bluuebunny/crossref_metadata_2025_split huggingface dataset:
Live‐attenuated influenza viruses as delivery vectors for Chlamydia vaccines
Authors: He Qing , Martinez‐Sobrido Luis , Eko Francis O. , Palese Peter , Garcia‐Sastre Adolfo , Lyn Deborah , Okenu Daniel , Bandea Claudiu , Ananaba Godwin A. , Black Carolyn M. , Igietseme Joseph U. 
Published: May 2007

SummaryEffective delivery systems are needed to design efficacious vaccines against the obligate intracellular bacterial pathogen, Chlamydia trachomatis. Potentially effective delivery vehicles should promote the induction of adequate levels of mucosal T‐cell and antibody responses that mediate long‐term protective immunity. Antigen targeting to the nasal‐associated lymphoid tissue (NALT) is effective for inducing high levels of specific immune effectors in the genital mucosa, and therefore suitable for vaccine delivery against genital chlamydial infection. We tested the hypothesis that live attenuated influenza A viruses are effective viral vectors for intranasal delivery of subunit vaccines against genital chlamydial infection. Recombinant influenza A/PR8/34 (H1N1) viruses were generated by insertion of immunodominant T‐cell epitopes from chlamydial major outer membrane protein into the stalk region of the neuraminidase gene. Intranasal immunization of mice with viral recombinants resulted in a strong T helper 1 (Th1) response against intact chlamydial elementary bodies. Also, immunized mice enjoyed a significant state of protective immunity (P > 0·002) by shedding less chlamydiae and rapidly clearing the infection. Furthermore, a high frequency of Chlamydia‐specific Th1 was measured in the genital mucosal and systemic draining lymphoid tissues within 24 hr after challenge of vaccinated mice. Moreover, multiple epitope delivery provided a vaccine advantage over single recombinants. Besides, long‐term protective immunity correlated with the preservation of a robustly high frequency of specific Th1 cells and elevated immunoglobulin G2a in genital secretions. Because live attenuated influenza virus vaccines are safe and acceptable for human use, they may provide a new and reliable approach to deliver efficacious vaccines against sexually transmitted diseases.
Glucocorticoids exert opposing effects on macrophage function dependent on their concentration
Authors: Lim Hee‐Young , Müller Nora , Herold Marco J. , Van Den Brandt Jens , Reichardt Holger M. 
Published: May 2007

SummaryGlucocorticoids (GCs) are involved in the modulation of macrophage function and thereby control the host's immune responses to pathogens. However, neither the role of hormone concentration nor the differential contribution of the glucocorticoid (GR) and the mineralocorticoid receptors (MR) to these activities are known. Here we show that low levels of corticosterone enhance NO production as well as mRNA expression of pro‐inflammatory cytokines, chemokines and enzymes required for mediator synthesis. In contrast, at high corticosterone concentrations macrophage function was strongly repressed. Importantly, inactivation of the GR by lentiviral delivery of siRNAs abrogated both the immunostimulatory and the immunosuppressive GC actions whereas inactivation of the MR had no effect. Furthermore, removal of endogenous GCs by adrenalectomy in vivo induced a preactivated state in macrophages that could be modulated by corticosterone. We conclude that GCs exert distinct effects on macrophage function dependent on their concentration, and that they primarily act through the GR despite concomitant expression of the MR.
Acid sphingomyelinase inhibition suppresses lipopolysaccharide‐mediated release of inflammatory cytokines from macrophages and protects against disease pathology in dextran sulphate sodium‐induced colitis in mice
Authors: Sakata Akira , Ochiai Takashi , Shimeno Hiroshi , Hikishima Sadao , Yokomatsu Tsutomu , Shibuya Shiroshi , Toda Akihisa , Eyanagi Reiko , Soeda Shinji 
Published: May 2007

SummaryLipopolysaccharide (LPS) and inflammatory cytokines cause activation of sphingomyelinases (SMases) and subsequent hydrolysis of sphingomyelin (SM) to produce a lipid messenger ceramide. The design of SMase inhibitors may offer new therapies for the treatment of LPS‐ and cytokine‐related inflammatory bowel disease. We synthesized a series of difluoromethylene analogues of SM (SMAs). We report here the effects of the most potent SMase inhibitor, SMA‐7, on the LPS‐mediated release of tumour necrosis factor‐α, interleukin‐1β and interleukin‐6 from THP‐1 macrophages and the pathology of dextran sulphate sodium (DSS)‐induced colitis in mice. SMA‐7 suppressed the LPS‐induced cytokine release and nuclear factor‐κB activation. LPS stimulation caused a four‐fold increase in acid SMase activation, but little increase in neutral SMase activity. The presence of 10 μm SMA‐7 caused acid SMase to remain at the control levels and reduced the formation of ceramide. HT‐29 cells had significantly decreased cell viability when incubated with media from LPS‐stimulated THP‐1 macrophages. However, incubating the colon cells in media from both SMA‐7 and LPS‐treated macrophages caused little decrease in viability, suggesting that ceramide has a role in the LPS‐stimulated signalling that releases cytotoxic factors against colon cells. Oral administration of SMA‐7 to mice with 2% DSS in the drinking water, for 10 or 21 consecutive days, reduced significantly the cytokine levels in the colon and the severity of colonic injury. These findings suggest a central role for acid SMase/ceramide signalling in the pathology of DSS‐induced colitis in mice, indicating a possible preventive or therapeutic role for SMase inhibitor in inflammatory bowel disease.
Synthesis of β2‐microglobulin‐free, disulphide‐linked HLA‐G5 homodimers in human placental villous cytotrophoblast cells
Authors: Morales Pedro J. , Pace Judith L. , Platt Jeralyn Sue , Langat Daudi K. , Hunt Joan S. 
Published: May 2007

SummaryHuman leucocyte antigen‐G (HLA‐G) is a natural immunosuppressant produced in human placentas that binds differently to the inhibitory leucocyte immunoglobulin‐like receptors LILRB1 (ILT2) and LILRB2 (ILT4) according to its biochemical structure. To predict the binding functions of the HLA‐G5 soluble isoform synthesized in placental villous cytotrophoblast (vCTB) cells, we investigated structural features of this protein. Biochemical and immunological studies showed that vCTB cell HLA‐G5 heavy (H)‐chain proteins are disulphide‐bonded homodimers unassociated with β2‐microglobulin (β2m) light‐chain proteins. Although comparatively low levels of β2m messenger RNA (mRNA) were identified by real‐time reverse transcription–polymerase chain reaction, immunoprecipitation studies failed to detect β2m protein even when specific mRNA was doubled by transduction of a lentivirus‐β2m complementary DNA into vCTB cells. No abnormalities were identified in the translational start codon of vCTB cell β2m mRNA and differentiation into syncytium did not promote β2m synthesis. The failure of vCTB cells to exhibit β2m in vitro was paralleled by a lack of detectable β2m in vCTB cells in vivo. Lack of the β2m protein could be the result of low levels of β2m transcripts or of as yet unidentified translational defects. Experiments with recombinant ectodomains of LILRB indicate that β2m‐free HLA‐G binds strongly to LILRB2, a receptor that is expressed by macrophages. This potentially immunosuppressive cell type is abundant in the pregnant uterus. Thus, our findings are consistent with the postulate that the natural β2m‐free homodimeric form of HLA‐G5 synthesized in primary vCTB cells could comprise a particularly effective tolerogenic molecule at the maternal–fetal interface.
Genetic and environmental risk factors for testicular cancer
Authors: Richiardi Lorenzo , Pettersson Andreas , Akre Olof 
Published: May 2007

SummaryGerm‐cell testicular cancer has a well‐characterized descriptive epidemiology, whereas the aetiology remains largely unknown. It is believed that exposures acting prenatally are instrumental to germ‐cell cancer development, although no specific exposure has been identified. Several epidemiological studies have investigated a number of indicators of prenatal exposures, such as birth order, gestational duration, birth weight, maternal age and nausea during pregnancy, but results are inconsistent. This paper briefly reviews the current support for genetic and environmental factors in testicular cancer aetiology. In particular, we have summarized the evidence suggesting a strong role of inherited susceptibility, which is probably carried by the effect of several unknown moderate‐risk genes. We have illustrated inconsistencies in the previous studies on prenatal factors by estimating the heterogeneity and pooled odds ratios among twelve studies investigating the association between low birth weight and testicular cancer. We have discussed the possibility that puberty is another time window during which environmental factors may increase the risk of testicular cancer. Finally, we have reviewed the results from studies on cryptorchidism and impaired fertility in relation to risk for testicular cancer. In conclusion, we propose that future aetiological studies on testicular cancer should take postnatal exposures acting during puberty into account and, whenever possible, investigate both main effects and interactions among prenatal factors, genetic factors and postnatal factors.
Rapid heating of intact leaves reveals initial effects of stromal oxidation on photosynthesis
Authors: SCHRADER STEPHEN M. , KLEINBECK KYLE R. , SHARKEY THOMAS D. 
Published: May 2007

ABSTRACTHeat stress in leaves under natural conditions is characterized by rapid fluctuations in temperature. These fluctuations can be on the order of 10 °C in 7 s. By using a specially modified gas‐exchange chamber, these conditions were mimicked in the laboratory to analyse the biochemical response to heat spikes. The decline in ribulose 1·5‐bisphosphate carboxylase/oxygenase (Rubisco) activity during prolonged heat stress is generally associated with an increase in ribulose 1,5‐bisphosphate (RuBP) levels. However, rapid heating caused an initial decline in RuBP which was subsequently followed by a small decline in Rubisco carbamylation. The ratio of RuBP to Rubisco sites declined from a saturating concentration to a sub‐saturating concentration, providing a possible mechanism for the decarbamylation of Rubisco. If RuBP is saturating (>1.8 RuBP Rubisco site−1), it acts as a cap on the catalytic site and keeps Rubisco activated. Measurements of triose‐phosphate levels and NADP‐malate dehydrogenase activation (a stromal redox proxy) indicated that the regeneration of RuBP by the Calvin cycle was limited by the availability of redox power.
Regulation of reactive oxygen species production by a 14‐3‐3 protein in elicited tobacco cells*
Authors: ELMAYAN TALINE , FROMENTIN JÉRÔME , RIONDET CHRISTOPHE , ALCARAZ GÉRARD , BLEIN JEAN‐PIERRE , SIMON‐PLAS FRANÇOISE 
Published: May 2007

ABSTRACTThe regulation of the system responsible for the production of reactive oxygen species (ROS) during plant–micro‐organism interaction is still largely unknown. The protein NtrbohD has been recently demonstrated as the plasma membrane oxidase responsible for ROS production in elicited tobacco cells. Here, its C‐terminus part was used as a bait in a two‐hybrid screen in order to identify putative regulators of this system. This led to the isolation of a cDNA coding for a member of the 14‐3‐3 protein family. The corresponding transcript was induced after infiltration of tobacco leaves with the fungal elicitor cryptogein. Tobacco cells transformed with an antisense construct of this 14‐3‐3 no longer accumulated ROS, which constitutes a functional validation of the two‐hybrid screen. This work provides new insights to the understanding of the regulation of ROS production in a signalling context and gives a new light to the possible role of 14‐3‐3 proteins in plant–micro‐organisms interactions.
Membrane recycling and calcium dynamics during settlement and adhesion of zoospores of the green alga Ulva linza
Authors: THOMPSON S. E. M. , CALLOW J. A. , CALLOW M. E. , WHEELER G. L. , TAYLOR A. R. , BROWNLEE C. 
Published: May 2007

ABSTRACTRecruitment of individuals of the marine alga Ulva linza on to a suitable habitat involves the settlement of motile zoospores on to a substratum during which a preformed adhesive is secreted by vesicular exocytosis. The fluorescent styryl dye FM 1‐43 and fluorescent Ca2+ indicators were used to follow membrane cycling and changes in cytosolic Ca2+ ([Ca2+]cyt) associated with settlement. When swimming zoospores were exposed continuously to FM 1‐43, the plasma membrane was preferentially labelled. During settlement, FM 1‐43‐labelled plasma membrane was rapidly internalized reflecting high membrane turnover. The internalized membrane was focused into a discrete region indicating targeting of membrane to an endosome‐like compartment. Acetoxymethyl (AM)‐ester derivatives were found to be unsuitable for monitoring [Ca2+]cyt because the dyes were rapidly sequestered from the cytoplasm into sub‐cellular compartments. [Ca2+]cyt was, however, reliably measured using dextran‐conjugated calcium indicators delivered into cells using a biolistic technique. Cells loaded with Oregon Green BAPTA‐1 dextran (Invitrogen, Paisley, UK) showed diffuse cytosolic loading and reliably responded to imposed changes in [Ca2+]cyt. During settlement, zoospores exhibited both localized and diffuse increases in [Ca2+]cyt implying a role for [Ca2+]cyt in exocytosis of the adhesive.
Activation of the heat shock response in plants by chlorophenols: transgenic Physcomitrella patens as a sensitive biosensor for organic pollutants
Authors: SAIDI YOUNOUSSE , DOMINI MARTA , CHOY FLEUR , ZRYD JEAN‐PIERRE , SCHWITZGUEBEL JEAN‐PAUL , GOLOUBINOFF PIERRE 
Published: May 2007

ABSTRACTThe ability to detect early molecular responses to various chemicals is central to the understanding of biological impact of pollutants in a context of varying environmental cues. To monitor stress responses in a model plant, we used transgenic moss Physcomitrella patens expressing the β‐glucuronidase reporter (GUS) under the control of the stress‐inducible promoter hsp17.3B. Following exposure to pollutants from the dye and paper industry, GUS activity was measured by monitoring a fluorescent product.Chlorophenols, heavy metals and sulphonated anthraquinones were found to specifically activate the hsp17.3B promoter (within hours) in correlation with long‐term toxicity effects (within days). At mildly elevated physiological temperatures, the chemical activation of this promoter was strongly amplified, which considerably increased the sensitivity of the bioassay. Together with the activation of hsp17.3B promoter, chlorophenols induced endogenous chaperones that transiently protected a recombinant thermolabile luciferase (LUC) from severe heat denaturation. This sensitive bioassay provides an early warning molecular sensor to industrial pollutants under varying environments, in anticipation to long‐term toxic effects in plants.Because of the strong cross‐talk between abiotic and chemical stresses that we find, this P. patens line is more likely to serve as a direct toxicity bioassay for pollutants combined with environmental cues, than as an indicator of absolute toxicity thresholds for various pollutants. It is also a powerful tool to study the role of heat shock proteins (HSPs) in plants exposed to combined chemical and environmental stresses.
Consequences of insect herbivory on grape fine root systems with different growth rates
Authors: BAUERLE T. L. , EISSENSTAT D. M. , GRANETT J. , GARDNER D. M. , SMART D. R. 
Published: May 2007

ABSTRACTHerbivory tolerance has been linked to plant growth rate where plants with fast growth rates are hypothesized to be more tolerant of herbivory than slower‐growing plants. Evidence supporting this theory has been taken primarily from observations of aboveground organs but rarely from roots. Grapevines differing in overall rates of new root production, were studied in Napa Valley, California over two growing seasons in an established vineyard infested with the sucking insect, grape phylloxera (Daktulosphaira vitifoliaeFitch). The experimental vineyard allowed for the comparison of two root systems that differed in rates of new root tip production (a ‘fast grower’,Vitis berlandieri × Vitis rupestriscv. 1103P, and a slower‐growing stock,Vitis riparia × Vitis rupestriscv. 101–14 Mgt). Each root system was grafted with a genetically identical shoot system (Vitis viniferacv. Merlot). Using minirhizotrons, we did not observe any evidence of spatial or temporal avoidance of insect populations by root growth. Insect infestations were abundant throughout the soil profile, and seasonal peaks in phylloxera populations generally closely followed peaks in new root production. Our data supported the hypothesis that insect infestation was proportional to the number of growing tips, as indicated by similar per cent infestation in spite of a threefold difference in root tip production. In addition, infested roots of the fast‐growing rootstock exhibited somewhat shorter median lifespans (60 d) than the slower‐growing rootstock (85 d). Lifespans of uninfested roots were similar for the two rootstocks (200 d). As a consequence of greater root mortality of younger roots, infested root populations in the fast‐growing rootstock had an older age structure. While there does not seem to be a trade‐off between potential growth rate and relative rate of root infestation in these cultivars, our study indicates that a fast‐growing root system may more readily shed infested roots that are presumably less effective in water and nutrient uptake. Thus, differences in root tip production may be linked to differences in the way plants cope with roots that are infested by sucking insects.
Involvement of hydrogen peroxide and nitric oxide in salt resistance in the calluses from Populus euphratica
Authors: ZHANG FENG , WANG YUPING , YANG YINGLI , WU HAO , WANG DI , LIU JIANQUAN 
Published: May 2007

ABSTRACTNitric oxide (NO) and hydrogen peroxide (H2O2) function as signalling molecules in plants under abiotic and biotic stresses. Calluses from Populus euphratica, which show salt tolerance, were used to study the interaction of NO and H2O2 in plant adaptation to salt resistance. The nitric oxide synthase (NOS) activity was identified in the calluses, and this activity was induced under 150 mM NaCl treatment. Under 150 mM NaCl treatment, the sodium (Na) percentage decreased, but the potassium (K) percentage and the K/Na ratio increased in P. euphratica calluses. Application of glucose/glucose oxidase (G/GO, a H2O2 donor) and sodium nitroprusside (SNP, a NO donor) revealed that both H2O2 and NO resulted in increased K/Na ratio in a concentration‐dependent manner. Diphenylene iodonium (DPI, an NADPH oxidase inhibitor) counteracted H2O2 and NO effect by increasing the Na percentage, decreasing the K percentage and K/Na ratio. NG‐monomethyl‐l‐Arg monoacetate (NMMA, an NO synthase inhibitor) and 2‐phenyl‐4,4,5,5‐tetramethyl‐imidazoline‐1‐oxyl‐3‐oxyde (PTIO, a specific NO scavenger) only reversed NO effect, but did not block H2O2 effect. The increased activity of plasma membrane (PM) H+‐ATPase caused by salt stress was reversed by treatment with DPI and NMMA. Exogenous H2O2 increased the activity of PM H+‐ATPase, but the effect could not be diminished by NMMA and PTIO. The NO‐induced increase of PM H+‐ATPase can be reversed by NMMA and PTIO, but not by DPI. Western blot analysis demonstrated that NO and H2O2 stimulated the expression of PM H+‐ATPase in P. euphratica calluses. These results indicate that NO and H2O2 served as intermediate molecules in inducing salt resistance in the calluses from P. euphratica under slat stress by increasing the K/Na ratio, which was dependent on the increased PM H+‐ATPase activity.
Extraordinary cross‐reactivity of an autoimmune T‐cell receptor recognizing specific peptides both on autologous and on allogeneic HLA class II molecules
Authors: Hansen B. E. , Rasmussen A. H , Jakobsen B. K. , Ryder L. P. , Svejgaard A. 
Published: May 2007

AbstractA T‐cell receptor’s (TCR) recognition of a human leukocyte antigen (HLA)–peptide complex (pHLA) is normally described as being restricted by the HLA molecule and specific for the peptide. This is, however, not always true. Several TCRs have been described, which cross‐react with other peptides bound to the restricting HLA molecule. This phenomenon has been considered a variant of molecular mimicry and is suggested to be one of the mechanisms behind autoimmunity. The positive selection of T cells in the thymus imposes low‐affinity recognition of the TCRs toward self‐pHLA, which increases the probability of the TCR to be promiscuous by nature, and further implies that the T‐cell repertoire contains TCRs prone to be autoreactive and thus able to induce autoimmunity. We present an autoimmune TCR showing extreme cross‐reactivity to several pHLA comprising both own HLA class II restriction element and allogeneic HLA class II restriction elements in complex with both self‐derived and microbially derived peptides. The existence of such a significant cross‐reactivity in the context of distinct HLA‐DR molecules might be more common among autoimmune TCRs than previously anticipated and potentially reveals a new way of designing altered peptide ligands for therapeutic use.
Xenotransfusions, past and present
Authors: Roux Françoise A. , Saï Pierre , Deschamps Jack‐Yves 
Published: May 2007

Abstract: The first blood transfusions in humans were xenotransfusions, carried out by Jean‐Baptiste Denis beginning in 1667. Richard Lower, Matthäus Purmann and Georges Mercklin also experimented with the use of animal blood for transfusion until this practice was forbidden in 1670, after the death of one of Denis’s patients. In the middle of the 19th century, xenotransfusion was rescued from oblivion by the work of Pierre Cyprien Oré. Franz Gesellius and Oscar Hasse fervently defended xenotransfusion, but Emil Ponfick and Leonard Landois stressed the potentially harmful effects of inter‐species transfusion from 1874 onward. Xenotransfusion was abandoned completely following the discovery of blood groups by Karl Landsteiner in 1900. From 2000, because of progress in xenotransplantation and the need of blood supply, xenotransfusion is again being considered. Pigs are the best potential donors. The development of α‐1,3‐galactosyltransferase gene‐knockout pigs has overcome the first hurdle to xenotransfusion. The main obstacle to porcine red blood cell transfusion is now the cellular response involving macrophages or natural killer cells.
The formal Darwinism project: a mid‐term report
Authors: GRAFEN A. 
Published: May 2007

AbstractFor 8 years I have been pursuing in print an ambitious and at times highly technical programme of work, the ‘Formal Darwinism Project’, whose essence is to underpin and formalize the fitness optimization ideas used by behavioural ecologists, using a new kind of argument linking the mathematics of motion and the mathematics of optimization. The value of the project is to give stronger support to current practices, and at the same time sharpening theoretical ideas and suggesting principled resolutions of some untidy areas, for example, how to define fitness. The aim is also to unify existing free‐standing theoretical structures, such as inclusive fitness theory, Evolutionary Stable Strategy (ESS) theory and bet‐hedging theory. The 40‐year‐old misunderstanding over the meaning of fitness optimization between mathematicians and biologists is explained. Most of the elements required for a general theory have now been implemented, but not together in the same framework, and ‘general time’ remains to be developed and integrated with the other elements to produce a final unified theory of neo‐Darwinian natural selection.