulation of the whisker pad were recorded during quiescence and cortical desynchronization produced by stimulation of the brainstem. Cortical desynchronization was accompanied by increases in baseline blood flow, volume and oxygenation. Haemodynamic responses to low‐frequency whisker stimuli (1 Hz) were attenuated during arousal compared with that observed during quiescence. During arousal it was possible to increase stimulus‐evoked haemodynamics by increasing the frequency of the stimulus. Neural responses to low‐frequency stimuli were also attenuated but to a far lesser extent than the reduction in the accompanying haemodynamics. In contrast, neuronal activity evoked by high‐frequency stimuli (40 Hz) was enhanced during arousal, but induced haemodynamic responses of a similar magnitude compared with that observed for the same high‐frequency stimulus presented during quiescence. These data suggest that there may be differences in stimulus‐evoked neural activity and accompanying haemodynamics during different information‐processing states.
Calcium‐activated potassium currents differentially modulate respiratory rhythm generation
Authors: Zavala‐Tecuapetla C. , Aguileta M.A. , Lopez‐Guerrero J.J. , González‐Marín M.C. , Peña F.
Published: April 2008

The pre‐Bötzinger complex (PBC) generates eupnea and sighs in normoxia and gasping during hypoxia through particular mixtures of intrinsic and synaptic properties. Among intrinsic properties, little is known about the role of Ca2+‐activated potassium channels in respiratory rhythms generation. To examine this role, we tested the effects of openers and blockers of the large‐conductance (BK) and small‐conductance (SK) Ca2+‐activated potassium channels on the respiratory rhythms recorded both in vitro and in vivo, as well as on the discharge pattern of respiratory neurons in the PBC. Activation of SK channels with 1‐ethyl‐2‐benzimidazolinone (1‐EBIO) abolished sigh‐like activity and inhibited eupneic‐like activity, whereas blockade of SK channels with apamine (APA) increased frequency in both rhythms. In hypoxia, APA did not affect the transition to gasping‐like activity. At the cellular level, activation of SK channels abolished pacemaker activity and decreased non‐pacemaker neurons discharge; opposite effects were observed with SK blockade. In contrast to SK channel modulation, either activation or blockade of BK channels with NS 1619 or iberiotoxin and paxilline, respectively, produced mild effects on eupneic‐like and sigh‐like bursts during normoxia in vitro. However, BK blockers prevented the changes associated with the transition to gasping‐like activity in vitro and perturbed gasping generation and autoresuscitation in vivo. At the cellular level BK channel modulation did not affect respiratory neurons discharge. We conclude that KCa participate in rhythm generation in a state‐dependent manner; SK channels are preferentially involved in rhythm generation in normoxia whereas BK channels participate in the transition to gasping generation in hypoxia.
Mass invariance of population nitrogen flux by terrestrial mammalian herbivores: an extension of the energetic equivalence rule
Authors: Habeck Christopher W. , Meehan Timothy D.
Published: April 2008

According to the energetic equivalence rule, energy use by a population is independent of average adult body mass. Energy use can be equated with carbon flux, and it has been suggested that population fluxes of other materials, such as nitrogen and phosphorus, might also be independent of body mass. We compiled data on individual nitrogen deposition rates (via faeces and urine) and average population densities of 26 species of mammalian herbivores to test the hypothesis of elemental equivalence for nitrogen. We found that the mass scaling of individual nitrogen flux was opposite to that of population density for the species in our dataset. By computing the product of individual nitrogen flux and average population density for each species in our dataset, we found that population‐level nitrogen flux was independent of species mass, averaging c. 3.22 g N ha−1 day−1. Results from this analysis can be used to understand the influence of mammalian herbivore communities on nitrogen cycling in terrestrial ecosystems.
Flexible, intensive insulin therapy and dietary freedom in adolescents and young adults with Type 1 diabetes: a prospective implementation study
Authors: Sämann A. , Lehmann T. , Kloos C. , Braun A. , Hunger‐Dathe W. , Wolf G. , Müller U. A.
Published: April 2008

Aims  To assess the outcome of a Diabetes Treatment and Teaching Programme (DTTP) on glycated haemoglobin (HbA1c), severe hypoglycaemia (SH) and severe ketoacidosis (SKA) in adolescents and young adults with Type 1 diabetes.

Methods  Quality‐assurance project with assessment of participants 1 year after participation in a DTTP (5‐day inpatient course, groups ≤ 10 patients, fixed curriculum of education/training, introduction of dietary freedom). Before–after analyses of participants aged 12–15, 15–18, 18–21 and 21–24 years. Main outcome measures were HbA1c, SH and SKA.

Results  For the 1592 participants, aged 12 to 24 years, mean age at enrolment was 19 ± 3 years, mean duration of diabetes was 7.3 ± 5.4 (range 0.3–24) years, mean baseline HbA1c declined from 8.8 ± 2.3% to 8.1 ± 2.0%. The incidence of SH was 0.31 vs. 0.11 events/patient/year; the incidence of SKA 0.17 vs. 0.07 events/patient/year. In mixed effects models taking into account effects of centres, age and diabetes duration, the mean difference was −0.64%[P < 0.001, 95% confidence interval (CI) −0.79 to −0.5] for HbA1c, −0.2 events/patient/year (P < 0.0001, 95% CI −0.28 to −0.12) for SH and −0.1 events/patient/year (P < 0.0001, 95% CI −0.14 to −0.06) for SKA.

Conclusions  Adolescents and young adults with Type 1 diabetes benefit from participation in a standard DTTP for flexible, intensive insulin therapy and dietary freedom.
Offspring birth weight, gestational age and maternal characteristics in relation to glucose status at age 53 years: evidence from a national birth cohort
Authors: Kuh D. , Mishra G. D. , Black S. , Lawlor D. A. , Smith G. Davey , Okell L. , Wadsworth M. , Hardy R.
Published: April 2008

Aims We investigated pathways linking offspring birth weight to maternal diabetes risk in later life by taking into account a range of prospective early‐life and adult maternal factors.

Methods In a national birth cohort study, we examined the relationship between offspring birth weight and maternal glycated haemoglobin (HbA1c) at age 53 years in 581 mothers who had a first birth between age 19 and 25 years, and had data on potential confounders or mediators.

Results Mean age at first birth was 21.5 years. After adjustment for maternal body mass index (BMI), mean percentage change in maternal HbA1cper kilogram increase in offspring birth weight was −1.8%[95% confidence interval (CI) −3.5, −0.1;P = 0.03]. This relationship was mostly accounted for by gestational age that was inversely related to maternal HbA1c(−0.9%; 95% CI −1.5, −0.4;P = 0.001). Other risk factors for high HbA1cwere smoking and high BMI at 53 years. There was a significant interaction between offspring birth weight and maternal childhood social class (P = 0.01). Mothers from a manual background with higher birth weight offspring had lower HbA1c(BMI adjusted: −3.1%; 95% CI −5.0, −1.1); this was not observed for mothers from a non‐manual background (BMI adjusted: 1.9%; 95% CI −1.3, 5.0).

Conclusions Short gestational age and low offspring birth weight may be part of a pathway linking impaired early maternal growth to diabetes risk in later life. A second possible pathway linking higher offspring birth weight to later maternal glucose status was also identified. These potential pathways require further investigation in cohorts with a wider maternal age range so that the early targeting of public health initiatives can be assessed.
Upper abdominal symptoms in patients with Type 1 diabetes: unrelated to impairment in gastric emptying caused by autonomic neuropathy
Authors: Punkkinen J. , Färkkilä M. , Mätzke S. , Korppi‐Tommola T. , Sane T. , Piirilä P. , Koskenpato J.
Published: April 2008

Aims  Diabetic gastroparesis is a common condition occurring in some 30–50% of patients with long‐term diabetes. Some studies have found a relationship between autonomic neuropathy and diabetic gastroparesis. In addition to autonomic neuropathy, acute changes in plasma glucose concentration can also affect gastric emptying. The objective was to examine the relationship between autonomic nerve function, glucose concentration, gastric emptying, and upper abdominal symptoms in Type 1 diabetic patients.

Methods  Gastric emptying of solids and liquids was measured with scintigraphy in 27 patients with longstanding Type 1 diabetes with upper abdominal symptoms. Autonomic nerve function was examined by standardized cardiovascular tests, and plasma glucose concentrations were measured during scintigraphy. Severity of abdominal symptoms and quality of life were explored by validated questionnaires.

Results  Seven patients (26%) had delayed gastric emptying of solids and three (11%) of liquids. Mean gastric half‐emptying time of solids was 128 ± 116 min and of liquids 42 ± 30 min. Of the 26 patients undergoing tests, 16 (62%) had autonomic nerve dysfunction. Autonomic neuropathy score (1.6 ± 1.7) correlated positively with the gastric emptying rate of solids (P = 0.006), a rate unrelated to symptom scores or plasma glucose concentrations during scintigraphy. Quality of life in patients with abdominal symptoms was lower than in the normal Finnish population.

Conclusions  Impaired gastric emptying of solids in patients with Type 1 diabetes is related to autonomic neuropathy, but not to actual glycaemic control. The upper abdominal symptoms observed in these patients cannot be explained, however, by impaired gastric emptying.
Pancreatic exocrine insufficiency is not common in HNF‐1α MODY
Authors: Klupa T. , Skupień J. , Gorczynska‐Kosiorz S. , Wanic K. , Kusnierz‐Cabala B. , Solnica B. , Sieradzki J. , Malecki M. T.
Published: April 2008

Aims  Exocrine pancreatic insufficiency has been described in Type 1 and Type 2 diabetes. The hepatocyte nuclear factor (HNF)‐1α gene associated with maturity‐onset diabetes of the young (MODY3) is expressed in several organs, including the exocrine pancreas. The aim of this study was to determine the prevalence of exocrine pancreas dysfunction in HNF‐1α MODY patients.

Methods  Thirty‐one diabetic HNF‐1α MODY patients (mean age 37.2 ± 14.6 years) and 35 healthy control subjects (39.1 ± 13.9 years) participated. In addition, 25 Type 1 diabetic (T1DM) subjects were also examined (mean age 30.6 ± 10.1 years). Exocrine pancreas function was assessed by measurement of stool elastase 1 (E1) activity. All diabetic patients and control subjects completed a gastrointestinal (GI) symptoms questionnaire.

Results  In all but two individuals, stool E1 levels were normal (> 200 µg/g). The only case of severely impaired pancreas exocrine function (E1 = 47.5 µg/g) was observed in the MODY3 group. The mean stool E1 elastase level in the HNF‐1α MODY group was significantly lower than in the control subjects (401.0 ± 118.4  vs. 482.7 ± 151.1 µg/g, P = 0.001). Similarly, E1 levels in T1DM were lower than in control subjects (344.8 ± 132.1 µg/g, P = 0.001); one patient with a moderate enzyme decrease was identified in this group. In addition, more frequent GI complaints were reported by HNF‐1α MODY patients when compared with control subjects and also with T1DM patients.

Conclusion  Pancreatic exocrine insufficiency is not common in HNF‐1α MODY diabetic patients, although their stool E1 levels are lower than in healthy control subjects.
THE MORAL IMPORTANCE OF SELECTING PEOPLE RANDOMLY
Authors: PETERSON MARTIN
Published: April 2008

This article discusses some ethical principles for distributing pandemic influenza vaccine and other indivisible goods. I argue that a number of principles for distributing pandemic influenza vaccine recently adopted by several national governments are morally unacceptable because they put too much emphasis on utilitarian considerations, such as the ability of the individual to contribute to society. Instead, it would be better to distribute vaccine by setting up a lottery. The argument for this view is based on a purely consequentialist account of morality; i.e. an action is right if and only if its outcome is optimal. However, unlike utilitarians I do not believe that alternatives should be ranked strictly according to the amount of happiness or preference satisfaction they bring about. Even a mere chance to get some vaccine matters morally, even if it is never realized.
MEDICAL CONFIDENTIALITY: LEGAL AND ETHICAL ASPECTS IN GREECE
Authors: PAPADODIMA STAVROULA A. , SPILIOPOULOU CHARA A. , SAKELLIADIS EMMANOUIL I.
Published: April 2008

Respect for confidentiality is firmly established in codes of ethics and law. Medical care and the patients' trust depend on the ability of the doctors to maintain confidentiality. Without a guarantee of confidentiality, many patients would want to avoid seeking medical assistance The principle of confidentiality, however, is not absolute and may be overridden by public interests. On some occasions (birth, death, infectious disease) there is a legal obligation on the part of the doctor to disclose but only to the appropriate authorities. Permissible disclosure can be granted by the patients' consent, for example, for the purpose of insurance they may wish to take out. Moreover, there are some ambivalent situations (such as criminal acts, or notification of sexual partner in case of a patient with AIDS) for which Greek law does not include relevant provisions, and the Codes of Medical Ethics do not offer clear guidelines. Therefore, the Greek doctor is called to estimate the situation and assume full responsibility for his decision. Finally, new considerations have arisen in the context of the recent advances in the field of telemedicine and electronic archiving. The paper discusses the current situation and legislation in Greece.
ENHANCEMENTS, EASY SHORTCUTS, AND THE RICHNESS OF HUMAN ACTIVITIES
Authors: SCHERMER MAARTJE
Published: April 2008

One argument that is frequently invoked against the technological enhancement of human functioning is that it is morally suspect, or even wrong, to take an easy shortcut. Some things that usually take effort, endurance or struggle can come easily with the use of an enhancer. This paper analyses the various arguments that circle round the idea that enhancement of human functioning is problematic because of the ‘easy shortcut’ that it offers. It discusses the concern that quick fixes lead to corrosion of character and the idea that suffering, pain, hard work and effort are essential for real and worthy achievements, and argues that these views are largely mistaken. Next, the paper argues that the core worry about taking an easy shortcut is that it makes us lose sight of the complexities of our means and ends; in other words, the argument warns against reducing the richness of human activities. A vocabulary of ‘practices’, ‘internal goods’ and ‘focal engagement’ will be used to articulate this argument further. The conclusion is that the easy shortcut argument has no general validity as an argument against enhancement ‘as such’. The paper urges us, however, to evaluate enhancement technologies not only in terms of their efficiency in reaching certain goals but also in terms of their contribution to intrinsically worthwhile human activities. It can point out some of the caveats, as well as the opportunities, of the use of enhancement technologies.
MAURICE POTRON'S LINEAR ECONOMIC MODEL: A DE FACTO PROOF OF ‘FUNDAMENTAL MARXIAN THEOREM’
Authors: Mori Kenji
Published: April 2008

Maurice Potron was a French mathematician whose largely unknown contributions to economic analysis should be acknowledged as pioneering achievements. The purpose of this paper is to (1) reconstruct Potron's core model in terms of modern input–output analysis, (2) show that Potron proved de facto Fundamental Marxian Theorem (FMT) 48 years earlier than Morishima, Seton and Okishio by adapting the Perron–Frobenius theorems to economic problems, and (3) claim that Potron proved de facto FMT by considering heterogeneous labours 65 years earlier and even more generally than Bowles and Gintis.
‘Late Mobilization’: Transnational Peasant Networks and Grassroots Organizing in Brazil and South Africa
Authors: BALETTI BRENDA , JOHNSON TAMARA M. , WOLFORD WENDY
Published: April 2008

In this paper, we analyze the political dynamics of the contemporary ‘transnational peasant network’ through a comparison of two movements: the Brazilian Movimento Dos Trabalhadores Rurais Sem Terra (MST) and the South African Landless People's Movement (LPM). We argue that transnational visions of ‘peasants’ often obscure relations between or within rural movements. One tangible benefit of the transnational peasant network is the exchange of ideas, experiences and information, but this exchange does not happen in a vacuum, rather it happens in the historically‐situated, power‐laden context of an uneven world system. Organized in 1984, MST activists from Brazil helped to train, educate and inspire South African activists after the LPM formed in 2001, but key elements of the MST's success were inappropriate or unworkable in the South African context. Ultimately, the transfer of movement knowledge from the MST to the LPM may have worked against the long‐term success of the latter.
Trade and Biotechnology in Latin America: Democratization, Contestation and the Politics of Mobilization
Authors: NEWELL PETER
Published: April 2008

This research explores the role of agrarian and environmental movements in contesting the development and promotion of agricultural biotechnology through trade liberalization in Latin America. Organized around themes of mobilization, participation and representation, it raises key questions about who mobilizes and how, and about the strategic dilemmas that arise when movements with different histories, membership bases and cultures of protest attempt to work together. Issues of accountability, representation and participation run through the analysis of strategies of organization and claim‐making adopted by an eclectic range of groups seeking to contest the role of biotechnology in the structure of agricultural production, the institutions that manage that relationship and the discourses which sustain it. In particular, analysis centres on their responsiveness to the concerns and agendas of poorer groups in the front line of the ‘gene revolution’ as it plays out in the Latin American countryside, in particular in Argentina and Brazil, the key players in biotechnology in the region.
Claiming the Grounds for Reform: Agrarian and Environmental Movements in Indonesia
Authors: LEE PELUSO NANCY , AFIFF SURAYA , RACHMAN NOER FAUZI
Published: April 2008

This essay examines the convergences, tensions and mutual influences of agrarian and environmental movements in Indonesia and their connections to transnational movements under state‐led development and neoliberal governance regimes. The authors argue that environmental movements of the last quarter of the twentieth century affected the strategies, struggles, mutual relations with, and public discourses of resurgent agrarian movements in diverse ways. Environmental movements had significant influences on national policy, law and practice within a decade of their emergence under the state‐led development regime of President Suharto. Environmental activists used the appearance of technical ‘apolitical’ concerns to their advantage. They mobilized at multiple scales, targeting laws and other institutions of state power at the same time as organizing the grassroots. The repression of the Suharto regime forced agrarian reform activists underground, while environmental issues were mainstreamed. Agrarian movements in Indonesia today, under a decentralized regime dominated by neoliberal policies, have faced new opportunities and constraints due to national and transnational influences of environmental and agrarian reform discourses and networks. We show how these influences have changed the political fields within which Indonesian agrarian movement groups operate: forming, shifting and struggling over critical alliances.