bluuebunny/crossref_metadata_2025_split huggingface dataset:
IgG4 breaking the rules
Authors: Aalberse Rob C. , Schuurman Janine 
Published: March 2003

SummaryImmunoglobulin G4 (IgG4) antibodies have been known for some time to be functionally monovalent. Recently, the structural basis for this monovalency has been elucidated: the in vivo exchange of IgG half‐molecules (one H‐plus one L‐chain) among IgG4. This process results in bispecific antibodies that in most situations will behave as functionally monovalent antibodies. The structural basis for the abnormal behaviour of IgG4 seems to be largely the result of a single amino acid change relative to human IgG1: the change of a proline in core hinge of IgG1 to serine. This results in a marked shift in the equilibrium between interchain disulphide bridges and intrachain disulphide bridges, which for IgG4 results in 25–75% absence of a covalent interaction between the H‐chains. Because of strong non‐covalent interactions between the CH3 domains (and possibly also between the CH1 domain and the trans‐CH2 domain) IgG4 is a stable four‐chain molecule and does not easily exchange half‐molecules under standard physiological conditions in vitro. We postulate that the exchange is catalysed in vivo by protein disulphide isomerase (PDI) and/or FcRn (the major histocompatibility complex (MHC)‐related Fc receptor) during transit of IgG4 in the endosomal pathway in endothelial cells. Because IgG4 is predominantly expressed under conditions of chronic antigen exposure, the biological relevance of this exchange of half‐molecules is that it generates antibodies that are unable to form large immune complexes and therefore have a low potential for inducing immune inflammation. In contrast to monovalent immunoglobulin fragments, these scrambled immunoglobulins have a normal half‐life. The significance of the ensuing bispecificity needs further evaluation, because this will be relevant only in situations where high IgG4 responses are found to two unrelated antigens that happen to be present in the body at the same time and place. In this context the significance of IgG4 autoreactivity might have to be re‐evaluated. The main function of IgG4, however, is presumably to interfere with immune inflammation induced by complement‐fixing antibodies, or, in the case of helminth infection or allergy, by IgE antibodies.
Intralobular ducts of human major salivary glands contain leptin and its receptor
Authors: De Matteis R. , Puxeddu R. , Riva A. , Cinti S. 
Published: March 2003

AbstractLeptin, a 16‐kDa hormone, plays an important role in the control of food intake and in energy homeostasis both in rodents and in man. Leptin is mainly produced and secreted by adipocytes, but other tissues and gastric glands have also recently been shown to produce it in a dual (endocrine and exocrine) mode. In addition, a leptin receptor has been detected in taste cells of mouse circumvallate papillae and in rat intestinal epithelium. These data prompted us to carry out a detailed study of human salivary glands as potential leptin‐producing organs. Biopsies of salivary glands (submandibular and parotid) obtained from male and female patients during surgery for different clinical indications were subjected to immunohistochemical study for the presence of leptin, its functional receptor, insulin and glucagon. The presence and cellular distribution of glucocorticoid receptor in leptin‐secreting cells were also investigated. Double immunohistochemical staining (silver–gold intensification and avidin–biotin–peroxidase) was used for the visualization of glucocorticoid receptor and leptin labelling, respectively. The results show that intralobular duct cells of submandibular and parotid glands are immunoreactive for leptin, leptin receptor and glucagon but not for insulin. Leptin was also detected in some microglobules in whole saliva obtained from four healthy volunteers. Co‐localization for leptin, leptin receptor and glucocorticoid receptor in the same cell type suggested a functional relationship between glucocorticoid hormone and leptin secretion also at the level of the salivary glands.
Shading by shrubs in a desert system reduces the physiological and demographic performance of an associated herbaceous perennial
Authors: Forseth I. N. , Wait D. A. , Casper B. B. 
Published: March 2003

Summary

A 2‐year field study examined the demographic consequences of association with shrubs in an herbaceous perennial, Cryptantha flava. Physiological data were collected to evaluate whether shrub effects were mediated primarily through water, nutrient or light availability.
Microclimatic conditions under the north side of shrubs differed from open microhabitats, primarily in light availability. Due to little photosynthetic acclimation to light, daily photosynthesis for plants under shrubs was reduced proportionally to the light regime.
Shading did not reduce stomatal conductance proportionally to photosynthesis, which led to decreased water use efficiency for plants under shrubs. Few differences were found in leaf water potential between microhabitats, indicating that little competition for water was occurring.
There was little evidence for shrub‐induced nutrient island effects. Soil nitrogen, phosphorus and organic content did not differ between open and shrub microhabitats. Leaf nitrogen content also differed little between plants in the two microhabitats.
Growth and flowering responses of individuals under shrubs were reduced relative to those in the open, even for plants located on the south side of shrubs.
Over this 2‐year period of average to above‐average rainfall, association of C. flava with shrubs was dominated by competition for light, rather than for water or nutrients. Future investigations will address whether this asymmetric competitive interaction changes during years with below‐average rainfall to a facilitative interaction, or one of increased competition for water.
Importance of physiological integration of dwarf bamboo to persistence in forest understorey: a field experiment
Authors: Saitoh Tomoyuki , Seiwa Kenji , Nishiwaki Aya 
Published: March 2003

Summary

Sasa spp., dwarf bamboo which dominate the undergrowth of temperate forests in Japan occur as clonal fragments in which ramets in light gaps to are connected to those in shaded understoreys by long rhizomes. We test whether persistence under shaded conditions is supported by translocation of assimilates from illuminated ramets. A dense population of Sasa palmata growing at an open site, was exposed to two light conditions (homogeneous: open–open and heterogeneous: open–shaded) and two rhizome connection treatments (intact and severed) in a full factorial design.
Ramet mass, and the mass of many parts of the clonal fragments, was much lower in the shade than in the open, but this effect was less marked when the rhizome connection was intact than when it was severed. Clone parts in shade may therefore be supported by translocation from connected clone parts in the open, with such physiological integration enhancing persistence where light supply is heterogeneous as in the gap–understorey continuum.
Above‐ground biomass was reduced sooner than that below ground. Clonal fragments of S. palmata recover via dormant buds on rhizomes, whose longer persistence would therefore enhance performance of the clonal fragment.
Specific leaf area (SLA) was greater in shade than in the open, irrespective of rhizome connection, suggesting that individual leaves show morphological plasticity independently of only physiological integration.
Relative labelling index: a novel stereological approach to test for non‐random immunogold labelling of organelles and membranes on transmission electron microscopy thin sections
Authors: Mayhew T. M. , Lucocq J. M. , Griffiths G. 
Published: March 2003

SummarySimple and efficient protocols for quantifying immunogold labelling of antigens localized in different cellular compartments (organelles or membranes) and statistically evaluating resulting labelling distributions are presented. Two key questions are addressed: (a) is compartmental labelling within an experimental group (e.g. control or treated) consistent with a random distribution? and (b) do labelling patterns vary between groups (e.g. control vs. treated)? Protocols rely on random sampling of cells and compartments. Numbers of gold particles lying on specified organelle compartments provide an observed frequency distribution. By superimposing test‐point lattices on cell profiles, design‐based stereology is used to determine numbers of points lying on those same compartments. Random points hit compartments with probabilities determined by their relative sizes and so provide a convenient internal standard, namely, the expected distribution if labelling is purely random. By applying test‐line lattices, and counting sites at which these intersect membrane traces, analogous procedures provide observed and expected labelling distributions for different classes of membranes. Dividing observed golds by expected golds provides a relative labelling index (RLI) for each compartment and, for random labelling, the predicted RLI = 1. In contrast to labelling densities of organelles (golds µm−2) or membranes (golds µm−1), RLI values are estimated without needing to know lattice constants (area per point or length per intersection) or specimen magnification. Gold distributions within a group are compared by chi‐squared analysis to test if the observed distribution differs significantly from random and, if it is non‐random, to identify compartments which are preferentially labelled (RLI > 1). Contingency table analysis allows labelling distributions in different groups of cells to be compared. Protocols are described and illustrated using worked specimen examples and real data.
The prevention of the staurosporine‐induced apoptosis by Bcl‐XL, but not by Bcl‐2 or caspase inhibitors, allows the extensive differentiation of human neuroblastoma cells
Authors: Yuste Víctor J. , Sánchez‐López Isabel , Solé Carme , Encinas Mario , Bayascas Jose R. , Boix Jacint , Comella Joan X. 
Published: March 2003

AbstractStaurosporine is one of the best apoptotic inducers in different cell types including neuroblastomas. In this study we have compared the efficiency and final outcome of three different anti‐apoptotic strategies in staurosporine‐treated SH‐SY5Y human neuroblastoma cells. At staurosporine concentrations up to 500 nm, z‐VAD.fmk a broad‐spectrum, noncompetitive inhibitor of caspases, reduced apoptosis in SH‐SY5Y cells. At higher concentrations, z‐VAD.fmk continued to inhibit caspases and the apoptotic phenotype but not cell death which seems to result from oxidative damage. Stable over‐expression of Bcl‐2 in SH‐SY5Y protected cells from death at doses of staurosporine up to 1 µm. At higher doses, cytochrome c release from mitochondria occurred, caspases were activated and cells died by apoptosis. Therefore, we conclude that Bcl‐2 increased the threshold for apoptotic cell death commitment. Over‐expression of Bcl‐XL was far more effective than Bcl‐2. Bcl‐XL transfected cells showed a remarkable resistance staurosporine‐induced cytochrome c release and associated apoptotic changes and survived for up to 15 days in 1 µm staurosporine. In these conditions, SH‐SY5Y displayed a remarkable phenotype of neuronal differentiation as assessed by neurite outgrowth and expression of neurofilament, Tau and MAP‐2 neuronal specific proteins.
Effect of endogenous serotonin on the binding of the 5‐HT1A PET ligand 18F‐MPPF in the rat hippocampus: kinetic β measurements combined with microdialysis
Authors: Zimmer Luc , Mauger Gweltas , Le Bars Didier , Bonmarchand Gregory , Luxen André , Pujol Jean‐François 
Published: March 2003

AbstractBy using a combination of an original β+‐sensitive␣intracerebral probe and microdialysis, the effect of increased endogenous serotonin on specific binding of 18F‐MPPF [4‐(2′‐methoxyphenyl)‐1‐[2′‐[N‐(2′′‐pyridinyl)‐p‐fluorobenzamido]ethyl]piperazine] to the serotonin‐1A (5‐HT1A) receptors was investigated in the hippocampus of the anaesthetized rat. Our β‐sensitive probe prototype was sensitive enough to obtain specific 18F‐MPPF time–activity curves in the rodent (hippocampus/cerebellum ratio ≈ 2). The serotonin neuronal release was pharmacologically enhanced using fenfluramine at three different doses (1, 2 and 10 mg/kg intravenous) multiplying by 2–15 the extracellular serotonin in the hippocampus. These extracellular variations of extracellular serotonin resulted in dose‐ranging decreases in 18F‐MPPF‐specific binding in the same rat. Our results showed for the first time that 18F‐MPPF binding could be modulated by modifications of extracellular serotonin in the rat hippocampus. These results were confirmed by the enhancement of extracellular radioactivity collected in dialysates after the displacement of 18F‐MPPF by fenfluramine. After modelization, 18F‐MPPF binding could constitute an interesting radiotracer for positron emission tomography in evaluating the serotonin endogenous levels in limbic areas of the human brain.
Relevance of different striatal markers in assessment of the MPP+‐induced dopaminergic nigrostriatal injury in rat
Authors: Barc Stéphanie , Page Guylène , Barrier Laurence , Garreau Lucette , Guilloteau Denis , Fauconneau Bernard , Chalon Sylvie 
Published: March 2003

AbstractMany striatal dopaminergic markers are available for estimating the degree of the nigrostriatal lesion by MPTP/MPP+, but the changes of these markers are not perfectly matched. In this study we investigated different striatal markers and determined which ones closely reflected the nigrostriatal alteration. The in vivo binding of (E)‐N‐(3‐iodoprop‐2‐enyl)‐	2‐β‐carbomethoxy‐3β‐(4′‐methylphenyl)nortropane (PE2I), a selective and potent inhibitor of the neuronal dopamine transporter (DAT) was considered as the reference index of injury of striatal dopaminergic nerve‐endings. Rats received a 10‐µg MPP+ injection in the right substantia nigra and were killed at 7 days after lesion. The results were as follows: (i) a decrease (66%) of the biodistribution of [125I]PE2I; (ii) a great reduction of the DAT expression measured by the binding of [125I]PE2I in striatal membranes (Bmax decreased by 54%) and in cerebral slices (88%); (iii) an 80% inhibition of the vesicular monoamine transporter expression revealed by the binding of [3H]dihydrotetrabenazine in cerebral slices; (iv) a robust decrease in the quantity of DA and its metabolites (about 50–60%); (v) a slight modification of the DAT activity with a decreased number of functional sites (Vmax decreased by 12%, p < 0.05) without change of the affinity in striatal synaptosomes. Among these markers the binding of [125I]PE2I in membrane homogenates and the content of DA, and its metabolites, in striatum could be the most relevant in vitro indexes of the degenerative state of the nigrostriatal pathway after MPP+ lesion.
Local and systemic increase in lipid peroxidation after moderate experimental traumatic brain injury
Authors: Praticò Domenico , Reiss Peter , Tang Lina X. , Sung Syan , Rokach Joshua , McIntosh Tracy K. 
Published: March 2003

AbstractTraumatic brain injury is a common event associated with neurological dysfunction. Oxidative damage, may contribute to some of these pathologic changes. We used a specific and sensitive marker of lipid peroxidation, the isoprostane 8,12‐iso‐iPF2α‐VI, to investigate whether local and also systemic lipid peroxidation were induced following lateral fluid percussion (FP) brain injury in the rat. Animals were anesthetized and subjected to lateral FP brain injury of moderate severity, or to sham injury as controls. Urine was collected before anesthesia (baseline), 6 and 24 h after injury. Blood was collected at baseline, 1, 6 and 24 h after injury. Animals were killed 24 h after surgery and their brains removed for biochemical analysis. No significant difference was observed at baseline (preinjury) for urine and plasma 8,12‐iso‐iPF2α‐VI levels between injured and sham‐operated animals. By contrast, plasma and urinary levels increased significantly already at 1 and further increased 24 h following brain injury, when compared to sham‐operated animals. Finally, compared with sham, injured animals had a significant increase in brain 8,12‐iso‐iPF2α‐VI levels. These results demonstrate that moderate brain injury induces widespread brain lipid peroxidation, which is accompanied by a similar increase in urine and plasma. Peripheral measurement of 8,12‐iso‐iPF2α‐VI levels after brain injury may be a reliable marker of brain oxidative damage.
High rates of extracellular superoxide production in bryophytes and lichens, and an oxidative burst in response to rehydration following desiccation
Authors: Minibayeva Farida , Beckett Richard Peter 
Published: March 2003

Summary

The mechanism of extracellular superoxide radical (O2·−) formation and the role of the oxidative burst in response to desiccation stress is reported here in bryophytes and lichens from habitats of contrasting water availability.
Rates of extracellular production of O2·− radicals were measured, before and after desiccation stress, by the oxidation of epinephrine to adrenochrome, determined spectrophotometrically.
Several desiccation‐sensitive lichens and bryophytes that grow in very wet microhabitats produced O2·− extracellularly at high rates, even when they were not stressed. In addition, some species showed a powerful burst of O2·− production during rehydration following desiccation. Production of high levels of O2·− and the existence of an inducible oxidative burst was best developed in cyanobacterial lichens, a hornwort and the two thalloid liverworts tested. Extracellular production of O2·− was almost absent from all mosses tested, a leafy liverwort, a filmy fern and from desiccation‐tolerant lichens.
Patterns of O2·− production are discussed in terms of their possible role as a defence against pathogenic fungi and bacteria.
A model coupling foliar monoterpene emissions to leaf photosynthetic characteristics in Mediterranean evergreen Quercus species
Authors: Niinemets Ülo , Seufert Günther , Steinbrecher Rainer , Tenhunen John D. 
Published: March 2003

Summary

A model was developed and parameterized to simulate monoterpene emission rates per unit leaf area (E) dependent on foliar photosynthetic potentials and activity of monoterpene synthases in the evergreen sclerophylls Quercus coccifera L. and Q. ilex L.
Assuming that total activity of monoterpene synthases controls the pathway flux, the product of leaf dry mass per unit area E was culculated as the fraction of total electron flow used for monoterpene synthesis (ɛ), the rate of photosynthetic electron transport (J) per unit leaf dry mass and the reciprocal of the electron cost of monoterpene synthesis. In the model, light effects on E result from light responses of J, and the temperature relationship of E combines temperature dependencies of J and the specific activity of monoterpene synthase (SS).
Having determined J from leaf photosynthesis data and deriving an estimate of SS from in vitro laboratory measurements, good fits to diurnal time‐courses of monoterpenoid emission rates were obtained using a single leaf‐dependent coefficient, the total monoterpene synthase activity in the leaves.
Our analysis demonstrates that using J as a surrogate of E leads to a realistic description of E, especially under stress conditions where the previous models fail. However, analysis of daily time courses of E indicated that storage of monoterpenoids in nonspecific leaf compartments might alter the correspondence between monoterpenoid synthesis and emission rates, especially after rapid environmental change.
Calcium signalling in stomatal responses to pollutants
Authors: McAinsh Martin R. , Evans Nicky H. , Montgomery Lucy T. , North Kathryn A. 
Published: March 2003

SummaryStomatal responses to air pollutants are complex, varying among species and with concentration, environmental conditions and age. In general, short‐term exposure to sulphur dioxide (SO2) promotes stomatal opening, whereas longer‐term exposure can cause partial stomatal closure. By contrast, the effects of oxides of nitrogen (NOx) are often small or insignificant. The effects of ozone, and oxidative stress, are equally complex. Short‐term exposure to ozone stimulates a rapid reduction in stomatal aperture, whilst longer‐term exposure causes stomatal responses to become sluggish. The response of stomata to abscisic acid (ABA) has been shown to be slower in plants exposed to a combination of SO2 and NO2 suggesting an adverse effect on guard cell ABA signal transduction. In addition, ozone causes a reduction in stomatal closure under drought conditions. There is an increasing body of evidence to suggest that air pollutants and oxidative stresses can have a marked effect on the Ca2+ homeostasis of guard cells and the intracellular machinery responsible for stomatal movements. Here we discuss the effects of air pollutants on stomatal responses and their possible effects on Ca2+ based signalling in guard cells focusing on the effects of ozone and oxidative stress.
Mechanisms of immunity to Haemonchus contortus infection in sheep
Authors: Balic A. , Bowles V. M. , Meeusen E. N. T. 
Published: March 2003

SummaryIn two separate experiments, sheep were immunized by nine to 12 weekly immunizing infections with 4000 Haemonchus contortus third stage larva (L3), drenched with anthelminthics and maintained free of H. contortus infection for a further 12 weeks. The anamnestic cellular immune responses in both the abomasal lymph node (ALN) and mucosa of the immunized sheep were examined 3 and 5 days post challenge with 50 000 H. contortus L3. Sheep in the two experiments clearly segregated out in two distinct groups, one in which challenge larvae were obviously present in the tissues of all 12 sheep at 3 and 5 days post challenge while no challenge larvae were detected in tissues of seven of the eight sheep in the other group. In sheep in which no tissue larvae were detected, very few changes were noted in either the ALN or mucosa. In contrast, dramatic changes were observed in the cellular profiles of the ALN and mucosa after challenge infection in sheep in which larvae were observed in the abomasal tissues. In the ALN, these changes were characterized by an increase in the relative percentage of γδ‐TCR+ T cells and B cells and an increase in the proportion of CD4+ T cells coexpressing the activation markers MHC class II and CD25. In the abomasal mucosa, an increase in the number of infiltrating CD4+ and γδ‐TCR+ T cells and B cells was observed by 3 days postinfection and these levels were further increased at 5 days postinfection. This infiltration of the abomasal mucosa by lymphocytes was accompanied by a dramatic increase in the number of infiltrating eosinophils, which were often in intimate association with the surface of H. contortus larvae. None of these changes occurred in the mucosa of the sheep that showed no sign of challenge larvae in the tissues; however, a transient increase in γδ T cells in the ALN and a drop in intraepithelial globule leucocytes were uniquely observed in these sheep at 5 days post challenge. These results suggest that two different types of immune responses can be generated after challenge infection of immunized sheep, one where tissue larvae are excluded from their tissue niche as observed previously and which is associated with changes in globular leucocyte population but no mobilization of the local immune system. In contrast, when challenge larvae reach their tissue niche, dramatic changes in the local immune system occur, including a pronounced infiltration of eosinophils. These two immune mechanisms may be associated with the rapid and delayed rejection of parasite infections in immune sheep.